--- _id: '9226' abstract: - lang: eng text: 'Half a century after Lewis Wolpert''s seminal conceptual advance on how cellular fates distribute in space, we provide a brief historical perspective on how the concept of positional information emerged and influenced the field of developmental biology and beyond. We focus on a modern interpretation of this concept in terms of information theory, largely centered on its application to cell specification in the early Drosophila embryo. We argue that a true physical variable (position) is encoded in local concentrations of patterning molecules, that this mapping is stochastic, and that the processes by which positions and corresponding cell fates are determined based on these concentrations need to take such stochasticity into account. With this approach, we shift the focus from biological mechanisms, molecules, genes and pathways to quantitative systems-level questions: where does positional information reside, how it is transformed and accessed during development, and what fundamental limits it is subject to?' acknowledgement: This work was supported in part by the National Science Foundation, through the Center for the Physics of Biological Function (PHY-1734030), by the National Institutes of Health (R01GM097275) and by the Fonds zur Förderung der wissenschaftlichen Forschung (FWF P28844). Deposited in PMC for release after 12 months. article_number: dev176065 article_processing_charge: No article_type: original author: - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Thomas full_name: Gregor, Thomas last_name: Gregor citation: ama: Tkačik G, Gregor T. The many bits of positional information. Development. 2021;148(2). doi:10.1242/dev.176065 apa: Tkačik, G., & Gregor, T. (2021). The many bits of positional information. Development. The Company of Biologists. https://doi.org/10.1242/dev.176065 chicago: Tkačik, Gašper, and Thomas Gregor. “The Many Bits of Positional Information.” Development. The Company of Biologists, 2021. https://doi.org/10.1242/dev.176065. ieee: G. Tkačik and T. Gregor, “The many bits of positional information,” Development, vol. 148, no. 2. The Company of Biologists, 2021. ista: Tkačik G, Gregor T. 2021. The many bits of positional information. Development. 148(2), dev176065. mla: Tkačik, Gašper, and Thomas Gregor. “The Many Bits of Positional Information.” Development, vol. 148, no. 2, dev176065, The Company of Biologists, 2021, doi:10.1242/dev.176065. short: G. Tkačik, T. Gregor, Development 148 (2021). date_created: 2021-03-07T23:01:25Z date_published: 2021-02-01T00:00:00Z date_updated: 2023-08-07T13:57:30Z day: '01' department: - _id: GaTk doi: 10.1242/dev.176065 external_id: isi: - '000613906000007' pmid: - '33526425' intvolume: ' 148' isi: 1 issue: '2' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1242/dev.176065 month: '02' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: Development publication_identifier: eissn: - 1477-9129 publication_status: published publisher: The Company of Biologists quality_controlled: '1' scopus_import: '1' status: public title: The many bits of positional information type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 148 year: '2021' ... --- _id: '9439' abstract: - lang: eng text: The ability to adapt to changes in stimulus statistics is a hallmark of sensory systems. Here, we developed a theoretical framework that can account for the dynamics of adaptation from an information processing perspective. We use this framework to optimize and analyze adaptive sensory codes, and we show that codes optimized for stationary environments can suffer from prolonged periods of poor performance when the environment changes. To mitigate the adversarial effects of these environmental changes, sensory systems must navigate tradeoffs between the ability to accurately encode incoming stimuli and the ability to rapidly detect and adapt to changes in the distribution of these stimuli. We derive families of codes that balance these objectives, and we demonstrate their close match to experimentally observed neural dynamics during mean and variance adaptation. Our results provide a unifying perspective on adaptation across a range of sensory systems, environments, and sensory tasks. acknowledgement: We thank D. Kastner and T. Münch for generously providing figures from their work. We also thank V. Jayaraman, M. Noorman, T. Ma, and K. Krishnamurthy for useful discussions and feedback on the manuscript. W.F.M. was funded by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie Grant Agreement No. 754411. A.M.H. was supported by the Howard Hughes Medical Institute. article_processing_charge: No article_type: original author: - first_name: Wiktor F full_name: Mlynarski, Wiktor F id: 358A453A-F248-11E8-B48F-1D18A9856A87 last_name: Mlynarski - first_name: Ann M. full_name: Hermundstad, Ann M. last_name: Hermundstad citation: ama: Mlynarski WF, Hermundstad AM. Efficient and adaptive sensory codes. Nature Neuroscience. 2021;24:998-1009. doi:10.1038/s41593-021-00846-0 apa: Mlynarski, W. F., & Hermundstad, A. M. (2021). Efficient and adaptive sensory codes. Nature Neuroscience. Springer Nature. https://doi.org/10.1038/s41593-021-00846-0 chicago: Mlynarski, Wiktor F, and Ann M. Hermundstad. “Efficient and Adaptive Sensory Codes.” Nature Neuroscience. Springer Nature, 2021. https://doi.org/10.1038/s41593-021-00846-0. ieee: W. F. Mlynarski and A. M. Hermundstad, “Efficient and adaptive sensory codes,” Nature Neuroscience, vol. 24. Springer Nature, pp. 998–1009, 2021. ista: Mlynarski WF, Hermundstad AM. 2021. Efficient and adaptive sensory codes. Nature Neuroscience. 24, 998–1009. mla: Mlynarski, Wiktor F., and Ann M. Hermundstad. “Efficient and Adaptive Sensory Codes.” Nature Neuroscience, vol. 24, Springer Nature, 2021, pp. 998–1009, doi:10.1038/s41593-021-00846-0. short: W.F. Mlynarski, A.M. Hermundstad, Nature Neuroscience 24 (2021) 998–1009. date_created: 2021-05-30T22:01:24Z date_published: 2021-05-20T00:00:00Z date_updated: 2023-08-08T13:51:14Z day: '20' department: - _id: GaTk doi: 10.1038/s41593-021-00846-0 ec_funded: 1 external_id: isi: - '000652577300003' intvolume: ' 24' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: 'https://doi.org/10.1101/669200 ' month: '05' oa: 1 oa_version: Preprint page: 998-1009 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: Nature Neuroscience publication_identifier: eissn: - 1546-1726 issn: - 1097-6256 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Efficient and adaptive sensory codes type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 24 year: '2021' ... --- _id: '9822' abstract: - lang: eng text: Attachment of adhesive molecules on cell culture surfaces to restrict cell adhesion to defined areas and shapes has been vital for the progress of in vitro research. In currently existing patterning methods, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome, and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable patterning step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes and that our innovative approach has great potential for further applications in cell science. acknowledgement: We would like to thank Charlott Leu for the production of our chromium wafers, Louise Ritter for her contribution of the IF stainings in Figure 4, Shokoufeh Teymouri for her help with the Bioinert coated slides, and finally Prof. Dr. Joachim Rädler for his valuable scientific guidance. article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Themistoklis full_name: Zisis, Themistoklis last_name: Zisis - first_name: Jan full_name: Schwarz, Jan id: 346C1EC6-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Miriam full_name: Balles, Miriam last_name: Balles - first_name: Maibritt full_name: Kretschmer, Maibritt last_name: Kretschmer - first_name: Maria full_name: Nemethova, Maria id: 34E27F1C-F248-11E8-B48F-1D18A9856A87 last_name: Nemethova - first_name: Remy P full_name: Chait, Remy P id: 3464AE84-F248-11E8-B48F-1D18A9856A87 last_name: Chait orcid: 0000-0003-0876-3187 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Janina full_name: Lange, Janina last_name: Lange - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-4561-241X - first_name: Stefan full_name: Zahler, Stefan last_name: Zahler citation: ama: Zisis T, Schwarz J, Balles M, et al. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. 2021;13(30):35545–35560. doi:10.1021/acsami.1c09850 apa: Zisis, T., Schwarz, J., Balles, M., Kretschmer, M., Nemethova, M., Chait, R. P., … Zahler, S. (2021). Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. American Chemical Society. https://doi.org/10.1021/acsami.1c09850 chicago: Zisis, Themistoklis, Jan Schwarz, Miriam Balles, Maibritt Kretschmer, Maria Nemethova, Remy P Chait, Robert Hauschild, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” ACS Applied Materials and Interfaces. American Chemical Society, 2021. https://doi.org/10.1021/acsami.1c09850. ieee: T. Zisis et al., “Sequential and switchable patterning for studying cellular processes under spatiotemporal control,” ACS Applied Materials and Interfaces, vol. 13, no. 30. American Chemical Society, pp. 35545–35560, 2021. ista: Zisis T, Schwarz J, Balles M, Kretschmer M, Nemethova M, Chait RP, Hauschild R, Lange J, Guet CC, Sixt MK, Zahler S. 2021. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. 13(30), 35545–35560. mla: Zisis, Themistoklis, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” ACS Applied Materials and Interfaces, vol. 13, no. 30, American Chemical Society, 2021, pp. 35545–35560, doi:10.1021/acsami.1c09850. short: T. Zisis, J. Schwarz, M. Balles, M. Kretschmer, M. Nemethova, R.P. Chait, R. Hauschild, J. Lange, C.C. Guet, M.K. Sixt, S. Zahler, ACS Applied Materials and Interfaces 13 (2021) 35545–35560. date_created: 2021-08-08T22:01:28Z date_published: 2021-08-04T00:00:00Z date_updated: 2023-08-10T14:22:48Z day: '04' ddc: - '620' - '570' department: - _id: MiSi - _id: GaTk - _id: Bio - _id: CaGu doi: 10.1021/acsami.1c09850 ec_funded: 1 external_id: isi: - '000683741400026' pmid: - '34283577' file: - access_level: open_access checksum: b043a91d9f9200e467b970b692687ed3 content_type: application/pdf creator: asandaue date_created: 2021-08-09T09:44:03Z date_updated: 2021-08-09T09:44:03Z file_id: '9833' file_name: 2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf file_size: 7123293 relation: main_file success: 1 file_date_updated: 2021-08-09T09:44:03Z has_accepted_license: '1' intvolume: ' 13' isi: 1 issue: '30' language: - iso: eng month: '08' oa: 1 oa_version: Published Version page: 35545–35560 pmid: 1 project: - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients publication: ACS Applied Materials and Interfaces publication_identifier: eissn: - '19448252' issn: - '19448244' publication_status: published publisher: American Chemical Society quality_controlled: '1' scopus_import: '1' status: public title: Sequential and switchable patterning for studying cellular processes under spatiotemporal control tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 13 year: '2021' ... --- _id: '9828' abstract: - lang: eng text: Amplitude demodulation is a classical operation used in signal processing. For a long time, its effective applications in practice have been limited to narrowband signals. In this work, we generalize amplitude demodulation to wideband signals. We pose demodulation as a recovery problem of an oversampled corrupted signal and introduce special iterative schemes belonging to the family of alternating projection algorithms to solve it. Sensibly chosen structural assumptions on the demodulation outputs allow us to reveal the high inferential accuracy of the method over a rich set of relevant signals. This new approach surpasses current state-of-the-art demodulation techniques apt to wideband signals in computational efficiency by up to many orders of magnitude with no sacrifice in quality. Such performance opens the door for applications of the amplitude demodulation procedure in new contexts. In particular, the new method makes online and large-scale offline data processing feasible, including the calculation of modulator-carrier pairs in higher dimensions and poor sampling conditions, independent of the signal bandwidth. We illustrate the utility and specifics of applications of the new method in practice by using natural speech and synthetic signals. acknowledgement: The author thanks his colleagues K. Huszár and G. Tkačik for valuable discussions and comments on the manuscript. article_processing_charge: No article_type: original author: - first_name: Mantas full_name: Gabrielaitis, Mantas id: 4D5B0CBC-F248-11E8-B48F-1D18A9856A87 last_name: Gabrielaitis orcid: 0000-0002-7758-2016 citation: ama: Gabrielaitis M. Fast and accurate amplitude demodulation of wideband signals. IEEE Transactions on Signal Processing. 2021;69:4039-4054. doi:10.1109/TSP.2021.3087899 apa: Gabrielaitis, M. (2021). Fast and accurate amplitude demodulation of wideband signals. IEEE Transactions on Signal Processing. Institute of Electrical and Electronics Engineers. https://doi.org/10.1109/TSP.2021.3087899 chicago: Gabrielaitis, Mantas. “Fast and Accurate Amplitude Demodulation of Wideband Signals.” IEEE Transactions on Signal Processing. Institute of Electrical and Electronics Engineers, 2021. https://doi.org/10.1109/TSP.2021.3087899. ieee: M. Gabrielaitis, “Fast and accurate amplitude demodulation of wideband signals,” IEEE Transactions on Signal Processing, vol. 69. Institute of Electrical and Electronics Engineers, pp. 4039–4054, 2021. ista: Gabrielaitis M. 2021. Fast and accurate amplitude demodulation of wideband signals. IEEE Transactions on Signal Processing. 69, 4039–4054. mla: Gabrielaitis, Mantas. “Fast and Accurate Amplitude Demodulation of Wideband Signals.” IEEE Transactions on Signal Processing, vol. 69, Institute of Electrical and Electronics Engineers, 2021, pp. 4039–54, doi:10.1109/TSP.2021.3087899. short: M. Gabrielaitis, IEEE Transactions on Signal Processing 69 (2021) 4039–4054. date_created: 2021-08-08T22:01:31Z date_published: 2021-06-09T00:00:00Z date_updated: 2023-08-10T14:19:33Z day: '09' department: - _id: GaTk doi: 10.1109/TSP.2021.3087899 external_id: arxiv: - '2102.04832' isi: - '000682123900002' intvolume: ' 69' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/2102.04832 month: '06' oa: 1 oa_version: Preprint page: 4039 - 4054 publication: IEEE Transactions on Signal Processing publication_identifier: eissn: - 1941-0476 issn: - 1053-587X publication_status: published publisher: Institute of Electrical and Electronics Engineers quality_controlled: '1' scopus_import: '1' status: public title: Fast and accurate amplitude demodulation of wideband signals type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 69 year: '2021' ... --- _id: '9362' abstract: - lang: eng text: A central goal in systems neuroscience is to understand the functions performed by neural circuits. Previous top-down models addressed this question by comparing the behaviour of an ideal model circuit, optimised to perform a given function, with neural recordings. However, this requires guessing in advance what function is being performed, which may not be possible for many neural systems. To address this, we propose an inverse reinforcement learning (RL) framework for inferring the function performed by a neural network from data. We assume that the responses of each neuron in a network are optimised so as to drive the network towards ‘rewarded’ states, that are desirable for performing a given function. We then show how one can use inverse RL to infer the reward function optimised by the network from observing its responses. This inferred reward function can be used to predict how the neural network should adapt its dynamics to perform the same function when the external environment or network structure changes. This could lead to theoretical predictions about how neural network dynamics adapt to deal with cell death and/or varying sensory stimulus statistics. acknowledgement: The authors would like to thank Ulisse Ferrari for useful discussions and feedback. article_number: e0248940 article_processing_charge: No article_type: original author: - first_name: Matthew J full_name: Chalk, Matthew J id: 2BAAC544-F248-11E8-B48F-1D18A9856A87 last_name: Chalk orcid: 0000-0001-7782-4436 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Olivier full_name: Marre, Olivier last_name: Marre citation: ama: Chalk MJ, Tkačik G, Marre O. Inferring the function performed by a recurrent neural network. PLoS ONE. 2021;16(4). doi:10.1371/journal.pone.0248940 apa: Chalk, M. J., Tkačik, G., & Marre, O. (2021). Inferring the function performed by a recurrent neural network. PLoS ONE. Public Library of Science. https://doi.org/10.1371/journal.pone.0248940 chicago: Chalk, Matthew J, Gašper Tkačik, and Olivier Marre. “Inferring the Function Performed by a Recurrent Neural Network.” PLoS ONE. Public Library of Science, 2021. https://doi.org/10.1371/journal.pone.0248940. ieee: M. J. Chalk, G. Tkačik, and O. Marre, “Inferring the function performed by a recurrent neural network,” PLoS ONE, vol. 16, no. 4. Public Library of Science, 2021. ista: Chalk MJ, Tkačik G, Marre O. 2021. Inferring the function performed by a recurrent neural network. PLoS ONE. 16(4), e0248940. mla: Chalk, Matthew J., et al. “Inferring the Function Performed by a Recurrent Neural Network.” PLoS ONE, vol. 16, no. 4, e0248940, Public Library of Science, 2021, doi:10.1371/journal.pone.0248940. short: M.J. Chalk, G. Tkačik, O. Marre, PLoS ONE 16 (2021). date_created: 2021-05-02T22:01:28Z date_published: 2021-04-15T00:00:00Z date_updated: 2023-10-18T08:17:42Z day: '15' ddc: - '570' department: - _id: GaTk doi: 10.1371/journal.pone.0248940 external_id: isi: - '000641474900072' pmid: - '33857170' file: - access_level: open_access checksum: c52da133850307d2031f552d998f00e8 content_type: application/pdf creator: kschuh date_created: 2021-05-04T13:22:19Z date_updated: 2021-05-04T13:22:19Z file_id: '9371' file_name: 2021_pone_Chalk.pdf file_size: 2768282 relation: main_file success: 1 file_date_updated: 2021-05-04T13:22:19Z has_accepted_license: '1' intvolume: ' 16' isi: 1 issue: '4' language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 publication: PLoS ONE publication_identifier: eissn: - '19326203' publication_status: published publisher: Public Library of Science quality_controlled: '1' scopus_import: '1' status: public title: Inferring the function performed by a recurrent neural network tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 16 year: '2021' ... --- _id: '8997' abstract: - lang: eng text: Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We provide analytical results for limiting cases, which agree well with numerical results. We systematically refine the model by including direct physical interactions of different antibiotics on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions that were derived using entropy maximization. We further refine the model to include the effects of antibiotics that mimic starvation and the presence of resistance genes. We describe the impact of a starvation-mimicking antibiotic on drug interactions analytically and verify it experimentally. Our extended model suggests a change in the type of drug interaction that depends on the strength of resistance, which challenges established rescaling paradigms. We experimentally show that the presence of unregulated resistance genes can lead to altered drug interaction, which agrees with the prediction of the model. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems. acknowledgement: 'This work was supported in part by Tum stipend of Knafelj foundation (to B.K.), Austrian Science Fund (FWF) standalone grants P 27201-B22 (to T.B.) and P 28844(to G.T.), HFSP program Grant RGP0042/2013 (to T.B.), German Research Foundation (DFG) individual grant BO 3502/2-1 (to T.B.), and German Research Foundation (DFG) Collaborative Research Centre (SFB) 1310 (to T.B.). ' article_number: e1008529 article_processing_charge: Yes article_type: original author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Tobias full_name: Bollenbach, Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X citation: ama: Kavcic B, Tkačik G, Bollenbach MT. Minimal biophysical model of combined antibiotic action. PLOS Computational Biology. 2021;17. doi:10.1371/journal.pcbi.1008529 apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2021). Minimal biophysical model of combined antibiotic action. PLOS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1008529 chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Minimal Biophysical Model of Combined Antibiotic Action.” PLOS Computational Biology. Public Library of Science, 2021. https://doi.org/10.1371/journal.pcbi.1008529. ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Minimal biophysical model of combined antibiotic action,” PLOS Computational Biology, vol. 17. Public Library of Science, 2021. ista: Kavcic B, Tkačik G, Bollenbach MT. 2021. Minimal biophysical model of combined antibiotic action. PLOS Computational Biology. 17, e1008529. mla: Kavcic, Bor, et al. “Minimal Biophysical Model of Combined Antibiotic Action.” PLOS Computational Biology, vol. 17, e1008529, Public Library of Science, 2021, doi:10.1371/journal.pcbi.1008529. short: B. Kavcic, G. Tkačik, M.T. Bollenbach, PLOS Computational Biology 17 (2021). date_created: 2021-01-08T07:16:18Z date_published: 2021-01-07T00:00:00Z date_updated: 2024-02-21T12:41:41Z day: '07' ddc: - '570' department: - _id: GaTk doi: 10.1371/journal.pcbi.1008529 external_id: isi: - '000608045000010' file: - access_level: open_access checksum: e29f2b42651bef8e034781de8781ffac content_type: application/pdf creator: dernst date_created: 2021-02-04T12:30:48Z date_updated: 2021-02-04T12:30:48Z file_id: '9092' file_name: 2021_PlosComBio_Kavcic.pdf file_size: 3690053 relation: main_file success: 1 file_date_updated: 2021-02-04T12:30:48Z has_accepted_license: '1' intvolume: ' 17' isi: 1 keyword: - Modelling and Simulation - Genetics - Molecular Biology - Antibiotics - Drug interactions language: - iso: eng month: '01' oa: 1 oa_version: Published Version project: - _id: 25E9AF9E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P27201-B22 name: Revealing the mechanisms underlying drug interactions - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: PLOS Computational Biology publication_identifier: issn: - 1553-7358 publication_status: published publisher: Public Library of Science quality_controlled: '1' related_material: record: - id: '7673' relation: earlier_version status: public - id: '8930' relation: research_data status: public status: public title: Minimal biophysical model of combined antibiotic action tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 17 year: '2021' ... --- _id: '9283' abstract: - lang: eng text: Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs. acknowledgement: "We thank J Bollback, L Hurst, M Lagator, C Nizak, O Rivoire, M Savageau, G Tkacik, and B Vicozo\r\nfor helpful discussions; A Dolinar and A Greshnova for technical assistance; T Bollenbach for supplying the strain JW0336; C Rusnac, and members of the Guet lab for comments. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n˚\r\n628377 (ANS) and an Austrian Science Fund (FWF) grant n˚ I 3901-B32 (CCG)." article_number: e65993 article_processing_charge: Yes article_type: original author: - first_name: Anna A full_name: Nagy-Staron, Anna A id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87 last_name: Nagy-Staron orcid: 0000-0002-1391-8377 - first_name: Kathrin full_name: Tomasek, Kathrin id: 3AEC8556-F248-11E8-B48F-1D18A9856A87 last_name: Tomasek orcid: 0000-0003-3768-877X - first_name: Caroline full_name: Caruso Carter, Caroline last_name: Caruso Carter - first_name: Elisabeth full_name: Sonnleitner, Elisabeth last_name: Sonnleitner - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X - first_name: Tiago full_name: Paixão, Tiago last_name: Paixão - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 citation: ama: Nagy-Staron AA, Tomasek K, Caruso Carter C, et al. Local genetic context shapes the function of a gene regulatory network. eLife. 2021;10. doi:10.7554/elife.65993 apa: Nagy-Staron, A. A., Tomasek, K., Caruso Carter, C., Sonnleitner, E., Kavcic, B., Paixão, T., & Guet, C. C. (2021). Local genetic context shapes the function of a gene regulatory network. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.65993 chicago: Nagy-Staron, Anna A, Kathrin Tomasek, Caroline Caruso Carter, Elisabeth Sonnleitner, Bor Kavcic, Tiago Paixão, and Calin C Guet. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.65993. ieee: A. A. Nagy-Staron et al., “Local genetic context shapes the function of a gene regulatory network,” eLife, vol. 10. eLife Sciences Publications, 2021. ista: Nagy-Staron AA, Tomasek K, Caruso Carter C, Sonnleitner E, Kavcic B, Paixão T, Guet CC. 2021. Local genetic context shapes the function of a gene regulatory network. eLife. 10, e65993. mla: Nagy-Staron, Anna A., et al. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” ELife, vol. 10, e65993, eLife Sciences Publications, 2021, doi:10.7554/elife.65993. short: A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic, T. Paixão, C.C. Guet, ELife 10 (2021). date_created: 2021-03-23T10:11:46Z date_published: 2021-03-08T00:00:00Z date_updated: 2024-02-21T12:41:57Z day: '08' ddc: - '570' department: - _id: GaTk - _id: CaGu doi: 10.7554/elife.65993 ec_funded: 1 external_id: isi: - '000631050900001' file: - access_level: open_access checksum: 3c2f44058c2dd45a5a1027f09d263f8e content_type: application/pdf creator: bkavcic date_created: 2021-03-23T10:12:58Z date_updated: 2021-03-23T10:12:58Z file_id: '9284' file_name: elife-65993-v2.pdf file_size: 1390469 relation: main_file success: 1 file_date_updated: 2021-03-23T10:12:58Z has_accepted_license: '1' intvolume: ' 10' isi: 1 keyword: - Genetics and Molecular Biology language: - iso: eng month: '03' oa: 1 oa_version: Published Version project: - _id: 2517526A-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '628377' name: 'The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic Networks to Genomic Studies' - _id: 268BFA92-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03901 name: 'CyberCircuits: Cybergenetic circuits to test composability of gene networks' publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' related_material: record: - id: '8951' relation: research_data status: public status: public title: Local genetic context shapes the function of a gene regulatory network tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 10 year: '2021' ... --- _id: '7553' abstract: - lang: eng text: Normative theories and statistical inference provide complementary approaches for the study of biological systems. A normative theory postulates that organisms have adapted to efficiently solve essential tasks, and proceeds to mathematically work out testable consequences of such optimality; parameters that maximize the hypothesized organismal function can be derived ab initio, without reference to experimental data. In contrast, statistical inference focuses on efficient utilization of data to learn model parameters, without reference to any a priori notion of biological function, utility, or fitness. Traditionally, these two approaches were developed independently and applied separately. Here we unify them in a coherent Bayesian framework that embeds a normative theory into a family of maximum-entropy “optimization priors.” This family defines a smooth interpolation between a data-rich inference regime (characteristic of “bottom-up” statistical models), and a data-limited ab inito prediction regime (characteristic of “top-down” normative theory). We demonstrate the applicability of our framework using data from the visual cortex, and argue that the flexibility it affords is essential to address a number of fundamental challenges relating to inference and prediction in complex, high-dimensional biological problems. acknowledgement: The authors thank Dario Ringach for providing the V1 receptive fields and Olivier Marre for providing the retinal receptive fields. W.M. was funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411. M.H. was funded in part by Human Frontiers Science grant no. HFSP RGP0032/2018. article_processing_charge: No author: - first_name: Wiktor F full_name: Mlynarski, Wiktor F id: 358A453A-F248-11E8-B48F-1D18A9856A87 last_name: Mlynarski - first_name: Michal full_name: Hledik, Michal id: 4171253A-F248-11E8-B48F-1D18A9856A87 last_name: Hledik - first_name: Thomas R full_name: Sokolowski, Thomas R id: 3E999752-F248-11E8-B48F-1D18A9856A87 last_name: Sokolowski orcid: 0000-0002-1287-3779 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Mlynarski WF, Hledik M, Sokolowski TR, Tkačik G. Statistical analysis and optimality of neural systems. Neuron. 2021;109(7):1227-1241.e5. doi:10.1016/j.neuron.2021.01.020 apa: Mlynarski, W. F., Hledik, M., Sokolowski, T. R., & Tkačik, G. (2021). Statistical analysis and optimality of neural systems. Neuron. Cell Press. https://doi.org/10.1016/j.neuron.2021.01.020 chicago: Mlynarski, Wiktor F, Michal Hledik, Thomas R Sokolowski, and Gašper Tkačik. “Statistical Analysis and Optimality of Neural Systems.” Neuron. Cell Press, 2021. https://doi.org/10.1016/j.neuron.2021.01.020. ieee: W. F. Mlynarski, M. Hledik, T. R. Sokolowski, and G. Tkačik, “Statistical analysis and optimality of neural systems,” Neuron, vol. 109, no. 7. Cell Press, p. 1227–1241.e5, 2021. ista: Mlynarski WF, Hledik M, Sokolowski TR, Tkačik G. 2021. Statistical analysis and optimality of neural systems. Neuron. 109(7), 1227–1241.e5. mla: Mlynarski, Wiktor F., et al. “Statistical Analysis and Optimality of Neural Systems.” Neuron, vol. 109, no. 7, Cell Press, 2021, p. 1227–1241.e5, doi:10.1016/j.neuron.2021.01.020. short: W.F. Mlynarski, M. Hledik, T.R. Sokolowski, G. Tkačik, Neuron 109 (2021) 1227–1241.e5. date_created: 2020-02-28T11:00:12Z date_published: 2021-04-07T00:00:00Z date_updated: 2024-03-06T14:22:51Z day: '07' department: - _id: GaTk doi: 10.1016/j.neuron.2021.01.020 ec_funded: 1 external_id: isi: - '000637809600006' intvolume: ' 109' isi: 1 issue: '7' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/848374 month: '04' oa: 1 oa_version: Preprint page: 1227-1241.e5 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: Neuron publication_status: published publisher: Cell Press quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/can-evolution-be-predicted/ record: - id: '15020' relation: dissertation_contains status: public scopus_import: '1' status: public title: Statistical analysis and optimality of neural systems type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 109 year: '2021' ... --- _id: '10077' abstract: - lang: eng text: Although much is known about how single neurons in the hippocampus represent an animal’s position, how cell-cell interactions contribute to spatial coding remains poorly understood. Using a novel statistical estimator and theoretical modeling, both developed in the framework of maximum entropy models, we reveal highly structured cell-to-cell interactions whose statistics depend on familiar vs. novel environment. In both conditions the circuit interactions optimize the encoding of spatial information, but for regimes that differ in the signal-to-noise ratio of their spatial inputs. Moreover, the topology of the interactions facilitates linear decodability, making the information easy to read out by downstream circuits. These findings suggest that the efficient coding hypothesis is not applicable only to individual neuron properties in the sensory periphery, but also to neural interactions in the central brain. acknowledgement: We thank Peter Baracskay, Karola Kaefer and Hugo Malagon-Vina for the acquisition of the data. We thank Federico Stella for comments on an earlier version of the manuscript. MN was supported by European Union Horizon 2020 grant 665385, JC was supported by European Research Council consolidator grant 281511, GT was supported by the Austrian Science Fund (FWF) grant P34015, CS was supported by an IST fellow grant, National Institute of Mental Health Award 1R01MH125571-01, by the National Science Foundation under NSF Award No. 1922658 and a Google faculty award. article_processing_charge: No author: - first_name: Michele full_name: Nardin, Michele id: 30BD0376-F248-11E8-B48F-1D18A9856A87 last_name: Nardin orcid: 0000-0001-8849-6570 - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Cristina full_name: Savin, Cristina id: 3933349E-F248-11E8-B48F-1D18A9856A87 last_name: Savin citation: ama: Nardin M, Csicsvari JL, Tkačik G, Savin C. The structure of hippocampal CA1 interactions optimizes spatial coding across experience. bioRxiv. doi:10.1101/2021.09.28.460602 apa: Nardin, M., Csicsvari, J. L., Tkačik, G., & Savin, C. (n.d.). The structure of hippocampal CA1 interactions optimizes spatial coding across experience. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2021.09.28.460602 chicago: Nardin, Michele, Jozsef L Csicsvari, Gašper Tkačik, and Cristina Savin. “The Structure of Hippocampal CA1 Interactions Optimizes Spatial Coding across Experience.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2021.09.28.460602. ieee: M. Nardin, J. L. Csicsvari, G. Tkačik, and C. Savin, “The structure of hippocampal CA1 interactions optimizes spatial coding across experience,” bioRxiv. Cold Spring Harbor Laboratory. ista: Nardin M, Csicsvari JL, Tkačik G, Savin C. The structure of hippocampal CA1 interactions optimizes spatial coding across experience. bioRxiv, 10.1101/2021.09.28.460602. mla: Nardin, Michele, et al. “The Structure of Hippocampal CA1 Interactions Optimizes Spatial Coding across Experience.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2021.09.28.460602. short: M. Nardin, J.L. Csicsvari, G. Tkačik, C. Savin, BioRxiv (n.d.). date_created: 2021-10-04T06:23:34Z date_published: 2021-09-29T00:00:00Z date_updated: 2024-03-27T23:30:16Z day: '29' department: - _id: GradSch - _id: JoCs - _id: GaTk doi: 10.1101/2021.09.28.460602 ec_funded: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/2021.09.28.460602 month: '09' oa: 1 oa_version: Preprint project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 257A4776-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281511' name: Memory-related information processing in neuronal circuits of the hippocampus and entorhinal cortex - _id: 626c45b5-2b32-11ec-9570-e509828c1ba6 grant_number: P34015 name: Efficient coding with biophysical realism publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory related_material: record: - id: '11932' relation: dissertation_contains status: public status: public title: The structure of hippocampal CA1 interactions optimizes spatial coding across experience tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: preprint user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2021' ... --- _id: '8105' abstract: - lang: eng text: Physical and biological systems often exhibit intermittent dynamics with bursts or avalanches (active states) characterized by power-law size and duration distributions. These emergent features are typical of systems at the critical point of continuous phase transitions, and have led to the hypothesis that such systems may self-organize at criticality, i.e. without any fine tuning of parameters. Since the introduction of the Bak-Tang-Wiesenfeld (BTW) model, the paradigm of self-organized criticality (SOC) has been very fruitful for the analysis of emergent collective behaviors in a number of systems, including the brain. Although considerable effort has been devoted in identifying and modeling scaling features of burst and avalanche statistics, dynamical aspects related to the temporal organization of bursts remain often poorly understood or controversial. Of crucial importance to understand the mechanisms responsible for emergent behaviors is the relationship between active and quiet periods, and the nature of the correlations. Here we investigate the dynamics of active (θ-bursts) and quiet states (δ-bursts) in brain activity during the sleep-wake cycle. We show the duality of power-law (θ, active phase) and exponential-like (δ, quiescent phase) duration distributions, typical of SOC, jointly emerge with power-law temporal correlations and anti-correlated coupling between active and quiet states. Importantly, we demonstrate that such temporal organization shares important similarities with earthquake dynamics, and propose that specific power-law correlations and coupling between active and quiet states are distinctive characteristics of a class of systems with self-organization at criticality. article_number: '00005' article_processing_charge: No article_type: original author: - first_name: Fabrizio full_name: Lombardi, Fabrizio id: A057D288-3E88-11E9-986D-0CF4E5697425 last_name: Lombardi orcid: 0000-0003-2623-5249 - first_name: Jilin W.J.L. full_name: Wang, Jilin W.J.L. last_name: Wang - first_name: Xiyun full_name: Zhang, Xiyun last_name: Zhang - first_name: Plamen Ch full_name: Ivanov, Plamen Ch last_name: Ivanov citation: ama: Lombardi F, Wang JWJL, Zhang X, Ivanov PC. Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality. EPJ Web of Conferences. 2020;230. doi:10.1051/epjconf/202023000005 apa: Lombardi, F., Wang, J. W. J. L., Zhang, X., & Ivanov, P. C. (2020). Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality. EPJ Web of Conferences. EDP Sciences. https://doi.org/10.1051/epjconf/202023000005 chicago: Lombardi, Fabrizio, Jilin W.J.L. Wang, Xiyun Zhang, and Plamen Ch Ivanov. “Power-Law Correlations and Coupling of Active and Quiet States Underlie a Class of Complex Systems with Self-Organization at Criticality.” EPJ Web of Conferences. EDP Sciences, 2020. https://doi.org/10.1051/epjconf/202023000005. ieee: F. Lombardi, J. W. J. L. Wang, X. Zhang, and P. C. Ivanov, “Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality,” EPJ Web of Conferences, vol. 230. EDP Sciences, 2020. ista: Lombardi F, Wang JWJL, Zhang X, Ivanov PC. 2020. Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality. EPJ Web of Conferences. 230, 00005. mla: Lombardi, Fabrizio, et al. “Power-Law Correlations and Coupling of Active and Quiet States Underlie a Class of Complex Systems with Self-Organization at Criticality.” EPJ Web of Conferences, vol. 230, 00005, EDP Sciences, 2020, doi:10.1051/epjconf/202023000005. short: F. Lombardi, J.W.J.L. Wang, X. Zhang, P.C. Ivanov, EPJ Web of Conferences 230 (2020). date_created: 2020-07-12T16:20:33Z date_published: 2020-03-11T00:00:00Z date_updated: 2021-01-12T08:16:55Z day: '11' ddc: - '530' department: - _id: GaTk doi: 10.1051/epjconf/202023000005 file: - access_level: open_access content_type: application/pdf creator: dernst date_created: 2020-07-22T06:17:11Z date_updated: 2020-07-22T06:17:11Z file_id: '8144' file_name: 2020_EPJWebConf_Lombardi.pdf file_size: 2197543 relation: main_file success: 1 file_date_updated: 2020-07-22T06:17:11Z has_accepted_license: '1' intvolume: ' 230' language: - iso: eng month: '03' oa: 1 oa_version: Published Version publication: EPJ Web of Conferences publication_identifier: issn: - 2100-014X publication_status: published publisher: EDP Sciences quality_controlled: '1' status: public title: Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 230 year: '2020' ... --- _id: '7490' abstract: - lang: eng text: In plants, clathrin mediated endocytosis (CME) represents the major route for cargo internalisation from the cell surface. It has been assumed to operate in an evolutionary conserved manner as in yeast and animals. Here we report characterisation of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement in electron microscopy and quantitative live imaging techniques. Arabidopsis CME appears to follow the constant curvature model and the bona fide CME population generates vesicles of a predominantly hexagonal-basket type; larger and with faster kinetics than in other models. Contrary to the existing paradigm, actin is dispensable for CME events at the plasma membrane but plays a unique role in collecting endocytic vesicles, sorting of internalised cargos and directional endosome movement that itself actively promote CME events. Internalized vesicles display a strongly delayed and sequential uncoating. These unique features highlight the independent evolution of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes. acknowledged_ssus: - _id: LifeSc - _id: Bio - _id: EM-Fac article_number: e52067 article_processing_charge: No article_type: original author: - first_name: Madhumitha full_name: Narasimhan, Madhumitha id: 44BF24D0-F248-11E8-B48F-1D18A9856A87 last_name: Narasimhan orcid: 0000-0002-8600-0671 - first_name: Alexander J full_name: Johnson, Alexander J id: 46A62C3A-F248-11E8-B48F-1D18A9856A87 last_name: Johnson orcid: 0000-0002-2739-8843 - first_name: Roshan full_name: Prizak, Roshan id: 4456104E-F248-11E8-B48F-1D18A9856A87 last_name: Prizak - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Shutang full_name: Tan, Shutang id: 2DE75584-F248-11E8-B48F-1D18A9856A87 last_name: Tan orcid: 0000-0002-0471-8285 - first_name: Barbara E full_name: Casillas Perez, Barbara E id: 351ED2AA-F248-11E8-B48F-1D18A9856A87 last_name: Casillas Perez - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 citation: ama: Narasimhan M, Johnson AJ, Prizak R, et al. Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. eLife. 2020;9. doi:10.7554/eLife.52067 apa: Narasimhan, M., Johnson, A. J., Prizak, R., Kaufmann, W., Tan, S., Casillas Perez, B. E., & Friml, J. (2020). Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.52067 chicago: Narasimhan, Madhumitha, Alexander J Johnson, Roshan Prizak, Walter Kaufmann, Shutang Tan, Barbara E Casillas Perez, and Jiří Friml. “Evolutionarily Unique Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.52067. ieee: M. Narasimhan et al., “Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants,” eLife, vol. 9. eLife Sciences Publications, 2020. ista: Narasimhan M, Johnson AJ, Prizak R, Kaufmann W, Tan S, Casillas Perez BE, Friml J. 2020. Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. eLife. 9, e52067. mla: Narasimhan, Madhumitha, et al. “Evolutionarily Unique Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” ELife, vol. 9, e52067, eLife Sciences Publications, 2020, doi:10.7554/eLife.52067. short: M. Narasimhan, A.J. Johnson, R. Prizak, W. Kaufmann, S. Tan, B.E. Casillas Perez, J. Friml, ELife 9 (2020). date_created: 2020-02-16T23:00:50Z date_published: 2020-01-23T00:00:00Z date_updated: 2023-08-18T06:33:07Z day: '23' ddc: - '570' - '580' department: - _id: JiFr - _id: GaTk - _id: EM-Fac - _id: SyCr doi: 10.7554/eLife.52067 ec_funded: 1 external_id: isi: - '000514104100001' pmid: - '31971511' file: - access_level: open_access checksum: 2052daa4be5019534f3a42f200a09f32 content_type: application/pdf creator: dernst date_created: 2020-02-18T07:21:16Z date_updated: 2020-07-14T12:47:59Z file_id: '7494' file_name: 2020_eLife_Narasimhan.pdf file_size: 7247468 relation: main_file file_date_updated: 2020-07-14T12:47:59Z has_accepted_license: '1' intvolume: ' 9' isi: 1 language: - iso: eng month: '01' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 261099A6-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742985' name: Tracing Evolution of Auxin Transport and Polarity in Plants - _id: 26538374-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03630 name: Molecular mechanisms of endocytic cargo recognition in plants publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 9 year: '2020' ... --- _id: '9779' article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Tamar full_name: Friedlander, Tamar last_name: Friedlander citation: ama: Grah R, Friedlander T. Distribution of crosstalk values. 2020. doi:10.1371/journal.pcbi.1007642.s003 apa: Grah, R., & Friedlander, T. (2020). Distribution of crosstalk values. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007642.s003 chicago: Grah, Rok, and Tamar Friedlander. “Distribution of Crosstalk Values.” Public Library of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s003. ieee: R. Grah and T. Friedlander, “Distribution of crosstalk values.” Public Library of Science, 2020. ista: Grah R, Friedlander T. 2020. Distribution of crosstalk values, Public Library of Science, 10.1371/journal.pcbi.1007642.s003. mla: Grah, Rok, and Tamar Friedlander. Distribution of Crosstalk Values. Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642.s003. short: R. Grah, T. Friedlander, (2020). date_created: 2021-08-06T07:24:37Z date_published: 2020-02-25T00:00:00Z date_updated: 2023-08-18T06:47:47Z day: '25' department: - _id: GaTk doi: 10.1371/journal.pcbi.1007642.s003 month: '02' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '7569' relation: research_data status: public status: public title: Distribution of crosstalk values type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2020' ... --- _id: '9776' article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Tamar full_name: Friedlander, Tamar last_name: Friedlander citation: ama: Grah R, Friedlander T. Supporting information. 2020. doi:10.1371/journal.pcbi.1007642.s001 apa: Grah, R., & Friedlander, T. (2020). Supporting information. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007642.s001 chicago: Grah, Rok, and Tamar Friedlander. “Supporting Information.” Public Library of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s001. ieee: R. Grah and T. Friedlander, “Supporting information.” Public Library of Science, 2020. ista: Grah R, Friedlander T. 2020. Supporting information, Public Library of Science, 10.1371/journal.pcbi.1007642.s001. mla: Grah, Rok, and Tamar Friedlander. Supporting Information. Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642.s001. short: R. Grah, T. Friedlander, (2020). date_created: 2021-08-06T07:15:04Z date_published: 2020-02-25T00:00:00Z date_updated: 2023-08-18T06:47:47Z day: '25' department: - _id: GaTk doi: 10.1371/journal.pcbi.1007642.s001 month: '02' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '7569' relation: used_in_publication status: public status: public title: Supporting information type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2020' ... --- _id: '7656' abstract: - lang: eng text: 'We propose that correlations among neurons are generically strong enough to organize neural activity patterns into a discrete set of clusters, which can each be viewed as a population codeword. Our reasoning starts with the analysis of retinal ganglion cell data using maximum entropy models, showing that the population is robustly in a frustrated, marginally sub-critical, or glassy, state. This leads to an argument that neural populations in many other brain areas might share this structure. Next, we use latent variable models to show that this glassy state possesses well-defined clusters of neural activity. Clusters have three appealing properties: (i) clusters exhibit error correction, i.e., they are reproducibly elicited by the same stimulus despite variability at the level of constituent neurons; (ii) clusters encode qualitatively different visual features than their constituent neurons; and (iii) clusters can be learned by downstream neural circuits in an unsupervised fashion. We hypothesize that these properties give rise to a “learnable” neural code which the cortical hierarchy uses to extract increasingly complex features without supervision or reinforcement.' article_number: '20' article_processing_charge: No article_type: original author: - first_name: Michael J. full_name: Berry, Michael J. last_name: Berry - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: 'Berry MJ, Tkačik G. Clustering of neural activity: A design principle for population codes. Frontiers in Computational Neuroscience. 2020;14. doi:10.3389/fncom.2020.00020' apa: 'Berry, M. J., & Tkačik, G. (2020). Clustering of neural activity: A design principle for population codes. Frontiers in Computational Neuroscience. Frontiers. https://doi.org/10.3389/fncom.2020.00020' chicago: 'Berry, Michael J., and Gašper Tkačik. “Clustering of Neural Activity: A Design Principle for Population Codes.” Frontiers in Computational Neuroscience. Frontiers, 2020. https://doi.org/10.3389/fncom.2020.00020.' ieee: 'M. J. Berry and G. Tkačik, “Clustering of neural activity: A design principle for population codes,” Frontiers in Computational Neuroscience, vol. 14. Frontiers, 2020.' ista: 'Berry MJ, Tkačik G. 2020. Clustering of neural activity: A design principle for population codes. Frontiers in Computational Neuroscience. 14, 20.' mla: 'Berry, Michael J., and Gašper Tkačik. “Clustering of Neural Activity: A Design Principle for Population Codes.” Frontiers in Computational Neuroscience, vol. 14, 20, Frontiers, 2020, doi:10.3389/fncom.2020.00020.' short: M.J. Berry, G. Tkačik, Frontiers in Computational Neuroscience 14 (2020). date_created: 2020-04-12T22:00:40Z date_published: 2020-03-13T00:00:00Z date_updated: 2023-08-18T10:30:11Z day: '13' ddc: - '570' department: - _id: GaTk doi: 10.3389/fncom.2020.00020 external_id: isi: - '000525543200001' pmid: - '32231528' file: - access_level: open_access checksum: 2b1da23823eae9cedbb42d701945b61e content_type: application/pdf creator: dernst date_created: 2020-04-14T12:20:39Z date_updated: 2020-07-14T12:48:01Z file_id: '7659' file_name: 2020_Frontiers_Berry.pdf file_size: 4082937 relation: main_file file_date_updated: 2020-07-14T12:48:01Z has_accepted_license: '1' intvolume: ' 14' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version pmid: 1 publication: Frontiers in Computational Neuroscience publication_identifier: eissn: - '16625188' publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: 'Clustering of neural activity: A design principle for population codes' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 14 year: '2020' ... --- _id: '8698' abstract: - lang: eng text: The brain represents and reasons probabilistically about complex stimuli and motor actions using a noisy, spike-based neural code. A key building block for such neural computations, as well as the basis for supervised and unsupervised learning, is the ability to estimate the surprise or likelihood of incoming high-dimensional neural activity patterns. Despite progress in statistical modeling of neural responses and deep learning, current approaches either do not scale to large neural populations or cannot be implemented using biologically realistic mechanisms. Inspired by the sparse and random connectivity of real neuronal circuits, we present a model for neural codes that accurately estimates the likelihood of individual spiking patterns and has a straightforward, scalable, efficient, learnable, and realistic neural implementation. This model’s performance on simultaneously recorded spiking activity of >100 neurons in the monkey visual and prefrontal cortices is comparable with or better than that of state-of-the-art models. Importantly, the model can be learned using a small number of samples and using a local learning rule that utilizes noise intrinsic to neural circuits. Slower, structural changes in random connectivity, consistent with rewiring and pruning processes, further improve the efficiency and sparseness of the resulting neural representations. Our results merge insights from neuroanatomy, machine learning, and theoretical neuroscience to suggest random sparse connectivity as a key design principle for neuronal computation. acknowledgement: We thank Udi Karpas, Roy Harpaz, Tal Tamir, Adam Haber, and Amir Bar for discussions and suggestions; and especially Oren Forkosh and Walter Senn for invaluable discussions of the learning rule. This work was supported by European Research Council Grant 311238 (to E.S.) and Israel Science Foundation Grant 1629/12 (to E.S.); as well as research support from Martin Kushner Schnur and Mr. and Mrs. Lawrence Feis (E.S.); National Institute of Mental Health Grant R01MH109180 (to R.K.); a Pew Scholarship in Biomedical Sciences (to R.K.); Simons Collaboration on the Global Brain Grant 542997 (to R.K. and E.S.); and a CRCNS (Collaborative Research in Computational Neuroscience) grant (to R.K. and E.S.). article_processing_charge: No article_type: original author: - first_name: Ori full_name: Maoz, Ori last_name: Maoz - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Mohamad Saleh full_name: Esteki, Mohamad Saleh last_name: Esteki - first_name: Roozbeh full_name: Kiani, Roozbeh last_name: Kiani - first_name: Elad full_name: Schneidman, Elad last_name: Schneidman citation: ama: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. Learning probabilistic neural representations with randomly connected circuits. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(40):25066-25073. doi:10.1073/pnas.1912804117 apa: Maoz, O., Tkačik, G., Esteki, M. S., Kiani, R., & Schneidman, E. (2020). Learning probabilistic neural representations with randomly connected circuits. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.1912804117 chicago: Maoz, Ori, Gašper Tkačik, Mohamad Saleh Esteki, Roozbeh Kiani, and Elad Schneidman. “Learning Probabilistic Neural Representations with Randomly Connected Circuits.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1912804117. ieee: O. Maoz, G. Tkačik, M. S. Esteki, R. Kiani, and E. Schneidman, “Learning probabilistic neural representations with randomly connected circuits,” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 40. National Academy of Sciences, pp. 25066–25073, 2020. ista: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. 2020. Learning probabilistic neural representations with randomly connected circuits. Proceedings of the National Academy of Sciences of the United States of America. 117(40), 25066–25073. mla: Maoz, Ori, et al. “Learning Probabilistic Neural Representations with Randomly Connected Circuits.” Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 40, National Academy of Sciences, 2020, pp. 25066–73, doi:10.1073/pnas.1912804117. short: O. Maoz, G. Tkačik, M.S. Esteki, R. Kiani, E. Schneidman, Proceedings of the National Academy of Sciences of the United States of America 117 (2020) 25066–25073. date_created: 2020-10-25T23:01:16Z date_published: 2020-10-06T00:00:00Z date_updated: 2023-08-22T12:11:23Z day: '06' ddc: - '570' department: - _id: GaTk doi: 10.1073/pnas.1912804117 external_id: isi: - '000579045200012' pmid: - '32948691' file: - access_level: open_access checksum: c6a24fdecf3f28faf447078e7a274a88 content_type: application/pdf creator: cziletti date_created: 2020-10-27T14:57:50Z date_updated: 2020-10-27T14:57:50Z file_id: '8713' file_name: 2020_PNAS_Maoz.pdf file_size: 1755359 relation: main_file success: 1 file_date_updated: 2020-10-27T14:57:50Z has_accepted_license: '1' intvolume: ' 117' isi: 1 issue: '40' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: 25066-25073 pmid: 1 publication: Proceedings of the National Academy of Sciences of the United States of America publication_identifier: eissn: - '10916490' issn: - '00278424' publication_status: published publisher: National Academy of Sciences quality_controlled: '1' scopus_import: '1' status: public title: Learning probabilistic neural representations with randomly connected circuits tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 117 year: '2020' ... --- _id: '8955' abstract: - lang: eng text: Skeletal muscle activity is continuously modulated across physiologic states to provide coordination, flexibility and responsiveness to body tasks and external inputs. Despite the central role the muscular system plays in facilitating vital body functions, the network of brain-muscle interactions required to control hundreds of muscles and synchronize their activation in relation to distinct physiologic states has not been investigated. Recent approaches have focused on general associations between individual brain rhythms and muscle activation during movement tasks. However, the specific forms of coupling, the functional network of cortico-muscular coordination, and how network structure and dynamics are modulated by autonomic regulation across physiologic states remains unknown. To identify and quantify the cortico-muscular interaction network and uncover basic features of neuro-autonomic control of muscle function, we investigate the coupling between synchronous bursts in cortical rhythms and peripheral muscle activation during sleep and wake. Utilizing the concept of time delay stability and a novel network physiology approach, we find that the brain-muscle network exhibits complex dynamic patterns of communication involving multiple brain rhythms across cortical locations and different electromyographic frequency bands. Moreover, our results show that during each physiologic state the cortico-muscular network is characterized by a specific profile of network links strength, where particular brain rhythms play role of main mediators of interaction and control. Further, we discover a hierarchical reorganization in network structure across physiologic states, with high connectivity and network link strength during wake, intermediate during REM and light sleep, and low during deep sleep, a sleep-stage stratification that demonstrates a unique association between physiologic states and cortico-muscular network structure. The reported empirical observations are consistent across individual subjects, indicating universal behavior in network structure and dynamics, and high sensitivity of cortico-muscular control to changes in autonomic regulation, even at low levels of physical activity and muscle tone during sleep. Our findings demonstrate previously unrecognized basic principles of brain-muscle network communication and control, and provide new perspectives on the regulatory mechanisms of brain dynamics and locomotor activation, with potential clinical implications for neurodegenerative, movement and sleep disorders, and for developing efficient treatment strategies. acknowledgement: We acknowledge support from the W. M. Keck Foundation, National Institutes of Health (NIH Grant 1R01-HL098437), the US-Israel Binational Science Foundation (BSF Grant 2012219), and the Office of Naval Research (ONR Grant 000141010078). FL acknowledges support also from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 754411. article_number: '558070' article_processing_charge: No article_type: original author: - first_name: Rossella full_name: Rizzo, Rossella last_name: Rizzo - first_name: Xiyun full_name: Zhang, Xiyun last_name: Zhang - first_name: Jilin W.J.L. full_name: Wang, Jilin W.J.L. last_name: Wang - first_name: Fabrizio full_name: Lombardi, Fabrizio id: A057D288-3E88-11E9-986D-0CF4E5697425 last_name: Lombardi orcid: 0000-0003-2623-5249 - first_name: Plamen Ch full_name: Ivanov, Plamen Ch last_name: Ivanov citation: ama: Rizzo R, Zhang X, Wang JWJL, Lombardi F, Ivanov PC. Network physiology of cortico–muscular interactions. Frontiers in Physiology. 2020;11. doi:10.3389/fphys.2020.558070 apa: Rizzo, R., Zhang, X., Wang, J. W. J. L., Lombardi, F., & Ivanov, P. C. (2020). Network physiology of cortico–muscular interactions. Frontiers in Physiology. Frontiers. https://doi.org/10.3389/fphys.2020.558070 chicago: Rizzo, Rossella, Xiyun Zhang, Jilin W.J.L. Wang, Fabrizio Lombardi, and Plamen Ch Ivanov. “Network Physiology of Cortico–Muscular Interactions.” Frontiers in Physiology. Frontiers, 2020. https://doi.org/10.3389/fphys.2020.558070. ieee: R. Rizzo, X. Zhang, J. W. J. L. Wang, F. Lombardi, and P. C. Ivanov, “Network physiology of cortico–muscular interactions,” Frontiers in Physiology, vol. 11. Frontiers, 2020. ista: Rizzo R, Zhang X, Wang JWJL, Lombardi F, Ivanov PC. 2020. Network physiology of cortico–muscular interactions. Frontiers in Physiology. 11, 558070. mla: Rizzo, Rossella, et al. “Network Physiology of Cortico–Muscular Interactions.” Frontiers in Physiology, vol. 11, 558070, Frontiers, 2020, doi:10.3389/fphys.2020.558070. short: R. Rizzo, X. Zhang, J.W.J.L. Wang, F. Lombardi, P.C. Ivanov, Frontiers in Physiology 11 (2020). date_created: 2020-12-20T23:01:18Z date_published: 2020-11-26T00:00:00Z date_updated: 2023-08-24T11:00:45Z day: '26' ddc: - '570' department: - _id: GaTk doi: 10.3389/fphys.2020.558070 ec_funded: 1 external_id: isi: - '000596849400001' pmid: - '33324233' file: - access_level: open_access checksum: ef9515b28c5619b7126c0f347958bcb3 content_type: application/pdf creator: dernst date_created: 2020-12-21T10:37:50Z date_updated: 2020-12-21T10:37:50Z file_id: '8961' file_name: 2020_Frontiers_Rizzo.pdf file_size: 13380030 relation: main_file success: 1 file_date_updated: 2020-12-21T10:37:50Z has_accepted_license: '1' intvolume: ' 11' isi: 1 language: - iso: eng month: '11' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: Frontiers in Physiology publication_identifier: eissn: - 1664042X publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: Network physiology of cortico–muscular interactions tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2020' ... --- _id: '9000' abstract: - lang: eng text: 'In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene-expression levels that is compatible with in vivo and in vitro biophysical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In nonequilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal nonequilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity, and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate,” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in nonequilibrium models is in a trade-off with gene-expression noise, predicting bursty dynamics—an experimentally observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space of nonequilibrium enhancer models to a much smaller subspace that optimally realizes biological function, we deliver a rich class of models that could be tractably inferred from data in the near future.' acknowledgement: G.T. was supported by Human Frontiers Science Program Grant RGP0034/2018. R.G. was supported by the Austrian Academy of Sciences DOC Fellowship. R.G. thanks S. Avvakumov for helpful discussions. article_processing_charge: No article_type: original author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Benjamin full_name: Zoller, Benjamin last_name: Zoller - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Grah R, Zoller B, Tkačik G. Nonequilibrium models of optimal enhancer function. PNAS. 2020;117(50):31614-31622. doi:10.1073/pnas.2006731117 apa: Grah, R., Zoller, B., & Tkačik, G. (2020). Nonequilibrium models of optimal enhancer function. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2006731117 chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Nonequilibrium Models of Optimal Enhancer Function.” PNAS. National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.2006731117. ieee: R. Grah, B. Zoller, and G. Tkačik, “Nonequilibrium models of optimal enhancer function,” PNAS, vol. 117, no. 50. National Academy of Sciences, pp. 31614–31622, 2020. ista: Grah R, Zoller B, Tkačik G. 2020. Nonequilibrium models of optimal enhancer function. PNAS. 117(50), 31614–31622. mla: Grah, Rok, et al. “Nonequilibrium Models of Optimal Enhancer Function.” PNAS, vol. 117, no. 50, National Academy of Sciences, 2020, pp. 31614–22, doi:10.1073/pnas.2006731117. short: R. Grah, B. Zoller, G. Tkačik, PNAS 117 (2020) 31614–31622. date_created: 2021-01-10T23:01:17Z date_published: 2020-12-15T00:00:00Z date_updated: 2023-08-24T11:10:22Z day: '15' ddc: - '570' department: - _id: GaTk doi: 10.1073/pnas.2006731117 external_id: isi: - '000600608300015' pmid: - '33268497' file: - access_level: open_access checksum: 69039cd402a571983aa6cb4815ffa863 content_type: application/pdf creator: dernst date_created: 2021-01-11T08:37:31Z date_updated: 2021-01-11T08:37:31Z file_id: '9004' file_name: 2020_PNAS_Grah.pdf file_size: 1199247 relation: main_file success: 1 file_date_updated: 2021-01-11T08:37:31Z has_accepted_license: '1' intvolume: ' 117' isi: 1 issue: '50' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 31614-31622 pmid: 1 project: - _id: 2665AAFE-B435-11E9-9278-68D0E5697425 grant_number: RGP0034/2018 name: Can evolution minimize spurious signaling crosstalk to reach optimal performance? - _id: 267C84F4-B435-11E9-9278-68D0E5697425 name: Biophysically realistic genotype-phenotype maps for regulatory networks publication: PNAS publication_identifier: eissn: - '10916490' issn: - '00278424' publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/new-compact-model-for-gene-regulation-in-higher-organisms/ scopus_import: '1' status: public title: Nonequilibrium models of optimal enhancer function tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 117 year: '2020' ... --- _id: '8084' abstract: - lang: eng text: Origin and functions of intermittent transitions among sleep stages, including brief awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing sleep on scales of seconds and minutes results from intrinsic non-equilibrium critical dynamics. We investigate θ- and δ-wave dynamics in control rats and in rats where the sleep-promoting ventrolateral preoptic nucleus (VLPO) is lesioned (male Sprague-Dawley rats). We demonstrate that bursts in θ and δ cortical rhythms exhibit complex temporal organization, with long-range correlations and robust duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, features typical of non-equilibrium systems self-organizing at criticality. We show that such non-equilibrium behavior relates to anti-correlated coupling between θ- and δ-bursts, persists across a range of time scales, and is independent of the dominant physiologic state; indications of a basic principle in sleep regulation. Further, we find that VLPO lesions lead to a modulation of cortical dynamics resulting in altered dynamical parameters of θ- and δ-bursts and significant reduction in θ–δ coupling. Our empirical findings and model simulations demonstrate that θ–δ coupling is essential for the emerging non-equilibrium critical dynamics observed across the sleep–wake cycle, and indicate that VLPO neurons may have dual role for both sleep and arousal/brief wake activation. The uncovered critical behavior in sleep- and wake-related cortical rhythms indicates a mechanism essential for the micro-architecture of spontaneous sleep-stage and arousal transitions within a novel, non-homeostatic paradigm of sleep regulation. article_processing_charge: No article_type: original author: - first_name: Fabrizio full_name: Lombardi, Fabrizio id: A057D288-3E88-11E9-986D-0CF4E5697425 last_name: Lombardi orcid: 0000-0003-2623-5249 - first_name: Manuel full_name: Gómez-Extremera, Manuel last_name: Gómez-Extremera - first_name: Pedro full_name: Bernaola-Galván, Pedro last_name: Bernaola-Galván - first_name: Ramalingam full_name: Vetrivelan, Ramalingam last_name: Vetrivelan - first_name: Clifford B. full_name: Saper, Clifford B. last_name: Saper - first_name: Thomas E. full_name: Scammell, Thomas E. last_name: Scammell - first_name: Plamen Ch. full_name: Ivanov, Plamen Ch. last_name: Ivanov citation: ama: Lombardi F, Gómez-Extremera M, Bernaola-Galván P, et al. Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake. Journal of Neuroscience. 2020;40(1):171-190. doi:10.1523/jneurosci.1278-19.2019 apa: Lombardi, F., Gómez-Extremera, M., Bernaola-Galván, P., Vetrivelan, R., Saper, C. B., Scammell, T. E., & Ivanov, P. C. (2020). Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/jneurosci.1278-19.2019 chicago: Lombardi, Fabrizio, Manuel Gómez-Extremera, Pedro Bernaola-Galván, Ramalingam Vetrivelan, Clifford B. Saper, Thomas E. Scammell, and Plamen Ch. Ivanov. “Critical Dynamics and Coupling in Bursts of Cortical Rhythms Indicate Non-Homeostatic Mechanism for Sleep-Stage Transitions and Dual Role of VLPO Neurons in Both Sleep and Wake.” Journal of Neuroscience. Society for Neuroscience, 2020. https://doi.org/10.1523/jneurosci.1278-19.2019. ieee: F. Lombardi et al., “Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake,” Journal of Neuroscience, vol. 40, no. 1. Society for Neuroscience, pp. 171–190, 2020. ista: Lombardi F, Gómez-Extremera M, Bernaola-Galván P, Vetrivelan R, Saper CB, Scammell TE, Ivanov PC. 2020. Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake. Journal of Neuroscience. 40(1), 171–190. mla: Lombardi, Fabrizio, et al. “Critical Dynamics and Coupling in Bursts of Cortical Rhythms Indicate Non-Homeostatic Mechanism for Sleep-Stage Transitions and Dual Role of VLPO Neurons in Both Sleep and Wake.” Journal of Neuroscience, vol. 40, no. 1, Society for Neuroscience, 2020, pp. 171–90, doi:10.1523/jneurosci.1278-19.2019. short: F. Lombardi, M. Gómez-Extremera, P. Bernaola-Galván, R. Vetrivelan, C.B. Saper, T.E. Scammell, P.C. Ivanov, Journal of Neuroscience 40 (2020) 171–190. date_created: 2020-07-05T15:24:51Z date_published: 2020-01-02T00:00:00Z date_updated: 2023-09-05T14:02:55Z day: '02' ddc: - '570' department: - _id: GaTk doi: 10.1523/jneurosci.1278-19.2019 ec_funded: 1 external_id: isi: - '000505167600016' pmid: - '31694962' file: - access_level: open_access content_type: application/pdf creator: dernst date_created: 2020-07-22T11:44:48Z date_updated: 2020-07-22T11:44:48Z file_id: '8150' file_name: 2020_JournNeuroscience_Lombardi.pdf file_size: 6646046 relation: main_file success: 1 file_date_updated: 2020-07-22T11:44:48Z has_accepted_license: '1' intvolume: ' 40' isi: 1 issue: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 171-190 pmid: 1 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: Journal of Neuroscience publication_identifier: eissn: - 1529-2401 issn: - 0270-6474 publication_status: published publisher: Society for Neuroscience quality_controlled: '1' scopus_import: '1' status: public title: Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 40 year: '2020' ... --- _id: '8155' abstract: - lang: eng text: "In the thesis we focus on the interplay of the biophysics and evolution of gene regulation. We start by addressing how the type of prokaryotic gene regulation – activation and repression – affects spurious binding to DNA, also known as\r\ntranscriptional crosstalk. We propose that regulatory interference caused by excess regulatory proteins in the dense cellular medium – global crosstalk – could be a factor in determining which type of gene regulatory network is evolutionarily preferred. Next,we use a normative approach in eukaryotic gene regulation to describe minimal\r\nnon-equilibrium enhancer models that optimize so-called regulatory phenotypes. We find a class of models that differ from standard thermodynamic equilibrium models by a single parameter that notably increases the regulatory performance. Next chapter addresses the question of genotype-phenotype-fitness maps of higher dimensional phenotypes. We show that our biophysically realistic approach allows us to understand how the mechanisms of promoter function constrain genotypephenotype maps, and how they affect the evolutionary trajectories of promoters.\r\nIn the last chapter we ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using mathematical modeling, we show that amplifications can tune gene expression in many environments, including those where transcription factor-based schemes are\r\nhard to evolve or maintain. " acknowledgement: For the duration of his PhD, Rok was a recipient of a DOC fellowship of the Austrian Academy of Sciences. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 citation: ama: Grah R. Gene regulation across scales – how biophysical constraints shape evolution. 2020. doi:10.15479/AT:ISTA:8155 apa: Grah, R. (2020). Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8155 chicago: Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints Shape Evolution.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8155. ieee: R. Grah, “Gene regulation across scales – how biophysical constraints shape evolution,” Institute of Science and Technology Austria, 2020. ista: Grah R. 2020. Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria. mla: Grah, Rok. Gene Regulation across Scales – How Biophysical Constraints Shape Evolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8155. short: R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape Evolution, Institute of Science and Technology Austria, 2020. date_created: 2020-07-23T09:51:28Z date_published: 2020-07-24T00:00:00Z date_updated: 2023-09-07T13:13:27Z day: '24' ddc: - '530' - '570' degree_awarded: PhD department: - _id: CaGu - _id: GaTk doi: 10.15479/AT:ISTA:8155 file: - access_level: open_access content_type: application/pdf creator: rgrah date_created: 2020-07-27T12:00:07Z date_updated: 2020-07-27T12:00:07Z file_id: '8176' file_name: Thesis_RokGrah_200727_convertedNew.pdf file_size: 16638998 relation: main_file success: 1 - access_level: closed content_type: application/zip creator: rgrah date_created: 2020-07-27T12:02:23Z date_updated: 2020-07-30T13:04:55Z file_id: '8177' file_name: Thesis_new.zip file_size: 347459978 relation: main_file file_date_updated: 2020-07-30T13:04:55Z has_accepted_license: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '310' project: - _id: 267C84F4-B435-11E9-9278-68D0E5697425 name: Biophysically realistic genotype-phenotype maps for regulatory networks publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7675' relation: part_of_dissertation status: public - id: '7569' relation: part_of_dissertation status: public - id: '7652' relation: part_of_dissertation status: public status: public supervisor: - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 title: Gene regulation across scales – how biophysical constraints shape evolution type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '7675' abstract: - lang: eng text: 'In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene expression levels that is compatible with in vivo and in vitro bio-physical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In non-equilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal non-equilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in non-equilibrium models is in a tradeoff with gene expression noise, predicting bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space to a much smaller subspace that optimally realizes biological function prior to inference from data, our normative approach holds promise for mathematical models in systems biology.' article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Benjamin full_name: Zoller, Benjamin last_name: Zoller - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Grah R, Zoller B, Tkačik G. Normative models of enhancer function. bioRxiv. 2020. doi:10.1101/2020.04.08.029405 apa: Grah, R., Zoller, B., & Tkačik, G. (2020). Normative models of enhancer function. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.08.029405 chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Normative Models of Enhancer Function.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.08.029405. ieee: R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,” bioRxiv. Cold Spring Harbor Laboratory, 2020. ista: Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv, 10.1101/2020.04.08.029405. mla: Grah, Rok, et al. “Normative Models of Enhancer Function.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.08.029405. short: R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020). date_created: 2020-04-23T10:12:51Z date_published: 2020-04-09T00:00:00Z date_updated: 2023-09-07T13:13:26Z day: '09' department: - _id: CaGu - _id: GaTk doi: 10.1101/2020.04.08.029405 language: - iso: eng main_file_link: - open_access: '1' url: 'https://doi.org/10.1101/2020.04.08.029405 ' month: '04' oa: 1 oa_version: Preprint project: - _id: 2665AAFE-B435-11E9-9278-68D0E5697425 grant_number: RGP0034/2018 name: Can evolution minimize spurious signaling crosstalk to reach optimal performance? - _id: 267C84F4-B435-11E9-9278-68D0E5697425 name: Biophysically realistic genotype-phenotype maps for regulatory networks publication: bioRxiv publication_status: published publisher: Cold Spring Harbor Laboratory related_material: record: - id: '8155' relation: dissertation_contains status: public status: public title: Normative models of enhancer function type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '7569' abstract: - lang: eng text: 'Genes differ in the frequency at which they are expressed and in the form of regulation used to control their activity. In particular, positive or negative regulation can lead to activation of a gene in response to an external signal. Previous works proposed that the form of regulation of a gene correlates with its frequency of usage: positive regulation when the gene is frequently expressed and negative regulation when infrequently expressed. Such network design means that, in the absence of their regulators, the genes are found in their least required activity state, hence regulatory intervention is often necessary. Due to the multitude of genes and regulators, spurious binding and unbinding events, called “crosstalk”, could occur. To determine how the form of regulation affects the global crosstalk in the network, we used a mathematical model that includes multiple regulators and multiple target genes. We found that crosstalk depends non-monotonically on the availability of regulators. Our analysis showed that excess use of regulation entailed by the formerly suggested network design caused high crosstalk levels in a large part of the parameter space. We therefore considered the opposite ‘idle’ design, where the default unregulated state of genes is their frequently required activity state. We found, that ‘idle’ design minimized the use of regulation and thus minimized crosstalk. In addition, we estimated global crosstalk of S. cerevisiae using transcription factors binding data. We demonstrated that even partial network data could suffice to estimate its global crosstalk, suggesting its applicability to additional organisms. We found that S. cerevisiae estimated crosstalk is lower than that of a random network, suggesting that natural selection reduces crosstalk. In summary, our study highlights a new type of protein production cost which is typically overlooked: that of regulatory interference caused by the presence of excess regulators in the cell. It demonstrates the importance of whole-network descriptions, which could show effects missed by single-gene models.' article_number: e1007642 article_processing_charge: No article_type: original author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Tamar full_name: Friedlander, Tamar last_name: Friedlander citation: ama: Grah R, Friedlander T. The relation between crosstalk and gene regulation form revisited. PLOS Computational Biology. 2020;16(2). doi:10.1371/journal.pcbi.1007642 apa: Grah, R., & Friedlander, T. (2020). The relation between crosstalk and gene regulation form revisited. PLOS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007642 chicago: Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene Regulation Form Revisited.” PLOS Computational Biology. Public Library of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642. ieee: R. Grah and T. Friedlander, “The relation between crosstalk and gene regulation form revisited,” PLOS Computational Biology, vol. 16, no. 2. Public Library of Science, 2020. ista: Grah R, Friedlander T. 2020. The relation between crosstalk and gene regulation form revisited. PLOS Computational Biology. 16(2), e1007642. mla: Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene Regulation Form Revisited.” PLOS Computational Biology, vol. 16, no. 2, e1007642, Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642. short: R. Grah, T. Friedlander, PLOS Computational Biology 16 (2020). date_created: 2020-03-06T07:39:38Z date_published: 2020-02-25T00:00:00Z date_updated: 2023-09-12T11:02:24Z day: '25' ddc: - '000' - '570' department: - _id: CaGu - _id: GaTk doi: 10.1371/journal.pcbi.1007642 external_id: isi: - '000526725200019' file: - access_level: open_access checksum: 5239dd134dc6e1c71fe7b3ce2953da37 content_type: application/pdf creator: dernst date_created: 2020-03-09T15:12:21Z date_updated: 2020-07-14T12:48:00Z file_id: '7579' file_name: 2020_PlosCompBio_Grah.pdf file_size: 2209325 relation: main_file file_date_updated: 2020-07-14T12:48:00Z has_accepted_license: '1' intvolume: ' 16' isi: 1 issue: '2' language: - iso: eng month: '02' oa: 1 oa_version: Published Version publication: PLOS Computational Biology publication_identifier: issn: - 1553-7358 publication_status: published publisher: Public Library of Science quality_controlled: '1' related_material: record: - id: '9716' relation: research_data status: deleted - id: '9776' relation: research_data status: public - id: '9779' relation: used_in_publication status: public - id: '8155' relation: dissertation_contains status: public - id: '9777' relation: research_data status: public scopus_import: '1' status: public title: The relation between crosstalk and gene regulation form revisited tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 16 year: '2020' ... --- _id: '9777' article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Tamar full_name: Friedlander, Tamar last_name: Friedlander citation: ama: Grah R, Friedlander T. Maximizing crosstalk. 2020. doi:10.1371/journal.pcbi.1007642.s002 apa: Grah, R., & Friedlander, T. (2020). Maximizing crosstalk. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007642.s002 chicago: Grah, Rok, and Tamar Friedlander. “Maximizing Crosstalk.” Public Library of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s002. ieee: R. Grah and T. Friedlander, “Maximizing crosstalk.” Public Library of Science, 2020. ista: Grah R, Friedlander T. 2020. Maximizing crosstalk, Public Library of Science, 10.1371/journal.pcbi.1007642.s002. mla: Grah, Rok, and Tamar Friedlander. Maximizing Crosstalk. Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642.s002. short: R. Grah, T. Friedlander, (2020). date_created: 2021-08-06T07:21:51Z date_published: 2020-02-25T00:00:00Z date_updated: 2023-09-12T11:02:25Z day: '25' department: - _id: GaTk doi: 10.1371/journal.pcbi.1007642.s002 main_file_link: - open_access: '1' url: https://doi.org/10.1371/journal.pcbi.1007642.s002 month: '02' oa: 1 oa_version: None publisher: Public Library of Science related_material: record: - id: '7569' relation: used_in_publication status: public status: public title: Maximizing crosstalk type: research_data_reference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '8097' abstract: - lang: eng text: 'Antibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by "translation bottlenecks": points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further show that growth laws, combined with drug uptake and binding kinetics, enable the direct prediction of a large fraction of observed interactions, yet fail to predict suppression. However, varying two translation bottlenecks simultaneously supports that dense traffic of ribosomes and competition for translation factors account for the previously unexplained suppression. These results highlight the importance of "continuous epistasis" in bacterial physiology.' acknowledged_ssus: - _id: LifeSc article_processing_charge: No author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X citation: ama: Kavcic B. Analysis scripts and research data for the paper “Mechanisms of drug interactions between translation-inhibiting antibiotics.” 2020. doi:10.15479/AT:ISTA:8097 apa: Kavcic, B. (2020). Analysis scripts and research data for the paper “Mechanisms of drug interactions between translation-inhibiting antibiotics.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8097 chicago: Kavcic, Bor. “Analysis Scripts and Research Data for the Paper ‘Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.’” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8097. ieee: B. Kavcic, “Analysis scripts and research data for the paper ‘Mechanisms of drug interactions between translation-inhibiting antibiotics.’” Institute of Science and Technology Austria, 2020. ista: Kavcic B. 2020. Analysis scripts and research data for the paper ‘Mechanisms of drug interactions between translation-inhibiting antibiotics’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:8097. mla: Kavcic, Bor. Analysis Scripts and Research Data for the Paper “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8097. short: B. Kavcic, (2020). contributor: - contributor_type: research_group first_name: Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - contributor_type: research_group first_name: Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach date_created: 2020-07-06T20:40:19Z date_published: 2020-07-15T00:00:00Z date_updated: 2024-02-21T12:40:51Z day: '15' department: - _id: GaTk doi: 10.15479/AT:ISTA:8097 file: - access_level: open_access checksum: 5c321dbbb6d4b3c85da786fd3ebbdc98 content_type: application/zip creator: bkavcic date_created: 2020-07-06T20:38:27Z date_updated: 2020-07-14T12:48:09Z file_id: '8098' file_name: natComm_2020_scripts.zip file_size: 255770756 relation: main_file file_date_updated: 2020-07-14T12:48:09Z has_accepted_license: '1' keyword: - Escherichia coli - antibiotic combinations - translation - growth laws - drug interactions - bacterial physiology - translation inhibitors month: '07' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria status: public title: Analysis scripts and research data for the paper "Mechanisms of drug interactions between translation-inhibiting antibiotics" tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '8930' abstract: - lang: eng text: Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We provide analytical results for limiting cases, which agree well with numerical results. We systematically refine the model by including direct physical interactions of different antibiotics on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions that were derived using entropy maximization. We further refine the model to include the effects of antibiotics that mimic starvation and the presence of resistance genes. We describe the impact of a starvation-mimicking antibiotic on drug interactions analytically and verify it experimentally. Our extended model suggests a change in the type of drug interaction that depends on the strength of resistance, which challenges established rescaling paradigms. We experimentally show that the presence of unregulated resistance genes can lead to altered drug interaction, which agrees with the prediction of the model. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems. article_processing_charge: No author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X citation: ama: Kavcic B. Analysis scripts and research data for the paper “Minimal biophysical model of combined antibiotic action.” 2020. doi:10.15479/AT:ISTA:8930 apa: Kavcic, B. (2020). Analysis scripts and research data for the paper “Minimal biophysical model of combined antibiotic action.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8930 chicago: Kavcic, Bor. “Analysis Scripts and Research Data for the Paper ‘Minimal Biophysical Model of Combined Antibiotic Action.’” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8930. ieee: B. Kavcic, “Analysis scripts and research data for the paper ‘Minimal biophysical model of combined antibiotic action.’” Institute of Science and Technology Austria, 2020. ista: Kavcic B. 2020. Analysis scripts and research data for the paper ‘Minimal biophysical model of combined antibiotic action’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:8930. mla: Kavcic, Bor. Analysis Scripts and Research Data for the Paper “Minimal Biophysical Model of Combined Antibiotic Action.” Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8930. short: B. Kavcic, (2020). contributor: - contributor_type: supervisor first_name: Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - contributor_type: supervisor first_name: Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach date_created: 2020-12-09T15:04:02Z date_published: 2020-12-10T00:00:00Z date_updated: 2024-02-21T12:41:42Z day: '10' ddc: - '570' department: - _id: GaTk doi: 10.15479/AT:ISTA:8930 file: - access_level: open_access checksum: 60a818edeffaa7da1ebf5f8fbea9ba18 content_type: application/zip creator: bkavcic date_created: 2020-12-09T15:00:19Z date_updated: 2020-12-09T15:00:19Z file_id: '8932' file_name: PLoSCompBiol2020_datarep.zip file_size: 315494370 relation: main_file success: 1 file_date_updated: 2020-12-09T15:00:19Z has_accepted_license: '1' keyword: - Escherichia coli - antibiotic combinations - translation - growth laws - drug interactions - bacterial physiology - translation inhibitors month: '12' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '8997' relation: used_in_publication status: public status: public title: Analysis scripts and research data for the paper "Minimal biophysical model of combined antibiotic action" tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '7383' abstract: - lang: eng text: Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature. article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 citation: ama: 'Grah R. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation. 2020. doi:10.15479/AT:ISTA:7383' apa: 'Grah, R. (2020). Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7383' chicago: 'Grah, Rok. “Matlab Scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7383.' ieee: 'R. Grah, “Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation.” Institute of Science and Technology Austria, 2020.' ista: 'Grah R. 2020. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation, Institute of Science and Technology Austria, 10.15479/AT:ISTA:7383.' mla: 'Grah, Rok. Matlab Scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression Regulation. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7383.' short: R. Grah, (2020). contributor: - contributor_type: project_leader first_name: Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 date_created: 2020-01-28T10:41:49Z date_published: 2020-01-28T00:00:00Z date_updated: 2024-02-21T12:42:31Z day: '28' department: - _id: CaGu - _id: GaTk doi: 10.15479/AT:ISTA:7383 file: - access_level: open_access checksum: 9d292cf5207b3829225f44c044cdb3fd content_type: application/zip creator: rgrah date_created: 2020-01-28T10:39:40Z date_updated: 2020-07-14T12:47:57Z file_id: '7384' file_name: Scripts.zip file_size: 73363365 relation: main_file - access_level: open_access checksum: 4076ceab32ef588cc233802bab24c1ab content_type: text/plain creator: rgrah date_created: 2020-01-28T10:39:30Z date_updated: 2020-07-14T12:47:57Z file_id: '7385' file_name: READ_ME_MAIN.txt file_size: 962 relation: main_file file_date_updated: 2020-07-14T12:47:57Z has_accepted_license: '1' keyword: - Matlab scripts - analysis of microfluidics - mathematical model month: '01' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '7652' relation: used_in_publication status: public status: public title: 'Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation' type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '8657' abstract: - lang: eng text: "Synthesis of proteins – translation – is a fundamental process of life. Quantitative studies anchor translation into the context of bacterial physiology and reveal several mathematical relationships, called “growth laws,” which capture physiological feedbacks between protein synthesis and cell growth. Growth laws describe the dependency of the ribosome abundance as a function of growth rate, which can change depending on the growth conditions. Perturbations of translation reveal that bacteria employ a compensatory strategy in which the reduced translation capability results in increased expression of the translation machinery.\r\nPerturbations of translation are achieved in various ways; clinically interesting is the application of translation-targeting antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology are often poorly understood. Bacterial responses to two or more simultaneously applied antibiotics are even more puzzling. The combined antibiotic effect determines the type of drug interaction, which ranges from synergy (the effect is stronger than expected) to antagonism (the effect is weaker) and suppression (one of the drugs loses its potency).\r\nIn the first part of this work, we systematically measure the pairwise interaction network for translation inhibitors that interfere with different steps in translation. We find that the interactions are surprisingly diverse and tend to be more antagonistic. To explore the underlying mechanisms, we begin with a minimal biophysical model of combined antibiotic action. We base this model on the kinetics of antibiotic uptake and binding together with the physiological response described by the growth laws. The biophysical model explains some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn the second part of this work, we hypothesize that elusive suppressive drug interactions result from the interplay between ribosomes halted in different stages of translation. To elucidate this putative mechanism of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using in- ducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks partially causes these interactions.\r\nWe extend this approach by varying two translation bottlenecks simultaneously. This approach reveals the suppression of translocation inhibition by inhibited translation. We rationalize this effect by modeling dense traffic of ribosomes that move on transcripts in a translation factor-mediated manner. This model predicts a dissolution of traffic jams caused by inhibited translocation when the density of ribosome traffic is reduced by lowered initiation. We base this model on the growth laws and quantitative relationships between different translation and growth parameters.\r\nIn the final part of this work, we describe a set of tools aimed at quantification of physiological and translation parameters. We further develop a simple model that directly connects the abundance of a translation factor with the growth rate, which allows us to extract physiological parameters describing initiation. We demonstrate the development of tools for measuring translation rate.\r\nThis thesis showcases how a combination of high-throughput growth rate mea- surements, genetics, and modeling can reveal mechanisms of drug interactions. Furthermore, by a gradual transition from combinations of antibiotics to precise genetic interventions, we demonstrated the equivalency between genetic and chemi- cal perturbations of translation. These findings tile the path for quantitative studies of antibiotic combinations and illustrate future approaches towards the quantitative description of translation." acknowledged_ssus: - _id: LifeSc - _id: M-Shop acknowledgement: I thank Life Science Facilities for their continuous support with providing top-notch laboratory materials, keeping the devices humming, and coordinating the repairs and building of custom-designed laboratory equipment with the MIBA Machine shop. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X citation: ama: 'Kavcic B. Perturbations of protein synthesis: from antibiotics to genetics and physiology. 2020. doi:10.15479/AT:ISTA:8657' apa: 'Kavcic, B. (2020). Perturbations of protein synthesis: from antibiotics to genetics and physiology. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8657' chicago: 'Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8657.' ieee: 'B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics and physiology,” Institute of Science and Technology Austria, 2020.' ista: 'Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics and physiology. Institute of Science and Technology Austria.' mla: 'Kavcic, Bor. Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8657.' short: 'B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology, Institute of Science and Technology Austria, 2020.' date_created: 2020-10-13T16:46:14Z date_published: 2020-10-14T00:00:00Z date_updated: 2023-09-07T13:20:48Z day: '14' ddc: - '571' - '530' - '570' degree_awarded: PhD department: - _id: GaTk doi: 10.15479/AT:ISTA:8657 file: - access_level: open_access checksum: d708ecd62b6fcc3bc1feb483b8dbe9eb content_type: application/pdf creator: bkavcic date_created: 2020-10-15T06:41:20Z date_updated: 2021-10-07T22:30:03Z embargo: 2021-10-06 file_id: '8663' file_name: kavcicB_thesis202009.pdf file_size: 52636162 relation: main_file - access_level: closed checksum: bb35f2352a04db19164da609f00501f3 content_type: application/zip creator: bkavcic date_created: 2020-10-15T06:41:53Z date_updated: 2021-10-07T22:30:03Z embargo_to: open_access file_id: '8664' file_name: 2020b.zip file_size: 321681247 relation: source_file file_date_updated: 2021-10-07T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '271' publication_identifier: isbn: - 978-3-99078-011-4 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7673' relation: part_of_dissertation status: public - id: '8250' relation: part_of_dissertation status: public status: public supervisor: - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X title: 'Perturbations of protein synthesis: from antibiotics to genetics and physiology' type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '8250' abstract: - lang: eng text: 'Antibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by “translation bottlenecks”: points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further show that growth laws, combined with drug uptake and binding kinetics, enable the direct prediction of a large fraction of observed interactions, yet fail to predict suppression. However, varying two translation bottlenecks simultaneously supports that dense traffic of ribosomes and competition for translation factors account for the previously unexplained suppression. These results highlight the importance of “continuous epistasis” in bacterial physiology.' acknowledgement: "We thank M. Hennessey-Wesen, I. Tomanek, K. Jain, A. Staron, K. Tomasek, M. Scott,\r\nK.C. Huang, and Z. Gitai for reading the manuscript and constructive comments. B.K. is\r\nindebted to C. Guet for additional guidance and generous support, which rendered this\r\nwork possible. B.K. thanks all members of Guet group for many helpful discussions and\r\nsharing of resources. B.K. additionally acknowledges the tremendous support from A.\r\nAngermayr and K. Mitosch with experimental work. We further thank E. Brown for\r\nhelpful comments regarding lamotrigine, and A. Buskirk for valuable suggestions\r\nregarding the ribosome footprint size. This work was supported in part by Austrian\r\nScience Fund (FWF) standalone grants P 27201-B22 (to T.B.) and P 28844 (to G.T.),\r\nHFSP program Grant RGP0042/2013 (to T.B.), German Research Foundation (DFG)\r\nstandalone grant BO 3502/2-1 (to T.B.), and German Research Foundation (DFG)\r\nCollaborative Research Centre (SFB) 1310 (to T.B.). Open access funding provided by\r\nProjekt DEAL." article_number: '4013' article_processing_charge: No article_type: original author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Tobias full_name: Bollenbach, Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X citation: ama: Kavcic B, Tkačik G, Bollenbach MT. Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. 2020;11. doi:10.1038/s41467-020-17734-z apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-020-17734-z chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications. Springer Nature, 2020. https://doi.org/10.1038/s41467-020-17734-z. ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions between translation-inhibiting antibiotics,” Nature Communications, vol. 11. Springer Nature, 2020. ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. 11, 4013. mla: Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications, vol. 11, 4013, Springer Nature, 2020, doi:10.1038/s41467-020-17734-z. short: B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020). date_created: 2020-08-12T09:13:50Z date_published: 2020-08-11T00:00:00Z date_updated: 2024-03-27T23:30:08Z day: '11' ddc: - '570' department: - _id: GaTk doi: 10.1038/s41467-020-17734-z external_id: isi: - '000562769300008' file: - access_level: open_access checksum: 986bebb308850a55850028d3d2b5b664 content_type: application/pdf creator: dernst date_created: 2020-08-17T07:36:57Z date_updated: 2020-08-17T07:36:57Z file_id: '8275' file_name: 2020_NatureComm_Kavcic.pdf file_size: 1965672 relation: main_file success: 1 file_date_updated: 2020-08-17T07:36:57Z has_accepted_license: '1' intvolume: ' 11' isi: 1 language: - iso: eng month: '08' oa: 1 oa_version: Published Version project: - _id: 25E9AF9E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P27201-B22 name: Revealing the mechanisms underlying drug interactions - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: Nature Communications publication_identifier: issn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: record: - id: '8657' relation: dissertation_contains status: public status: public title: Mechanisms of drug interactions between translation-inhibiting antibiotics tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2020' ... --- _id: '7673' abstract: - lang: eng text: Combining drugs can improve the efficacy of treatments. However, predicting the effect of drug combinations is still challenging. The combined potency of drugs determines the drug interaction, which is classified as synergistic, additive, antagonistic, or suppressive. While probabilistic, non-mechanistic models exist, there is currently no biophysical model that can predict antibiotic interactions. Here, we present a physiologically relevant model of the combined action of antibiotics that inhibit protein synthesis by targeting the ribosome. This model captures the kinetics of antibiotic binding and transport, and uses bacterial growth laws to predict growth in the presence of antibiotic combinations. We find that this biophysical model can produce all drug interaction types except suppression. We show analytically that antibiotics which cannot bind to the ribosome simultaneously generally act as substitutes for one another, leading to additive drug interactions. Previously proposed null expectations for higher-order drug interactions follow as a limiting case of our model. We further extend the model to include the effects of direct physical or allosteric interactions between individual drugs on the ribosome. Notably, such direct interactions profoundly change the combined drug effect, depending on the kinetic parameters of the drugs used. The model makes additional predictions for the effects of resistance genes on drug interactions and for interactions between ribosome-targeting antibiotics and antibiotics with other targets. These findings enhance our understanding of the interplay between drug action and cell physiology and are a key step toward a general framework for predicting drug interactions. article_processing_charge: No author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Tobias full_name: Bollenbach, Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X citation: ama: Kavcic B, Tkačik G, Bollenbach MT. A minimal biophysical model of combined antibiotic action. bioRxiv. 2020. doi:10.1101/2020.04.18.047886 apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). A minimal biophysical model of combined antibiotic action. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.18.047886 chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “A Minimal Biophysical Model of Combined Antibiotic Action.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.18.047886. ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “A minimal biophysical model of combined antibiotic action,” bioRxiv. Cold Spring Harbor Laboratory, 2020. ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. A minimal biophysical model of combined antibiotic action. bioRxiv, 10.1101/2020.04.18.047886. mla: Kavcic, Bor, et al. “A Minimal Biophysical Model of Combined Antibiotic Action.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.18.047886. short: B. Kavcic, G. Tkačik, M.T. Bollenbach, BioRxiv (2020). date_created: 2020-04-22T08:27:56Z date_published: 2020-04-18T00:00:00Z date_updated: 2024-03-27T23:30:08Z day: '18' department: - _id: GaTk doi: 10.1101/2020.04.18.047886 language: - iso: eng main_file_link: - open_access: '1' url: 'https://doi.org/10.1101/2020.04.18.047886 ' month: '04' oa: 1 oa_version: Preprint project: - _id: 25E9AF9E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P27201-B22 name: Revealing the mechanisms underlying drug interactions - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: bioRxiv publication_status: published publisher: Cold Spring Harbor Laboratory related_material: record: - id: '8997' relation: later_version status: public - id: '8657' relation: dissertation_contains status: public status: public title: A minimal biophysical model of combined antibiotic action type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '7652' abstract: - lang: eng text: Organisms cope with change by taking advantage of transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. Here, we investigate whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations in Escherichia coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy-number and, therefore, expression-level polymorphisms. This amplification-mediated gene expression tuning (AMGET) occurs on timescales that are similar to canonical gene regulation and can respond to rapid environmental changes. Mathematical modelling shows that amplifications also tune gene expression in stochastic environments in which transcription-factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune the expression of any gene, without leaving any genomic signature. acknowledgement: We thank L. Hurst, N. Barton, M. Pleska, M. Steinrück, B. Kavcic and A. Staron for input on the manuscript, and To. Bergmiller and R. Chait for help with microfluidics experiments. I.T. is a recipient the OMV fellowship. R.G. is a recipient of a DOC (Doctoral Fellowship Programme of the Austrian Academy of Sciences) Fellowship of the Austrian Academy of Sciences. article_processing_charge: No article_type: original author: - first_name: Isabella full_name: Tomanek, Isabella id: 3981F020-F248-11E8-B48F-1D18A9856A87 last_name: Tomanek orcid: 0000-0001-6197-363X - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: M. full_name: Lagator, M. last_name: Lagator - first_name: A. M. C. full_name: Andersson, A. M. C. last_name: Andersson - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 citation: ama: Tomanek I, Grah R, Lagator M, et al. Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. 2020;4(4):612-625. doi:10.1038/s41559-020-1132-7 apa: Tomanek, I., Grah, R., Lagator, M., Andersson, A. M. C., Bollback, J. P., Tkačik, G., & Guet, C. C. (2020). Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. Springer Nature. https://doi.org/10.1038/s41559-020-1132-7 chicago: Tomanek, Isabella, Rok Grah, M. Lagator, A. M. C. Andersson, Jonathan P Bollback, Gašper Tkačik, and Calin C Guet. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Nature Ecology & Evolution. Springer Nature, 2020. https://doi.org/10.1038/s41559-020-1132-7. ieee: I. Tomanek et al., “Gene amplification as a form of population-level gene expression regulation,” Nature Ecology & Evolution, vol. 4, no. 4. Springer Nature, pp. 612–625, 2020. ista: Tomanek I, Grah R, Lagator M, Andersson AMC, Bollback JP, Tkačik G, Guet CC. 2020. Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. 4(4), 612–625. mla: Tomanek, Isabella, et al. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Nature Ecology & Evolution, vol. 4, no. 4, Springer Nature, 2020, pp. 612–25, doi:10.1038/s41559-020-1132-7. short: I. Tomanek, R. Grah, M. Lagator, A.M.C. Andersson, J.P. Bollback, G. Tkačik, C.C. Guet, Nature Ecology & Evolution 4 (2020) 612–625. date_created: 2020-04-08T15:20:53Z date_published: 2020-04-01T00:00:00Z date_updated: 2024-03-27T23:30:36Z day: '01' ddc: - '570' department: - _id: GaTk - _id: CaGu doi: 10.1038/s41559-020-1132-7 external_id: isi: - '000519008300005' file: - access_level: open_access checksum: ef3bbf42023e30b2c24a6278025d2040 content_type: application/pdf creator: dernst date_created: 2020-10-09T09:56:01Z date_updated: 2020-10-09T09:56:01Z file_id: '8640' file_name: 2020_NatureEcolEvo_Tomanek.pdf file_size: 745242 relation: main_file success: 1 file_date_updated: 2020-10-09T09:56:01Z has_accepted_license: '1' intvolume: ' 4' isi: 1 issue: '4' language: - iso: eng month: '04' oa: 1 oa_version: Submitted Version page: 612-625 project: - _id: 267C84F4-B435-11E9-9278-68D0E5697425 name: Biophysically realistic genotype-phenotype maps for regulatory networks publication: Nature Ecology & Evolution publication_identifier: issn: - 2397-334X publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/how-to-thrive-without-gene-regulation/ record: - id: '8155' relation: dissertation_contains status: public - id: '7383' relation: research_data status: public - id: '7016' relation: research_data status: public - id: '8653' relation: used_in_publication status: public scopus_import: '1' status: public title: Gene amplification as a form of population-level gene expression regulation type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 4 year: '2020' ... --- _id: '7552' abstract: - lang: eng text: 'There is increasing evidence that protein binding to specific sites along DNA can activate the reading out of genetic information without coming into direct physical contact with the gene. There also is evidence that these distant but interacting sites are embedded in a liquid droplet of proteins which condenses out of the surrounding solution. We argue that droplet-mediated interactions can account for crucial features of gene regulation only if the droplet is poised at a non-generic point in its phase diagram. We explore a minimal model that embodies this idea, show that this model has a natural mechanism for self-tuning, and suggest direct experimental tests. ' article_processing_charge: No author: - first_name: William full_name: Bialek, William last_name: Bialek - first_name: Thomas full_name: Gregor, Thomas last_name: Gregor - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Bialek W, Gregor T, Tkačik G. Action at a distance in transcriptional regulation. arXiv:191208579. apa: Bialek, W., Gregor, T., & Tkačik, G. (n.d.). Action at a distance in transcriptional regulation. arXiv:1912.08579. ArXiv. chicago: Bialek, William, Thomas Gregor, and Gašper Tkačik. “Action at a Distance in Transcriptional Regulation.” ArXiv:1912.08579. ArXiv, n.d. ieee: W. Bialek, T. Gregor, and G. Tkačik, “Action at a distance in transcriptional regulation,” arXiv:1912.08579. ArXiv. ista: Bialek W, Gregor T, Tkačik G. Action at a distance in transcriptional regulation. arXiv:1912.08579, . mla: Bialek, William, et al. “Action at a Distance in Transcriptional Regulation.” ArXiv:1912.08579, ArXiv. short: W. Bialek, T. Gregor, G. Tkačik, ArXiv:1912.08579 (n.d.). date_created: 2020-02-28T10:57:08Z date_published: 2019-12-18T00:00:00Z date_updated: 2021-01-12T08:14:09Z day: '18' department: - _id: GaTk external_id: arxiv: - '1912.08579' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1912.08579 month: '12' oa: 1 oa_version: Preprint page: '5' project: - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: arXiv:1912.08579 publication_status: submitted publisher: ArXiv status: public title: Action at a distance in transcriptional regulation type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2019' ... --- _id: '5945' abstract: - lang: eng text: In developing organisms, spatially prescribed cell identities are thought to be determined by the expression levels of multiple genes. Quantitative tests of this idea, however, require a theoretical framework capable of exposing the rules and precision of cell specification over developmental time. We use the gap gene network in the early fly embryo as an example to show how expression levels of the four gap genes can be jointly decoded into an optimal specification of position with 1% accuracy. The decoder correctly predicts, with no free parameters, the dynamics of pair-rule expression patterns at different developmental time points and in various mutant backgrounds. Precise cellular identities are thus available at the earliest stages of development, contrasting the prevailing view of positional information being slowly refined across successive layers of the patterning network. Our results suggest that developmental enhancers closely approximate a mathematically optimal decoding strategy. article_processing_charge: No article_type: original author: - first_name: Mariela D. full_name: Petkova, Mariela D. last_name: Petkova - first_name: Gasper full_name: Tkacik, Gasper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkacik orcid: 0000-0002-6699-1455 - first_name: William full_name: Bialek, William last_name: Bialek - first_name: Eric F. full_name: Wieschaus, Eric F. last_name: Wieschaus - first_name: Thomas full_name: Gregor, Thomas last_name: Gregor citation: ama: Petkova MD, Tkačik G, Bialek W, Wieschaus EF, Gregor T. Optimal decoding of cellular identities in a genetic network. Cell. 2019;176(4):844-855.e15. doi:10.1016/j.cell.2019.01.007 apa: Petkova, M. D., Tkačik, G., Bialek, W., Wieschaus, E. F., & Gregor, T. (2019). Optimal decoding of cellular identities in a genetic network. Cell. Cell Press. https://doi.org/10.1016/j.cell.2019.01.007 chicago: Petkova, Mariela D., Gašper Tkačik, William Bialek, Eric F. Wieschaus, and Thomas Gregor. “Optimal Decoding of Cellular Identities in a Genetic Network.” Cell. Cell Press, 2019. https://doi.org/10.1016/j.cell.2019.01.007. ieee: M. D. Petkova, G. Tkačik, W. Bialek, E. F. Wieschaus, and T. Gregor, “Optimal decoding of cellular identities in a genetic network,” Cell, vol. 176, no. 4. Cell Press, p. 844–855.e15, 2019. ista: Petkova MD, Tkačik G, Bialek W, Wieschaus EF, Gregor T. 2019. Optimal decoding of cellular identities in a genetic network. Cell. 176(4), 844–855.e15. mla: Petkova, Mariela D., et al. “Optimal Decoding of Cellular Identities in a Genetic Network.” Cell, vol. 176, no. 4, Cell Press, 2019, p. 844–855.e15, doi:10.1016/j.cell.2019.01.007. short: M.D. Petkova, G. Tkačik, W. Bialek, E.F. Wieschaus, T. Gregor, Cell 176 (2019) 844–855.e15. date_created: 2019-02-10T22:59:16Z date_published: 2019-02-07T00:00:00Z date_updated: 2023-08-24T14:42:47Z day: '07' department: - _id: GaTk doi: 10.1016/j.cell.2019.01.007 external_id: isi: - '000457969200015' pmid: - '30712870' intvolume: ' 176' isi: 1 issue: '4' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.cell.2019.01.007 month: '02' oa: 1 oa_version: Published Version page: 844-855.e15 pmid: 1 project: - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: Cell publication_status: published publisher: Cell Press quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/cells-find-their-identity-using-a-mathematically-optimal-strategy/ scopus_import: '1' status: public title: Optimal decoding of cellular identities in a genetic network type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 176 year: '2019' ... --- _id: '6049' abstract: - lang: eng text: 'In this article it is shown that large systems with many interacting units endowing multiple phases display self-oscillations in the presence of linear feedback between the control and order parameters, where an Andronov–Hopf bifurcation takes over the phase transition. This is simply illustrated through the mean field Landau theory whose feedback dynamics turn out to be described by the Van der Pol equation and it is then validated for the fully connected Ising model following heat bath dynamics. Despite its simplicity, this theory accounts potentially for a rich range of phenomena: here it is applied to describe in a stylized way (i) excess demand-price cycles due to strong herding in a simple agent-based market model; (ii) congestion waves in queuing networks triggered by user feedback to delays in overloaded conditions; and (iii) metabolic network oscillations resulting from cell growth control in a bistable phenotypic landscape.' article_number: '045002' article_processing_charge: Yes (in subscription journal) author: - first_name: Daniele full_name: De Martino, Daniele id: 3FF5848A-F248-11E8-B48F-1D18A9856A87 last_name: De Martino orcid: 0000-0002-5214-4706 citation: ama: 'De Martino D. Feedback-induced self-oscillations in large interacting systems subjected to phase transitions. Journal of Physics A: Mathematical and Theoretical. 2019;52(4). doi:10.1088/1751-8121/aaf2dd' apa: 'De Martino, D. (2019). Feedback-induced self-oscillations in large interacting systems subjected to phase transitions. Journal of Physics A: Mathematical and Theoretical. IOP Publishing. https://doi.org/10.1088/1751-8121/aaf2dd' chicago: 'De Martino, Daniele. “Feedback-Induced Self-Oscillations in Large Interacting Systems Subjected to Phase Transitions.” Journal of Physics A: Mathematical and Theoretical. IOP Publishing, 2019. https://doi.org/10.1088/1751-8121/aaf2dd.' ieee: 'D. De Martino, “Feedback-induced self-oscillations in large interacting systems subjected to phase transitions,” Journal of Physics A: Mathematical and Theoretical, vol. 52, no. 4. IOP Publishing, 2019.' ista: 'De Martino D. 2019. Feedback-induced self-oscillations in large interacting systems subjected to phase transitions. Journal of Physics A: Mathematical and Theoretical. 52(4), 045002.' mla: 'De Martino, Daniele. “Feedback-Induced Self-Oscillations in Large Interacting Systems Subjected to Phase Transitions.” Journal of Physics A: Mathematical and Theoretical, vol. 52, no. 4, 045002, IOP Publishing, 2019, doi:10.1088/1751-8121/aaf2dd.' short: 'D. De Martino, Journal of Physics A: Mathematical and Theoretical 52 (2019).' date_created: 2019-02-24T22:59:19Z date_published: 2019-01-07T00:00:00Z date_updated: 2023-08-24T14:49:23Z day: '07' ddc: - '570' department: - _id: GaTk doi: 10.1088/1751-8121/aaf2dd ec_funded: 1 external_id: isi: - '000455379500001' file: - access_level: open_access checksum: 1112304ad363a6d8afaeccece36473cf content_type: application/pdf creator: kschuh date_created: 2019-04-19T12:18:57Z date_updated: 2020-07-14T12:47:17Z file_id: '6344' file_name: 2019_IOP_DeMartino.pdf file_size: 1804557 relation: main_file file_date_updated: 2020-07-14T12:47:17Z has_accepted_license: '1' intvolume: ' 52' isi: 1 issue: '4' language: - iso: eng month: '01' oa: 1 oa_version: Published Version project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: 'Journal of Physics A: Mathematical and Theoretical' publication_status: published publisher: IOP Publishing quality_controlled: '1' scopus_import: '1' status: public title: Feedback-induced self-oscillations in large interacting systems subjected to phase transitions tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 52 year: '2019' ... --- _id: '6046' abstract: - lang: eng text: Sudden stress often triggers diverse, temporally structured gene expression responses in microbes, but it is largely unknown how variable in time such responses are and if genes respond in the same temporal order in every single cell. Here, we quantified timing variability of individual promoters responding to sublethal antibiotic stress using fluorescent reporters, microfluidics, and time‐lapse microscopy. We identified lower and upper bounds that put definite constraints on timing variability, which varies strongly among promoters and conditions. Timing variability can be interpreted using results from statistical kinetics, which enable us to estimate the number of rate‐limiting molecular steps underlying different responses. We found that just a few critical steps control some responses while others rely on dozens of steps. To probe connections between different stress responses, we then tracked the temporal order and response time correlations of promoter pairs in individual cells. Our results support that, when bacteria are exposed to the antibiotic nitrofurantoin, the ensuing oxidative stress and SOS responses are part of the same causal chain of molecular events. In contrast, under trimethoprim, the acid stress response and the SOS response are part of different chains of events running in parallel. Our approach reveals fundamental constraints on gene expression timing and provides new insights into the molecular events that underlie the timing of stress responses. acknowledged_ssus: - _id: Bio article_number: e8470 article_processing_charge: No author: - first_name: Karin full_name: Mitosch, Karin id: 39B66846-F248-11E8-B48F-1D18A9856A87 last_name: Mitosch - first_name: Georg full_name: Rieckh, Georg id: 34DA8BD6-F248-11E8-B48F-1D18A9856A87 last_name: Rieckh - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X citation: ama: Mitosch K, Rieckh G, Bollenbach MT. Temporal order and precision of complex stress responses in individual bacteria. Molecular systems biology. 2019;15(2). doi:10.15252/msb.20188470 apa: Mitosch, K., Rieckh, G., & Bollenbach, M. T. (2019). Temporal order and precision of complex stress responses in individual bacteria. Molecular Systems Biology. Embo Press. https://doi.org/10.15252/msb.20188470 chicago: Mitosch, Karin, Georg Rieckh, and Mark Tobias Bollenbach. “Temporal Order and Precision of Complex Stress Responses in Individual Bacteria.” Molecular Systems Biology. Embo Press, 2019. https://doi.org/10.15252/msb.20188470. ieee: K. Mitosch, G. Rieckh, and M. T. Bollenbach, “Temporal order and precision of complex stress responses in individual bacteria,” Molecular systems biology, vol. 15, no. 2. Embo Press, 2019. ista: Mitosch K, Rieckh G, Bollenbach MT. 2019. Temporal order and precision of complex stress responses in individual bacteria. Molecular systems biology. 15(2), e8470. mla: Mitosch, Karin, et al. “Temporal Order and Precision of Complex Stress Responses in Individual Bacteria.” Molecular Systems Biology, vol. 15, no. 2, e8470, Embo Press, 2019, doi:10.15252/msb.20188470. short: K. Mitosch, G. Rieckh, M.T. Bollenbach, Molecular Systems Biology 15 (2019). date_created: 2019-02-24T22:59:18Z date_published: 2019-02-14T00:00:00Z date_updated: 2023-08-24T14:49:53Z day: '14' department: - _id: GaTk doi: 10.15252/msb.20188470 external_id: isi: - '000459628300003' pmid: - '30765425' intvolume: ' 15' isi: 1 issue: '2' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pubmed/30765425 month: '02' oa: 1 oa_version: Submitted Version pmid: 1 project: - _id: 25E9AF9E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P27201-B22 name: Revealing the mechanisms underlying drug interactions - _id: 25EB3A80-B435-11E9-9278-68D0E5697425 grant_number: RGP0042/2013 name: Revealing the fundamental limits of cell growth publication: Molecular systems biology publication_status: published publisher: Embo Press quality_controlled: '1' scopus_import: '1' status: public title: Temporal order and precision of complex stress responses in individual bacteria type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 15 year: '2019' ... --- _id: '6784' abstract: - lang: eng text: Mathematical models have been used successfully at diverse scales of biological organization, ranging from ecology and population dynamics to stochastic reaction events occurring between individual molecules in single cells. Generally, many biological processes unfold across multiple scales, with mutations being the best studied example of how stochasticity at the molecular scale can influence outcomes at the population scale. In many other contexts, however, an analogous link between micro- and macro-scale remains elusive, primarily due to the challenges involved in setting up and analyzing multi-scale models. Here, we employ such a model to investigate how stochasticity propagates from individual biochemical reaction events in the bacterial innate immune system to the ecology of bacteria and bacterial viruses. We show analytically how the dynamics of bacterial populations are shaped by the activities of immunity-conferring enzymes in single cells and how the ecological consequences imply optimal bacterial defense strategies against viruses. Our results suggest that bacterial populations in the presence of viruses can either optimize their initial growth rate or their population size, with the first strategy favoring simple immunity featuring a single restriction modification system and the second strategy favoring complex bacterial innate immunity featuring several simultaneously active restriction modification systems. article_number: e1007168 article_processing_charge: No article_type: original author: - first_name: Jakob full_name: Ruess, Jakob id: 4A245D00-F248-11E8-B48F-1D18A9856A87 last_name: Ruess orcid: 0000-0003-1615-3282 - first_name: Maros full_name: Pleska, Maros id: 4569785E-F248-11E8-B48F-1D18A9856A87 last_name: Pleska orcid: 0000-0001-7460-7479 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Ruess J, Pleska M, Guet CC, Tkačik G. Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. 2019;15(7). doi:10.1371/journal.pcbi.1007168 apa: Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168 chicago: Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” PLoS Computational Biology. Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168. ieee: J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Molecular noise of innate immunity shapes bacteria-phage ecologies,” PLoS Computational Biology, vol. 15, no. 7. Public Library of Science, 2019. ista: Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. 15(7), e1007168. mla: Ruess, Jakob, et al. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” PLoS Computational Biology, vol. 15, no. 7, e1007168, Public Library of Science, 2019, doi:10.1371/journal.pcbi.1007168. short: J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15 (2019). date_created: 2019-08-11T21:59:19Z date_published: 2019-07-02T00:00:00Z date_updated: 2023-08-29T07:10:06Z day: '02' ddc: - '570' department: - _id: CaGu - _id: GaTk doi: 10.1371/journal.pcbi.1007168 external_id: isi: - '000481577700032' file: - access_level: open_access checksum: 7ded4721b41c2a0fc66a1c634540416a content_type: application/pdf creator: dernst date_created: 2019-08-12T12:27:26Z date_updated: 2020-07-14T12:47:40Z file_id: '6803' file_name: 2019_PlosComputBiology_Ruess.pdf file_size: 2200003 relation: main_file file_date_updated: 2020-07-14T12:47:40Z has_accepted_license: '1' intvolume: ' 15' isi: 1 issue: '7' language: - iso: eng month: '07' oa: 1 oa_version: Published Version project: - _id: 251D65D8-B435-11E9-9278-68D0E5697425 grant_number: '24210' name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level - _id: 251BCBEC-B435-11E9-9278-68D0E5697425 grant_number: RGY0079/2011 name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems publication: PLoS Computational Biology publication_identifier: eissn: - 1553-7358 publication_status: published publisher: Public Library of Science quality_controlled: '1' related_material: record: - id: '9786' relation: research_data status: public scopus_import: '1' status: public title: Molecular noise of innate immunity shapes bacteria-phage ecologies tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 15 year: '2019' ... --- _id: '9786' article_processing_charge: No author: - first_name: Jakob full_name: Ruess, Jakob id: 4A245D00-F248-11E8-B48F-1D18A9856A87 last_name: Ruess orcid: 0000-0003-1615-3282 - first_name: Maros full_name: Pleska, Maros id: 4569785E-F248-11E8-B48F-1D18A9856A87 last_name: Pleska orcid: 0000-0001-7460-7479 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Ruess J, Pleska M, Guet CC, Tkačik G. Supporting text and results. 2019. doi:10.1371/journal.pcbi.1007168.s001 apa: Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Supporting text and results. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168.s001 chicago: Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Supporting Text and Results.” Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.s001. ieee: J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Supporting text and results.” Public Library of Science, 2019. ista: Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Supporting text and results, Public Library of Science, 10.1371/journal.pcbi.1007168.s001. mla: Ruess, Jakob, et al. Supporting Text and Results. Public Library of Science, 2019, doi:10.1371/journal.pcbi.1007168.s001. short: J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, (2019). date_created: 2021-08-06T08:23:43Z date_published: 2019-07-02T00:00:00Z date_updated: 2023-08-29T07:10:05Z day: '02' department: - _id: CaGu - _id: GaTk doi: 10.1371/journal.pcbi.1007168.s001 month: '07' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '6784' relation: used_in_publication status: public status: public title: Supporting text and results type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2019' ... --- _id: '7422' abstract: - lang: eng text: Biochemical reactions often occur at low copy numbers but at once in crowded and diverse environments. Space and stochasticity therefore play an essential role in biochemical networks. Spatial-stochastic simulations have become a prominent tool for understanding how stochasticity at the microscopic level influences the macroscopic behavior of such systems. While particle-based models guarantee the level of detail necessary to accurately describe the microscopic dynamics at very low copy numbers, the algorithms used to simulate them typically imply trade-offs between computational efficiency and biochemical accuracy. eGFRD (enhanced Green’s Function Reaction Dynamics) is an exact algorithm that evades such trade-offs by partitioning the N-particle system into M ≤ N analytically tractable one- and two-particle systems; the analytical solutions (Green’s functions) then are used to implement an event-driven particle-based scheme that allows particles to make large jumps in time and space while retaining access to their state variables at arbitrary simulation times. Here we present “eGFRD2,” a new eGFRD version that implements the principle of eGFRD in all dimensions, thus enabling efficient particle-based simulation of biochemical reaction-diffusion processes in the 3D cytoplasm, on 2D planes representing membranes, and on 1D elongated cylinders representative of, e.g., cytoskeletal tracks or DNA; in 1D, it also incorporates convective motion used to model active transport. We find that, for low particle densities, eGFRD2 is up to 6 orders of magnitude faster than conventional Brownian dynamics. We exemplify the capabilities of eGFRD2 by simulating an idealized model of Pom1 gradient formation, which involves 3D diffusion, active transport on microtubules, and autophosphorylation on the membrane, confirming recent experimental and theoretical results on this system to hold under genuinely stochastic conditions. article_number: '054108' article_processing_charge: No article_type: original author: - first_name: Thomas R full_name: Sokolowski, Thomas R id: 3E999752-F248-11E8-B48F-1D18A9856A87 last_name: Sokolowski orcid: 0000-0002-1287-3779 - first_name: Joris full_name: Paijmans, Joris last_name: Paijmans - first_name: Laurens full_name: Bossen, Laurens last_name: Bossen - first_name: Thomas full_name: Miedema, Thomas last_name: Miedema - first_name: Martijn full_name: Wehrens, Martijn last_name: Wehrens - first_name: Nils B. full_name: Becker, Nils B. last_name: Becker - first_name: Kazunari full_name: Kaizu, Kazunari last_name: Kaizu - first_name: Koichi full_name: Takahashi, Koichi last_name: Takahashi - first_name: Marileen full_name: Dogterom, Marileen last_name: Dogterom - first_name: Pieter Rein full_name: ten Wolde, Pieter Rein last_name: ten Wolde citation: ama: Sokolowski TR, Paijmans J, Bossen L, et al. eGFRD in all dimensions. The Journal of Chemical Physics. 2019;150(5). doi:10.1063/1.5064867 apa: Sokolowski, T. R., Paijmans, J., Bossen, L., Miedema, T., Wehrens, M., Becker, N. B., … ten Wolde, P. R. (2019). eGFRD in all dimensions. The Journal of Chemical Physics. AIP Publishing. https://doi.org/10.1063/1.5064867 chicago: Sokolowski, Thomas R, Joris Paijmans, Laurens Bossen, Thomas Miedema, Martijn Wehrens, Nils B. Becker, Kazunari Kaizu, Koichi Takahashi, Marileen Dogterom, and Pieter Rein ten Wolde. “EGFRD in All Dimensions.” The Journal of Chemical Physics. AIP Publishing, 2019. https://doi.org/10.1063/1.5064867. ieee: T. R. Sokolowski et al., “eGFRD in all dimensions,” The Journal of Chemical Physics, vol. 150, no. 5. AIP Publishing, 2019. ista: Sokolowski TR, Paijmans J, Bossen L, Miedema T, Wehrens M, Becker NB, Kaizu K, Takahashi K, Dogterom M, ten Wolde PR. 2019. eGFRD in all dimensions. The Journal of Chemical Physics. 150(5), 054108. mla: Sokolowski, Thomas R., et al. “EGFRD in All Dimensions.” The Journal of Chemical Physics, vol. 150, no. 5, 054108, AIP Publishing, 2019, doi:10.1063/1.5064867. short: T.R. Sokolowski, J. Paijmans, L. Bossen, T. Miedema, M. Wehrens, N.B. Becker, K. Kaizu, K. Takahashi, M. Dogterom, P.R. ten Wolde, The Journal of Chemical Physics 150 (2019). date_created: 2020-01-30T10:34:36Z date_published: 2019-02-07T00:00:00Z date_updated: 2023-09-06T14:59:28Z day: '07' department: - _id: GaTk doi: 10.1063/1.5064867 external_id: arxiv: - '1708.09364' isi: - '000458109300009' intvolume: ' 150' isi: 1 issue: '5' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1708.09364 month: '02' oa: 1 oa_version: Preprint publication: The Journal of Chemical Physics publication_identifier: eissn: - 1089-7690 issn: - 0021-9606 publication_status: published publisher: AIP Publishing quality_controlled: '1' status: public title: eGFRD in all dimensions type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 150 year: '2019' ... --- _id: '6900' abstract: - lang: eng text: Across diverse biological systems—ranging from neural networks to intracellular signaling and genetic regulatory networks—the information about changes in the environment is frequently encoded in the full temporal dynamics of the network nodes. A pressing data-analysis challenge has thus been to efficiently estimate the amount of information that these dynamics convey from experimental data. Here we develop and evaluate decoding-based estimation methods to lower bound the mutual information about a finite set of inputs, encoded in single-cell high-dimensional time series data. For biological reaction networks governed by the chemical Master equation, we derive model-based information approximations and analytical upper bounds, against which we benchmark our proposed model-free decoding estimators. In contrast to the frequently-used k-nearest-neighbor estimator, decoding-based estimators robustly extract a large fraction of the available information from high-dimensional trajectories with a realistic number of data samples. We apply these estimators to previously published data on Erk and Ca2+ signaling in mammalian cells and to yeast stress-response, and find that substantial amount of information about environmental state can be encoded by non-trivial response statistics even in stationary signals. We argue that these single-cell, decoding-based information estimates, rather than the commonly-used tests for significant differences between selected population response statistics, provide a proper and unbiased measure for the performance of biological signaling networks. article_processing_charge: No author: - first_name: Sarah A full_name: Cepeda Humerez, Sarah A id: 3DEE19A4-F248-11E8-B48F-1D18A9856A87 last_name: Cepeda Humerez - first_name: Jakob full_name: Ruess, Jakob last_name: Ruess orcid: 0000-0003-1615-3282 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Cepeda Humerez SA, Ruess J, Tkačik G. Estimating information in time-varying signals. PLoS computational biology. 2019;15(9):e1007290. doi:10.1371/journal.pcbi.1007290 apa: Cepeda Humerez, S. A., Ruess, J., & Tkačik, G. (2019). Estimating information in time-varying signals. PLoS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007290 chicago: Cepeda Humerez, Sarah A, Jakob Ruess, and Gašper Tkačik. “Estimating Information in Time-Varying Signals.” PLoS Computational Biology. Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007290. ieee: S. A. Cepeda Humerez, J. Ruess, and G. Tkačik, “Estimating information in time-varying signals,” PLoS computational biology, vol. 15, no. 9. Public Library of Science, p. e1007290, 2019. ista: Cepeda Humerez SA, Ruess J, Tkačik G. 2019. Estimating information in time-varying signals. PLoS computational biology. 15(9), e1007290. mla: Cepeda Humerez, Sarah A., et al. “Estimating Information in Time-Varying Signals.” PLoS Computational Biology, vol. 15, no. 9, Public Library of Science, 2019, p. e1007290, doi:10.1371/journal.pcbi.1007290. short: S.A. Cepeda Humerez, J. Ruess, G. Tkačik, PLoS Computational Biology 15 (2019) e1007290. date_created: 2019-09-22T22:00:37Z date_published: 2019-09-03T00:00:00Z date_updated: 2023-09-07T12:55:21Z day: '03' ddc: - '570' department: - _id: GaTk doi: 10.1371/journal.pcbi.1007290 external_id: isi: - '000489741800021' pmid: - '31479447' file: - access_level: open_access checksum: 81bdce1361c9aa8395d6fa635fb6ab47 content_type: application/pdf creator: kschuh date_created: 2019-10-01T10:53:45Z date_updated: 2020-07-14T12:47:44Z file_id: '6925' file_name: 2019_PLoS_Cepeda-Humerez.pdf file_size: 3081855 relation: main_file file_date_updated: 2020-07-14T12:47:44Z has_accepted_license: '1' intvolume: ' 15' isi: 1 issue: '9' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: e1007290 pmid: 1 project: - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: PLoS computational biology publication_identifier: eissn: - '15537358' publication_status: published publisher: Public Library of Science quality_controlled: '1' related_material: record: - id: '6473' relation: part_of_dissertation status: public scopus_import: '1' status: public title: Estimating information in time-varying signals tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 15 year: '2019' ... --- _id: '196' abstract: - lang: eng text: 'The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. ' acknowledgement: "M.L. is grateful to the members of the C Guet and G Tkacik groups for valuable comments and support. M.S. is grateful to Nikita Kalinin for inspiring communications.\r\n" article_processing_charge: No article_type: original author: - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Mikhail full_name: Shkolnikov, Mikhail id: 35084A62-F248-11E8-B48F-1D18A9856A87 last_name: Shkolnikov orcid: 0000-0002-4310-178X citation: ama: Lang M, Shkolnikov M. Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. 2019;116(8):2821-2830. doi:10.1073/pnas.1812015116 apa: Lang, M., & Shkolnikov, M. (2019). Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1812015116 chicago: Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2019. https://doi.org/10.1073/pnas.1812015116. ieee: M. Lang and M. Shkolnikov, “Harmonic dynamics of the Abelian sandpile,” Proceedings of the National Academy of Sciences, vol. 116, no. 8. National Academy of Sciences, pp. 2821–2830, 2019. ista: Lang M, Shkolnikov M. 2019. Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. 116(8), 2821–2830. mla: Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” Proceedings of the National Academy of Sciences, vol. 116, no. 8, National Academy of Sciences, 2019, pp. 2821–30, doi:10.1073/pnas.1812015116. short: M. Lang, M. Shkolnikov, Proceedings of the National Academy of Sciences 116 (2019) 2821–2830. date_created: 2018-12-11T11:45:08Z date_published: 2019-02-19T00:00:00Z date_updated: 2023-09-11T14:09:34Z day: '19' department: - _id: CaGu - _id: GaTk - _id: TaHa doi: 10.1073/pnas.1812015116 external_id: arxiv: - '1806.10823' isi: - '000459074400013' pmid: - ' 30728300' intvolume: ' 116' isi: 1 issue: '8' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1073/pnas.1812015116 month: '02' oa: 1 oa_version: Published Version page: 2821-2830 pmid: 1 publication: Proceedings of the National Academy of Sciences publication_identifier: eissn: - 1091-6490 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: link: - description: News on IST Webpage relation: press_release url: https://ist.ac.at/en/news/famous-sandpile-model-shown-to-move-like-a-traveling-sand-dune/ scopus_import: '1' status: public title: Harmonic dynamics of the Abelian sandpile type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 116 year: '2019' ... --- _id: '5817' abstract: - lang: eng text: We theoretically study the shapes of lipid vesicles confined to a spherical cavity, elaborating a framework based on the so-called limiting shapes constructed from geometrically simple structural elements such as double-membrane walls and edges. Partly inspired by numerical results, the proposed non-compartmentalized and compartmentalized limiting shapes are arranged in the bilayer-couple phase diagram which is then compared to its free-vesicle counterpart. We also compute the area-difference-elasticity phase diagram of the limiting shapes and we use it to interpret shape transitions experimentally observed in vesicles confined within another vesicle. The limiting-shape framework may be generalized to theoretically investigate the structure of certain cell organelles such as the mitochondrion. article_processing_charge: No article_type: original author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X - first_name: A. full_name: Sakashita, A. last_name: Sakashita - first_name: H. full_name: Noguchi, H. last_name: Noguchi - first_name: P. full_name: Ziherl, P. last_name: Ziherl citation: ama: Kavcic B, Sakashita A, Noguchi H, Ziherl P. Limiting shapes of confined lipid vesicles. Soft Matter. 2019;15(4):602-614. doi:10.1039/c8sm01956h apa: Kavcic, B., Sakashita, A., Noguchi, H., & Ziherl, P. (2019). Limiting shapes of confined lipid vesicles. Soft Matter. Royal Society of Chemistry. https://doi.org/10.1039/c8sm01956h chicago: Kavcic, Bor, A. Sakashita, H. Noguchi, and P. Ziherl. “Limiting Shapes of Confined Lipid Vesicles.” Soft Matter. Royal Society of Chemistry, 2019. https://doi.org/10.1039/c8sm01956h. ieee: B. Kavcic, A. Sakashita, H. Noguchi, and P. Ziherl, “Limiting shapes of confined lipid vesicles,” Soft Matter, vol. 15, no. 4. Royal Society of Chemistry, pp. 602–614, 2019. ista: Kavcic B, Sakashita A, Noguchi H, Ziherl P. 2019. Limiting shapes of confined lipid vesicles. Soft Matter. 15(4), 602–614. mla: Kavcic, Bor, et al. “Limiting Shapes of Confined Lipid Vesicles.” Soft Matter, vol. 15, no. 4, Royal Society of Chemistry, 2019, pp. 602–14, doi:10.1039/c8sm01956h. short: B. Kavcic, A. Sakashita, H. Noguchi, P. Ziherl, Soft Matter 15 (2019) 602–614. date_created: 2019-01-11T07:37:47Z date_published: 2019-01-10T00:00:00Z date_updated: 2023-09-13T08:47:16Z day: '10' ddc: - '530' department: - _id: GaTk doi: 10.1039/c8sm01956h external_id: isi: - '000457329700003' pmid: - '30629082' file: - access_level: open_access checksum: 614c337d6424ccd3d48d1b1f9513510d content_type: application/pdf creator: bkavcic date_created: 2020-10-09T11:00:05Z date_updated: 2020-10-09T11:00:05Z file_id: '8641' file_name: lmt_sftmtr_V8.pdf file_size: 5370762 relation: main_file success: 1 file_date_updated: 2020-10-09T11:00:05Z has_accepted_license: '1' intvolume: ' 15' isi: 1 issue: '4' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/3.0/ month: '01' oa: 1 oa_version: Submitted Version page: 602-614 pmid: 1 publication: Soft Matter publication_identifier: eissn: - 1744-6848 issn: - 1744-683X publication_status: published publisher: Royal Society of Chemistry quality_controlled: '1' scopus_import: '1' status: public title: Limiting shapes of confined lipid vesicles tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/3.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0) short: CC BY-NC-ND (3.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 15 year: '2019' ... --- _id: '6473' abstract: - lang: eng text: "Single cells are constantly interacting with their environment and each other, more importantly, the accurate perception of environmental cues is crucial for growth, survival, and reproduction. This communication between cells and their environment can be formalized in mathematical terms and be quantified as the information flow between them, as prescribed by information theory. \r\nThe recent availability of real–time dynamical patterns of signaling molecules in single cells has allowed us to identify encoding about the identity of the environment in the time–series. However, efficient estimation of the information transmitted by these signals has been a data–analysis challenge due to the high dimensionality of the trajectories and the limited number of samples. In the first part of this thesis, we develop and evaluate decoding–based estimation methods to lower bound the mutual information and derive model–based precise information estimates for biological reaction networks governed by the chemical master equation. This is followed by applying the decoding-based methods to study the intracellular representation of extracellular changes in budding yeast, by observing the transient dynamics of nuclear translocation of 10 transcription factors in response to 3 stress conditions. Additionally, we apply these estimators to previously published data on ERK and Ca2+ signaling and yeast stress response. We argue that this single cell decoding-based measure of information provides an unbiased, quantitative and interpretable measure for the fidelity of biological signaling processes. \r\nFinally, in the last section, we deal with gene regulation which is primarily controlled by transcription factors (TFs) that bind to the DNA to activate gene expression. The possibility that non-cognate TFs activate transcription diminishes the accuracy of regulation with potentially disastrous effects for the cell. This ’crosstalk’ acts as a previously unexplored source of noise in biochemical networks and puts a strong constraint on their performance. To mitigate erroneous initiation we propose an out of equilibrium scheme that implements kinetic proofreading. We show that such architectures are favored over their equilibrium counterparts for complex organisms despite introducing noise in gene expression. " alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Sarah A full_name: Cepeda Humerez, Sarah A id: 3DEE19A4-F248-11E8-B48F-1D18A9856A87 last_name: Cepeda Humerez citation: ama: Cepeda Humerez SA. Estimating information flow in single cells. 2019. doi:10.15479/AT:ISTA:6473 apa: Cepeda Humerez, S. A. (2019). Estimating information flow in single cells. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6473 chicago: Cepeda Humerez, Sarah A. “Estimating Information Flow in Single Cells.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6473. ieee: S. A. Cepeda Humerez, “Estimating information flow in single cells,” Institute of Science and Technology Austria, 2019. ista: Cepeda Humerez SA. 2019. Estimating information flow in single cells. Institute of Science and Technology Austria. mla: Cepeda Humerez, Sarah A. Estimating Information Flow in Single Cells. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6473. short: S.A. Cepeda Humerez, Estimating Information Flow in Single Cells, Institute of Science and Technology Austria, 2019. date_created: 2019-05-21T00:11:23Z date_published: 2019-05-23T00:00:00Z date_updated: 2023-09-19T15:13:26Z day: '23' ddc: - '004' degree_awarded: PhD department: - _id: GaTk doi: 10.15479/AT:ISTA:6473 file: - access_level: closed checksum: 75f9184c1346e10a5de5f9cc7338309a content_type: application/zip creator: scepeda date_created: 2019-05-23T11:18:16Z date_updated: 2020-07-14T12:47:31Z file_id: '6480' file_name: Thesis_Cepeda.zip file_size: 23937464 relation: source_file - access_level: open_access checksum: afdc0633ddbd71d5b13550d7fb4f4454 content_type: application/pdf creator: scepeda date_created: 2019-05-23T11:18:13Z date_updated: 2020-07-14T12:47:31Z file_id: '6481' file_name: CepedaThesis.pdf file_size: 16646985 relation: main_file file_date_updated: 2020-07-14T12:47:31Z has_accepted_license: '1' keyword: - Information estimation - Time-series - data analysis language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '135' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '1576' relation: dissertation_contains status: public - id: '6900' relation: dissertation_contains status: public - id: '281' relation: dissertation_contains status: public - id: '2016' relation: dissertation_contains status: public status: public supervisor: - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 title: Estimating information flow in single cells tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6071' abstract: - lang: eng text: 'Transcription factors, by binding to specific sequences on the DNA, control the precise spatio-temporal expression of genes inside a cell. However, this specificity is limited, leading to frequent incorrect binding of transcription factors that might have deleterious consequences on the cell. By constructing a biophysical model of TF-DNA binding in the context of gene regulation, I will first explore how regulatory constraints can strongly shape the distribution of a population in sequence space. Then, by directly linking this to a picture of multiple types of transcription factors performing their functions simultaneously inside the cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions between transcription factors and binding sites that lead to erroneous regulatory states -- and understand the constraints this places on the design of regulatory systems. I will then develop a generic theoretical framework to investigate the coevolution of multiple transcription factors and multiple binding sites, in the context of a gene regulatory network that performs a certain function. As a particular tractable version of this problem, I will consider the evolution of two transcription factors when they transmit upstream signals to downstream target genes. Specifically, I will describe the evolutionary steady states and the evolutionary pathways involved, along with their timescales, of a system that initially undergoes a transcription factor duplication event. To connect this important theoretical model to the prominent biological event of transcription factor duplication giving rise to paralogous families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription factors, a major family in humans, and focus on the patterns of evolution that paralogs have undergone in their various protein domains in the recent past. ' alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Roshan full_name: Prizak, Roshan id: 4456104E-F248-11E8-B48F-1D18A9856A87 last_name: Prizak citation: ama: Prizak R. Coevolution of transcription factors and their binding sites in sequence space. 2019. doi:10.15479/at:ista:th6071 apa: Prizak, R. (2019). Coevolution of transcription factors and their binding sites in sequence space. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:th6071 chicago: Prizak, Roshan. “Coevolution of Transcription Factors and Their Binding Sites in Sequence Space.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/at:ista:th6071. ieee: R. Prizak, “Coevolution of transcription factors and their binding sites in sequence space,” Institute of Science and Technology Austria, 2019. ista: Prizak R. 2019. Coevolution of transcription factors and their binding sites in sequence space. Institute of Science and Technology Austria. mla: Prizak, Roshan. Coevolution of Transcription Factors and Their Binding Sites in Sequence Space. Institute of Science and Technology Austria, 2019, doi:10.15479/at:ista:th6071. short: R. Prizak, Coevolution of Transcription Factors and Their Binding Sites in Sequence Space, Institute of Science and Technology Austria, 2019. date_created: 2019-03-06T16:16:10Z date_published: 2019-03-11T00:00:00Z date_updated: 2023-09-22T10:00:48Z day: '11' ddc: - '576' degree_awarded: PhD department: - _id: GaTk - _id: NiBa doi: 10.15479/at:ista:th6071 file: - access_level: open_access checksum: e60a72de35d270b31f1a23d50f224ec0 content_type: application/pdf creator: rprizak date_created: 2019-03-06T16:05:07Z date_updated: 2020-07-14T12:47:18Z file_id: '6072' file_name: Thesis_final_PDFA_RoshanPrizak.pdf file_size: 20995465 relation: main_file - access_level: closed checksum: 67c2630333d05ebafef5f018863a8465 content_type: application/zip creator: rprizak date_created: 2019-03-06T16:09:39Z date_updated: 2020-07-14T12:47:18Z file_id: '6073' file_name: thesis_v2_merge.zip file_size: 85705272 relation: source_file title: Latex files file_date_updated: 2020-07-14T12:47:18Z has_accepted_license: '1' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: '189' project: - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '1358' relation: part_of_dissertation status: public - id: '955' relation: part_of_dissertation status: public status: public supervisor: - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 title: Coevolution of transcription factors and their binding sites in sequence space type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '7103' abstract: - lang: eng text: Origin and functions of intermittent transitions among sleep stages, including short awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing the sleep-wake cycle results from an underlying non-equilibrium critical dynamics, bridging collective behaviors across spatio-temporal scales. We investigate θ and δ wave dynamics in control rats and in rats with lesions of sleep-promoting neurons in the parafacial zone. We demonstrate that intermittent bursts in θ and δ rhythms exhibit a complex temporal organization, with long-range power-law correlations and a robust duality of power law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, typical features of non-equilibrium systems self-organizing at criticality. Crucially, such temporal organization relates to anti-correlated coupling between θ- and δ-bursts, and is independent of the dominant physiologic state and lesions, a solid indication of a basic principle in sleep dynamics. article_number: e1007268 article_processing_charge: No article_type: original author: - first_name: Jilin W. J. L. full_name: Wang, Jilin W. J. L. last_name: Wang - first_name: Fabrizio full_name: Lombardi, Fabrizio id: A057D288-3E88-11E9-986D-0CF4E5697425 last_name: Lombardi orcid: 0000-0003-2623-5249 - first_name: Xiyun full_name: Zhang, Xiyun last_name: Zhang - first_name: Christelle full_name: Anaclet, Christelle last_name: Anaclet - first_name: Plamen Ch. full_name: Ivanov, Plamen Ch. last_name: Ivanov citation: ama: Wang JWJL, Lombardi F, Zhang X, Anaclet C, Ivanov PC. Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture. PLoS Computational Biology. 2019;15(11). doi:10.1371/journal.pcbi.1007268 apa: Wang, J. W. J. L., Lombardi, F., Zhang, X., Anaclet, C., & Ivanov, P. C. (2019). Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture. PLoS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007268 chicago: Wang, Jilin W. J. L., Fabrizio Lombardi, Xiyun Zhang, Christelle Anaclet, and Plamen Ch. Ivanov. “Non-Equilibrium Critical Dynamics of Bursts in θ and δ Rhythms as Fundamental Characteristic of Sleep and Wake Micro-Architecture.” PLoS Computational Biology. Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007268. ieee: J. W. J. L. Wang, F. Lombardi, X. Zhang, C. Anaclet, and P. C. Ivanov, “Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture,” PLoS Computational Biology, vol. 15, no. 11. Public Library of Science, 2019. ista: Wang JWJL, Lombardi F, Zhang X, Anaclet C, Ivanov PC. 2019. Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture. PLoS Computational Biology. 15(11), e1007268. mla: Wang, Jilin W. J. L., et al. “Non-Equilibrium Critical Dynamics of Bursts in θ and δ Rhythms as Fundamental Characteristic of Sleep and Wake Micro-Architecture.” PLoS Computational Biology, vol. 15, no. 11, e1007268, Public Library of Science, 2019, doi:10.1371/journal.pcbi.1007268. short: J.W.J.L. Wang, F. Lombardi, X. Zhang, C. Anaclet, P.C. Ivanov, PLoS Computational Biology 15 (2019). date_created: 2019-11-25T08:20:47Z date_published: 2019-11-01T00:00:00Z date_updated: 2023-10-17T12:30:07Z day: '01' ddc: - '570' - '000' department: - _id: GaTk doi: 10.1371/journal.pcbi.1007268 ec_funded: 1 external_id: isi: - '000500976100014' pmid: - '31725712' file: - access_level: open_access checksum: 2a096a9c6dcc6eaa94077b2603bc6c12 content_type: application/pdf creator: dernst date_created: 2019-11-25T08:24:01Z date_updated: 2020-07-14T12:47:49Z file_id: '7104' file_name: 2019_PLOSComBio_Wang.pdf file_size: 3982516 relation: main_file file_date_updated: 2020-07-14T12:47:49Z has_accepted_license: '1' intvolume: ' 15' isi: 1 issue: '11' language: - iso: eng month: '11' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: PLoS Computational Biology publication_identifier: issn: - 1553-7358 publication_status: published publisher: Public Library of Science quality_controlled: '1' scopus_import: '1' status: public title: Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 15 year: '2019' ... --- _id: '6090' abstract: - lang: eng text: Cells need to reliably sense external ligand concentrations to achieve various biological functions such as chemotaxis or signaling. The molecular recognition of ligands by surface receptors is degenerate in many systems, leading to crosstalk between ligand-receptor pairs. Crosstalk is often thought of as a deviation from optimal specific recognition, as the binding of noncognate ligands can interfere with the detection of the receptor's cognate ligand, possibly leading to a false triggering of a downstream signaling pathway. Here we quantify the optimal precision of sensing the concentrations of multiple ligands by a collection of promiscuous receptors. We demonstrate that crosstalk can improve precision in concentration sensing and discrimination tasks. To achieve superior precision, the additional information about ligand concentrations contained in short binding events of the noncognate ligand should be exploited. We present a proofreading scheme to realize an approximate estimation of multiple ligand concentrations that reaches a precision close to the derived optimal bounds. Our results help rationalize the observed ubiquity of receptor crosstalk in molecular sensing. article_number: '022423' article_processing_charge: No author: - first_name: Martín full_name: Carballo-Pacheco, Martín last_name: Carballo-Pacheco - first_name: Jonathan full_name: Desponds, Jonathan last_name: Desponds - first_name: Tatyana full_name: Gavrilchenko, Tatyana last_name: Gavrilchenko - first_name: Andreas full_name: Mayer, Andreas last_name: Mayer - first_name: Roshan full_name: Prizak, Roshan id: 4456104E-F248-11E8-B48F-1D18A9856A87 last_name: Prizak - first_name: Gautam full_name: Reddy, Gautam last_name: Reddy - first_name: Ilya full_name: Nemenman, Ilya last_name: Nemenman - first_name: Thierry full_name: Mora, Thierry last_name: Mora citation: ama: Carballo-Pacheco M, Desponds J, Gavrilchenko T, et al. Receptor crosstalk improves concentration sensing of multiple ligands. Physical Review E. 2019;99(2). doi:10.1103/PhysRevE.99.022423 apa: Carballo-Pacheco, M., Desponds, J., Gavrilchenko, T., Mayer, A., Prizak, R., Reddy, G., … Mora, T. (2019). Receptor crosstalk improves concentration sensing of multiple ligands. Physical Review E. American Physical Society. https://doi.org/10.1103/PhysRevE.99.022423 chicago: Carballo-Pacheco, Martín, Jonathan Desponds, Tatyana Gavrilchenko, Andreas Mayer, Roshan Prizak, Gautam Reddy, Ilya Nemenman, and Thierry Mora. “Receptor Crosstalk Improves Concentration Sensing of Multiple Ligands.” Physical Review E. American Physical Society, 2019. https://doi.org/10.1103/PhysRevE.99.022423. ieee: M. Carballo-Pacheco et al., “Receptor crosstalk improves concentration sensing of multiple ligands,” Physical Review E, vol. 99, no. 2. American Physical Society, 2019. ista: Carballo-Pacheco M, Desponds J, Gavrilchenko T, Mayer A, Prizak R, Reddy G, Nemenman I, Mora T. 2019. Receptor crosstalk improves concentration sensing of multiple ligands. Physical Review E. 99(2), 022423. mla: Carballo-Pacheco, Martín, et al. “Receptor Crosstalk Improves Concentration Sensing of Multiple Ligands.” Physical Review E, vol. 99, no. 2, 022423, American Physical Society, 2019, doi:10.1103/PhysRevE.99.022423. short: M. Carballo-Pacheco, J. Desponds, T. Gavrilchenko, A. Mayer, R. Prizak, G. Reddy, I. Nemenman, T. Mora, Physical Review E 99 (2019). date_created: 2019-03-10T22:59:20Z date_published: 2019-02-26T00:00:00Z date_updated: 2024-02-28T13:12:06Z day: '26' department: - _id: NiBa - _id: GaTk doi: 10.1103/PhysRevE.99.022423 external_id: isi: - '000459916500007' intvolume: ' 99' isi: 1 issue: '2' language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/448118v1.abstract month: '02' oa: 1 oa_version: Preprint publication: Physical Review E publication_status: published publisher: American Physical Society quality_controlled: '1' scopus_import: '1' status: public title: Receptor crosstalk improves concentration sensing of multiple ligands type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 99 year: '2019' ... --- _id: '7606' abstract: - lang: eng text: We derive a tight lower bound on equivocation (conditional entropy), or equivalently a tight upper bound on mutual information between a signal variable and channel outputs. The bound is in terms of the joint distribution of the signals and maximum a posteriori decodes (most probable signals given channel output). As part of our derivation, we describe the key properties of the distribution of signals, channel outputs and decodes, that minimizes equivocation and maximizes mutual information. This work addresses a problem in data analysis, where mutual information between signals and decodes is sometimes used to lower bound the mutual information between signals and channel outputs. Our result provides a corresponding upper bound. article_number: '8989292' article_processing_charge: No author: - first_name: Michal full_name: Hledik, Michal id: 4171253A-F248-11E8-B48F-1D18A9856A87 last_name: Hledik - first_name: Thomas R full_name: Sokolowski, Thomas R id: 3E999752-F248-11E8-B48F-1D18A9856A87 last_name: Sokolowski orcid: 0000-0002-1287-3779 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: 'Hledik M, Sokolowski TR, Tkačik G. A tight upper bound on mutual information. In: IEEE Information Theory Workshop, ITW 2019. IEEE; 2019. doi:10.1109/ITW44776.2019.8989292' apa: 'Hledik, M., Sokolowski, T. R., & Tkačik, G. (2019). A tight upper bound on mutual information. In IEEE Information Theory Workshop, ITW 2019. Visby, Sweden: IEEE. https://doi.org/10.1109/ITW44776.2019.8989292' chicago: Hledik, Michal, Thomas R Sokolowski, and Gašper Tkačik. “A Tight Upper Bound on Mutual Information.” In IEEE Information Theory Workshop, ITW 2019. IEEE, 2019. https://doi.org/10.1109/ITW44776.2019.8989292. ieee: M. Hledik, T. R. Sokolowski, and G. Tkačik, “A tight upper bound on mutual information,” in IEEE Information Theory Workshop, ITW 2019, Visby, Sweden, 2019. ista: Hledik M, Sokolowski TR, Tkačik G. 2019. A tight upper bound on mutual information. IEEE Information Theory Workshop, ITW 2019. Information Theory Workshop, 8989292. mla: Hledik, Michal, et al. “A Tight Upper Bound on Mutual Information.” IEEE Information Theory Workshop, ITW 2019, 8989292, IEEE, 2019, doi:10.1109/ITW44776.2019.8989292. short: M. Hledik, T.R. Sokolowski, G. Tkačik, in:, IEEE Information Theory Workshop, ITW 2019, IEEE, 2019. conference: end_date: 2019-08-28 location: Visby, Sweden name: Information Theory Workshop start_date: 2019-08-25 date_created: 2020-03-22T23:00:47Z date_published: 2019-08-01T00:00:00Z date_updated: 2024-03-06T14:22:51Z day: '01' department: - _id: GaTk doi: 10.1109/ITW44776.2019.8989292 ec_funded: 1 external_id: arxiv: - '1812.01475' isi: - '000540384500015' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1812.01475 month: '08' oa: 1 oa_version: Preprint project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: IEEE Information Theory Workshop, ITW 2019 publication_identifier: isbn: - '9781538669006' publication_status: published publisher: IEEE quality_controlled: '1' related_material: record: - id: '15020' relation: dissertation_contains status: public scopus_import: '1' status: public title: A tight upper bound on mutual information type: conference user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '306' abstract: - lang: eng text: A cornerstone of statistical inference, the maximum entropy framework is being increasingly applied to construct descriptive and predictive models of biological systems, especially complex biological networks, from large experimental data sets. Both its broad applicability and the success it obtained in different contexts hinge upon its conceptual simplicity and mathematical soundness. Here we try to concisely review the basic elements of the maximum entropy principle, starting from the notion of ‘entropy’, and describe its usefulness for the analysis of biological systems. As examples, we focus specifically on the problem of reconstructing gene interaction networks from expression data and on recent work attempting to expand our system-level understanding of bacterial metabolism. Finally, we highlight some extensions and potential limitations of the maximum entropy approach, and point to more recent developments that are likely to play a key role in the upcoming challenges of extracting structures and information from increasingly rich, high-throughput biological data. article_number: e00596 author: - first_name: Andrea full_name: De Martino, Andrea last_name: De Martino - first_name: Daniele full_name: De Martino, Daniele id: 3FF5848A-F248-11E8-B48F-1D18A9856A87 last_name: De Martino orcid: 0000-0002-5214-4706 citation: ama: De Martino A, De Martino D. An introduction to the maximum entropy approach and its application to inference problems in biology. Heliyon. 2018;4(4). doi:10.1016/j.heliyon.2018.e00596 apa: De Martino, A., & De Martino, D. (2018). An introduction to the maximum entropy approach and its application to inference problems in biology. Heliyon. Elsevier. https://doi.org/10.1016/j.heliyon.2018.e00596 chicago: De Martino, Andrea, and Daniele De Martino. “An Introduction to the Maximum Entropy Approach and Its Application to Inference Problems in Biology.” Heliyon. Elsevier, 2018. https://doi.org/10.1016/j.heliyon.2018.e00596. ieee: A. De Martino and D. De Martino, “An introduction to the maximum entropy approach and its application to inference problems in biology,” Heliyon, vol. 4, no. 4. Elsevier, 2018. ista: De Martino A, De Martino D. 2018. An introduction to the maximum entropy approach and its application to inference problems in biology. Heliyon. 4(4), e00596. mla: De Martino, Andrea, and Daniele De Martino. “An Introduction to the Maximum Entropy Approach and Its Application to Inference Problems in Biology.” Heliyon, vol. 4, no. 4, e00596, Elsevier, 2018, doi:10.1016/j.heliyon.2018.e00596. short: A. De Martino, D. De Martino, Heliyon 4 (2018). date_created: 2018-12-11T11:45:44Z date_published: 2018-04-01T00:00:00Z date_updated: 2021-01-12T07:40:46Z day: '01' ddc: - '530' department: - _id: GaTk doi: 10.1016/j.heliyon.2018.e00596 ec_funded: 1 file: - access_level: open_access checksum: 67010cf5e3b3e0637c659371714a715a content_type: application/pdf creator: dernst date_created: 2019-02-06T07:36:24Z date_updated: 2020-07-14T12:45:59Z file_id: '5929' file_name: 2018_Heliyon_DeMartino.pdf file_size: 994490 relation: main_file file_date_updated: 2020-07-14T12:45:59Z has_accepted_license: '1' intvolume: ' 4' issue: '4' language: - iso: eng month: '04' oa: 1 oa_version: Published Version project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Heliyon publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: 1 status: public title: An introduction to the maximum entropy approach and its application to inference problems in biology tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 4 year: '2018' ... --- _id: '305' abstract: - lang: eng text: The hanging-drop network (HDN) is a technology platform based on a completely open microfluidic network at the bottom of an inverted, surface-patterned substrate. The platform is predominantly used for the formation, culturing, and interaction of self-assembled spherical microtissues (spheroids) under precisely controlled flow conditions. Here, we describe design, fabrication, and operation of microfluidic hanging-drop networks. acknowledgement: This work was financially supported by FP7 of the EU through the project “Body on a chip,” ICT-FET-296257, and the ERC Advanced Grant “NeuroCMOS” (contract 267351), as well as by an individual Ambizione Grant 142440 from the Swiss National Science Foundation for Olivier Frey. The research leading to these results also received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. [291734]. We would like to thank Alexander Stettler, ETH Zurich for his expertise and support in the cleanroom, and we acknowledge the Single Cell Unit of D-BSSE, ETH Zurich for assistance in microscopy issues. M.L. is grateful to the members of the Guet and Tkačik groups, IST Austria, for valuable comments and support. alternative_title: - MIMB author: - first_name: Patrick full_name: Misun, Patrick last_name: Misun - first_name: Axel full_name: Birchler, Axel last_name: Birchler - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Andreas full_name: Hierlemann, Andreas last_name: Hierlemann - first_name: Olivier full_name: Frey, Olivier last_name: Frey citation: ama: Misun P, Birchler A, Lang M, Hierlemann A, Frey O. Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. 2018;1771:183-202. doi:10.1007/978-1-4939-7792-5_15 apa: Misun, P., Birchler, A., Lang, M., Hierlemann, A., & Frey, O. (2018). Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. Springer. https://doi.org/10.1007/978-1-4939-7792-5_15 chicago: Misun, Patrick, Axel Birchler, Moritz Lang, Andreas Hierlemann, and Olivier Frey. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods in Molecular Biology. Springer, 2018. https://doi.org/10.1007/978-1-4939-7792-5_15. ieee: P. Misun, A. Birchler, M. Lang, A. Hierlemann, and O. Frey, “Fabrication and operation of microfluidic hanging drop networks,” Methods in Molecular Biology, vol. 1771. Springer, pp. 183–202, 2018. ista: Misun P, Birchler A, Lang M, Hierlemann A, Frey O. 2018. Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. 1771, 183–202. mla: Misun, Patrick, et al. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods in Molecular Biology, vol. 1771, Springer, 2018, pp. 183–202, doi:10.1007/978-1-4939-7792-5_15. short: P. Misun, A. Birchler, M. Lang, A. Hierlemann, O. Frey, Methods in Molecular Biology 1771 (2018) 183–202. date_created: 2018-12-11T11:45:43Z date_published: 2018-01-01T00:00:00Z date_updated: 2021-01-12T07:40:42Z day: '01' department: - _id: CaGu - _id: GaTk doi: 10.1007/978-1-4939-7792-5_15 ec_funded: 1 intvolume: ' 1771' language: - iso: eng month: '01' oa_version: None page: 183 - 202 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Methods in Molecular Biology publication_status: published publisher: Springer publist_id: '7574' quality_controlled: '1' scopus_import: 1 status: public title: Fabrication and operation of microfluidic hanging drop networks type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 1771 year: '2018' ... --- _id: '281' abstract: - lang: eng text: 'Although cells respond specifically to environments, how environmental identity is encoded intracellularly is not understood. Here, we study this organization of information in budding yeast by estimating the mutual information between environmental transitions and the dynamics of nuclear translocation for 10 transcription factors. Our method of estimation is general, scalable, and based on decoding from single cells. The dynamics of the transcription factors are necessary to encode the highest amounts of extracellular information, and we show that information is transduced through two channels: Generalists (Msn2/4, Tod6 and Dot6, Maf1, and Sfp1) can encode the nature of multiple stresses, but only if stress is high; specialists (Hog1, Yap1, and Mig1/2) encode one particular stress, but do so more quickly and for a wider range of magnitudes. In particular, Dot6 encodes almost as much information as Msn2, the master regulator of the environmental stress response. Each transcription factor reports differently, and it is only their collective behavior that distinguishes between multiple environmental states. Changes in the dynamics of the localization of transcription factors thus constitute a precise, distributed internal representation of extracellular change. We predict that such multidimensional representations are common in cellular decision-making.' acknowledgement: This work was supported by the Biotechnology and Biological Sciences Research Council (J.M.J.P., I.F., and P.S.S.), the Engineering and Physical Sciences Research Council (EPSRC) (A.A.G.), and Austrian Science Fund Grant FWF P28844 (to G.T.). article_processing_charge: No article_type: original author: - first_name: Alejandro full_name: Granados, Alejandro last_name: Granados - first_name: Julian full_name: Pietsch, Julian last_name: Pietsch - first_name: Sarah A full_name: Cepeda Humerez, Sarah A id: 3DEE19A4-F248-11E8-B48F-1D18A9856A87 last_name: Cepeda Humerez - first_name: Isebail full_name: Farquhar, Isebail last_name: Farquhar - first_name: Gasper full_name: Tkacik, Gasper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkacik orcid: 0000-0002-6699-1455 - first_name: Peter full_name: Swain, Peter last_name: Swain citation: ama: Granados A, Pietsch J, Cepeda Humerez SA, Farquhar I, Tkačik G, Swain P. Distributed and dynamic intracellular organization of extracellular information. PNAS. 2018;115(23):6088-6093. doi:10.1073/pnas.1716659115 apa: Granados, A., Pietsch, J., Cepeda Humerez, S. A., Farquhar, I., Tkačik, G., & Swain, P. (2018). Distributed and dynamic intracellular organization of extracellular information. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1716659115 chicago: Granados, Alejandro, Julian Pietsch, Sarah A Cepeda Humerez, Isebail Farquhar, Gašper Tkačik, and Peter Swain. “Distributed and Dynamic Intracellular Organization of Extracellular Information.” PNAS. National Academy of Sciences, 2018. https://doi.org/10.1073/pnas.1716659115. ieee: A. Granados, J. Pietsch, S. A. Cepeda Humerez, I. Farquhar, G. Tkačik, and P. Swain, “Distributed and dynamic intracellular organization of extracellular information,” PNAS, vol. 115, no. 23. National Academy of Sciences, pp. 6088–6093, 2018. ista: Granados A, Pietsch J, Cepeda Humerez SA, Farquhar I, Tkačik G, Swain P. 2018. Distributed and dynamic intracellular organization of extracellular information. PNAS. 115(23), 6088–6093. mla: Granados, Alejandro, et al. “Distributed and Dynamic Intracellular Organization of Extracellular Information.” PNAS, vol. 115, no. 23, National Academy of Sciences, 2018, pp. 6088–93, doi:10.1073/pnas.1716659115. short: A. Granados, J. Pietsch, S.A. Cepeda Humerez, I. Farquhar, G. Tkačik, P. Swain, PNAS 115 (2018) 6088–6093. date_created: 2018-12-11T11:45:35Z date_published: 2018-06-05T00:00:00Z date_updated: 2023-09-11T12:58:24Z day: '05' department: - _id: GaTk doi: 10.1073/pnas.1716659115 external_id: isi: - '000434114900071' pmid: - '29784812' intvolume: ' 115' isi: 1 issue: '23' language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/early/2017/09/21/192039 month: '06' oa: 1 oa_version: Preprint page: 6088 - 6093 pmid: 1 project: - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: PNAS publication_status: published publisher: National Academy of Sciences publist_id: '7618' quality_controlled: '1' related_material: record: - id: '6473' relation: part_of_dissertation status: public scopus_import: '1' status: public title: Distributed and dynamic intracellular organization of extracellular information type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 115 year: '2018' ... --- _id: '316' abstract: - lang: eng text: 'Self-incompatibility (SI) is a genetically based recognition system that functions to prevent self-fertilization and mating among related plants. An enduring puzzle in SI is how the high diversity observed in nature arises and is maintained. Based on the underlying recognition mechanism, SI can be classified into two main groups: self- and non-self recognition. Most work has focused on diversification within self-recognition systems despite expected differences between the two groups in the evolutionary pathways and outcomes of diversification. Here, we use a deterministic population genetic model and stochastic simulations to investigate how novel S-haplotypes evolve in a gametophytic non-self recognition (SRNase/S Locus F-box (SLF)) SI system. For this model the pathways for diversification involve either the maintenance or breakdown of SI and can vary in the order of mutations of the female (SRNase) and male (SLF) components. We show analytically that diversification can occur with high inbreeding depression and self-pollination, but this varies with evolutionary pathway and level of completeness (which determines the number of potential mating partners in the population), and in general is more likely for lower haplotype number. The conditions for diversification are broader in stochastic simulations of finite population size. However, the number of haplotypes observed under high inbreeding and moderate to high self-pollination is less than that commonly observed in nature. Diversification was observed through pathways that maintain SI as well as through self-compatible intermediates. Yet the lifespan of diversified haplotypes was sensitive to their level of completeness. By examining diversification in a non-self recognition SI system, this model extends our understanding of the evolution and maintenance of haplotype diversity observed in a self recognition system common in flowering plants.' article_processing_charge: No article_type: original author: - first_name: Katarina full_name: Bodova, Katarina id: 2BA24EA0-F248-11E8-B48F-1D18A9856A87 last_name: Bodova orcid: 0000-0002-7214-0171 - first_name: Tadeas full_name: Priklopil, Tadeas id: 3C869AA0-F248-11E8-B48F-1D18A9856A87 last_name: Priklopil - first_name: David full_name: Field, David id: 419049E2-F248-11E8-B48F-1D18A9856A87 last_name: Field orcid: 0000-0002-4014-8478 - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Melinda full_name: Pickup, Melinda id: 2C78037E-F248-11E8-B48F-1D18A9856A87 last_name: Pickup orcid: 0000-0001-6118-0541 citation: ama: Bodova K, Priklopil T, Field D, Barton NH, Pickup M. Evolutionary pathways for the generation of new self-incompatibility haplotypes in a non-self recognition system. Genetics. 2018;209(3):861-883. doi:10.1534/genetics.118.300748 apa: Bodova, K., Priklopil, T., Field, D., Barton, N. H., & Pickup, M. (2018). Evolutionary pathways for the generation of new self-incompatibility haplotypes in a non-self recognition system. Genetics. Genetics Society of America. https://doi.org/10.1534/genetics.118.300748 chicago: Bodova, Katarina, Tadeas Priklopil, David Field, Nicholas H Barton, and Melinda Pickup. “Evolutionary Pathways for the Generation of New Self-Incompatibility Haplotypes in a Non-Self Recognition System.” Genetics. Genetics Society of America, 2018. https://doi.org/10.1534/genetics.118.300748. ieee: K. Bodova, T. Priklopil, D. Field, N. H. Barton, and M. Pickup, “Evolutionary pathways for the generation of new self-incompatibility haplotypes in a non-self recognition system,” Genetics, vol. 209, no. 3. Genetics Society of America, pp. 861–883, 2018. ista: Bodova K, Priklopil T, Field D, Barton NH, Pickup M. 2018. Evolutionary pathways for the generation of new self-incompatibility haplotypes in a non-self recognition system. Genetics. 209(3), 861–883. mla: Bodova, Katarina, et al. “Evolutionary Pathways for the Generation of New Self-Incompatibility Haplotypes in a Non-Self Recognition System.” Genetics, vol. 209, no. 3, Genetics Society of America, 2018, pp. 861–83, doi:10.1534/genetics.118.300748. short: K. Bodova, T. Priklopil, D. Field, N.H. Barton, M. Pickup, Genetics 209 (2018) 861–883. date_created: 2018-12-11T11:45:47Z date_published: 2018-07-01T00:00:00Z date_updated: 2023-09-11T13:57:43Z day: '01' department: - _id: NiBa - _id: GaTk doi: 10.1534/genetics.118.300748 ec_funded: 1 external_id: isi: - '000437171700017' intvolume: ' 209' isi: 1 issue: '3' language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/node/80098.abstract month: '07' oa: 1 oa_version: Preprint page: 861-883 project: - _id: 25B36484-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '329960' name: Mating system and the evolutionary dynamics of hybrid zones - _id: 25B07788-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '250152' name: Limits to selection in biology and in evolutionary computation - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Genetics publication_status: published publisher: Genetics Society of America quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/recognizing-others-but-not-yourself-new-insights-into-the-evolution-of-plant-mating/ record: - id: '9813' relation: research_data status: public scopus_import: '1' status: public title: Evolutionary pathways for the generation of new self-incompatibility haplotypes in a non-self recognition system type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 209 year: '2018' ... --- _id: '9813' abstract: - lang: eng text: 'File S1 contains figures that clarify the following features: (i) effect of population size on the average number/frequency of SI classes, (ii) changes in the minimal completeness deficit in time for a single class, and (iii) diversification diagrams for all studied pathways, including the summary figure for k = 8. File S2 contains the code required for a stochastic simulation of the SLF system with an example. This file also includes the output in the form of figures and tables.' article_processing_charge: No author: - first_name: Katarína full_name: Bod'ová, Katarína id: 2BA24EA0-F248-11E8-B48F-1D18A9856A87 last_name: Bod'ová orcid: 0000-0002-7214-0171 - first_name: Tadeas full_name: Priklopil, Tadeas id: 3C869AA0-F248-11E8-B48F-1D18A9856A87 last_name: Priklopil - first_name: David full_name: Field, David id: 419049E2-F248-11E8-B48F-1D18A9856A87 last_name: Field orcid: 0000-0002-4014-8478 - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Melinda full_name: Pickup, Melinda id: 2C78037E-F248-11E8-B48F-1D18A9856A87 last_name: Pickup orcid: 0000-0001-6118-0541 citation: ama: Bodova K, Priklopil T, Field D, Barton NH, Pickup M. Supplemental material for Bodova et al., 2018. 2018. doi:10.25386/genetics.6148304.v1 apa: Bodova, K., Priklopil, T., Field, D., Barton, N. H., & Pickup, M. (2018). Supplemental material for Bodova et al., 2018. Genetics Society of America. https://doi.org/10.25386/genetics.6148304.v1 chicago: Bodova, Katarina, Tadeas Priklopil, David Field, Nicholas H Barton, and Melinda Pickup. “Supplemental Material for Bodova et Al., 2018.” Genetics Society of America, 2018. https://doi.org/10.25386/genetics.6148304.v1. ieee: K. Bodova, T. Priklopil, D. Field, N. H. Barton, and M. Pickup, “Supplemental material for Bodova et al., 2018.” Genetics Society of America, 2018. ista: Bodova K, Priklopil T, Field D, Barton NH, Pickup M. 2018. Supplemental material for Bodova et al., 2018, Genetics Society of America, 10.25386/genetics.6148304.v1. mla: Bodova, Katarina, et al. Supplemental Material for Bodova et Al., 2018. Genetics Society of America, 2018, doi:10.25386/genetics.6148304.v1. short: K. Bodova, T. Priklopil, D. Field, N.H. Barton, M. Pickup, (2018). date_created: 2021-08-06T13:04:32Z date_published: 2018-04-30T00:00:00Z date_updated: 2023-09-11T13:57:42Z day: '30' department: - _id: NiBa - _id: GaTk doi: 10.25386/genetics.6148304.v1 main_file_link: - open_access: '1' url: https://doi.org/10.25386/genetics.6148304.v1 month: '04' oa: 1 oa_version: Published Version publisher: Genetics Society of America related_material: record: - id: '316' relation: used_in_publication status: public status: public title: Supplemental material for Bodova et al., 2018 type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2018' ... --- _id: '406' abstract: - lang: eng text: 'Recent developments in automated tracking allow uninterrupted, high-resolution recording of animal trajectories, sometimes coupled with the identification of stereotyped changes of body pose or other behaviors of interest. Analysis and interpretation of such data represents a challenge: the timing of animal behaviors may be stochastic and modulated by kinematic variables, by the interaction with the environment or with the conspecifics within the animal group, and dependent on internal cognitive or behavioral state of the individual. Existing models for collective motion typically fail to incorporate the discrete, stochastic, and internal-state-dependent aspects of behavior, while models focusing on individual animal behavior typically ignore the spatial aspects of the problem. Here we propose a probabilistic modeling framework to address this gap. Each animal can switch stochastically between different behavioral states, with each state resulting in a possibly different law of motion through space. Switching rates for behavioral transitions can depend in a very general way, which we seek to identify from data, on the effects of the environment as well as the interaction between the animals. We represent the switching dynamics as a Generalized Linear Model and show that: (i) forward simulation of multiple interacting animals is possible using a variant of the Gillespie’s Stochastic Simulation Algorithm; (ii) formulated properly, the maximum likelihood inference of switching rate functions is tractably solvable by gradient descent; (iii) model selection can be used to identify factors that modulate behavioral state switching and to appropriately adjust model complexity to data. To illustrate our framework, we apply it to two synthetic models of animal motion and to real zebrafish tracking data. ' acknowledgement: This work was supported by the Human Frontier Science Program RGP0065/2012 (GT, ES). article_processing_charge: Yes author: - first_name: Katarína full_name: Bod’Ová, Katarína last_name: Bod’Ová - first_name: Gabriel full_name: Mitchell, Gabriel id: 315BCD80-F248-11E8-B48F-1D18A9856A87 last_name: Mitchell - first_name: Roy full_name: Harpaz, Roy last_name: Harpaz - first_name: Elad full_name: Schneidman, Elad last_name: Schneidman - first_name: Gasper full_name: Tkacik, Gasper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkacik orcid: 0000-0002-6699-1455 citation: ama: Bod’Ová K, Mitchell G, Harpaz R, Schneidman E, Tkačik G. Probabilistic models of individual and collective animal behavior. PLoS One. 2018;13(3). doi:10.1371/journal.pone.0193049 apa: Bod’Ová, K., Mitchell, G., Harpaz, R., Schneidman, E., & Tkačik, G. (2018). Probabilistic models of individual and collective animal behavior. PLoS One. Public Library of Science. https://doi.org/10.1371/journal.pone.0193049 chicago: Bod’Ová, Katarína, Gabriel Mitchell, Roy Harpaz, Elad Schneidman, and Gašper Tkačik. “Probabilistic Models of Individual and Collective Animal Behavior.” PLoS One. Public Library of Science, 2018. https://doi.org/10.1371/journal.pone.0193049. ieee: K. Bod’Ová, G. Mitchell, R. Harpaz, E. Schneidman, and G. Tkačik, “Probabilistic models of individual and collective animal behavior,” PLoS One, vol. 13, no. 3. Public Library of Science, 2018. ista: Bod’Ová K, Mitchell G, Harpaz R, Schneidman E, Tkačik G. 2018. Probabilistic models of individual and collective animal behavior. PLoS One. 13(3). mla: Bod’Ová, Katarína, et al. “Probabilistic Models of Individual and Collective Animal Behavior.” PLoS One, vol. 13, no. 3, Public Library of Science, 2018, doi:10.1371/journal.pone.0193049. short: K. Bod’Ová, G. Mitchell, R. Harpaz, E. Schneidman, G. Tkačik, PLoS One 13 (2018). date_created: 2018-12-11T11:46:18Z date_published: 2018-03-07T00:00:00Z date_updated: 2023-09-15T12:06:19Z day: '07' ddc: - '530' - '571' department: - _id: GaTk doi: 10.1371/journal.pone.0193049 external_id: isi: - '000426896800032' file: - access_level: open_access checksum: 684229493db75b43e98a46cd922da497 content_type: application/pdf creator: system date_created: 2018-12-12T10:15:43Z date_updated: 2020-07-14T12:46:22Z file_id: '5165' file_name: IST-2018-995-v1+1_2018_Bodova_Probabilistic.pdf file_size: 6887358 relation: main_file file_date_updated: 2020-07-14T12:46:22Z has_accepted_license: '1' intvolume: ' 13' isi: 1 issue: '3' language: - iso: eng month: '03' oa: 1 oa_version: Submitted Version project: - _id: 255008E4-B435-11E9-9278-68D0E5697425 grant_number: RGP0065/2012 name: Information processing and computation in fish groups publication: PLoS One publication_status: published publisher: Public Library of Science publist_id: '7423' pubrep_id: '995' quality_controlled: '1' related_material: record: - id: '9831' relation: research_data status: public scopus_import: '1' status: public title: Probabilistic models of individual and collective animal behavior tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 13 year: '2018' ...