--- DOAJ_listed: '1' OA_place: publisher OA_type: gold PlanS_conform: '1' _id: '21282' abstract: - lang: eng text: 'Developmental patterning comprises processes that range from purely instructed, where external signals specify cell fates, to fully self-organized, where spatial patterns emerge autonomously through cellular interactions. We propose that both extremes—as well as the continuum of intermediate cases—can be conceptualized as information-processing systems, whose operation can be described using “Marr''s three levels of analysis”: the computational problem being solved, the algorithms employed, and their molecular implementation. At the first level, we argue that normative theories, such as information-theoretic optimization principles, provide a formalization of the computational problem. At the second level, we show how simplified information-processing architectures provide a framework for developmental algorithms, which are formalized mathematically using dynamical systems theory. At the third level, the implementation of developmental algorithms is described by mechanistic biophysical and gene regulatory network models.' acknowledgement: We thank Edouard Hannezo, Anna Kicheva, Fridtjof Brauns, and all members of the Brückner and Tkačik groups for feedback and inspiring discussions. This work was supported in part by European Research Council ERC-2023-SyG “Dynatrans” Grant No. 101118866 (G.T.). This work was conducted while visiting the Okinawa Institute of Science and Technology (OIST) through the Theoretical Sciences Visiting Program (TSVP); at the Kavli Institute for Theoretical Physics (KITP) Santa Barbara, supported by NSF Grant No. PHY-1748958 and the Gordon and Betty Moore Foundation Grant No. 2919.02; and at Lucullus, Vienna. article_number: '017001' article_processing_charge: Yes article_type: original arxiv: 1 author: - first_name: David full_name: Brückner, David id: e1e86031-6537-11eb-953a-f7ab92be508d last_name: Brückner orcid: 0000-0001-7205-2975 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: 'Brückner D, Tkačik G. Marr’s three levels for embryonic development: Information, dynamical systems, gene networks. PRX Life. 2026;4. doi:10.1103/fdcf-dkws' apa: 'Brückner, D., & Tkačik, G. (2026). Marr’s three levels for embryonic development: Information, dynamical systems, gene networks. PRX Life. American Physical Society. https://doi.org/10.1103/fdcf-dkws' chicago: 'Brückner, David, and Gašper Tkačik. “Marr’s Three Levels for Embryonic Development: Information, Dynamical Systems, Gene Networks.” PRX Life. American Physical Society, 2026. https://doi.org/10.1103/fdcf-dkws.' ieee: 'D. Brückner and G. Tkačik, “Marr’s three levels for embryonic development: Information, dynamical systems, gene networks,” PRX Life, vol. 4. American Physical Society, 2026.' ista: 'Brückner D, Tkačik G. 2026. Marr’s three levels for embryonic development: Information, dynamical systems, gene networks. PRX Life. 4, 017001.' mla: 'Brückner, David, and Gašper Tkačik. “Marr’s Three Levels for Embryonic Development: Information, Dynamical Systems, Gene Networks.” PRX Life, vol. 4, 017001, American Physical Society, 2026, doi:10.1103/fdcf-dkws.' short: D. Brückner, G. Tkačik, PRX Life 4 (2026). corr_author: '1' date_created: 2026-02-17T08:29:10Z date_published: 2026-01-23T00:00:00Z date_updated: 2026-02-24T07:00:16Z day: '23' ddc: - '570' department: - _id: GaTk doi: 10.1103/fdcf-dkws external_id: arxiv: - '2510.24536' file: - access_level: open_access checksum: 99ef02dd741c4536eeefd12d409d5269 content_type: application/pdf creator: dernst date_created: 2026-02-24T06:57:44Z date_updated: 2026-02-24T06:57:44Z file_id: '21352' file_name: 2026_PRXLife_Brueckner.pdf file_size: 1147994 relation: main_file success: 1 file_date_updated: 2026-02-24T06:57:44Z has_accepted_license: '1' intvolume: ' 4' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '01' oa: 1 oa_version: Published Version project: - _id: 7bfe6a29-9f16-11ee-852c-c0da5e2045d9 grant_number: '101118866' name: 'Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos' publication: PRX Life publication_identifier: eissn: - 2835-8279 publication_status: published publisher: American Physical Society quality_controlled: '1' status: public title: 'Marr''s three levels for embryonic development: Information, dynamical systems, gene networks' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 4 year: '2026' ... --- OA_place: publisher OA_type: hybrid _id: '21759' abstract: - lang: eng text: 'Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that bind transcription factor (TF) proteins to up- or down-regulate target genes. Decades-long efforts yielded TF-DNA interaction models that predict how strongly an individual TF binds arbitrary DNA sequences and how individual binding events on the CRE combine to affect gene expression. These insights can be synthesized into a global, biophysically realistic, and quantitative genotype-phenotype (GP) map for gene regulation, a ‘holy grail’ for the application of evolutionary theory. A global map provides a rare opportunity to simulate the long-term evolution of regulatory sequences and pose several fundamental questions: How long does it take to evolve CREs de novo? How many non-trivial regulatory functions exist in sequence space? How connected are they? For which regulatory architecture is CRE evolution most rapid and evolvable? In this article, the second of a two-part series, we review the application of evolutionary concepts — epistasis, robustness, evolvability, tunability, plasticity, and bet-hedging — to the evolution of gene regulatory sequences. We then evaluate the potential for a unifying theory for the evolution of regulatory sequences and identify key open challenges.' acknowledgement: "We thank Calin Guet and Santiago Herrera-Álvarez for essential contributions to this manuscript.\r\nE.M. acknowledges support from the APART-USA fellowship, jointly funded by the Austrian Academy of Sciences (ÖAW) and the Institute of Science and Technology Austria (ISTA). N.B. acknowledges funding from the ERC Advanced Grant 101055327 “HaplotypeStructure”.\r\nThis study was also supported by the European Molecular Biology Laboratory (N.O.B., J.C.)." article_number: '102472' article_processing_charge: Yes (via OA deal) article_type: review author: - first_name: Elia full_name: Mascolo, Elia id: 776a6ed0-a053-11f0-8635-80b95e0e0d53 last_name: Mascolo orcid: 0000-0003-2977-7844 - first_name: Reka E full_name: Körei, Reka E id: 50FDE43E-AA30-11E9-A72B-8A12E6697425 last_name: Körei - first_name: Noa O. full_name: Borst, Noa O. last_name: Borst - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Justin full_name: Crocker, Justin last_name: Crocker - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: 'Mascolo E, Körei RE, Borst NO, Barton NH, Crocker J, Tkačik G. Long-term evolution of regulatory DNA sequences. Part 2: Theory and future challenges. Current Opinion in Genetics and Development. 2026;98. doi:10.1016/j.gde.2026.102472' apa: 'Mascolo, E., Körei, R. E., Borst, N. O., Barton, N. H., Crocker, J., & Tkačik, G. (2026). Long-term evolution of regulatory DNA sequences. Part 2: Theory and future challenges. Current Opinion in Genetics and Development. Elsevier. https://doi.org/10.1016/j.gde.2026.102472' chicago: 'Mascolo, Elia, Reka E Körei, Noa O. Borst, Nicholas H Barton, Justin Crocker, and Gašper Tkačik. “Long-Term Evolution of Regulatory DNA Sequences. Part 2: Theory and Future Challenges.” Current Opinion in Genetics and Development. Elsevier, 2026. https://doi.org/10.1016/j.gde.2026.102472.' ieee: 'E. Mascolo, R. E. Körei, N. O. Borst, N. H. Barton, J. Crocker, and G. Tkačik, “Long-term evolution of regulatory DNA sequences. Part 2: Theory and future challenges,” Current Opinion in Genetics and Development, vol. 98. Elsevier, 2026.' ista: 'Mascolo E, Körei RE, Borst NO, Barton NH, Crocker J, Tkačik G. 2026. Long-term evolution of regulatory DNA sequences. Part 2: Theory and future challenges. Current Opinion in Genetics and Development. 98, 102472.' mla: 'Mascolo, Elia, et al. “Long-Term Evolution of Regulatory DNA Sequences. Part 2: Theory and Future Challenges.” Current Opinion in Genetics and Development, vol. 98, 102472, Elsevier, 2026, doi:10.1016/j.gde.2026.102472.' short: E. Mascolo, R.E. Körei, N.O. Borst, N.H. Barton, J. Crocker, G. Tkačik, Current Opinion in Genetics and Development 98 (2026). corr_author: '1' date_created: 2026-04-26T22:01:46Z date_published: 2026-04-15T00:00:00Z date_updated: 2026-04-28T12:41:00Z day: '15' department: - _id: GaTk - _id: NiBa doi: 10.1016/j.gde.2026.102472 intvolume: ' 98' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.gde.2026.102472 month: '04' oa: 1 oa_version: Published Version project: - _id: bd6958e0-d553-11ed-ba76-86eba6a76c00 grant_number: '101055327' name: Understanding the evolution of continuous genomes publication: Current Opinion in Genetics and Development publication_identifier: eissn: - 1879-0380 issn: - 0959-437X publication_status: epub_ahead publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: 'Long-term evolution of regulatory DNA sequences. Part 2: Theory and future challenges' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 98 year: '2026' ... --- OA_place: publisher OA_type: hybrid _id: '19785' abstract: - lang: eng text: 'We consider a family of totally asymmetric simple exclusion processes (TASEPs), consisting of particles on a lattice that require binding by a “token” in various physical configurations to advance over the lattice. Using a combination of theory and simulations, we address the following questions: (i) How does token binding kinetics affect the current-density relation on the lattice? (ii) How does this current-density relation depend on the scarcity of tokens? (iii) How do tokens propagate the effects of the locally imposed disorder (such as a slow site) over the entire lattice? (iv) How does a shared pool of tokens couple concurrent TASEPs running on multiple lattices? and (v) How do our results translate to TASEPs with open boundaries that exchange particles with the reservoir? Since real particle motion (including in biological systems that inspired the standard TASEP model, e.g., protein synthesis or movement of molecular motors) is often catalyzed, regulated, actuated, or otherwise mediated, the token-driven TASEP dynamics analyzed in this paper should allow for a better understanding of real systems and enable a closer match between TASEP theory and experimental observations.' acknowledgement: B.K. thanks Stefano Elefante, Simon Rella, and Michal Hledík for their help with the usage of the cluster. B.K. additionally thanks Călin Guet and his group for help and advice. We thank M. Hennessey-Wesen and Luca Ciandrini for constructive comments on the paper. We thank Ankita Gupta (Indian Institute of Technology) for spotting a typographical error in Eq. (50) in the preprint version of this paper. article_number: '054122' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Kavcic B, Tkačik G. Token-driven totally asymmetric simple exclusion processes. Physical Review E. 2025;111(5). doi:10.1103/physreve.111.054122 apa: Kavcic, B., & Tkačik, G. (2025). Token-driven totally asymmetric simple exclusion processes. Physical Review E. American Physical Society. https://doi.org/10.1103/physreve.111.054122 chicago: Kavcic, Bor, and Gašper Tkačik. “Token-Driven Totally Asymmetric Simple Exclusion Processes.” Physical Review E. American Physical Society, 2025. https://doi.org/10.1103/physreve.111.054122. ieee: B. Kavcic and G. Tkačik, “Token-driven totally asymmetric simple exclusion processes,” Physical Review E, vol. 111, no. 5. American Physical Society, 2025. ista: Kavcic B, Tkačik G. 2025. Token-driven totally asymmetric simple exclusion processes. Physical Review E. 111(5), 054122. mla: Kavcic, Bor, and Gašper Tkačik. “Token-Driven Totally Asymmetric Simple Exclusion Processes.” Physical Review E, vol. 111, no. 5, 054122, American Physical Society, 2025, doi:10.1103/physreve.111.054122. short: B. Kavcic, G. Tkačik, Physical Review E 111 (2025). corr_author: '1' date_created: 2025-06-03T09:01:55Z date_published: 2025-05-19T00:00:00Z date_updated: 2025-09-30T12:44:55Z day: '19' ddc: - '570' department: - _id: GaTk doi: 10.1103/physreve.111.054122 external_id: isi: - '001496415600007' file: - access_level: open_access checksum: e8851ccd7cd0525c08c7308710413e74 content_type: application/pdf creator: dernst date_created: 2025-06-03T09:18:20Z date_updated: 2025-06-03T09:18:20Z file_id: '19787' file_name: 2025_PhysRevE_Kavcic.pdf file_size: 2766143 relation: main_file success: 1 file_date_updated: 2025-06-03T09:18:20Z has_accepted_license: '1' intvolume: ' 111' isi: 1 issue: '5' language: - iso: eng month: '05' oa: 1 oa_version: Published Version publication: Physical Review E publication_identifier: eissn: - 2470-0053 issn: - 2470-0045 publication_status: published publisher: American Physical Society quality_controlled: '1' related_material: record: - id: '19658' relation: research_data status: public scopus_import: '1' status: public title: Token-driven totally asymmetric simple exclusion processes tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 111 year: '2025' ... --- OA_place: publisher OA_type: hybrid _id: '18849' abstract: - lang: eng text: Many biological systems operate near the physical limits to their performance, suggesting that aspects of their behavior and underlying mechanisms could be derived from optimization principles. However, such principles have often been applied only in simplified models. Here, we explore a detailed mechanistic model of the gap gene network in the Drosophila embryo, optimizing its 50+ parameters to maximize the information that gene expression levels provide about nuclear positions. This optimization is conducted under realistic constraints, such as limits on the number of available molecules. Remarkably, the optimal networks we derive closely match the architecture and spatial gene expression profiles observed in the real organism. Our framework quantifies the tradeoffs involved in maximizing functional performance and allows for the exploration of alternative network configurations, addressing the question of which features are necessary and which are contingent. Our results suggest that multiple solutions to the optimization problem might exist across closely related organisms, offering insights into the evolution of gene regulatory networks. acknowledgement: We thank Nicholas H. Barton for his comments on the manuscript, Benjamin Zoller for helpful discussions, and Aleksandra Walczak and Curtis Callan for early collaborations that shaped this work. Special thanks to Eric F. Wieschaus for many persistently inspiring conversations. This work was supported in part by the Human Frontiers Science Program; the Austrian Science Fund (FWF P28844); by the European Research Council grant DynaTrans (101118866); by U.S. NSF, through the Center for the Physics of Biological Function (PHY–1734030); by NIH Grants R01GM097275, U01DA047730, and U01DK127429; by the John Simon Guggenheim Memorial Foundation; and by the LOEWE priority program “Center for Multiscale Modeling in Life Sciences” (CMMS), sponsored by the Hessian Ministry for Science and Research, Arts and Culture (HMWK). article_number: e2402925121 article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Thomas R full_name: Sokolowski, Thomas R id: 3E999752-F248-11E8-B48F-1D18A9856A87 last_name: Sokolowski orcid: 0000-0002-1287-3779 - first_name: Thomas full_name: Gregor, Thomas last_name: Gregor - first_name: William full_name: Bialek, William last_name: Bialek - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Sokolowski TR, Gregor T, Bialek W, Tkačik G. Deriving a genetic regulatory network from an optimization principle. Proceedings of the National Academy of Sciences. 2025;122(1). doi:10.1073/pnas.2402925121 apa: Sokolowski, T. R., Gregor, T., Bialek, W., & Tkačik, G. (2025). Deriving a genetic regulatory network from an optimization principle. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2402925121 chicago: Sokolowski, Thomas R, Thomas Gregor, William Bialek, and Gašper Tkačik. “Deriving a Genetic Regulatory Network from an Optimization Principle.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2025. https://doi.org/10.1073/pnas.2402925121. ieee: T. R. Sokolowski, T. Gregor, W. Bialek, and G. Tkačik, “Deriving a genetic regulatory network from an optimization principle,” Proceedings of the National Academy of Sciences, vol. 122, no. 1. National Academy of Sciences, 2025. ista: Sokolowski TR, Gregor T, Bialek W, Tkačik G. 2025. Deriving a genetic regulatory network from an optimization principle. Proceedings of the National Academy of Sciences. 122(1), e2402925121. mla: Sokolowski, Thomas R., et al. “Deriving a Genetic Regulatory Network from an Optimization Principle.” Proceedings of the National Academy of Sciences, vol. 122, no. 1, e2402925121, National Academy of Sciences, 2025, doi:10.1073/pnas.2402925121. short: T.R. Sokolowski, T. Gregor, W. Bialek, G. Tkačik, Proceedings of the National Academy of Sciences 122 (2025). corr_author: '1' date_created: 2025-01-19T23:01:50Z date_published: 2025-01-07T00:00:00Z date_updated: 2026-02-16T12:26:51Z day: '07' ddc: - '570' department: - _id: GaTk doi: 10.1073/pnas.2402925121 external_id: isi: - '001392772400001' pmid: - '39752518' file: - access_level: open_access checksum: 8dbfc7d495413340225ebfae69b0cf9a content_type: application/pdf creator: dernst date_created: 2025-01-20T10:10:04Z date_updated: 2025-01-20T10:10:04Z file_id: '18862' file_name: 2025_PNAS_Sokolowski.pdf file_size: 19073585 relation: main_file success: 1 file_date_updated: 2025-01-20T10:10:04Z has_accepted_license: '1' intvolume: ' 122' isi: 1 issue: '1' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ month: '01' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation - _id: 7bfe6a29-9f16-11ee-852c-c0da5e2045d9 grant_number: '101118866' name: 'Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos' - _id: 2665AAFE-B435-11E9-9278-68D0E5697425 grant_number: RGP0034/2018 name: Can evolution minimize spurious signaling crosstalk to reach optimal performance? publication: Proceedings of the National Academy of Sciences publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' scopus_import: '1' status: public title: Deriving a genetic regulatory network from an optimization principle tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 122 year: '2025' ... --- APC_amount: 2750 USD OA_place: publisher OA_type: hybrid _id: '18850' abstract: - lang: eng text: 'Biophysical constraints limit the specificity with which transcription factors (TFs) can target regulatory DNA. While individual nontarget binding events may be low affinity, the sheer number of such interactions could present a challenge for gene regulation by degrading its precision or possibly leading to an erroneous induction state. Chromatin can prevent nontarget binding by rendering DNA physically inaccessible to TFs, at the cost of energy-consuming remodeling orchestrated by pioneer factors (PFs). Under what conditions and by how much can chromatin reduce regulatory errors on a global scale? We use a theoretical approach to compare two scenarios for gene regulation: one that relies on TF binding to free DNA alone and one that uses a combination of TFs and chromatin-regulating PFs to achieve desired gene expression patterns. We find, first, that chromatin effectively silences groups of genes that should be simultaneously OFF, thereby allowing more accurate graded control of expression for the remaining ON genes. Second, chromatin buffers the deleterious consequences of nontarget binding as the number of OFF genes grows, permitting a substantial expansion in regulatory complexity. Third, chromatin-based regulation productively co-opts nontarget TF binding for ON genes in order to establish a “leaky” baseline expression level, which targeted activator or repressor binding subsequently up- or down-modulates. Thus, on a global scale, using chromatin simultaneously alleviates pressure for high specificity of regulatory interactions and enables an increase in genome size with minimal impact on global expression error.' acknowledgement: M.L.P. was supported by the European Molecular Biology Laboratory (EMBL) Interdisciplinary Postdoc Programme (EIPOD4 fellowships), cofunded by Marie SkÅ‚odowska-Curie Actions (Grant Agreement No. 847543). J.C. and M.L.P. were supported by EMBL Core Funding and Theory@EMBL. This work is supported by European Research Council Grant DynaTrans (101118866) to G.T. We would like to thank the members of the J.C. and G.T. groups, especially Natalia Misunou, Michal Hledík, and Réka Borbély, for helpful feedback and discussion. We also thank EMBL IT Services for the use of high performance computing resources. article_number: e2411887121 article_processing_charge: No article_type: original author: - first_name: Mindy Liu full_name: Perkins, Mindy Liu last_name: Perkins - first_name: Justin full_name: Crocker, Justin last_name: Crocker - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Perkins ML, Crocker J, Tkačik G. Chromatin enables precise and scalable gene regulation with factors of limited specificity. Proceedings of the National Academy of Sciences. 2025;122(1). doi:10.1073/pnas.2411887121 apa: Perkins, M. L., Crocker, J., & Tkačik, G. (2025). Chromatin enables precise and scalable gene regulation with factors of limited specificity. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2411887121 chicago: Perkins, Mindy Liu, Justin Crocker, and Gašper Tkačik. “Chromatin Enables Precise and Scalable Gene Regulation with Factors of Limited Specificity.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2025. https://doi.org/10.1073/pnas.2411887121. ieee: M. L. Perkins, J. Crocker, and G. Tkačik, “Chromatin enables precise and scalable gene regulation with factors of limited specificity,” Proceedings of the National Academy of Sciences, vol. 122, no. 1. National Academy of Sciences, 2025. ista: Perkins ML, Crocker J, Tkačik G. 2025. Chromatin enables precise and scalable gene regulation with factors of limited specificity. Proceedings of the National Academy of Sciences. 122(1), e2411887121. mla: Perkins, Mindy Liu, et al. “Chromatin Enables Precise and Scalable Gene Regulation with Factors of Limited Specificity.” Proceedings of the National Academy of Sciences, vol. 122, no. 1, e2411887121, National Academy of Sciences, 2025, doi:10.1073/pnas.2411887121. short: M.L. Perkins, J. Crocker, G. Tkačik, Proceedings of the National Academy of Sciences 122 (2025). corr_author: '1' date_created: 2025-01-19T23:01:51Z date_published: 2025-01-07T00:00:00Z date_updated: 2026-02-16T12:27:25Z day: '07' ddc: - '570' department: - _id: GaTk doi: 10.1073/pnas.2411887121 external_id: isi: - '001392765300001' pmid: - '39793086' file: - access_level: open_access checksum: 86a8d25a6e282aeb4128f1d0b86ff911 content_type: application/pdf creator: dernst date_created: 2025-01-20T09:38:32Z date_updated: 2025-01-20T09:38:32Z file_id: '18859' file_name: 2025_PNAS_Perkins.pdf file_size: 30943709 relation: main_file success: 1 file_date_updated: 2025-01-20T09:38:32Z has_accepted_license: '1' intvolume: ' 122' isi: 1 issue: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 7bfe6a29-9f16-11ee-852c-c0da5e2045d9 grant_number: '101118866' name: 'Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos' publication: Proceedings of the National Academy of Sciences publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: link: - relation: software url: https://github.com/officerredshirt/network_crosstalk scopus_import: '1' status: public title: Chromatin enables precise and scalable gene regulation with factors of limited specificity tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 122 year: '2025' ... --- OA_place: publisher OA_type: hybrid _id: '18936' abstract: - lang: eng text: A major obstacle to predictive understanding of evolution stems from the complexity of biological systems, which prevents detailed characterization of key evolutionary properties. Here, we highlight some of the major sources of complexity that arise when relating molecular mechanisms to their evolutionary consequences and ask whether accounting for every mechanistic detail is important to accurately predict evolutionary outcomes. To do this, we developed a mechanistic model of a bacterial promoter regulated by 2 proteins, allowing us to connect any promoter genotype to 6 phenotypes that capture the dynamics of gene expression following an environmental switch. Accounting for the mechanisms that govern how this system works enabled us to provide an in-depth picture of how regulated bacterial promoters might evolve. More importantly, we used the model to explore which factors that contribute to the complexity of this system are essential for understanding its evolution, and which can be simplified without information loss. We found that several key evolutionary properties—the distribution of phenotypic and fitness effects of mutations, the evolutionary trajectories during selection for regulation—can be accurately captured without accounting for all, or even most, parameters of the system. Our findings point to the need for a mechanistic approach to studying evolution, as it enables tackling biological complexity and in doing so improves the ability to predict evolutionary outcomes. acknowledgement: "The authors thank Nick Barton, Stepan Denisov, Claudia Igler, Srdjan Sarikas, Anna Staron, and the anonymous reviewers for useful comments and discussions that helped improve our work.\r\nFunding for this work was provided by the Wellcome Trust–Royal Society Sir Henry Dale Fellowship (216779/Z/19/Z) and the Royal Society Research Grant (RG\\R2\\232522) to M.L." article_number: iyae191 article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Mato full_name: Lagator, Mato id: 345D25EC-F248-11E8-B48F-1D18A9856A87 last_name: Lagator citation: ama: 'Grah R, Guet CC, Tkačik G, Lagator M. Linking molecular mechanisms to their evolutionary consequences: a primer. Genetics. 2025;229(2). doi:10.1093/genetics/iyae191' apa: 'Grah, R., Guet, C. C., Tkačik, G., & Lagator, M. (2025). Linking molecular mechanisms to their evolutionary consequences: a primer. Genetics. Oxford University Press. https://doi.org/10.1093/genetics/iyae191' chicago: 'Grah, Rok, Calin C Guet, Gašper Tkačik, and Mato Lagator. “Linking Molecular Mechanisms to Their Evolutionary Consequences: A Primer.” Genetics. Oxford University Press, 2025. https://doi.org/10.1093/genetics/iyae191.' ieee: 'R. Grah, C. C. Guet, G. Tkačik, and M. Lagator, “Linking molecular mechanisms to their evolutionary consequences: a primer,” Genetics, vol. 229, no. 2. Oxford University Press, 2025.' ista: 'Grah R, Guet CC, Tkačik G, Lagator M. 2025. Linking molecular mechanisms to their evolutionary consequences: a primer. Genetics. 229(2), iyae191.' mla: 'Grah, Rok, et al. “Linking Molecular Mechanisms to Their Evolutionary Consequences: A Primer.” Genetics, vol. 229, no. 2, iyae191, Oxford University Press, 2025, doi:10.1093/genetics/iyae191.' short: R. Grah, C.C. Guet, G. Tkačik, M. Lagator, Genetics 229 (2025). corr_author: '1' date_created: 2025-01-29T08:21:35Z date_published: 2025-02-01T00:00:00Z date_updated: 2025-05-19T14:08:02Z day: '01' ddc: - '570' department: - _id: CaGu - _id: GaTk doi: 10.1093/genetics/iyae191 external_id: isi: - '001379194200001' pmid: - '39601269' file: - access_level: open_access checksum: f730e416795969449ef49d97b82ac494 content_type: application/pdf creator: dernst date_created: 2025-04-16T09:41:04Z date_updated: 2025-04-16T09:41:04Z file_id: '19580' file_name: 2025_Genetics_Grah.pdf file_size: 1511688 relation: main_file success: 1 file_date_updated: 2025-04-16T09:41:04Z has_accepted_license: '1' intvolume: ' 229' isi: 1 issue: '2' language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 publication: Genetics publication_identifier: eissn: - 1943-2631 publication_status: published publisher: Oxford University Press quality_controlled: '1' scopus_import: '1' status: public title: 'Linking molecular mechanisms to their evolutionary consequences: a primer' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 229 year: '2025' ... --- OA_place: publisher OA_type: hybrid _id: '19453' abstract: - lang: eng text: A key feature of biological and artificial neural networks is the progressive refinement of their neural representations with experience. In neuroscience, this fact has inspired several recent studies in sensory and motor systems. However, less is known about how higher associational cortical areas, such as the hippocampus, modify representations throughout the learning of complex tasks. Here, we focus on associative learning, a process that requires forming a connection between the representations of different variables for appropriate behavioral response. We trained rats in a space-context associative task and monitored hippocampal neural activity throughout the entire learning period, over several days. This allowed us to assess changes in the representations of context, movement direction, and position, as well as their relationship to behavior. We identified a hierarchical representational structure in the encoding of these three task variables that was preserved throughout learning. Nevertheless, we also observed changes at the lower levels of the hierarchy where context was encoded. These changes were local in neural activity space and restricted to physical positions where context identification was necessary for correct decision-making, supporting better context decoding and contextual code compression. Our results demonstrate that the hippocampal code not only accommodates hierarchical relationships between different variables but also enables efficient learning through minimal changes in neural activity space. Beyond the hippocampus, our work reveals a representation learning mechanism that might be implemented in other biological and artificial networks performing similar tasks. acknowledgement: We would like to thank Rebecca Morse for performing the recordings in one of the animals under the supervision of H.S.C.C., Jago Wallenschus for the technical support, especially with maze design, Wiktor Mlynarski for the advice and discussions and Andrea Cumpelik for suggestions during the writing. M.N. was supported by the Howard Hughes Medical Institute. H.S.C.C. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 665385. article_number: e2417025122 article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Heloisa full_name: Chiossi, Heloisa id: 2BBA502C-F248-11E8-B48F-1D18A9856A87 last_name: Chiossi orcid: 0009-0004-2973-278X - first_name: Michele full_name: Nardin, Michele id: 30BD0376-F248-11E8-B48F-1D18A9856A87 last_name: Nardin orcid: 0000-0001-8849-6570 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 citation: ama: Chiossi HSC, Nardin M, Tkačik G, Csicsvari JL. Learning reshapes the hippocampal representation hierarchy. Proceedings of the National Academy of Sciences. 2025;122(11). doi:10.1073/pnas.2417025122 apa: Chiossi, H. S. C., Nardin, M., Tkačik, G., & Csicsvari, J. L. (2025). Learning reshapes the hippocampal representation hierarchy. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2417025122 chicago: Chiossi, Heloisa S. C., Michele Nardin, Gašper Tkačik, and Jozsef L Csicsvari. “Learning Reshapes the Hippocampal Representation Hierarchy.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2025. https://doi.org/10.1073/pnas.2417025122. ieee: H. S. C. Chiossi, M. Nardin, G. Tkačik, and J. L. Csicsvari, “Learning reshapes the hippocampal representation hierarchy,” Proceedings of the National Academy of Sciences, vol. 122, no. 11. National Academy of Sciences, 2025. ista: Chiossi HSC, Nardin M, Tkačik G, Csicsvari JL. 2025. Learning reshapes the hippocampal representation hierarchy. Proceedings of the National Academy of Sciences. 122(11), e2417025122. mla: Chiossi, Heloisa S. C., et al. “Learning Reshapes the Hippocampal Representation Hierarchy.” Proceedings of the National Academy of Sciences, vol. 122, no. 11, e2417025122, National Academy of Sciences, 2025, doi:10.1073/pnas.2417025122. short: H.S.C. Chiossi, M. Nardin, G. Tkačik, J.L. Csicsvari, Proceedings of the National Academy of Sciences 122 (2025). corr_author: '1' date_created: 2025-03-25T07:38:35Z date_published: 2025-03-10T00:00:00Z date_updated: 2025-09-30T11:11:51Z day: '10' ddc: - '570' department: - _id: GaTk - _id: JoCs doi: 10.1073/pnas.2417025122 ec_funded: 1 external_id: isi: - '001459499500001' pmid: - '40063792' file: - access_level: open_access checksum: 1217207c254553154faa065964990988 content_type: application/pdf creator: dernst date_created: 2025-03-25T07:49:04Z date_updated: 2025-03-25T07:49:04Z file_id: '19454' file_name: 2025_PNAS_Chiossi.pdf file_size: 1553502 relation: main_file success: 1 file_date_updated: 2025-03-25T07:49:04Z has_accepted_license: '1' intvolume: ' 122' isi: 1 issue: '11' language: - iso: eng month: '03' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: Proceedings of the National Academy of Sciences publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: link: - relation: software url: https://github.com/hchiossi/hpc-hierarchy record: - id: '18991' relation: research_data status: public scopus_import: '1' status: public title: Learning reshapes the hippocampal representation hierarchy tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 122 year: '2025' ... --- OA_place: publisher OA_type: gold _id: '19658' abstract: - lang: eng text: 'We consider a family of totally asymmetric simple exclusion processes (TASEPs), consisting of particles on a lattice that require binding by a "token" in various physical configurations to advance over the lattice. Using a combination of theory and simulations, we address the following questions: (i) How token binding kinetics affects the current-density relation on the lattice; (ii) How this current-density relation depends on the scarcity of tokens; (iii) How tokens propagate the effects of the locally-imposed disorder (such as a slow site) over the entire lattice; (iv) How a shared pool of tokens couples concurrent TASEPs running on multiple lattices; (v) How our results translate to TASEPs with open boundaries that exchange particles with the reservoir. Since real particle motion (including in biological systems that inspired the standard TASEP model, e.g., protein synthesis or movement of molecular motors) is often catalyzed, regulated, actuated, or otherwise mediated, the token-driven TASEP dynamics analyzed in this paper should allow for a better understanding of real systems and enable a closer match between TASEP theory and experimental observations.' article_processing_charge: No author: - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Tkačik G. Token-driven totally asymmetric simple exclusion processes. 2025. doi:10.15479/AT:ISTA:19658 apa: Tkačik, G. (2025). Token-driven totally asymmetric simple exclusion processes. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:19658 chicago: Tkačik, Gašper. “Token-Driven Totally Asymmetric Simple Exclusion Processes.” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT:ISTA:19658. ieee: G. Tkačik, “Token-driven totally asymmetric simple exclusion processes.” Institute of Science and Technology Austria, 2025. ista: Tkačik G. 2025. Token-driven totally asymmetric simple exclusion processes, Institute of Science and Technology Austria, 10.15479/AT:ISTA:19658. mla: Tkačik, Gašper. Token-Driven Totally Asymmetric Simple Exclusion Processes. Institute of Science and Technology Austria, 2025, doi:10.15479/AT:ISTA:19658. short: G. Tkačik, (2025). contributor: - contributor_type: researcher first_name: Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X corr_author: '1' date_created: 2025-05-08T05:43:38Z date_published: 2025-05-08T00:00:00Z date_updated: 2025-09-30T12:44:54Z day: '08' ddc: - '570' department: - _id: GaTk doi: 10.15479/AT:ISTA:19658 file: - access_level: open_access checksum: 5c15966e4139f10281ab03575f753f82 content_type: application/zip creator: gtkacik date_created: 2025-05-08T05:41:31Z date_updated: 2025-05-08T05:41:31Z file_id: '19659' file_name: pre_tasep_export_data.zip file_size: 7387217 relation: main_file success: 1 - access_level: open_access checksum: 939a9341feee946a2399cab226fe69e8 content_type: text/plain creator: gtkacik date_created: 2025-05-12T07:36:23Z date_updated: 2025-05-12T07:36:23Z file_id: '19678' file_name: readme.txt file_size: 587 relation: main_file file_date_updated: 2025-05-12T07:36:23Z has_accepted_license: '1' license: https://creativecommons.org/licenses/by-sa/4.0/ month: '05' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '19785' relation: used_in_publication status: public status: public title: Token-driven totally asymmetric simple exclusion processes tmp: image: /images/cc_by_sa.png legal_code_url: https://creativecommons.org/licenses/by-sa/4.0/legalcode name: Creative Commons Attribution-ShareAlike 4.0 International Public License (CC BY-SA 4.0) short: CC BY-SA (4.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2025' ... --- OA_place: publisher OA_type: hybrid _id: '19701' abstract: - lang: eng text: 'Living systems are characterized by controlled flows of matter, energy, and information. While the biophysics community has productively engaged with the first two, addressing information flows has been more challenging, with some scattered success in evolutionary theory and a more coherent track record in neuroscience. Nevertheless, interdisciplinary work of the past two decades at the interface of biophysics, quantitative biology, and engineering has led to an emerging mathematical language for describing information flows at the molecular scale. This is where the central processes of life unfold: from detection and transduction of environmental signals to the readout or copying of genetic information and the triggering of adaptive cellular responses. Such processes are coordinated by complex biochemical reaction networks that operate at room temperature, are out of equilibrium, and use low copy numbers of diverse molecular species with limited interaction specificity. Here we review how flows of information through biochemical networks can be formalized using information-theoretic quantities, quantified from data, and computed within various modeling frameworks. Optimization of information flows is presented as a candidate design principle that navigates the relevant time, energy, crosstalk, and metabolic constraints to predict reliable cellular signaling and gene regulation architectures built of individually noisy components.' acknowledgement: G.T. acknowledges the support of the Human Frontiers Science Program (HFSP), the Austrian Science Fund (FWF 10.55776/P34015, 10.55776/P28844), and the European Research Council Synergy DYNATRANS (ERC-2023-SyG 101118866) grant. P.R.t.W. performed his work at the research institute AMOLF and acknowledges support from the Dutch Research Council (NWO) and funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement 885065). article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Pieter Rein Ten full_name: Wolde, Pieter Rein Ten last_name: Wolde citation: ama: Tkačik G, Wolde PRT. Information processing in biochemical networks. Annual review of biophysics. 2025;54:249-274. doi:10.1146/annurev-biophys-060524-102720 apa: Tkačik, G., & Wolde, P. R. T. (2025). Information processing in biochemical networks. Annual Review of Biophysics. Annual Reviews. https://doi.org/10.1146/annurev-biophys-060524-102720 chicago: Tkačik, Gašper, and Pieter Rein Ten Wolde. “Information Processing in Biochemical Networks.” Annual Review of Biophysics. Annual Reviews, 2025. https://doi.org/10.1146/annurev-biophys-060524-102720. ieee: G. Tkačik and P. R. T. Wolde, “Information processing in biochemical networks,” Annual review of biophysics, vol. 54. Annual Reviews, pp. 249–274, 2025. ista: Tkačik G, Wolde PRT. 2025. Information processing in biochemical networks. Annual review of biophysics. 54, 249–274. mla: Tkačik, Gašper, and Pieter Rein Ten Wolde. “Information Processing in Biochemical Networks.” Annual Review of Biophysics, vol. 54, Annual Reviews, 2025, pp. 249–74, doi:10.1146/annurev-biophys-060524-102720. short: G. Tkačik, P.R.T. Wolde, Annual Review of Biophysics 54 (2025) 249–274. corr_author: '1' date_created: 2025-05-18T22:02:50Z date_published: 2025-05-01T00:00:00Z date_updated: 2025-09-30T12:33:33Z day: '01' ddc: - '570' department: - _id: GaTk doi: 10.1146/annurev-biophys-060524-102720 external_id: isi: - '001488641500013' pmid: - '39929539' file: - access_level: open_access checksum: 9ab623b2bc45dcd5fdd2c9577ea8ae9f content_type: application/pdf creator: dernst date_created: 2025-05-19T07:55:51Z date_updated: 2025-05-19T07:55:51Z file_id: '19710' file_name: 2025_AnnualReviewBiophysics_Tkacik.pdf file_size: 317925 relation: main_file success: 1 file_date_updated: 2025-05-19T07:55:51Z has_accepted_license: '1' intvolume: ' 54' isi: 1 language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: 249-274 pmid: 1 project: - _id: 626c45b5-2b32-11ec-9570-e509828c1ba6 grant_number: P34015 name: Efficient coding with biophysical realism - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation - _id: 7bfe6a29-9f16-11ee-852c-c0da5e2045d9 grant_number: '101118866' name: 'Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos' publication: Annual review of biophysics publication_identifier: eissn: - 1936-1238 publication_status: published publisher: Annual Reviews quality_controlled: '1' scopus_import: '1' status: public title: Information processing in biochemical networks tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 54 year: '2025' ... --- OA_place: publisher OA_type: hybrid _id: '19626' abstract: - lang: eng text: Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the noncanonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g., control of costly-to-induce multidrug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multidrug resistance is crucial for effective public health measures. acknowledged_ssus: - _id: Bio acknowledgement: K.J. thanks B. Wu, I. Tomanek, K. Tomasek for detailed discussions on the manuscript, all other members from the Guet laboratory for valuable feedback, R. Chait, & Imaging and Optics Facility, Institute of Science and Technology Austria for helping with microscopy, Dr. Sudha Rao and Dr. Raja Mugasimangalam, Genotypic Technology India for allowing time off to address the revisions. K.J. acknowledges Institute of Science and Technology fellowship IC1006FELL02, R.H. was supported in part by Chan Zuckerberg Initiative and Donor Advised-Fund grant 2020-225401 (https://doi.org/10.37921/120055ratwvi), O.O.B. acknowledges Fonds Zur Förderung der Wissenschaftlichen Forschung (FWF) Grant ESP253-B, R.R. acknowledges FWF Grant 10.55776/ESP219, C.C.G. acknowledges FWF I5127-B. article_number: e2413709122 article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Kirti full_name: Jain, Kirti id: 330F0278-F248-11E8-B48F-1D18A9856A87 last_name: Jain orcid: 0000-0002-3809-0449 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Olga full_name: Bochkareva, Olga id: C4558D3C-6102-11E9-A62E-F418E6697425 last_name: Bochkareva orcid: 0000-0003-1006-6639 - first_name: Roderich full_name: Römhild, Roderich id: 68E56E44-62B0-11EA-B963-444F3DDC885E last_name: Römhild orcid: 0000-0001-9480-5261 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 citation: ama: Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Pulsatile basal gene expression as a fitness determinant in bacteria. Proceedings of the National Academy of Sciences. 2025;122(15). doi:10.1073/pnas.2413709122 apa: Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., & Guet, C. C. (2025). Pulsatile basal gene expression as a fitness determinant in bacteria. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2413709122 chicago: Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2025. https://doi.org/10.1073/pnas.2413709122. ieee: K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Pulsatile basal gene expression as a fitness determinant in bacteria,” Proceedings of the National Academy of Sciences, vol. 122, no. 15. National Academy of Sciences, 2025. ista: Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Pulsatile basal gene expression as a fitness determinant in bacteria. Proceedings of the National Academy of Sciences. 122(15), e2413709122. mla: Jain, Kirti, et al. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” Proceedings of the National Academy of Sciences, vol. 122, no. 15, e2413709122, National Academy of Sciences, 2025, doi:10.1073/pnas.2413709122. short: K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings of the National Academy of Sciences 122 (2025). corr_author: '1' date_created: 2025-04-27T22:02:13Z date_published: 2025-04-15T00:00:00Z date_updated: 2026-04-28T13:35:46Z day: '15' ddc: - '570' department: - _id: CaGu - _id: Bio - _id: FyKo - _id: GaTk doi: 10.1073/pnas.2413709122 external_id: isi: - '001471235200001' pmid: - '40193613' file: - access_level: open_access checksum: 115a687f40009660eb4b38b4f6559d41 content_type: application/pdf creator: dernst date_created: 2025-06-24T07:27:43Z date_updated: 2025-06-24T07:27:43Z file_id: '19888' file_name: 2025_PNAS_Jain.pdf file_size: 2949523 relation: main_file success: 1 file_date_updated: 2025-06-24T07:27:43Z has_accepted_license: '1' intvolume: ' 122' isi: 1 issue: '15' language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 project: - _id: c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473 grant_number: CZI01 name: Tools for automation and feedback microscopy - _id: bd6f94d1-d553-11ed-ba76-ae9f07250f74 grant_number: E219 name: Non-canonical antibiotic interactions - _id: 34e076d6-11ca-11ed-8bc3-aec76c41a181 grant_number: I05127 name: Evolutionary analysis of gene regulation publication: Proceedings of the National Academy of Sciences publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: link: - description: News on ISTA website relation: press_release url: https://ista.ac.at/en/news/clockwork-just-for-antibiotic-resistance/ record: - id: '19294' relation: research_data status: public scopus_import: '1' status: public title: Pulsatile basal gene expression as a fitness determinant in bacteria tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd volume: 122 year: '2025' ... --- OA_place: repository OA_type: gold _id: '19294' abstract: - lang: eng text: Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of non-functional “promoter leakiness”, merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the non-canonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g. control of costly-to-induce multi-drug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multi-drug resistance is crucial for effective public health measures. article_processing_charge: No author: - first_name: Kirti full_name: Jain, Kirti id: 330F0278-F248-11E8-B48F-1D18A9856A87 last_name: Jain orcid: 0000-0002-3809-0449 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Olga full_name: Bochkareva, Olga id: C4558D3C-6102-11E9-A62E-F418E6697425 last_name: Bochkareva orcid: 0000-0003-1006-6639 - first_name: Roderich full_name: Römhild, Roderich id: 68E56E44-62B0-11EA-B963-444F3DDC885E last_name: Römhild orcid: 0000-0001-9480-5261 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 citation: ama: Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Data for “Pulsatile basal gene expression as a fitness determinant in bacteria.” 2025. doi:10.15479/AT:ISTA:19294 apa: Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., & Guet, C. C. (2025). Data for “Pulsatile basal gene expression as a fitness determinant in bacteria.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:19294 chicago: Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Data for ‘Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.’” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT:ISTA:19294. ieee: K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Data for ‘Pulsatile basal gene expression as a fitness determinant in bacteria.’” Institute of Science and Technology Austria, 2025. ista: Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Data for ‘Pulsatile basal gene expression as a fitness determinant in bacteria’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:19294. mla: Jain, Kirti, et al. Data for “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” Institute of Science and Technology Austria, 2025, doi:10.15479/AT:ISTA:19294. short: K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, (2025). corr_author: '1' date_created: 2025-03-04T13:27:21Z date_published: 2025-03-04T00:00:00Z date_updated: 2026-04-28T13:35:45Z day: '04' ddc: - '570' department: - _id: CaGu - _id: Bio - _id: FyKo - _id: GaTk doi: 10.15479/AT:ISTA:19294 file: - access_level: open_access checksum: 11a5bab307a4e1e1598a1577d8a2fbb5 content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet creator: dernst date_created: 2025-03-04T13:08:52Z date_updated: 2025-03-04T13:08:52Z file_id: '19295' file_name: Data1.xlsx file_size: 269054 relation: main_file success: 1 - access_level: open_access checksum: 3b057894322639f0c1e11fb2e84173e6 content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet creator: dernst date_created: 2025-03-04T13:08:52Z date_updated: 2025-03-04T13:08:52Z file_id: '19296' file_name: Data2.xlsx file_size: 87143 relation: main_file success: 1 - access_level: open_access checksum: a551e1b79a138bb97ab96979aa475b3c content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet creator: dernst date_created: 2025-03-04T13:08:52Z date_updated: 2025-03-04T13:08:52Z file_id: '19297' file_name: Data3.xlsx file_size: 129101 relation: main_file success: 1 - access_level: open_access checksum: d6909c9bf111f859058082b1a2f970c4 content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet creator: dernst date_created: 2025-03-04T13:08:52Z date_updated: 2025-03-04T13:08:52Z file_id: '19298' file_name: Data4.xlsx file_size: 86243 relation: main_file success: 1 - access_level: open_access checksum: e5725a3a118a3f06846104906c8792c7 content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet creator: dernst date_created: 2025-03-04T13:08:52Z date_updated: 2025-03-04T13:08:52Z file_id: '19299' file_name: Data5.xlsx file_size: 26049 relation: main_file success: 1 - access_level: open_access checksum: 16763c127049f14bd587dc885677dce1 content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet creator: dernst date_created: 2025-03-04T13:08:52Z date_updated: 2025-03-04T13:08:52Z file_id: '19300' file_name: RawData_2_3.xlsx file_size: 7327253 relation: main_file success: 1 - access_level: open_access checksum: 2f3e1a368b4e3abc46bf37e02724f0f4 content_type: text/plain creator: dernst date_created: 2025-03-05T07:39:38Z date_updated: 2025-03-05T07:39:38Z file_id: '19301' file_name: Readme.txt file_size: 606 relation: main_file success: 1 file_date_updated: 2025-03-05T07:39:38Z has_accepted_license: '1' month: '03' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '19626' relation: used_in_publication status: public status: public title: Data for "Pulsatile basal gene expression as a fitness determinant in bacteria" tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2025' ... --- APC_amount: 2570,79 EUR OA_place: publisher OA_type: hybrid _id: '17123' abstract: - lang: eng text: A key feature of many developmental systems is their ability to self-organize spatial patterns of functionally distinct cell fates. To ensure proper biological function, such patterns must be established reproducibly, by controlling and even harnessing intrinsic and extrinsic fluctuations. While the relevant molecular processes are increasingly well understood, we lack a principled framework to quantify the performance of such stochastic self-organizing systems. To that end, we introduce an information-theoretic measure for self-organized fate specification during embryonic development. We show that the proposed measure assesses the total information content of fate patterns and decomposes it into interpretable contributions corresponding to the positional and correlational information. By optimizing the proposed measure, our framework provides a normative theory for developmental circuits, which we demonstrate on lateral inhibition, cell type proportioning, and reaction–diffusion models of self-organization. This paves a way toward a classification of developmental systems based on a common information-theoretic language, thereby organizing the zoo of implicated chemical and mechanical signaling processes. acknowledgement: We thank Wiktor Młynarski, Juraj Majek, Michal Hledík, Fridtjof Brauns, Nikolas Claussen, Benjamin Zoller, Erwin Frey, Thomas Gregor, and Edouard Hannezo for inspiring discussions. D.B.B. was supported by the NOMIS foundation as a NOMIS Fellow and by an European Molecular Biology Organization (EMBO) Postdoctoral Fellowship (ALTF 343-2022). This research was performed in part at the Aspen Center for Physics, which is supported by NSF Grant No. PHY-1607611, and Kavli Institute for Theoretical Physics (KITP) Santa Barbara, supported by NSF Grant No. PHY-1748958 and the Gordon and Betty Moore Foundation Grant No. 2919.02. article_number: e2322326121 article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: David full_name: Brückner, David id: e1e86031-6537-11eb-953a-f7ab92be508d last_name: Brückner orcid: 0000-0001-7205-2975 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Brückner D, Tkačik G. Information content and optimization of self-organized developmental systems. Proceedings of the National Academy of Sciences of the United States of America. 2024;121(23). doi:10.1073/pnas.2322326121 apa: Brückner, D., & Tkačik, G. (2024). Information content and optimization of self-organized developmental systems. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2322326121 chicago: Brückner, David, and Gašper Tkačik. “Information Content and Optimization of Self-Organized Developmental Systems.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2024. https://doi.org/10.1073/pnas.2322326121. ieee: D. Brückner and G. Tkačik, “Information content and optimization of self-organized developmental systems,” Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 23. National Academy of Sciences, 2024. ista: Brückner D, Tkačik G. 2024. Information content and optimization of self-organized developmental systems. Proceedings of the National Academy of Sciences of the United States of America. 121(23), e2322326121. mla: Brückner, David, and Gašper Tkačik. “Information Content and Optimization of Self-Organized Developmental Systems.” Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 23, e2322326121, National Academy of Sciences, 2024, doi:10.1073/pnas.2322326121. short: D. Brückner, G. Tkačik, Proceedings of the National Academy of Sciences of the United States of America 121 (2024). corr_author: '1' date_created: 2024-06-09T22:01:02Z date_published: 2024-06-04T00:00:00Z date_updated: 2025-09-08T07:51:01Z day: '04' ddc: - '570' department: - _id: EdHa - _id: GaTk doi: 10.1073/pnas.2322326121 external_id: isi: - '001244835000006' pmid: - '38819997' file: - access_level: open_access checksum: 59797a75db7beb3721ed7a4d14c241f9 content_type: application/pdf creator: dernst date_created: 2024-06-10T10:27:37Z date_updated: 2024-06-10T10:27:37Z file_id: '17130' file_name: 2024_PNAS_Brueckner.pdf file_size: 12329234 relation: main_file success: 1 file_date_updated: 2024-06-10T10:27:37Z has_accepted_license: '1' intvolume: ' 121' isi: 1 issue: '23' language: - iso: eng month: '06' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 34e2a5b5-11ca-11ed-8bc3-b2265616ef0b grant_number: ALTF 343-2022 name: A mechano-chemical theory for stem cell fate decisions in organoid development publication: Proceedings of the National Academy of Sciences of the United States of America publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: link: - relation: software url: https://github.com/dbrueckner/SelforgInformation - description: News on the ISTA website relation: press_release url: https://ista.ac.at/en/news/the-embryo-assembles-itself/ scopus_import: '1' status: public title: Information content and optimization of self-organized developmental systems tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 121 year: '2024' ... --- APC_amount: 3062,93 EUR OA_place: publisher OA_type: hybrid _id: '18525' abstract: - lang: eng text: As their statistical power grows, genome-wide association studies (GWAS) have identified an increasing number of loci underlying quantitative traits of interest. These loci are scattered throughout the genome and are individually responsible only for small fractions of the total heritable trait variance. The recently proposed omnigenic model provides a conceptual framework to explain these observations by postulating that numerous distant loci contribute to each complex trait via effect propagation through intracellular regulatory networks. We formalize this conceptual framework by proposing the “quantitative omnigenic model” (QOM), a statistical model that combines prior knowledge of the regulatory network topology with genomic data. By applying our model to gene expression traits in yeast, we demonstrate that QOM achieves similar gene expression prediction performance to traditional GWAS with hundreds of times less parameters, while simultaneously extracting candidate causal and quantitative chains of effect propagation through the regulatory network for every individual gene. We estimate the fraction of heritable trait variance in cis- and in trans-, break the latter down by effect propagation order, assess the trans- variance not attributable to transcriptional regulation, and show that QOM correctly accounts for the low-dimensional structure of gene expression covariance. We furthermore demonstrate the relevance of QOM for systems biology, by employing it as a statistical test for the quality of regulatory network reconstructions, and linking it to the propagation of nontranscriptional (including environmental) effects. acknowledgement: N.R.acknowledges the support of the Austrian Academy of Sciences through the Doctoral Fellowship Programme (DOC) of the Austrian Academy of Sciences 26917. M.H. and G.T. were supported in part by the Human Frontiers Science Program Grant RGP0034/2018. We thank Nicholas H. Barton, Fyodor Kondrashov, and Matthew R. Robinson for fruitful discussions. article_number: e2402340121 article_processing_charge: Yes article_type: original author: - first_name: Natalia full_name: Ruzickova, Natalia id: D2761128-D73D-11E9-A1BF-BA0DE6697425 last_name: Ruzickova - first_name: Michal full_name: Hledik, Michal id: 4171253A-F248-11E8-B48F-1D18A9856A87 last_name: Hledik - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Ruzickova N, Hledik M, Tkačik G. Quantitative omnigenic model discovers interpretable genome-wide associations. Proceedings of the National Academy of Sciences of the United States of America. 2024;121(44). doi:10.1073/pnas.2402340121 apa: Ruzickova, N., Hledik, M., & Tkačik, G. (2024). Quantitative omnigenic model discovers interpretable genome-wide associations. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2402340121 chicago: Ruzickova, Natalia, Michal Hledik, and Gašper Tkačik. “Quantitative Omnigenic Model Discovers Interpretable Genome-Wide Associations.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2024. https://doi.org/10.1073/pnas.2402340121. ieee: N. Ruzickova, M. Hledik, and G. Tkačik, “Quantitative omnigenic model discovers interpretable genome-wide associations,” Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 44. National Academy of Sciences, 2024. ista: Ruzickova N, Hledik M, Tkačik G. 2024. Quantitative omnigenic model discovers interpretable genome-wide associations. Proceedings of the National Academy of Sciences of the United States of America. 121(44), e2402340121. mla: Ruzickova, Natalia, et al. “Quantitative Omnigenic Model Discovers Interpretable Genome-Wide Associations.” Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 44, e2402340121, National Academy of Sciences, 2024, doi:10.1073/pnas.2402340121. short: N. Ruzickova, M. Hledik, G. Tkačik, Proceedings of the National Academy of Sciences of the United States of America 121 (2024). corr_author: '1' date_created: 2024-11-10T23:01:59Z date_published: 2024-10-29T00:00:00Z date_updated: 2026-04-07T12:02:39Z day: '29' ddc: - '570' department: - _id: GaTk - _id: NiBa doi: 10.1073/pnas.2402340121 external_id: isi: - '001349462600001' pmid: - '39441639' file: - access_level: open_access checksum: d930e2ccf9ec900c7d7509a78cfb3564 content_type: application/pdf creator: dernst date_created: 2024-11-11T09:31:00Z date_updated: 2024-11-11T09:31:00Z file_id: '18536' file_name: 2024_PNAS_Ruzickova.pdf file_size: 25529709 relation: main_file success: 1 file_date_updated: 2024-11-11T09:31:00Z has_accepted_license: '1' intvolume: ' 121' isi: 1 issue: '44' language: - iso: eng month: '10' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 7bec9174-9f16-11ee-852c-ded9fe5f810e name: Collective behaviour of cells in pancreatic Islets of Langerhans - _id: 2665AAFE-B435-11E9-9278-68D0E5697425 grant_number: RGP0034/2018 name: Can evolution minimize spurious signaling crosstalk to reach optimal performance? publication: Proceedings of the National Academy of Sciences of the United States of America publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: record: - id: '20357' relation: dissertation_contains status: public scopus_import: '1' status: public title: Quantitative omnigenic model discovers interpretable genome-wide associations tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 121 year: '2024' ... --- DOAJ_listed: '1' OA_place: publisher OA_type: gold _id: '18902' acknowledgement: 'MZ is supported by National Science Center, Poland, 2021/42/E/NZ2/00188, the Polish National Agency for Academic Exchange, and by a grant from the Priority Research Area DigiWorld under the Strategic Programme Excellence Initiative at Jagiellonian University. Work in JB’s lab is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council and Wellcome Trust (all under CC001051). Work in the AK lab is supported by ISTA, the European Research Council under Horizon Europe: grant 101044579, and Austrian Science Fund (FWF): F78 (Neural Stem Cell Modulation).' article_number: '929' article_processing_charge: Yes article_type: letter_note author: - first_name: Marcin full_name: Zagorski, Marcin last_name: Zagorski - first_name: Nathalie full_name: Brandenberg, Nathalie last_name: Brandenberg - first_name: Matthias full_name: Lutolf, Matthias last_name: Lutolf - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X - first_name: James full_name: Briscoe, James last_name: Briscoe - first_name: Anna full_name: Kicheva, Anna id: 3959A2A0-F248-11E8-B48F-1D18A9856A87 last_name: Kicheva orcid: 0000-0003-4509-4998 citation: ama: Zagorski M, Brandenberg N, Lutolf M, et al. Assessing the precision of morphogen gradients in neural tube development. Nature Communications. 2024;15. doi:10.1038/s41467-024-45148-8 apa: Zagorski, M., Brandenberg, N., Lutolf, M., Tkačik, G., Bollenbach, M. T., Briscoe, J., & Kicheva, A. (2024). Assessing the precision of morphogen gradients in neural tube development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-024-45148-8 chicago: Zagorski, Marcin, Nathalie Brandenberg, Matthias Lutolf, Gašper Tkačik, Mark Tobias Bollenbach, James Briscoe, and Anna Kicheva. “Assessing the Precision of Morphogen Gradients in Neural Tube Development.” Nature Communications. Springer Nature, 2024. https://doi.org/10.1038/s41467-024-45148-8. ieee: M. Zagorski et al., “Assessing the precision of morphogen gradients in neural tube development,” Nature Communications, vol. 15. Springer Nature, 2024. ista: Zagorski M, Brandenberg N, Lutolf M, Tkačik G, Bollenbach MT, Briscoe J, Kicheva A. 2024. Assessing the precision of morphogen gradients in neural tube development. Nature Communications. 15, 929. mla: Zagorski, Marcin, et al. “Assessing the Precision of Morphogen Gradients in Neural Tube Development.” Nature Communications, vol. 15, 929, Springer Nature, 2024, doi:10.1038/s41467-024-45148-8. short: M. Zagorski, N. Brandenberg, M. Lutolf, G. Tkačik, M.T. Bollenbach, J. Briscoe, A. Kicheva, Nature Communications 15 (2024). corr_author: '1' date_created: 2025-01-27T13:01:01Z date_published: 2024-02-01T00:00:00Z date_updated: 2025-12-30T10:57:08Z day: '01' ddc: - '570' department: - _id: GaTk - _id: AnKi doi: 10.1038/s41467-024-45148-8 external_id: isi: - '001156218500022' pmid: - '38302459' file: - access_level: open_access checksum: acf75f2b6fa84a64d1f590dd4a53cbf7 content_type: application/pdf creator: dernst date_created: 2025-01-27T13:04:03Z date_updated: 2025-01-27T13:04:03Z file_id: '18903' file_name: 2024_NatureComm_Zagorski.pdf file_size: 4723831 relation: main_file success: 1 file_date_updated: 2025-01-27T13:04:03Z has_accepted_license: '1' intvolume: ' 15' isi: 1 language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 project: - _id: bd7e737f-d553-11ed-ba76-d69ffb5ee3aa grant_number: '101044579' name: Mechanisms of tissue size regulation in spinal cord development - _id: 059DF620-7A3F-11EA-A408-12923DDC885E grant_number: F7802 name: Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen control of growth and pattern in the spinal cord publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Assessing the precision of morphogen gradients in neural tube development tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 15 year: '2024' ... --- _id: '14515' abstract: - lang: eng text: Most natural and engineered information-processing systems transmit information via signals that vary in time. Computing the information transmission rate or the information encoded in the temporal characteristics of these signals requires the mutual information between the input and output signals as a function of time, i.e., between the input and output trajectories. Yet, this is notoriously difficult because of the high-dimensional nature of the trajectory space, and all existing techniques require approximations. We present an exact Monte Carlo technique called path weight sampling (PWS) that, for the first time, makes it possible to compute the mutual information between input and output trajectories for any stochastic system that is described by a master equation. The principal idea is to use the master equation to evaluate the exact conditional probability of an individual output trajectory for a given input trajectory and average this via Monte Carlo sampling in trajectory space to obtain the mutual information. We present three variants of PWS, which all generate the trajectories using the standard stochastic simulation algorithm. While direct PWS is a brute-force method, Rosenbluth-Rosenbluth PWS exploits the analogy between signal trajectory sampling and polymer sampling, and thermodynamic integration PWS is based on a reversible work calculation in trajectory space. PWS also makes it possible to compute the mutual information between input and output trajectories for systems with hidden internal states as well as systems with feedback from output to input. Applying PWS to the bacterial chemotaxis system, consisting of 182 coupled chemical reactions, demonstrates not only that the scheme is highly efficient but also that the number of receptor clusters is much smaller than hitherto believed, while their size is much larger. acknowledgement: "We thank Bela Mulder, Tom Shimizu, Fotios Avgidis, Peter Bolhuis, and Daan Frenkel for useful discussions and a careful reading of the manuscript, and we thank Age Tjalma for support with obtaining the Gaussian approximation of the chemotaxis system. This work is part of the Dutch Research Council (NWO) and was performed at the research institute AMOLF. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 885065) and was\r\nfinancially supported by NWO through the “Building a Synthetic Cell (BaSyC)” Gravitation Grant (024.003.019)." article_number: '041017' article_processing_charge: Yes article_type: original arxiv: 1 author: - first_name: Manuel full_name: Reinhardt, Manuel last_name: Reinhardt - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Pieter Rein full_name: Ten Wolde, Pieter Rein last_name: Ten Wolde citation: ama: 'Reinhardt M, Tkačik G, Ten Wolde PR. Path weight sampling: Exact Monte Carlo computation of the mutual information between stochastic trajectories. Physical Review X. 2023;13(4). doi:10.1103/PhysRevX.13.041017' apa: 'Reinhardt, M., Tkačik, G., & Ten Wolde, P. R. (2023). Path weight sampling: Exact Monte Carlo computation of the mutual information between stochastic trajectories. Physical Review X. American Physical Society. https://doi.org/10.1103/PhysRevX.13.041017' chicago: 'Reinhardt, Manuel, Gašper Tkačik, and Pieter Rein Ten Wolde. “Path Weight Sampling: Exact Monte Carlo Computation of the Mutual Information between Stochastic Trajectories.” Physical Review X. American Physical Society, 2023. https://doi.org/10.1103/PhysRevX.13.041017.' ieee: 'M. Reinhardt, G. Tkačik, and P. R. Ten Wolde, “Path weight sampling: Exact Monte Carlo computation of the mutual information between stochastic trajectories,” Physical Review X, vol. 13, no. 4. American Physical Society, 2023.' ista: 'Reinhardt M, Tkačik G, Ten Wolde PR. 2023. Path weight sampling: Exact Monte Carlo computation of the mutual information between stochastic trajectories. Physical Review X. 13(4), 041017.' mla: 'Reinhardt, Manuel, et al. “Path Weight Sampling: Exact Monte Carlo Computation of the Mutual Information between Stochastic Trajectories.” Physical Review X, vol. 13, no. 4, 041017, American Physical Society, 2023, doi:10.1103/PhysRevX.13.041017.' short: M. Reinhardt, G. Tkačik, P.R. Ten Wolde, Physical Review X 13 (2023). date_created: 2023-11-12T23:00:55Z date_published: 2023-10-26T00:00:00Z date_updated: 2025-09-09T13:18:24Z day: '26' ddc: - '530' department: - _id: GaTk doi: 10.1103/PhysRevX.13.041017 external_id: arxiv: - '2203.03461' isi: - '001122894200001' file: - access_level: open_access checksum: 32574aeebcca7347a4152c611b66b3d5 content_type: application/pdf creator: dernst date_created: 2023-11-13T09:00:19Z date_updated: 2023-11-13T09:00:19Z file_id: '14522' file_name: 2023_PhysReviewX_Reinhardt.pdf file_size: 1595223 relation: main_file success: 1 file_date_updated: 2023-11-13T09:00:19Z has_accepted_license: '1' intvolume: ' 13' isi: 1 issue: '4' language: - iso: eng month: '10' oa: 1 oa_version: Published Version publication: Physical Review X publication_identifier: eissn: - 2160-3308 publication_status: published publisher: American Physical Society quality_controlled: '1' scopus_import: '1' status: public title: 'Path weight sampling: Exact Monte Carlo computation of the mutual information between stochastic trajectories' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 13 year: '2023' ... --- _id: '12762' abstract: - lang: eng text: Neurons in the brain are wired into adaptive networks that exhibit collective dynamics as diverse as scale-specific oscillations and scale-free neuronal avalanches. Although existing models account for oscillations and avalanches separately, they typically do not explain both phenomena, are too complex to analyze analytically or intractable to infer from data rigorously. Here we propose a feedback-driven Ising-like class of neural networks that captures avalanches and oscillations simultaneously and quantitatively. In the simplest yet fully microscopic model version, we can analytically compute the phase diagram and make direct contact with human brain resting-state activity recordings via tractable inference of the model’s two essential parameters. The inferred model quantitatively captures the dynamics over a broad range of scales, from single sensor oscillations to collective behaviors of extreme events and neuronal avalanches. Importantly, the inferred parameters indicate that the co-existence of scale-specific (oscillations) and scale-free (avalanches) dynamics occurs close to a non-equilibrium critical point at the onset of self-sustained oscillations. acknowledgement: This research was funded in whole, or in part, by the Austrian Science Fund (FWF) (grant no. PT1013M03318 to F.L. and no. P34015 to G.T.). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The study was supported by the European Union Horizon 2020 research and innovation program under the Marie Sklodowska-Curie action (grant agreement No. 754411 to F.L.). article_processing_charge: No article_type: original arxiv: 1 author: - first_name: Fabrizio full_name: Lombardi, Fabrizio id: A057D288-3E88-11E9-986D-0CF4E5697425 last_name: Lombardi orcid: 0000-0003-2623-5249 - first_name: Selver full_name: Pepic, Selver id: F93245C4-C3CA-11E9-B4F0-C6F4E5697425 last_name: Pepic - first_name: Oren full_name: Shriki, Oren last_name: Shriki - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Daniele full_name: De Martino, Daniele id: 3FF5848A-F248-11E8-B48F-1D18A9856A87 last_name: De Martino orcid: 0000-0002-5214-4706 citation: ama: Lombardi F, Pepic S, Shriki O, Tkačik G, De Martino D. Statistical modeling of adaptive neural networks explains co-existence of avalanches and oscillations in resting human brain. Nature Computational Science. 2023;3:254-263. doi:10.1038/s43588-023-00410-9 apa: Lombardi, F., Pepic, S., Shriki, O., Tkačik, G., & De Martino, D. (2023). Statistical modeling of adaptive neural networks explains co-existence of avalanches and oscillations in resting human brain. Nature Computational Science. Springer Nature. https://doi.org/10.1038/s43588-023-00410-9 chicago: Lombardi, Fabrizio, Selver Pepic, Oren Shriki, Gašper Tkačik, and Daniele De Martino. “Statistical Modeling of Adaptive Neural Networks Explains Co-Existence of Avalanches and Oscillations in Resting Human Brain.” Nature Computational Science. Springer Nature, 2023. https://doi.org/10.1038/s43588-023-00410-9. ieee: F. Lombardi, S. Pepic, O. Shriki, G. Tkačik, and D. De Martino, “Statistical modeling of adaptive neural networks explains co-existence of avalanches and oscillations in resting human brain,” Nature Computational Science, vol. 3. Springer Nature, pp. 254–263, 2023. ista: Lombardi F, Pepic S, Shriki O, Tkačik G, De Martino D. 2023. Statistical modeling of adaptive neural networks explains co-existence of avalanches and oscillations in resting human brain. Nature Computational Science. 3, 254–263. mla: Lombardi, Fabrizio, et al. “Statistical Modeling of Adaptive Neural Networks Explains Co-Existence of Avalanches and Oscillations in Resting Human Brain.” Nature Computational Science, vol. 3, Springer Nature, 2023, pp. 254–63, doi:10.1038/s43588-023-00410-9. short: F. Lombardi, S. Pepic, O. Shriki, G. Tkačik, D. De Martino, Nature Computational Science 3 (2023) 254–263. corr_author: '1' date_created: 2023-03-26T22:01:08Z date_published: 2023-03-20T00:00:00Z date_updated: 2025-09-09T12:23:42Z day: '20' ddc: - '570' department: - _id: GaTk - _id: GradSch doi: 10.1038/s43588-023-00410-9 ec_funded: 1 external_id: arxiv: - '2108.06686' isi: - '000968161800002' pmid: - '38177880' file: - access_level: open_access checksum: 7c63b2b2edfd68aaffe96d70ca6a865a content_type: application/pdf creator: dernst date_created: 2023-08-16T12:39:57Z date_updated: 2023-08-16T12:39:57Z file_id: '14073' file_name: 2023_NatureCompScience_Lombardi.pdf file_size: 4474284 relation: main_file success: 1 file_date_updated: 2023-08-16T12:39:57Z has_accepted_license: '1' intvolume: ' 3' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: 254-263 pmid: 1 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _id: eb943429-77a9-11ec-83b8-9f471cdf5c67 grant_number: M03318 name: Functional Advantages of Critical Brain Dynamics - _id: 626c45b5-2b32-11ec-9570-e509828c1ba6 grant_number: P34015 name: Efficient coding with biophysical realism publication: Nature Computational Science publication_identifier: eissn: - 2662-8457 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Statistical modeling of adaptive neural networks explains co-existence of avalanches and oscillations in resting human brain tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 3 year: '2023' ... --- _id: '13127' abstract: - lang: eng text: Cooperative disease defense emerges as group-level collective behavior, yet how group members make the underlying individual decisions is poorly understood. Using garden ants and fungal pathogens as an experimental model, we derive the rules governing individual ant grooming choices and show how they produce colony-level hygiene. Time-resolved behavioral analysis, pathogen quantification, and probabilistic modeling reveal that ants increase grooming and preferentially target highly-infectious individuals when perceiving high pathogen load, but transiently suppress grooming after having been groomed by nestmates. Ants thus react to both, the infectivity of others and the social feedback they receive on their own contagiousness. While inferred solely from momentary ant decisions, these behavioral rules quantitatively predict hour-long experimental dynamics, and synergistically combine into efficient colony-wide pathogen removal. Our analyses show that noisy individual decisions based on only local, incomplete, yet dynamically-updated information on pathogen threat and social feedback can lead to potent collective disease defense. acknowledged_ssus: - _id: LifeSc acknowledgement: We thank Mike Bidochka for the fungal strains, the ISTA Social Immunity Team for ant collection, Hanna Leitner for experimental and molecular support, Jennifer Robb and Lukas Lindorfer for microscopy, and the LabSupport Facility at ISTA for general laboratory support. We further thank Victor Mireles, Iain Couzin, Fabian Theis and the Social Immunity Team for continued feedback throughout, and Michael Sixt, Yuko Ulrich, Koos Boomsma, Erika Dawson, Megan Kutzer and Hinrich Schulenburg for comments on the manuscript. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant No. 771402; EPIDEMICSonCHIP) to SC, from the Scientific Grant Agency of the Slovak Republic (Grant No. 1/0521/20) to KB, and the Human Frontier Science Program (Grant No. RGP0065/2012) to GT. article_number: '3232' article_processing_charge: Yes article_type: original author: - first_name: Barbara E full_name: Casillas Perez, Barbara E id: 351ED2AA-F248-11E8-B48F-1D18A9856A87 last_name: Casillas Perez - first_name: Katarína full_name: Bod'Ová, Katarína id: 2BA24EA0-F248-11E8-B48F-1D18A9856A87 last_name: Bod'Ová orcid: 0000-0002-7214-0171 - first_name: Anna V full_name: Grasse, Anna V id: 406F989C-F248-11E8-B48F-1D18A9856A87 last_name: Grasse - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Sylvia full_name: Cremer, Sylvia id: 2F64EC8C-F248-11E8-B48F-1D18A9856A87 last_name: Cremer orcid: 0000-0002-2193-3868 citation: ama: Casillas Perez BE, Bodova K, Grasse AV, Tkačik G, Cremer S. Dynamic pathogen detection and social feedback shape collective hygiene in ants. Nature Communications. 2023;14. doi:10.1038/s41467-023-38947-y apa: Casillas Perez, B. E., Bodova, K., Grasse, A. V., Tkačik, G., & Cremer, S. (2023). Dynamic pathogen detection and social feedback shape collective hygiene in ants. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-023-38947-y chicago: Casillas Perez, Barbara E, Katarina Bodova, Anna V Grasse, Gašper Tkačik, and Sylvia Cremer. “Dynamic Pathogen Detection and Social Feedback Shape Collective Hygiene in Ants.” Nature Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-38947-y. ieee: B. E. Casillas Perez, K. Bodova, A. V. Grasse, G. Tkačik, and S. Cremer, “Dynamic pathogen detection and social feedback shape collective hygiene in ants,” Nature Communications, vol. 14. Springer Nature, 2023. ista: Casillas Perez BE, Bodova K, Grasse AV, Tkačik G, Cremer S. 2023. Dynamic pathogen detection and social feedback shape collective hygiene in ants. Nature Communications. 14, 3232. mla: Casillas Perez, Barbara E., et al. “Dynamic Pathogen Detection and Social Feedback Shape Collective Hygiene in Ants.” Nature Communications, vol. 14, 3232, Springer Nature, 2023, doi:10.1038/s41467-023-38947-y. short: B.E. Casillas Perez, K. Bodova, A.V. Grasse, G. Tkačik, S. Cremer, Nature Communications 14 (2023). corr_author: '1' date_created: 2023-06-11T22:00:40Z date_published: 2023-06-03T00:00:00Z date_updated: 2025-04-14T07:47:53Z day: '03' ddc: - '570' department: - _id: SyCr - _id: GaTk doi: 10.1038/s41467-023-38947-y ec_funded: 1 external_id: isi: - '001002562700005' pmid: - '37270641' file: - access_level: open_access checksum: 4af0393e3ed47b3fc46e68b81c3c1007 content_type: application/pdf creator: dernst date_created: 2023-06-13T08:05:46Z date_updated: 2023-06-13T08:05:46Z file_id: '13132' file_name: 2023_NatureComm_CasillasPerez.pdf file_size: 2358167 relation: main_file success: 1 file_date_updated: 2023-06-13T08:05:46Z has_accepted_license: '1' intvolume: ' 14' isi: 1 language: - iso: eng month: '06' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 2649B4DE-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '771402' name: Epidemics in ant societies on a chip - _id: 255008E4-B435-11E9-9278-68D0E5697425 grant_number: RGP0065/2012 name: Information processing and computation in fish groups publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: record: - id: '12945' relation: research_data status: public scopus_import: '1' status: public title: Dynamic pathogen detection and social feedback shape collective hygiene in ants tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 14 year: '2023' ... --- _id: '14656' abstract: - lang: eng text: Although much is known about how single neurons in the hippocampus represent an animal's position, how circuit interactions contribute to spatial coding is less well understood. Using a novel statistical estimator and theoretical modeling, both developed in the framework of maximum entropy models, we reveal highly structured CA1 cell-cell interactions in male rats during open field exploration. The statistics of these interactions depend on whether the animal is in a familiar or novel environment. In both conditions the circuit interactions optimize the encoding of spatial information, but for regimes that differ in the informativeness of their spatial inputs. This structure facilitates linear decodability, making the information easy to read out by downstream circuits. Overall, our findings suggest that the efficient coding hypothesis is not only applicable to individual neuron properties in the sensory periphery, but also to neural interactions in the central brain. acknowledgement: M.N. was supported by the European Union Horizon 2020 Grant 665385. J.C. was supported by the European Research Council Consolidator Grant 281511. G.T. was supported by the Austrian Science Fund (FWF) Grant P34015. C.S. was supported by an Institute of Science and Technology fellow award and by the National Science Foundation (NSF) Award No. 1922658. We thank Peter Baracskay, Karola Kaefer, and Hugo Malagon-Vina for the acquisition of the data. We also thank Federico Stella, Wiktor Młynarski, Dori Derdikman, Colin Bredenberg, Roman Huszar, Heloisa Chiossi, Lorenzo Posani, and Mohamady El-Gaby for comments on an earlier version of the manuscript. article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Michele full_name: Nardin, Michele id: 30BD0376-F248-11E8-B48F-1D18A9856A87 last_name: Nardin orcid: 0000-0001-8849-6570 - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Cristina full_name: Savin, Cristina id: 3933349E-F248-11E8-B48F-1D18A9856A87 last_name: Savin citation: ama: Nardin M, Csicsvari JL, Tkačik G, Savin C. The structure of hippocampal CA1 interactions optimizes spatial coding across experience. The Journal of Neuroscience. 2023;43(48):8140-8156. doi:10.1523/JNEUROSCI.0194-23.2023 apa: Nardin, M., Csicsvari, J. L., Tkačik, G., & Savin, C. (2023). The structure of hippocampal CA1 interactions optimizes spatial coding across experience. The Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.0194-23.2023 chicago: Nardin, Michele, Jozsef L Csicsvari, Gašper Tkačik, and Cristina Savin. “The Structure of Hippocampal CA1 Interactions Optimizes Spatial Coding across Experience.” The Journal of Neuroscience. Society for Neuroscience, 2023. https://doi.org/10.1523/JNEUROSCI.0194-23.2023. ieee: M. Nardin, J. L. Csicsvari, G. Tkačik, and C. Savin, “The structure of hippocampal CA1 interactions optimizes spatial coding across experience,” The Journal of Neuroscience, vol. 43, no. 48. Society for Neuroscience, pp. 8140–8156, 2023. ista: Nardin M, Csicsvari JL, Tkačik G, Savin C. 2023. The structure of hippocampal CA1 interactions optimizes spatial coding across experience. The Journal of Neuroscience. 43(48), 8140–8156. mla: Nardin, Michele, et al. “The Structure of Hippocampal CA1 Interactions Optimizes Spatial Coding across Experience.” The Journal of Neuroscience, vol. 43, no. 48, Society for Neuroscience, 2023, pp. 8140–56, doi:10.1523/JNEUROSCI.0194-23.2023. short: M. Nardin, J.L. Csicsvari, G. Tkačik, C. Savin, The Journal of Neuroscience 43 (2023) 8140–8156. date_created: 2023-12-10T23:00:58Z date_published: 2023-11-29T00:00:00Z date_updated: 2025-09-09T13:37:51Z day: '29' ddc: - '570' department: - _id: JoCs - _id: GaTk doi: 10.1523/JNEUROSCI.0194-23.2023 ec_funded: 1 external_id: isi: - '001148071000005' pmid: - '37758476' file: - access_level: open_access checksum: e2503c8f84be1050e28f64320f1d5bd2 content_type: application/pdf creator: dernst date_created: 2023-12-11T11:30:37Z date_updated: 2024-06-02T22:30:03Z embargo: 2024-06-01 file_id: '14674' file_name: 2023_JourNeuroscience_Nardin.pdf file_size: 2280632 relation: main_file file_date_updated: 2024-06-02T22:30:03Z has_accepted_license: '1' intvolume: ' 43' isi: 1 issue: '48' language: - iso: eng month: '11' oa: 1 oa_version: Published Version page: 8140-8156 pmid: 1 project: - _id: 257A4776-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281511' name: Memory-related information processing in neuronal circuits of the hippocampus and entorhinal cortex - _id: 626c45b5-2b32-11ec-9570-e509828c1ba6 grant_number: P34015 name: Efficient coding with biophysical realism - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: The Journal of Neuroscience publication_identifier: eissn: - 1529-2401 publication_status: published publisher: Society for Neuroscience quality_controlled: '1' related_material: record: - id: '10077' relation: earlier_version status: public scopus_import: '1' status: public title: The structure of hippocampal CA1 interactions optimizes spatial coding across experience tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 43 year: '2023' ... --- _id: '12156' abstract: - lang: eng text: Models of transcriptional regulation that assume equilibrium binding of transcription factors have been less successful at predicting gene expression from sequence in eukaryotes than in bacteria. This could be due to the non-equilibrium nature of eukaryotic regulation. Unfortunately, the space of possible non-equilibrium mechanisms is vast and predominantly uninteresting. The key question is therefore how this space can be navigated efficiently, to focus on mechanisms and models that are biologically relevant. In this review, we advocate for the normative role of theory—theory that prescribes rather than just describes—in providing such a focus. Theory should expand its remit beyond inferring mechanistic models from data, towards identifying non-equilibrium gene regulatory schemes that may have been evolutionarily selected, despite their energy consumption, because they are precise, reliable, fast, or otherwise outperform regulation at equilibrium. We illustrate our reasoning by toy examples for which we provide simulation code. acknowledgement: 'This work was supported through the Center for the Physics of Biological Function (PHYe1734030) and by National Institutes of Health Grants R01GM097275 and U01DK127429 (TG). GT acknowledges the support of the Austrian Science Fund grant FWF P28844 and the Human Frontiers Science Program. ' article_number: '100435' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Benjamin full_name: Zoller, Benjamin last_name: Zoller - first_name: Thomas full_name: Gregor, Thomas last_name: Gregor - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: '1' citation: ama: Zoller B, Gregor T, Tkačik G. Eukaryotic gene regulation at equilibrium, or non? Current Opinion in Systems Biology. 2022;31(9). doi:10.1016/j.coisb.2022.100435 apa: Zoller, B., Gregor, T., & Tkačik, G. (2022). Eukaryotic gene regulation at equilibrium, or non? Current Opinion in Systems Biology. Elsevier. https://doi.org/10.1016/j.coisb.2022.100435 chicago: Zoller, Benjamin, Thomas Gregor, and Gašper Tkačik. “Eukaryotic Gene Regulation at Equilibrium, or Non?” Current Opinion in Systems Biology. Elsevier, 2022. https://doi.org/10.1016/j.coisb.2022.100435. ieee: B. Zoller, T. Gregor, and G. Tkačik, “Eukaryotic gene regulation at equilibrium, or non?,” Current Opinion in Systems Biology, vol. 31, no. 9. Elsevier, 2022. ista: Zoller B, Gregor T, Tkačik G. 2022. Eukaryotic gene regulation at equilibrium, or non? Current Opinion in Systems Biology. 31(9), 100435. mla: Zoller, Benjamin, et al. “Eukaryotic Gene Regulation at Equilibrium, or Non?” Current Opinion in Systems Biology, vol. 31, no. 9, 100435, Elsevier, 2022, doi:10.1016/j.coisb.2022.100435. short: B. Zoller, T. Gregor, G. Tkačik, Current Opinion in Systems Biology 31 (2022). corr_author: '1' date_created: 2023-01-12T12:08:51Z date_published: 2022-09-01T00:00:00Z date_updated: 2025-06-11T13:47:43Z day: '01' ddc: - '570' department: - _id: GaTk doi: 10.1016/j.coisb.2022.100435 external_id: pmid: - '36590072' file: - access_level: open_access checksum: 97ef01e0cc60cdc84f45640a0f248fb0 content_type: application/pdf creator: dernst date_created: 2023-01-24T12:14:10Z date_updated: 2023-01-24T12:14:10Z file_id: '12362' file_name: 2022_CurrentBiology_Zoller.pdf file_size: 2214944 relation: main_file success: 1 file_date_updated: 2023-01-24T12:14:10Z has_accepted_license: '1' intvolume: ' 31' issue: '9' keyword: - Applied Mathematics - Computer Science Applications - Drug Discovery - General Biochemistry - Genetics and Molecular Biology - Modeling and Simulation language: - iso: eng month: '09' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: Current Opinion in Systems Biology publication_identifier: issn: - 2452-3100 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Eukaryotic gene regulation at equilibrium, or non? tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 31 year: '2022' ... --- _id: '12332' abstract: - lang: eng text: Activity of sensory neurons is driven not only by external stimuli but also by feedback signals from higher brain areas. Attention is one particularly important internal signal whose presumed role is to modulate sensory representations such that they only encode information currently relevant to the organism at minimal cost. This hypothesis has, however, not yet been expressed in a normative computational framework. Here, by building on normative principles of probabilistic inference and efficient coding, we developed a model of dynamic population coding in the visual cortex. By continuously adapting the sensory code to changing demands of the perceptual observer, an attention-like modulation emerges. This modulation can dramatically reduce the amount of neural activity without deteriorating the accuracy of task-specific inferences. Our results suggest that a range of seemingly disparate cortical phenomena such as intrinsic gain modulation, attention-related tuning modulation, and response variability could be manifestations of the same underlying principles, which combine efficient sensory coding with optimal probabilistic inference in dynamic environments. acknowledgement: "We thank Robbe Goris for generously providing figures from his work and Ann M. Hermundstad for helpful discussions.\r\nGT & WM were supported by the Austrian Science Fund Standalone Grant P 34015 \"Efficient Coding with Biophysical Realism\" (https://pf.fwf.ac.at/) WM was additionally supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 754411 (https://ec.europa.eu/research/mariecurieactions/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." article_processing_charge: No article_type: original author: - first_name: Wiktor F full_name: Mlynarski, Wiktor F id: 358A453A-F248-11E8-B48F-1D18A9856A87 last_name: Mlynarski - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: '1' citation: ama: Mlynarski WF, Tkačik G. Efficient coding theory of dynamic attentional modulation. PLoS Biology. 2022;20(12):e3001889. doi:10.1371/journal.pbio.3001889 apa: Mlynarski, W. F., & Tkačik, G. (2022). Efficient coding theory of dynamic attentional modulation. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.3001889 chicago: Mlynarski, Wiktor F, and Gašper Tkačik. “Efficient Coding Theory of Dynamic Attentional Modulation.” PLoS Biology. Public Library of Science, 2022. https://doi.org/10.1371/journal.pbio.3001889. ieee: W. F. Mlynarski and G. Tkačik, “Efficient coding theory of dynamic attentional modulation,” PLoS Biology, vol. 20, no. 12. Public Library of Science, p. e3001889, 2022. ista: Mlynarski WF, Tkačik G. 2022. Efficient coding theory of dynamic attentional modulation. PLoS Biology. 20(12), e3001889. mla: Mlynarski, Wiktor F., and Gašper Tkačik. “Efficient Coding Theory of Dynamic Attentional Modulation.” PLoS Biology, vol. 20, no. 12, Public Library of Science, 2022, p. e3001889, doi:10.1371/journal.pbio.3001889. short: W.F. Mlynarski, G. Tkačik, PLoS Biology 20 (2022) e3001889. corr_author: '1' date_created: 2023-01-22T23:00:55Z date_published: 2022-12-21T00:00:00Z date_updated: 2025-06-11T13:57:01Z day: '21' ddc: - '570' department: - _id: GaTk doi: 10.1371/journal.pbio.3001889 ec_funded: 1 external_id: isi: - '000925192000001' pmid: - '36542662' file: - access_level: open_access checksum: 5d7f1111a87e5f2c1bf92f8886738894 content_type: application/pdf creator: dernst date_created: 2023-01-23T08:46:40Z date_updated: 2023-01-23T08:46:40Z file_id: '12337' file_name: 2022_PloSBiology_Mlynarski.pdf file_size: 4248838 relation: main_file success: 1 file_date_updated: 2023-01-23T08:46:40Z has_accepted_license: '1' intvolume: ' 20' isi: 1 issue: '12' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: e3001889 pmid: 1 project: - _id: 626c45b5-2b32-11ec-9570-e509828c1ba6 grant_number: P34015 name: Efficient coding with biophysical realism - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: PLoS Biology publication_identifier: eissn: - 1545-7885 publication_status: published publisher: Public Library of Science quality_controlled: '1' scopus_import: '1' status: public title: Efficient coding theory of dynamic attentional modulation tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 20 year: '2022' ...