--- 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 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' ... --- 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: 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' ... --- DOAJ_listed: '1' OA_place: publisher OA_type: gold PlanS_conform: '1' _id: '21269' abstract: - lang: eng text: The spatial organization of chromatin within the nucleus plays a crucial role in gene expression and genome function. However, the quantitative relationship between this organization and nuclear biochemical processes remains under debate. In this study, we present a graph-based generative model, bioSBM, designed to capture long-range chromatin interaction patterns from Hi-C data and, importantly, simultaneously link these patterns to biochemical features. Applying bioSBM to Hi-C maps of the GM12878 lymphoblastoid cell line, we identified a latent structure of chromatin interactions, revealing seven distinct communities that strongly align with known biological annotations. Additionally, we infer a linear transformation that maps biochemical observables, such as histone marks, to the parameters of the generative graph model, enabling accurate genome-wide predictions of chromatin contact maps on out-of-sample data, both within the same cell line and on the completely unseen HCT116 cell line under RAD21 depletion. These findings highlight bioSBM's potential as a powerful tool for elucidating the relationship between biochemistry and chromatin architecture and predicting long-range genome organization from independent biochemical data. acknowledgement: G.S. acknowledges co-funding from Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE1 - Project FAIR “Future Artificial Intelligence Research”. This resource was co-financed by the Next Generation EU [DM 1555 del 11.10.22]. A.R. acknowledges financial support from PNRR Grant CN 00000013 CN-HPC, M4C2I1.4, spoke 7, funded by Next Generation EU. article_number: '043006' article_processing_charge: Yes article_type: original arxiv: 1 author: - first_name: Chen Y full_name: Zhang, Chen Y id: 81b43fb8-c9d5-11ef-bf68-ade532a1f204 last_name: Zhang - first_name: Angelo full_name: Rosa, Angelo last_name: Rosa - first_name: Guido full_name: Sanguinetti, Guido last_name: Sanguinetti citation: ama: 'Zhang CY, Rosa A, Sanguinetti G. bioSBM: A random graph model to integrate epigenomic data in chromatin structure prediction. PRX Life. 2025;3(4). doi:10.1103/gy1p-4256' apa: 'Zhang, C. Y., Rosa, A., & Sanguinetti, G. (2025). bioSBM: A random graph model to integrate epigenomic data in chromatin structure prediction. PRX Life. American Physical Society. https://doi.org/10.1103/gy1p-4256' chicago: 'Zhang, Chen Y, Angelo Rosa, and Guido Sanguinetti. “BioSBM: A Random Graph Model to Integrate Epigenomic Data in Chromatin Structure Prediction.” PRX Life. American Physical Society, 2025. https://doi.org/10.1103/gy1p-4256.' ieee: 'C. Y. Zhang, A. Rosa, and G. Sanguinetti, “bioSBM: A random graph model to integrate epigenomic data in chromatin structure prediction,” PRX Life, vol. 3, no. 4. American Physical Society, 2025.' ista: 'Zhang CY, Rosa A, Sanguinetti G. 2025. bioSBM: A random graph model to integrate epigenomic data in chromatin structure prediction. PRX Life. 3(4), 043006.' mla: 'Zhang, Chen Y., et al. “BioSBM: A Random Graph Model to Integrate Epigenomic Data in Chromatin Structure Prediction.” PRX Life, vol. 3, no. 4, 043006, American Physical Society, 2025, doi:10.1103/gy1p-4256.' short: C.Y. Zhang, A. Rosa, G. Sanguinetti, PRX Life 3 (2025). corr_author: '1' date_created: 2026-02-17T07:53:01Z date_published: 2025-10-21T00:00:00Z date_updated: 2026-02-18T08:01:00Z day: '21' ddc: - '570' department: - _id: GaTk doi: 10.1103/gy1p-4256 external_id: arxiv: - '2409.14425' file: - access_level: open_access checksum: 76ddfee3efdb4c9d085059b5a142ed78 content_type: application/pdf creator: dernst date_created: 2026-02-18T07:57:39Z date_updated: 2026-02-18T07:57:39Z file_id: '21314' file_name: 2025_PRXLife_Zhang.pdf file_size: 1888053 relation: main_file success: 1 file_date_updated: 2026-02-18T07:57:39Z has_accepted_license: '1' intvolume: ' 3' issue: '4' language: - iso: eng month: '10' oa: 1 oa_version: Published Version publication: PRX Life publication_identifier: issn: - 2835-8279 publication_status: published publisher: American Physical Society quality_controlled: '1' status: public title: 'bioSBM: A random graph model to integrate epigenomic data in chromatin structure prediction' 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: 3 year: '2025' ... --- OA_place: publisher _id: '20357' acknowledged_ssus: - _id: ScienComp - _id: E-Lib acknowledgement: "I would also like to acknowledge the Austrian Academy of Sciences for funding through the\r\nDOC Fellowship program (fellowship number 26917), the Grants Office at ISTA for their\r\nassistance with the application, and the Scientific Computing Unit for their support regarding\r\nhigh-performance computation.\r\n" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Natalia full_name: Ruzickova, Natalia id: D2761128-D73D-11E9-A1BF-BA0DE6697425 last_name: Ruzickova citation: ama: Ruzickova N. Effect propagation in biological networks. 2025. doi:10.15479/AT-ISTA-20357 apa: Ruzickova, N. (2025). Effect propagation in biological networks. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20357 chicago: Ruzickova, Natalia. “Effect Propagation in Biological Networks.” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-20357. ieee: N. Ruzickova, “Effect propagation in biological networks,” Institute of Science and Technology Austria, 2025. ista: Ruzickova N. 2025. Effect propagation in biological networks. Institute of Science and Technology Austria. mla: Ruzickova, Natalia. Effect Propagation in Biological Networks. Institute of Science and Technology Austria, 2025, doi:10.15479/AT-ISTA-20357. short: N. Ruzickova, Effect Propagation in Biological Networks, Institute of Science and Technology Austria, 2025. corr_author: '1' date_created: 2025-09-15T17:04:48Z date_published: 2025-09-15T00:00:00Z date_updated: 2026-04-07T12:02:39Z day: '15' ddc: - '570' - '530' degree_awarded: PhD department: - _id: GradSch - _id: GaTk doi: 10.15479/AT-ISTA-20357 file: - access_level: closed checksum: 991e81bc16a76b4e0c352567728fd2c5 content_type: application/pdf creator: nruzicko date_created: 2025-09-16T12:56:06Z date_updated: 2025-11-27T10:00:25Z embargo: 2026-09-14 embargo_to: open_access file_id: '20360' file_name: 2025_Ruzickova_Natalia_Thesis.pdf file_size: 43518367 relation: main_file title: Effect propagation in biological networks - access_level: closed checksum: c4ab257adad116083d8a97fac69b2dde content_type: application/zip creator: nruzicko date_created: 2025-09-16T12:59:23Z date_updated: 2025-09-16T12:59:23Z file_id: '20361' file_name: 2025_Ruzickova_Natalia_Thesis_source.zip file_size: 53464789 relation: source_file file_date_updated: 2025-11-27T10:00:25Z has_accepted_license: '1' keyword: - gene regulation - networks - omnigenic model - pancreas - collective behaviour language: - iso: eng month: '09' oa_version: Published Version page: '160' project: - _id: 7bec9174-9f16-11ee-852c-ded9fe5f810e name: Collective behaviour of cells in pancreatic Islets of Langerhans publication_identifier: isbn: - 978-3-99078-066-4 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '18525' relation: part_of_dissertation status: public status: public supervisor: - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 title: Effect propagation in biological networks type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2025' ... --- OA_place: publisher _id: '20811' abstract: - lang: eng text: "\tThis thesis is organized into two parts, each comprising two chapters: Chapter 1 and 2 offer models for the evolution of vaccine resistance in response to diverse vaccination strategies. Chapter 3 and 4 review the statistics of records, their connection to models of innovation and an application to the cultural evolution of sports.\r\n\tIn chapter 1 we present a modelling study from 2021 on the evolution of SARS-CoV-2. At that time the vaccine-resistant Omicron variant had not yet evolved. In our model we consider a population that is becoming vaccinated over time, while a pathogen is spreading in the population and eventually becoming resistant to the vaccine. We explore effective pharmaceutical and non-pharmaceutical interventions to prevent the emergence of vaccine resistance. \r\n\tIn chapter 2 we model a particular set of complex vaccination strategies, mosaic and pyramid vaccination, where an immunologically diverse portfolio of vaccines is considered. We find that a bet-hatching strategy, in which vaccine types are distributed in the population, is effective at hindering the evolution of vaccine resistance if mutation rates are high. \r\n\tIn chapter 3 we switch gears and present a review on the statistics of records. We highlight similarities and analogies to other models in the fields of statistical physics, evolution and innovation. This offers interesting complimentary perspectives on well-known models. \r\n\tIn chapter 4 we apply models of record statistics and innovation to study cultural evolution in sport. We propose a model of sport evolution that combines deterministic improvements in performance and stochastic bursts of improvements due to innovation. " alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Simon full_name: Rella, Simon id: B4765ACA-AA38-11E9-AC9A-0930E6697425 last_name: Rella citation: ama: 'Rella S. Adaptive processes in biology and culture : Models of evolving vaccine resistance and the record statistics of innovation. 2025. doi:10.15479/AT-ISTA-20811' apa: 'Rella, S. (2025). Adaptive processes in biology and culture : Models of evolving vaccine resistance and the record statistics of innovation. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20811' chicago: 'Rella, Simon. “Adaptive Processes in Biology and Culture : Models of Evolving Vaccine Resistance and the Record Statistics of Innovation.” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-20811.' ieee: 'S. Rella, “Adaptive processes in biology and culture : Models of evolving vaccine resistance and the record statistics of innovation,” Institute of Science and Technology Austria, 2025.' ista: 'Rella S. 2025. Adaptive processes in biology and culture : Models of evolving vaccine resistance and the record statistics of innovation. Institute of Science and Technology Austria.' mla: 'Rella, Simon. Adaptive Processes in Biology and Culture : Models of Evolving Vaccine Resistance and the Record Statistics of Innovation. Institute of Science and Technology Austria, 2025, doi:10.15479/AT-ISTA-20811.' short: 'S. Rella, Adaptive Processes in Biology and Culture : Models of Evolving Vaccine Resistance and the Record Statistics of Innovation, Institute of Science and Technology Austria, 2025.' corr_author: '1' date_created: 2025-12-12T14:39:56Z date_published: 2025-12-15T00:00:00Z date_updated: 2026-04-07T12:34:58Z day: '15' ddc: - '616' - '576' - '614' - '519' degree_awarded: PhD department: - _id: GradSch - _id: GaTk - _id: FyKo doi: 10.15479/AT-ISTA-20811 file: - access_level: open_access checksum: a0bd7a585720e60df284101b8afdf6bb content_type: application/pdf creator: srella date_created: 2025-12-16T21:49:52Z date_updated: 2025-12-16T21:49:52Z file_id: '20831' file_name: 2025_Rella_Simon_Thesis.pdf file_size: 29019662 relation: main_file success: 1 - access_level: open_access checksum: b8b3a90932ae1d96d307838710f46e32 content_type: application/zip creator: srella date_created: 2025-12-16T21:52:19Z date_updated: 2025-12-16T21:52:19Z file_id: '20832' file_name: 2025_Rella_Simon_Thesis_Sourcefiles.zip file_size: 42094025 relation: source_file file_date_updated: 2025-12-16T21:52:19Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '95' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '18307' relation: part_of_dissertation status: public - id: '9905' relation: part_of_dissertation status: public status: public supervisor: - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Fyodor full_name: Kondrashov, Fyodor id: 44FDEF62-F248-11E8-B48F-1D18A9856A87 last_name: Kondrashov orcid: 0000-0001-8243-4694 title: 'Adaptive processes in biology and culture : Models of evolving vaccine resistance and the record statistics of innovation' 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: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2025' ... --- APC_amount: 3261,23 EUR 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: 2026-05-06T12:43:59Z 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' ... --- APC_amount: 3317,75 EUR 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: 2026-05-06T13:12:01Z 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 122 year: '2025' ... --- OA_place: repository OA_type: gold _id: '18991' abstract: - lang: eng text: Research data for the article "Learning reshapes the hippocampal representation hierarchy" from Chiossi et al. (PNAS, 2025). The data includes hippocampal CA1 unit activity and behaviour tracking of 5 Long Evans rats during the learning of an associative memory task. Detailed information can be found in the 'readme.txt' file. acknowledged_ssus: - _id: PreCl - _id: M-Shop acknowledgement: Thanks to Rebecca Morse for performing one of the experiments under H.S.C.C. supervision and Jago Wallenschus for technical support, especially with maze design. article_processing_charge: No author: - first_name: Heloisa full_name: Chiossi, Heloisa id: 2BBA502C-F248-11E8-B48F-1D18A9856A87 last_name: Chiossi orcid: 0009-0004-2973-278X citation: ama: Chiossi HSC. Research data for the publication “Learning reshapes the hippocampal representation hierarchy.” 2025. doi:10.15479/AT:ISTA:18991 apa: Chiossi, H. S. C. (2025). Research data for the publication “Learning reshapes the hippocampal representation hierarchy.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:18991 chicago: Chiossi, Heloisa S. C. “Research Data for the Publication ‘Learning Reshapes the Hippocampal Representation Hierarchy.’” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT:ISTA:18991. ieee: H. S. C. Chiossi, “Research data for the publication ‘Learning reshapes the hippocampal representation hierarchy.’” Institute of Science and Technology Austria, 2025. ista: Chiossi HSC. 2025. Research data for the publication ‘Learning reshapes the hippocampal representation hierarchy’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:18991. mla: Chiossi, Heloisa S. C. Research Data for the Publication “Learning Reshapes the Hippocampal Representation Hierarchy.” Institute of Science and Technology Austria, 2025, doi:10.15479/AT:ISTA:18991. short: H.S.C. Chiossi, (2025). contributor: - contributor_type: researcher first_name: Michele id: 30BD0376-F248-11E8-B48F-1D18A9856A87 last_name: Nardin orcid: 0000-0001-8849-6570 - contributor_type: supervisor first_name: Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - contributor_type: supervisor first_name: Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 corr_author: '1' date_created: 2025-02-04T10:36:18Z date_published: 2025-02-04T00:00:00Z date_updated: 2026-05-06T13:12:00Z day: '04' ddc: - '570' department: - _id: GradSch - _id: JoCs - _id: GaTk doi: 10.15479/AT:ISTA:18991 file: - access_level: open_access checksum: 04d761ed42e8879abffde04a560409ce content_type: application/zip creator: hchiossi date_created: 2025-02-04T10:16:52Z date_updated: 2025-02-04T10:16:52Z file_id: '18992' file_name: Chiossi_etal_2025_PNAS_data.zip file_size: 769383201 relation: main_file success: 1 - access_level: open_access checksum: 50602931dcd33e4f009ed46af11335f3 content_type: text/plain creator: hchiossi date_created: 2025-02-04T10:18:33Z date_updated: 2025-02-04T10:18:33Z file_id: '18993' file_name: readme.txt file_size: 3215 relation: main_file success: 1 file_date_updated: 2025-02-04T10:18:33Z has_accepted_license: '1' keyword: - hippocampus - electrophysiology - behavior month: '02' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '19453' relation: used_in_publication status: public status: public title: Research data for the publication "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: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2025' ... --- APC_amount: 1260 EUR DOAJ_listed: '1' OA_place: publisher OA_type: gold PlanS_conform: '1' _id: '20664' abstract: - lang: eng text: Conference travel contributes to the climate footprint of academic research. Here, we provide a quantitative estimate of the carbon emissions associated with conference attendance by analyzing travel data from participants of 10 international conferences in the field of magnetic resonance, namely EUROMAR, ENC and ICMRBS. We find that attending a EUROMAR conference produces, on average, more than 1 t CO2 eq.. For the analyzed conferences outside Europe, the corresponding value is about 2–3 times higher, on average, with intercontinental trips amounting to up to 5 t. We compare these conference-related emissions to other activities associated with research and show that conference travel is a substantial portion of the total climate footprint of a researcher in magnetic resonance. We explore several strategies to reduce these emissions, including the impact of selecting conference venues more strategically and the possibility of decentralized conferences. Through a detailed comparison of train versus air travel – accounting for both direct and infrastructure-related emissions – we demonstrate that train travel offers considerable carbon savings. These data may provide a basis for strategic choices of future conferences in the field and for individuals deciding on their conference attendance. acknowledgement: 'First and foremost, we are grateful to the conference organizers who have provided data, either in the form of tables or by pointing us to abstract books. We thank the reviewers and the handling editor (Gottfried Otting) for the careful reading and suggestions. This project emerged from an interactive course about energy and climate, held at IST Austria by Jeroen Dobbelaere, Georgios Katsaros and Paul Schanda. We are grateful to ISTA''s Graduate School for enabling this interdisciplinary course and to all participating students. We thank the following persons for discussions and/or comments about the manuscript: Helene Van Melckebeke, Mei Hong, Jeff Hoch, Gottfried Otting and Matthias Ernst. For the preparation of the manuscript, AI tools have been used, namely for finding relevant literature (ChatGPT) and for correcting the text (Writefull, within Overleaf LaTeX).' article_processing_charge: Yes article_type: original author: - first_name: Lucky full_name: Kapoor, Lucky id: 84b9700b-15b2-11ec-abd3-831089e67615 last_name: Kapoor orcid: 0000-0001-8319-2148 - first_name: Natalia full_name: Ruzickova, Natalia id: D2761128-D73D-11E9-A1BF-BA0DE6697425 last_name: Ruzickova - first_name: Predrag full_name: Zivadinovic, Predrag id: 68AA0E5A-AFDA-11E9-9994-141DE6697425 last_name: Zivadinovic - first_name: Valentin full_name: Leitner, Valentin id: 4c665ce3-0016-11ec-bea0-e44de7a4fa3d last_name: Leitner - first_name: Maria A full_name: Sisak, Maria A id: 44A03D04-AEA4-11E9-B225-EA2DE6697425 last_name: Sisak - first_name: Cecelia N full_name: Mweka, Cecelia N id: 2a69ab4b-896a-11ed-bdf8-cb8641cf2b21 last_name: Mweka - first_name: Jeroen A full_name: Dobbelaere, Jeroen A id: c15a5412-de82-11ed-b809-8dc1aa996e40 last_name: Dobbelaere - first_name: Georgios full_name: Katsaros, Georgios id: 38DB5788-F248-11E8-B48F-1D18A9856A87 last_name: Katsaros orcid: 0000-0001-8342-202X - first_name: Paul full_name: Schanda, Paul id: 7B541462-FAF6-11E9-A490-E8DFE5697425 last_name: Schanda orcid: 0000-0002-9350-7606 citation: ama: 'Kapoor L, Ruzickova N, Zivadinovic P, et al. Quantifying the carbon footprint of conference travel: The case of NMR meetings. Magnetic Resonance. 2025;6(2):243-256. doi:10.5194/mr-6-243-2025' apa: 'Kapoor, L., Ruzickova, N., Zivadinovic, P., Leitner, V., Sisak, M. A., Mweka, C. N., … Schanda, P. (2025). Quantifying the carbon footprint of conference travel: The case of NMR meetings. Magnetic Resonance. Copernicus Publications. https://doi.org/10.5194/mr-6-243-2025' chicago: 'Kapoor, Lucky, Natalia Ruzickova, Predrag Zivadinovic, Valentin Leitner, Maria A Sisak, Cecelia N Mweka, Jeroen A Dobbelaere, Georgios Katsaros, and Paul Schanda. “Quantifying the Carbon Footprint of Conference Travel: The Case of NMR Meetings.” Magnetic Resonance. Copernicus Publications, 2025. https://doi.org/10.5194/mr-6-243-2025.' ieee: 'L. Kapoor et al., “Quantifying the carbon footprint of conference travel: The case of NMR meetings,” Magnetic Resonance, vol. 6, no. 2. Copernicus Publications, pp. 243–256, 2025.' ista: 'Kapoor L, Ruzickova N, Zivadinovic P, Leitner V, Sisak MA, Mweka CN, Dobbelaere JA, Katsaros G, Schanda P. 2025. Quantifying the carbon footprint of conference travel: The case of NMR meetings. Magnetic Resonance. 6(2), 243–256.' mla: 'Kapoor, Lucky, et al. “Quantifying the Carbon Footprint of Conference Travel: The Case of NMR Meetings.” Magnetic Resonance, vol. 6, no. 2, Copernicus Publications, 2025, pp. 243–56, doi:10.5194/mr-6-243-2025.' short: L. Kapoor, N. Ruzickova, P. Zivadinovic, V. Leitner, M.A. Sisak, C.N. Mweka, J.A. Dobbelaere, G. Katsaros, P. Schanda, Magnetic Resonance 6 (2025) 243–256. corr_author: '1' date_created: 2025-11-23T23:01:39Z date_published: 2025-11-10T00:00:00Z date_updated: 2026-05-20T08:01:13Z day: '10' ddc: - '000' department: - _id: JoFi - _id: GaTk - _id: JoCs - _id: EvBe - _id: TaHa - _id: GradSch - _id: GeKa - _id: PaSc doi: 10.5194/mr-6-243-2025 file: - access_level: open_access checksum: c63dd47b0e77f9451821436bb77d27c9 content_type: application/pdf creator: dernst date_created: 2025-11-24T08:25:19Z date_updated: 2025-11-24T08:25:19Z file_id: '20672' file_name: 2025_MagneticResonance_Kapoor.pdf file_size: 3081399 relation: main_file success: 1 file_date_updated: 2025-11-24T08:25:19Z has_accepted_license: '1' intvolume: ' 6' issue: '2' language: - iso: eng month: '11' oa: 1 oa_version: Published Version page: 243-256 project: - _id: B67AFEDC-15C9-11EA-A837-991A96BB2854 name: IST Austria Open Access Fund publication: Magnetic Resonance publication_identifier: eissn: - 2699-0016 publication_status: published publisher: Copernicus Publications quality_controlled: '1' related_material: link: - description: News on ISTA website relation: research_data url: https://ista.ac.at/en/news/carbon-footprint-of-conference-travel/ record: - id: '20242' relation: research_data status: public scopus_import: '1' status: public title: 'Quantifying the carbon footprint of conference travel: The case of NMR meetings' 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: 6 year: '2025' ... --- APC_amount: 5949 EUR 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: 2026-05-20T08:33:08Z 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 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: 2026-05-20T08:33:07Z 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' ... --- _id: '14901' abstract: - lang: eng text: Global services like navigation, communication, and Earth observation have increased dramatically in the 21st century due to advances in outer space industries. But as orbits become increasingly crowded with both satellites and inevitable space debris pollution, continued operations become endangered by the heightened risks of debris collisions in orbit. Kessler Syndrome is the term for when a critical threshold of orbiting debris triggers a runaway positive feedback loop of debris collisions, creating debris congestion that can render orbits unusable. As this potential tipping point becomes more widely recognized, there have been renewed calls for debris mitigation and removal. Here, we combine complex systems and social-ecological systems approaches to study how these efforts may affect space debris accumulation and the likelihood of reaching Kessler Syndrome. Specifically, we model how debris levels are affected by future launch rates, cleanup activities, and collisions between extant debris. We contextualize and interpret our dynamic model within a discussion of existing space debris governance and other social, economic, and geopolitical factors that may influence effective collective management of the orbital commons. In line with previous studies, our model finds that debris congestion may be reached in less than 200 years, though a holistic management strategy combining removal and mitigation actions can avoid such outcomes while continuing space activities. Moreover, although active debris removal may be particularly effective, the current lack of market and governance support may impede its implementation. Research into these critical dynamics and the multi-faceted variables that influence debris outcomes can support policymakers in curating impactful governance strategies and realistic transition pathways to sustaining debris-free orbits. Overall, our study is useful for communicating about space debris sustainability in policy and education settings by providing an exploration of policy portfolio options supported by a simple and clear social-ecological modeling approach. acknowledgement: The authors would like to thank the special issue co-editors, Marco Janssen and Xiao-Shan Yap, and the anonymous reviewers for their comments that helped improve the manuscript. The paper also benefited from suggestions by other author participants in this special issue. We would also like to thank the 2022 Santa Fe Institute Complex Systems Summer School for providing space to initiate this study. article_processing_charge: Yes article_type: original author: - first_name: Keiko full_name: Nomura, Keiko last_name: Nomura - first_name: Simon full_name: Rella, Simon id: B4765ACA-AA38-11E9-AC9A-0930E6697425 last_name: Rella - first_name: Haily full_name: Merritt, Haily last_name: Merritt - first_name: Mathieu full_name: Baltussen, Mathieu last_name: Baltussen - first_name: Darcy full_name: Bird, Darcy last_name: Bird - first_name: Annika full_name: Tjuka, Annika last_name: Tjuka - first_name: Dan full_name: Falk, Dan last_name: Falk citation: ama: Nomura K, Rella S, Merritt H, et al. Tipping points of space debris in low earth orbit. International Journal of the Commons. 2024;18(1). doi:10.5334/ijc.1275 apa: Nomura, K., Rella, S., Merritt, H., Baltussen, M., Bird, D., Tjuka, A., & Falk, D. (2024). Tipping points of space debris in low earth orbit. International Journal of the Commons. Ubiquity Press. https://doi.org/10.5334/ijc.1275 chicago: Nomura, Keiko, Simon Rella, Haily Merritt, Mathieu Baltussen, Darcy Bird, Annika Tjuka, and Dan Falk. “Tipping Points of Space Debris in Low Earth Orbit.” International Journal of the Commons. Ubiquity Press, 2024. https://doi.org/10.5334/ijc.1275. ieee: K. Nomura et al., “Tipping points of space debris in low earth orbit,” International Journal of the Commons, vol. 18, no. 1. Ubiquity Press, 2024. ista: Nomura K, Rella S, Merritt H, Baltussen M, Bird D, Tjuka A, Falk D. 2024. Tipping points of space debris in low earth orbit. International Journal of the Commons. 18(1). mla: Nomura, Keiko, et al. “Tipping Points of Space Debris in Low Earth Orbit.” International Journal of the Commons, vol. 18, no. 1, Ubiquity Press, 2024, doi:10.5334/ijc.1275. short: K. Nomura, S. Rella, H. Merritt, M. Baltussen, D. Bird, A. Tjuka, D. Falk, International Journal of the Commons 18 (2024). date_created: 2024-01-30T11:58:02Z date_published: 2024-01-11T00:00:00Z date_updated: 2024-02-05T10:10:27Z day: '11' ddc: - '550' department: - _id: GradSch - _id: GaTk doi: 10.5334/ijc.1275 file: - access_level: open_access checksum: b80ebc889033c365d8f8c05a0c655382 content_type: application/pdf creator: dernst date_created: 2024-02-05T10:06:35Z date_updated: 2024-02-05T10:06:35Z file_id: '14939' file_name: 2023_IntJourCommons_Nomura.pdf file_size: 1305786 relation: main_file success: 1 file_date_updated: 2024-02-05T10:06:35Z has_accepted_license: '1' intvolume: ' 18' issue: '1' keyword: - Sociology and Political Science language: - iso: eng month: '01' oa: 1 oa_version: Published Version publication: International Journal of the Commons publication_identifier: issn: - 1875-0281 publication_status: published publisher: Ubiquity Press quality_controlled: '1' scopus_import: '1' status: public title: Tipping points of space debris in low earth orbit 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: 18 year: '2024' ... --- 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' ... --- OA_place: publisher OA_type: hybrid _id: '18307' abstract: - lang: eng text: Vaccination is the most effective tool to control infectious diseases. However, the evolution of vaccine resistance, exemplified by vaccine resistance in SARS-CoV-2, remains a concern. Here, we model complex vaccination strategies against a pathogen with multiple epitopes—molecules targeted by the vaccine. We found that a vaccine targeting one epitope was ineffective in preventing vaccine escape. Vaccine resistance in highly infectious pathogens was prevented by the full-epitope vaccine, that is, one targeting all available epitopes, but only when the rate of pathogen evolution was low. Strikingly, a bet-hedging strategy of random administration of vaccines targeting different epitopes was the most effective in preventing vaccine resistance in pathogens with the low rate of infection and high rate of evolution. Thus, complex vaccination strategies, when biologically feasible, may be preferable to the currently used single-vaccine approaches for long-term control of disease outbreaks, especially when applied to livestock with near 100% vaccination rates. acknowledgement: We thank Raimundo Julian Saona Urmeneta, Maike Morrison, Sergey Kryazhimskiy, Hiroki Ishikawa, Simone Pigolotti, and Shingo Miyauchi for fruitful discussions. We also thank the participants of the FRISBI seminar at ISTA for useful comments. article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Simon full_name: Rella, Simon id: B4765ACA-AA38-11E9-AC9A-0930E6697425 last_name: Rella - first_name: Yuliya A. full_name: Kulikova, Yuliya A. last_name: Kulikova - first_name: Aygul full_name: Minnegalieva, Aygul id: 87DF77F0-1D9A-11EA-B6AE-CE443DDC885E last_name: Minnegalieva - first_name: Fyodor full_name: Kondrashov, Fyodor id: 44FDEF62-F248-11E8-B48F-1D18A9856A87 last_name: Kondrashov orcid: 0000-0001-8243-4694 citation: ama: 'Rella S, Kulikova YA, Minnegalieva A, Kondrashov F. Complex vaccination strategies prevent the emergence of vaccine resistance. Evolution: International journal of organic evolution. 2024;78(10):1722-1738. doi:10.1093/evolut/qpae106' apa: 'Rella, S., Kulikova, Y. A., Minnegalieva, A., & Kondrashov, F. (2024). Complex vaccination strategies prevent the emergence of vaccine resistance. Evolution: International Journal of Organic Evolution. Oxford University Press. https://doi.org/10.1093/evolut/qpae106' chicago: 'Rella, Simon, Yuliya A. Kulikova, Aygul Minnegalieva, and Fyodor Kondrashov. “Complex Vaccination Strategies Prevent the Emergence of Vaccine Resistance.” Evolution: International Journal of Organic Evolution. Oxford University Press, 2024. https://doi.org/10.1093/evolut/qpae106.' ieee: 'S. Rella, Y. A. Kulikova, A. Minnegalieva, and F. Kondrashov, “Complex vaccination strategies prevent the emergence of vaccine resistance,” Evolution: International journal of organic evolution, vol. 78, no. 10. Oxford University Press, pp. 1722–1738, 2024.' ista: 'Rella S, Kulikova YA, Minnegalieva A, Kondrashov F. 2024. Complex vaccination strategies prevent the emergence of vaccine resistance. Evolution: International journal of organic evolution. 78(10), 1722–1738.' mla: 'Rella, Simon, et al. “Complex Vaccination Strategies Prevent the Emergence of Vaccine Resistance.” Evolution: International Journal of Organic Evolution, vol. 78, no. 10, Oxford University Press, 2024, pp. 1722–38, doi:10.1093/evolut/qpae106.' short: 'S. Rella, Y.A. Kulikova, A. Minnegalieva, F. Kondrashov, Evolution: International Journal of Organic Evolution 78 (2024) 1722–1738.' corr_author: '1' date_created: 2024-10-13T22:01:50Z date_published: 2024-10-01T00:00:00Z date_updated: 2026-04-07T12:34:57Z day: '01' ddc: - '570' department: - _id: GaTk doi: 10.1093/evolut/qpae106 external_id: isi: - '001286581900001' pmid: - '38990788' file: - access_level: open_access checksum: 5c6e8475bb88b07d424a5130d5e91e74 content_type: application/pdf creator: dernst date_created: 2024-10-21T09:34:50Z date_updated: 2024-10-21T09:34:50Z file_id: '18453' file_name: 2024_Evolution_Rella.pdf file_size: 29360811 relation: main_file success: 1 file_date_updated: 2024-10-21T09:34:50Z has_accepted_license: '1' intvolume: ' 78' isi: 1 issue: '10' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: 1722-1738 pmid: 1 publication: 'Evolution: International journal of organic evolution' publication_identifier: eissn: - 1558-5646 publication_status: published publisher: Oxford University Press quality_controlled: '1' related_material: link: - relation: software url: https://github.com/Simon-Re/complex-vaccination record: - id: '14862' relation: research_data status: public - id: '20811' relation: dissertation_contains status: public scopus_import: '1' status: public title: Complex vaccination strategies prevent the emergence of vaccine resistance 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: 78 year: '2024' ...