[{"month":"02","intvolume":" 150","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1708.09364"}],"oa_version":"Preprint","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."}],"volume":150,"issue":"5","language":[{"iso":"eng"}],"publication_identifier":{"issn":["0021-9606"],"eissn":["1089-7690"]},"publication_status":"published","status":"public","type":"journal_article","article_type":"original","_id":"7422","department":[{"_id":"GaTk"}],"date_updated":"2023-09-06T14:59:28Z","quality_controlled":"1","publisher":"AIP Publishing","oa":1,"doi":"10.1063/1.5064867","date_published":"2019-02-07T00:00:00Z","date_created":"2020-01-30T10:34:36Z","day":"07","publication":"The Journal of Chemical Physics","isi":1,"year":"2019","article_number":"054108","title":"eGFRD in all dimensions","author":[{"first_name":"Thomas R","id":"3E999752-F248-11E8-B48F-1D18A9856A87","last_name":"Sokolowski","full_name":"Sokolowski, Thomas R","orcid":"0000-0002-1287-3779"},{"last_name":"Paijmans","full_name":"Paijmans, Joris","first_name":"Joris"},{"full_name":"Bossen, Laurens","last_name":"Bossen","first_name":"Laurens"},{"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"},{"full_name":"Kaizu, Kazunari","last_name":"Kaizu","first_name":"Kazunari"},{"first_name":"Koichi","full_name":"Takahashi, Koichi","last_name":"Takahashi"},{"first_name":"Marileen","last_name":"Dogterom","full_name":"Dogterom, Marileen"},{"first_name":"Pieter Rein","full_name":"ten Wolde, Pieter Rein","last_name":"ten Wolde"}],"external_id":{"arxiv":["1708.09364"],"isi":["000458109300009"]},"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ieee":"T. R. Sokolowski et al., “eGFRD in all dimensions,” The Journal of Chemical Physics, vol. 150, no. 5. AIP Publishing, 2019.","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).","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","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.","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.","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."}},{"project":[{"name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27","call_identifier":"FWF","_id":"254E9036-B435-11E9-9278-68D0E5697425"}],"title":"Estimating information in time-varying signals","author":[{"last_name":"Cepeda Humerez","full_name":"Cepeda Humerez, Sarah A","id":"3DEE19A4-F248-11E8-B48F-1D18A9856A87","first_name":"Sarah A"},{"last_name":"Ruess","full_name":"Ruess, Jakob","orcid":"0000-0003-1615-3282","first_name":"Jakob"},{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455"}],"article_processing_charge":"No","external_id":{"isi":["000489741800021"],"pmid":["31479447"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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","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.","short":"S.A. Cepeda Humerez, J. Ruess, G. Tkačik, PLoS Computational Biology 15 (2019) 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.","ista":"Cepeda Humerez SA, Ruess J, Tkačik G. 2019. Estimating information in time-varying signals. PLoS computational biology. 15(9), e1007290.","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."},"quality_controlled":"1","publisher":"Public Library of Science","oa":1,"date_published":"2019-09-03T00:00:00Z","doi":"10.1371/journal.pcbi.1007290","date_created":"2019-09-22T22:00:37Z","page":"e1007290","day":"03","publication":"PLoS computational biology","isi":1,"has_accepted_license":"1","year":"2019","status":"public","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"6900","file_date_updated":"2020-07-14T12:47:44Z","department":[{"_id":"GaTk"}],"ddc":["570"],"date_updated":"2023-09-07T12:55:21Z","month":"09","intvolume":" 15","scopus_import":"1","pmid":1,"oa_version":"Published Version","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."}],"volume":15,"issue":"9","related_material":{"record":[{"relation":"part_of_dissertation","id":"6473","status":"public"}]},"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"6925","checksum":"81bdce1361c9aa8395d6fa635fb6ab47","date_updated":"2020-07-14T12:47:44Z","file_size":3081855,"creator":"kschuh","date_created":"2019-10-01T10:53:45Z","file_name":"2019_PLoS_Cepeda-Humerez.pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["15537358"]},"publication_status":"published"},{"date_updated":"2023-09-11T14:09:34Z","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"TaHa"}],"_id":"196","status":"public","type":"journal_article","article_type":"original","language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"eissn":["1091-6490"]},"volume":116,"issue":"8","related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/famous-sandpile-model-shown-to-move-like-a-traveling-sand-dune/","description":"News on IST Webpage"}]},"pmid":1,"oa_version":"Published Version","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. "}],"intvolume":" 116","month":"02","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1073/pnas.1812015116"}],"scopus_import":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Lang M, Shkolnikov M. 2019. Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. 116(8), 2821–2830.","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.","short":"M. Lang, M. Shkolnikov, Proceedings of the National Academy of Sciences 116 (2019) 2821–2830.","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","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","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."},"title":"Harmonic dynamics of the Abelian sandpile","external_id":{"isi":["000459074400013"],"pmid":[" 30728300"],"arxiv":["1806.10823"]},"article_processing_charge":"No","author":[{"full_name":"Lang, Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz"},{"first_name":"Mikhail","id":"35084A62-F248-11E8-B48F-1D18A9856A87","last_name":"Shkolnikov","full_name":"Shkolnikov, Mikhail","orcid":"0000-0002-4310-178X"}],"publication":"Proceedings of the National Academy of Sciences","day":"19","year":"2019","isi":1,"date_created":"2018-12-11T11:45:08Z","doi":"10.1073/pnas.1812015116","date_published":"2019-02-19T00:00:00Z","page":"2821-2830","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","oa":1,"quality_controlled":"1","publisher":"National Academy of Sciences"},{"date_created":"2019-01-11T07:37:47Z","date_published":"2019-01-10T00:00:00Z","doi":"10.1039/c8sm01956h","page":"602-614","publication":"Soft Matter","day":"10","year":"2019","isi":1,"has_accepted_license":"1","oa":1,"quality_controlled":"1","publisher":"Royal Society of Chemistry","title":"Limiting shapes of confined lipid vesicles","external_id":{"isi":["000457329700003"],"pmid":["30629082"]},"article_processing_charge":"No","author":[{"last_name":"Kavcic","orcid":"0000-0001-6041-254X","full_name":"Kavcic, Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","first_name":"Bor"},{"first_name":"A.","full_name":"Sakashita, A.","last_name":"Sakashita"},{"full_name":"Noguchi, H.","last_name":"Noguchi","first_name":"H."},{"first_name":"P.","last_name":"Ziherl","full_name":"Ziherl, P."}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"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.","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.","short":"B. Kavcic, A. Sakashita, H. Noguchi, P. Ziherl, Soft Matter 15 (2019) 602–614.","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","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","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.","ista":"Kavcic B, Sakashita A, Noguchi H, Ziherl P. 2019. Limiting shapes of confined lipid vesicles. Soft Matter. 15(4), 602–614."},"license":"https://creativecommons.org/licenses/by-nc-nd/3.0/","issue":"4","volume":15,"language":[{"iso":"eng"}],"file":[{"success":1,"file_id":"8641","checksum":"614c337d6424ccd3d48d1b1f9513510d","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"lmt_sftmtr_V8.pdf","date_created":"2020-10-09T11:00:05Z","file_size":5370762,"date_updated":"2020-10-09T11:00:05Z","creator":"bkavcic"}],"publication_status":"published","publication_identifier":{"issn":["1744-683X"],"eissn":["1744-6848"]},"intvolume":" 15","month":"01","scopus_import":"1","oa_version":"Submitted Version","pmid":1,"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."}],"department":[{"_id":"GaTk"}],"file_date_updated":"2020-10-09T11:00:05Z","ddc":["530"],"date_updated":"2023-09-13T08:47:16Z","status":"public","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/3.0/legalcode","short":"CC BY-NC-ND (3.0)"},"type":"journal_article","article_type":"original","_id":"5817"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"dissertation","keyword":["Information estimation","Time-series","data analysis"],"status":"public","_id":"6473","file_date_updated":"2020-07-14T12:47:31Z","department":[{"_id":"GaTk"}],"date_updated":"2023-09-19T15:13:26Z","supervisor":[{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"}],"ddc":["004"],"alternative_title":["ISTA Thesis"],"month":"05","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. "}],"oa_version":"Published Version","related_material":{"record":[{"id":"1576","status":"public","relation":"dissertation_contains"},{"relation":"dissertation_contains","status":"public","id":"6900"},{"relation":"dissertation_contains","id":"281","status":"public"},{"relation":"dissertation_contains","status":"public","id":"2016"}]},"degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"]},"language":[{"iso":"eng"}],"file":[{"relation":"source_file","access_level":"closed","content_type":"application/zip","file_id":"6480","checksum":"75f9184c1346e10a5de5f9cc7338309a","creator":"scepeda","file_size":23937464,"date_updated":"2020-07-14T12:47:31Z","file_name":"Thesis_Cepeda.zip","date_created":"2019-05-23T11:18:16Z"},{"date_updated":"2020-07-14T12:47:31Z","file_size":16646985,"creator":"scepeda","date_created":"2019-05-23T11:18:13Z","file_name":"CepedaThesis.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"6481","checksum":"afdc0633ddbd71d5b13550d7fb4f4454"}],"article_processing_charge":"No","author":[{"id":"3DEE19A4-F248-11E8-B48F-1D18A9856A87","first_name":"Sarah A","full_name":"Cepeda Humerez, Sarah A","last_name":"Cepeda Humerez"}],"title":"Estimating information flow in single cells","citation":{"ista":"Cepeda Humerez SA. 2019. Estimating information flow in single cells. Institute of Science and Technology Austria.","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.","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","ama":"Cepeda Humerez SA. Estimating information flow in single cells. 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.","ieee":"S. A. Cepeda Humerez, “Estimating information flow in single cells,” Institute of Science and Technology Austria, 2019.","mla":"Cepeda Humerez, Sarah A. Estimating Information Flow in Single Cells. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6473."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa":1,"publisher":"Institute of Science and Technology Austria","page":"135","date_created":"2019-05-21T00:11:23Z","doi":"10.15479/AT:ISTA:6473","date_published":"2019-05-23T00:00:00Z","year":"2019","has_accepted_license":"1","day":"23"},{"date_updated":"2023-09-22T10:00:48Z","supervisor":[{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","last_name":"Tkačik"}],"ddc":["576"],"department":[{"_id":"GaTk"},{"_id":"NiBa"}],"file_date_updated":"2020-07-14T12:47:18Z","_id":"6071","type":"dissertation","status":"public","degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"]},"language":[{"iso":"eng"}],"file":[{"date_created":"2019-03-06T16:05:07Z","file_name":"Thesis_final_PDFA_RoshanPrizak.pdf","date_updated":"2020-07-14T12:47:18Z","file_size":20995465,"creator":"rprizak","file_id":"6072","checksum":"e60a72de35d270b31f1a23d50f224ec0","content_type":"application/pdf","access_level":"open_access","relation":"main_file"},{"date_created":"2019-03-06T16:09:39Z","title":"Latex files","file_name":"thesis_v2_merge.zip","date_updated":"2020-07-14T12:47:18Z","file_size":85705272,"creator":"rprizak","checksum":"67c2630333d05ebafef5f018863a8465","file_id":"6073","content_type":"application/zip","access_level":"closed","relation":"source_file"}],"related_material":{"record":[{"status":"public","id":"1358","relation":"part_of_dissertation"},{"status":"public","id":"955","relation":"part_of_dissertation"}]},"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. "}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"month":"03","citation":{"ista":"Prizak R. 2019. Coevolution of transcription factors and their binding sites in sequence space. Institute of Science and Technology Austria.","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.","short":"R. Prizak, Coevolution of Transcription Factors and Their Binding Sites in Sequence Space, Institute of Science and Technology Austria, 2019.","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","ama":"Prizak R. Coevolution of transcription factors and their binding sites in sequence space. 2019. doi:10.15479/at:ista:th6071","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."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_processing_charge":"No","author":[{"first_name":"Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87","full_name":"Prizak, Roshan","last_name":"Prizak"}],"title":"Coevolution of transcription factors and their binding sites in sequence space","project":[{"grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation","call_identifier":"FWF","_id":"254E9036-B435-11E9-9278-68D0E5697425"}],"year":"2019","has_accepted_license":"1","day":"11","page":"189","date_created":"2019-03-06T16:16:10Z","doi":"10.15479/at:ista:th6071","date_published":"2019-03-11T00:00:00Z","oa":1,"publisher":"Institute of Science and Technology Austria"},{"doi":"10.1371/journal.pcbi.1007268","date_published":"2019-11-01T00:00:00Z","date_created":"2019-11-25T08:20:47Z","day":"01","publication":"PLoS Computational Biology","isi":1,"has_accepted_license":"1","year":"2019","publisher":"Public Library of Science","quality_controlled":"1","oa":1,"title":"Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture","author":[{"last_name":"Wang","full_name":"Wang, Jilin W. J. L.","first_name":"Jilin W. J. L."},{"first_name":"Fabrizio","id":"A057D288-3E88-11E9-986D-0CF4E5697425","orcid":"0000-0003-2623-5249","full_name":"Lombardi, Fabrizio","last_name":"Lombardi"},{"full_name":"Zhang, Xiyun","last_name":"Zhang","first_name":"Xiyun"},{"first_name":"Christelle","last_name":"Anaclet","full_name":"Anaclet, Christelle"},{"first_name":"Plamen Ch.","full_name":"Ivanov, Plamen Ch.","last_name":"Ivanov"}],"external_id":{"isi":["000500976100014"],"pmid":["31725712"]},"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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.","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.","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","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","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.","short":"J.W.J.L. Wang, F. Lombardi, X. Zhang, C. Anaclet, P.C. Ivanov, PLoS Computational Biology 15 (2019).","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."},"project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"}],"article_number":"e1007268","issue":"11","volume":15,"ec_funded":1,"file":[{"file_name":"2019_PLOSComBio_Wang.pdf","date_created":"2019-11-25T08:24:01Z","creator":"dernst","file_size":3982516,"date_updated":"2020-07-14T12:47:49Z","file_id":"7104","checksum":"2a096a9c6dcc6eaa94077b2603bc6c12","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["1553-7358"]},"publication_status":"published","month":"11","intvolume":" 15","scopus_import":"1","pmid":1,"oa_version":"Published Version","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."}],"file_date_updated":"2020-07-14T12:47:49Z","department":[{"_id":"GaTk"}],"ddc":["570","000"],"date_updated":"2023-10-17T12:30:07Z","status":"public","type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"7103"},{"quality_controlled":"1","publisher":"American Physical Society","oa":1,"day":"26","publication":"Physical Review E","isi":1,"year":"2019","date_published":"2019-02-26T00:00:00Z","doi":"10.1103/PhysRevE.99.022423","date_created":"2019-03-10T22:59:20Z","article_number":"022423","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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.","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).","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.","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","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"},"title":"Receptor crosstalk improves concentration sensing of multiple ligands","author":[{"first_name":"Martín","last_name":"Carballo-Pacheco","full_name":"Carballo-Pacheco, Martín"},{"last_name":"Desponds","full_name":"Desponds, Jonathan","first_name":"Jonathan"},{"first_name":"Tatyana","full_name":"Gavrilchenko, Tatyana","last_name":"Gavrilchenko"},{"first_name":"Andreas","last_name":"Mayer","full_name":"Mayer, Andreas"},{"full_name":"Prizak, Roshan","last_name":"Prizak","first_name":"Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Reddy","full_name":"Reddy, Gautam","first_name":"Gautam"},{"full_name":"Nemenman, Ilya","last_name":"Nemenman","first_name":"Ilya"},{"first_name":"Thierry","last_name":"Mora","full_name":"Mora, Thierry"}],"external_id":{"isi":["000459916500007"]},"article_processing_charge":"No","oa_version":"Preprint","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."}],"month":"02","intvolume":" 99","scopus_import":"1","main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/448118v1.abstract","open_access":"1"}],"language":[{"iso":"eng"}],"publication_status":"published","volume":99,"issue":"2","_id":"6090","status":"public","type":"journal_article","date_updated":"2024-02-28T13:12:06Z","department":[{"_id":"NiBa"},{"_id":"GaTk"}]},{"oa":1,"publisher":"IEEE","quality_controlled":"1","date_created":"2020-03-22T23:00:47Z","date_published":"2019-08-01T00:00:00Z","doi":"10.1109/ITW44776.2019.8989292","year":"2019","isi":1,"publication":"IEEE Information Theory Workshop, ITW 2019","day":"01","project":[{"name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"article_number":"8989292","external_id":{"arxiv":["1812.01475"],"isi":["000540384500015"]},"article_processing_charge":"No","author":[{"first_name":"Michal","id":"4171253A-F248-11E8-B48F-1D18A9856A87","full_name":"Hledik, Michal","last_name":"Hledik"},{"orcid":"0000-0002-1287-3779","full_name":"Sokolowski, Thomas R","last_name":"Sokolowski","id":"3E999752-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas R"},{"orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"}],"title":"A tight upper bound on mutual information","citation":{"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.","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.","short":"M. Hledik, T.R. Sokolowski, G. Tkačik, in:, IEEE Information Theory Workshop, ITW 2019, IEEE, 2019.","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","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."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1812.01475"}],"scopus_import":"1","month":"08","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."}],"oa_version":"Preprint","ec_funded":1,"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"15020"}]},"publication_status":"published","publication_identifier":{"isbn":["9781538669006"]},"language":[{"iso":"eng"}],"conference":{"end_date":"2019-08-28","location":"Visby, Sweden","start_date":"2019-08-25","name":"Information Theory Workshop"},"type":"conference","status":"public","_id":"7606","department":[{"_id":"GaTk"}],"date_updated":"2024-03-06T14:22:51Z"},{"_id":"306","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","status":"public","date_updated":"2021-01-12T07:40:46Z","ddc":["530"],"file_date_updated":"2020-07-14T12:45:59Z","department":[{"_id":"GaTk"}],"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."}],"oa_version":"Published Version","scopus_import":1,"intvolume":" 4","month":"04","publication_status":"published","language":[{"iso":"eng"}],"file":[{"date_created":"2019-02-06T07:36:24Z","file_name":"2018_Heliyon_DeMartino.pdf","creator":"dernst","date_updated":"2020-07-14T12:45:59Z","file_size":994490,"checksum":"67010cf5e3b3e0637c659371714a715a","file_id":"5929","access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"ec_funded":1,"issue":"4","volume":4,"article_number":"e00596","project":[{"name":"International IST Postdoc Fellowship Programme","grant_number":"291734","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"citation":{"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.","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.","short":"A. De Martino, D. De Martino, Heliyon 4 (2018).","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","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","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."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"De Martino","full_name":"De Martino, Andrea","first_name":"Andrea"},{"first_name":"Daniele","id":"3FF5848A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5214-4706","full_name":"De Martino, Daniele","last_name":"De Martino"}],"title":"An introduction to the maximum entropy approach and its application to inference problems in biology","oa":1,"publisher":"Elsevier","quality_controlled":"1","year":"2018","has_accepted_license":"1","publication":"Heliyon","day":"01","date_created":"2018-12-11T11:45:44Z","doi":"10.1016/j.heliyon.2018.e00596","date_published":"2018-04-01T00:00:00Z"}]