--- _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: 2024-03-28T23:30:08Z 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: 2024-03-28T23:30:08Z 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: 2024-03-28T23:30:37Z 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' ...