[{"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."}],"oa_version":"Published Version","pmid":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.cell.2019.01.007"}],"scopus_import":"1","intvolume":" 176","month":"02","publication_status":"published","language":[{"iso":"eng"}],"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/"}]},"volume":176,"issue":"4","_id":"5945","article_type":"original","type":"journal_article","status":"public","date_updated":"2023-08-24T14:42:47Z","department":[{"_id":"GaTk"}],"oa":1,"publisher":"Cell Press","quality_controlled":"1","year":"2019","isi":1,"publication":"Cell","day":"07","page":"844-855.e15","date_created":"2019-02-10T22:59:16Z","doi":"10.1016/j.cell.2019.01.007","date_published":"2019-02-07T00:00:00Z","project":[{"name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"citation":{"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.","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.","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","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.","short":"M.D. Petkova, G. Tkačik, W. Bialek, E.F. Wieschaus, T. Gregor, Cell 176 (2019) 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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","external_id":{"pmid":["30712870"],"isi":["000457969200015"]},"author":[{"first_name":"Mariela D.","full_name":"Petkova, Mariela D.","last_name":"Petkova"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gasper","full_name":"Tkacik, Gasper","orcid":"0000-0002-6699-1455","last_name":"Tkacik"},{"full_name":"Bialek, William","last_name":"Bialek","first_name":"William"},{"first_name":"Eric F.","full_name":"Wieschaus, Eric F.","last_name":"Wieschaus"},{"last_name":"Gregor","full_name":"Gregor, Thomas","first_name":"Thomas"}],"title":"Optimal decoding of cellular identities in a genetic network"},{"project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"}],"article_number":"045002","article_processing_charge":"Yes (in subscription journal)","external_id":{"isi":["000455379500001"]},"author":[{"orcid":"0000-0002-5214-4706","full_name":"De Martino, Daniele","last_name":"De Martino","id":"3FF5848A-F248-11E8-B48F-1D18A9856A87","first_name":"Daniele"}],"title":"Feedback-induced self-oscillations in large interacting systems subjected to phase transitions","citation":{"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.","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.","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","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","short":"D. De Martino, Journal of Physics A: Mathematical and Theoretical 52 (2019).","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"publisher":"IOP Publishing","quality_controlled":"1","date_created":"2019-02-24T22:59:19Z","doi":"10.1088/1751-8121/aaf2dd","date_published":"2019-01-07T00:00:00Z","year":"2019","isi":1,"has_accepted_license":"1","publication":"Journal of Physics A: Mathematical and Theoretical","day":"07","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","_id":"6049","file_date_updated":"2020-07-14T12:47:17Z","department":[{"_id":"GaTk"}],"date_updated":"2023-08-24T14:49:23Z","ddc":["570"],"scopus_import":"1","intvolume":" 52","month":"01","abstract":[{"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.","lang":"eng"}],"oa_version":"Published Version","license":"https://creativecommons.org/licenses/by/4.0/","ec_funded":1,"issue":"4","volume":52,"publication_status":"published","language":[{"iso":"eng"}],"file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"6344","checksum":"1112304ad363a6d8afaeccece36473cf","creator":"kschuh","date_updated":"2020-07-14T12:47:17Z","file_size":1804557,"date_created":"2019-04-19T12:18:57Z","file_name":"2019_IOP_DeMartino.pdf"}]},{"publication_status":"published","language":[{"iso":"eng"}],"volume":15,"issue":"2","acknowledged_ssus":[{"_id":"Bio"}],"abstract":[{"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.","lang":"eng"}],"oa_version":"Submitted Version","pmid":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pubmed/30765425","open_access":"1"}],"scopus_import":"1","intvolume":" 15","month":"02","date_updated":"2023-08-24T14:49:53Z","department":[{"_id":"GaTk"}],"_id":"6046","type":"journal_article","status":"public","year":"2019","isi":1,"publication":"Molecular systems biology","day":"14","date_created":"2019-02-24T22:59:18Z","doi":"10.15252/msb.20188470","date_published":"2019-02-14T00:00:00Z","oa":1,"publisher":"Embo Press","quality_controlled":"1","citation":{"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.","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.","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","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","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.","short":"K. Mitosch, G. Rieckh, M.T. Bollenbach, Molecular Systems Biology 15 (2019).","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","external_id":{"pmid":["30765425"],"isi":["000459628300003"]},"author":[{"last_name":"Mitosch","full_name":"Mitosch, Karin","first_name":"Karin","id":"39B66846-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Rieckh","full_name":"Rieckh, Georg","id":"34DA8BD6-F248-11E8-B48F-1D18A9856A87","first_name":"Georg"},{"first_name":"Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","last_name":"Bollenbach","full_name":"Bollenbach, Mark Tobias","orcid":"0000-0003-4398-476X"}],"title":"Temporal order and precision of complex stress responses in individual bacteria","article_number":"e8470","project":[{"call_identifier":"FWF","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","name":"Revealing the mechanisms underlying drug interactions","grant_number":"P27201-B22"},{"grant_number":"RGP0042/2013","name":"Revealing the fundamental limits of cell growth","_id":"25EB3A80-B435-11E9-9278-68D0E5697425"}]},{"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"file_date_updated":"2020-07-14T12:47:40Z","ddc":["570"],"date_updated":"2023-08-29T07:10:06Z","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":"6784","issue":"7","volume":15,"related_material":{"record":[{"status":"public","id":"9786","relation":"research_data"}]},"file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_id":"6803","checksum":"7ded4721b41c2a0fc66a1c634540416a","creator":"dernst","file_size":2200003,"date_updated":"2020-07-14T12:47:40Z","file_name":"2019_PlosComputBiology_Ruess.pdf","date_created":"2019-08-12T12:27:26Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1553-7358"]},"publication_status":"published","month":"07","intvolume":" 15","scopus_import":"1","oa_version":"Published Version","abstract":[{"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.","lang":"eng"}],"title":"Molecular noise of innate immunity shapes bacteria-phage ecologies","author":[{"id":"4A245D00-F248-11E8-B48F-1D18A9856A87","first_name":"Jakob","full_name":"Ruess, Jakob","orcid":"0000-0003-1615-3282","last_name":"Ruess"},{"id":"4569785E-F248-11E8-B48F-1D18A9856A87","first_name":"Maros","last_name":"Pleska","full_name":"Pleska, Maros","orcid":"0000-0001-7460-7479"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"},{"last_name":"Tkačik","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"isi":["000481577700032"]},"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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.","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.","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","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","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.","short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15 (2019).","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."},"project":[{"name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level","grant_number":"24210","_id":"251D65D8-B435-11E9-9278-68D0E5697425"},{"name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems","grant_number":"RGY0079/2011","_id":"251BCBEC-B435-11E9-9278-68D0E5697425"}],"article_number":"e1007168","doi":"10.1371/journal.pcbi.1007168","date_published":"2019-07-02T00:00:00Z","date_created":"2019-08-11T21:59:19Z","day":"02","publication":"PLoS Computational Biology","isi":1,"has_accepted_license":"1","year":"2019","publisher":"Public Library of Science","quality_controlled":"1","oa":1},{"year":"2019","day":"02","date_published":"2019-07-02T00:00:00Z","doi":"10.1371/journal.pcbi.1007168.s001","related_material":{"record":[{"id":"6784","status":"public","relation":"used_in_publication"}]},"date_created":"2021-08-06T08:23:43Z","oa_version":"Published Version","publisher":"Public Library of Science","month":"07","citation":{"mla":"Ruess, Jakob, et al. Supporting Text and Results. Public Library of Science, 2019, doi: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.","short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, (2019).","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.","ista":"Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Supporting text and results, Public Library of Science, 10.1371/journal.pcbi.1007168.s001."},"date_updated":"2023-08-29T07:10:05Z","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","author":[{"id":"4A245D00-F248-11E8-B48F-1D18A9856A87","first_name":"Jakob","full_name":"Ruess, Jakob","orcid":"0000-0003-1615-3282","last_name":"Ruess"},{"last_name":"Pleska","orcid":"0000-0001-7460-7479","full_name":"Pleska, Maros","first_name":"Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet"},{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","title":"Supporting text and results","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"_id":"9786","type":"research_data_reference","status":"public"},{"volume":150,"issue":"5","language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1089-7690"],"issn":["0021-9606"]},"publication_status":"published","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."}],"department":[{"_id":"GaTk"}],"date_updated":"2023-09-06T14:59:28Z","status":"public","article_type":"original","type":"journal_article","_id":"7422","date_published":"2019-02-07T00:00:00Z","doi":"10.1063/1.5064867","date_created":"2020-01-30T10:34:36Z","day":"07","publication":"The Journal of Chemical Physics","isi":1,"year":"2019","publisher":"AIP Publishing","quality_controlled":"1","oa":1,"title":"eGFRD in all dimensions","author":[{"first_name":"Thomas R","id":"3E999752-F248-11E8-B48F-1D18A9856A87","full_name":"Sokolowski, Thomas R","orcid":"0000-0002-1287-3779","last_name":"Sokolowski"},{"last_name":"Paijmans","full_name":"Paijmans, Joris","first_name":"Joris"},{"last_name":"Bossen","full_name":"Bossen, Laurens","first_name":"Laurens"},{"first_name":"Thomas","last_name":"Miedema","full_name":"Miedema, Thomas"},{"last_name":"Wehrens","full_name":"Wehrens, Martijn","first_name":"Martijn"},{"first_name":"Nils B.","full_name":"Becker, Nils B.","last_name":"Becker"},{"last_name":"Kaizu","full_name":"Kaizu, Kazunari","first_name":"Kazunari"},{"full_name":"Takahashi, Koichi","last_name":"Takahashi","first_name":"Koichi"},{"full_name":"Dogterom, Marileen","last_name":"Dogterom","first_name":"Marileen"},{"first_name":"Pieter Rein","last_name":"ten Wolde","full_name":"ten Wolde, Pieter Rein"}],"external_id":{"arxiv":["1708.09364"],"isi":["000458109300009"]},"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"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.","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","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","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).","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.","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."},"article_number":"054108"},{"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":[{"first_name":"Sarah A","id":"3DEE19A4-F248-11E8-B48F-1D18A9856A87","full_name":"Cepeda Humerez, Sarah A","last_name":"Cepeda Humerez"},{"first_name":"Jakob","orcid":"0000-0003-1615-3282","full_name":"Ruess, Jakob","last_name":"Ruess"},{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","last_name":"Tkačik"}],"article_processing_charge":"No","external_id":{"pmid":["31479447"],"isi":["000489741800021"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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.","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.","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","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","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.","ista":"Cepeda Humerez SA, Ruess J, Tkačik G. 2019. Estimating information in time-varying signals. PLoS computational biology. 15(9), e1007290."},"publisher":"Public Library of Science","quality_controlled":"1","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","oa_version":"Published Version","pmid":1,"abstract":[{"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.","lang":"eng"}],"volume":15,"issue":"9","related_material":{"record":[{"relation":"part_of_dissertation","id":"6473","status":"public"}]},"file":[{"creator":"kschuh","file_size":3081855,"date_updated":"2020-07-14T12:47:44Z","file_name":"2019_PLoS_Cepeda-Humerez.pdf","date_created":"2019-10-01T10:53:45Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_id":"6925","checksum":"81bdce1361c9aa8395d6fa635fb6ab47"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["15537358"]},"publication_status":"published"},{"oa":1,"quality_controlled":"1","publisher":"National Academy of Sciences","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","date_created":"2018-12-11T11:45:08Z","date_published":"2019-02-19T00:00:00Z","doi":"10.1073/pnas.1812015116","page":"2821-2830","publication":"Proceedings of the National Academy of Sciences","day":"19","year":"2019","isi":1,"title":"Harmonic dynamics of the Abelian sandpile","external_id":{"pmid":[" 30728300"],"isi":["000459074400013"],"arxiv":["1806.10823"]},"article_processing_charge":"No","author":[{"first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","last_name":"Lang","full_name":"Lang, Moritz"},{"last_name":"Shkolnikov","full_name":"Shkolnikov, Mikhail","orcid":"0000-0002-4310-178X","first_name":"Mikhail","id":"35084A62-F248-11E8-B48F-1D18A9856A87"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"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.","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.","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.","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"},"intvolume":" 116","month":"02","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1073/pnas.1812015116"}],"scopus_import":"1","pmid":1,"oa_version":"Published Version","abstract":[{"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. ","lang":"eng"}],"issue":"8","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/"}]},"volume":116,"language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"eissn":["1091-6490"]},"status":"public","article_type":"original","type":"journal_article","_id":"196","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"TaHa"}],"date_updated":"2023-09-11T14:09:34Z"},{"title":"Limiting shapes of confined lipid vesicles","article_processing_charge":"No","external_id":{"pmid":["30629082"],"isi":["000457329700003"]},"author":[{"last_name":"Kavcic","full_name":"Kavcic, Bor","orcid":"0000-0001-6041-254X","first_name":"Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"A.","full_name":"Sakashita, A.","last_name":"Sakashita"},{"first_name":"H.","last_name":"Noguchi","full_name":"Noguchi, H."},{"first_name":"P.","last_name":"Ziherl","full_name":"Ziherl, P."}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Kavcic B, Sakashita A, Noguchi H, Ziherl P. 2019. Limiting shapes of confined lipid vesicles. Soft Matter. 15(4), 602–614.","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.","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","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.","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."},"oa":1,"publisher":"Royal Society of Chemistry","quality_controlled":"1","date_created":"2019-01-11T07:37:47Z","doi":"10.1039/c8sm01956h","date_published":"2019-01-10T00:00:00Z","page":"602-614","publication":"Soft Matter","day":"10","year":"2019","isi":1,"has_accepted_license":"1","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","department":[{"_id":"GaTk"}],"file_date_updated":"2020-10-09T11:00:05Z","ddc":["530"],"date_updated":"2023-09-13T08:47:16Z","intvolume":" 15","month":"01","scopus_import":"1","pmid":1,"oa_version":"Submitted Version","abstract":[{"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.","lang":"eng"}],"license":"https://creativecommons.org/licenses/by-nc-nd/3.0/","issue":"4","volume":15,"language":[{"iso":"eng"}],"file":[{"date_created":"2020-10-09T11:00:05Z","file_name":"lmt_sftmtr_V8.pdf","date_updated":"2020-10-09T11:00:05Z","file_size":5370762,"creator":"bkavcic","checksum":"614c337d6424ccd3d48d1b1f9513510d","file_id":"8641","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"publication_status":"published","publication_identifier":{"eissn":["1744-6848"],"issn":["1744-683X"]}},{"citation":{"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.","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.","ieee":"S. A. Cepeda Humerez, “Estimating information flow in single cells,” Institute of Science and Technology Austria, 2019.","short":"S.A. Cepeda Humerez, Estimating Information Flow in Single Cells, Institute of Science and Technology Austria, 2019.","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"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","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","oa":1,"publisher":"Institute of Science and Technology Austria","year":"2019","has_accepted_license":"1","day":"23","page":"135","date_created":"2019-05-21T00:11:23Z","date_published":"2019-05-23T00:00:00Z","doi":"10.15479/AT:ISTA:6473","_id":"6473","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","date_updated":"2023-09-19T15:13:26Z","supervisor":[{"full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"ddc":["004"],"file_date_updated":"2020-07-14T12:47:31Z","department":[{"_id":"GaTk"}],"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","alternative_title":["ISTA Thesis"],"month":"05","degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"]},"language":[{"iso":"eng"}],"file":[{"date_created":"2019-05-23T11:18:16Z","file_name":"Thesis_Cepeda.zip","date_updated":"2020-07-14T12:47:31Z","file_size":23937464,"creator":"scepeda","checksum":"75f9184c1346e10a5de5f9cc7338309a","file_id":"6480","content_type":"application/zip","access_level":"closed","relation":"source_file"},{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"6481","checksum":"afdc0633ddbd71d5b13550d7fb4f4454","creator":"scepeda","date_updated":"2020-07-14T12:47:31Z","file_size":16646985,"date_created":"2019-05-23T11:18:13Z","file_name":"CepedaThesis.pdf"}],"related_material":{"record":[{"relation":"dissertation_contains","id":"1576","status":"public"},{"relation":"dissertation_contains","id":"6900","status":"public"},{"relation":"dissertation_contains","status":"public","id":"281"},{"status":"public","id":"2016","relation":"dissertation_contains"}]}}]