[{"oa":1,"publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"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.","file":[{"success":1,"relation":"main_file","access_level":"open_access","file_size":25529709,"file_id":"18536","date_created":"2024-11-11T09:31:00Z","creator":"dernst","file_name":"2024_PNAS_Ruzickova.pdf","date_updated":"2024-11-11T09:31:00Z","content_type":"application/pdf","checksum":"d930e2ccf9ec900c7d7509a78cfb3564"}],"pmid":1,"APC_amount":"3062,93 EUR","intvolume":"       121","isi":1,"author":[{"id":"D2761128-D73D-11E9-A1BF-BA0DE6697425","first_name":"Natalia","last_name":"Ruzickova","full_name":"Ruzickova, Natalia"},{"first_name":"Michal","id":"4171253A-F248-11E8-B48F-1D18A9856A87","full_name":"Hledik, Michal","last_name":"Hledik"},{"orcid":"0000-0002-6699-1455","last_name":"Tkačik","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"}],"file_date_updated":"2024-11-11T09:31:00Z","scopus_import":"1","publication":"Proceedings of the National Academy of Sciences of the United States of America","quality_controlled":"1","volume":121,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","abstract":[{"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.","lang":"eng"}],"article_number":"e2402340121","publication_status":"published","language":[{"iso":"eng"}],"corr_author":"1","department":[{"_id":"GaTk"},{"_id":"NiBa"}],"external_id":{"pmid":["39441639"],"isi":["001349462600001"]},"date_created":"2024-11-10T23:01:59Z","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"status":"public","type":"journal_article","day":"29","publisher":"National Academy of Sciences","issue":"44","oa_version":"Published Version","year":"2024","date_updated":"2026-04-07T12:02:39Z","project":[{"name":"Collective behaviour of cells in pancreatic Islets of Langerhans","_id":"7bec9174-9f16-11ee-852c-ded9fe5f810e"},{"name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?","grant_number":"RGP0034/2018","_id":"2665AAFE-B435-11E9-9278-68D0E5697425"}],"date_published":"2024-10-29T00:00:00Z","has_accepted_license":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","title":"Quantitative omnigenic model discovers interpretable genome-wide associations","month":"10","_id":"18525","citation":{"chicago":"Ruzickova, Natalia, Michal Hledik, and Gašper Tkačik. “Quantitative Omnigenic Model Discovers Interpretable Genome-Wide Associations.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2402340121\">https://doi.org/10.1073/pnas.2402340121</a>.","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.","ama":"Ruzickova N, Hledik M, Tkačik G. Quantitative omnigenic model discovers interpretable genome-wide associations. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2024;121(44). doi:<a href=\"https://doi.org/10.1073/pnas.2402340121\">10.1073/pnas.2402340121</a>","apa":"Ruzickova, N., Hledik, M., &#38; Tkačik, G. (2024). Quantitative omnigenic model discovers interpretable genome-wide associations. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2402340121\">https://doi.org/10.1073/pnas.2402340121</a>","ieee":"N. Ruzickova, M. Hledik, and G. Tkačik, “Quantitative omnigenic model discovers interpretable genome-wide associations,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 44. National Academy of Sciences, 2024.","mla":"Ruzickova, Natalia, et al. “Quantitative Omnigenic Model Discovers Interpretable Genome-Wide Associations.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 44, e2402340121, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2402340121\">10.1073/pnas.2402340121</a>.","short":"N. Ruzickova, M. Hledik, G. Tkačik, Proceedings of the National Academy of Sciences of the United States of America 121 (2024)."},"related_material":{"record":[{"id":"20357","status":"public","relation":"dissertation_contains"}]},"article_processing_charge":"Yes","ddc":["570"],"OA_place":"publisher","doi":"10.1073/pnas.2402340121","article_type":"original","OA_type":"hybrid"},{"month":"02","title":"Genetic information and biological optimization","_id":"15020","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"7606"},{"id":"12081","relation":"part_of_dissertation","status":"public"},{"id":"7553","relation":"part_of_dissertation","status":"public"}]},"citation":{"ieee":"M. Hledik, “Genetic information and biological optimization,” Institute of Science and Technology Austria, 2024.","short":"M. Hledik, Genetic Information and Biological Optimization, Institute of Science and Technology Austria, 2024.","mla":"Hledik, Michal. <i>Genetic Information and Biological Optimization</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:15020\">10.15479/at:ista:15020</a>.","ista":"Hledik M. 2024. Genetic information and biological optimization. Institute of Science and Technology Austria.","chicago":"Hledik, Michal. “Genetic Information and Biological Optimization.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:15020\">https://doi.org/10.15479/at:ista:15020</a>.","apa":"Hledik, M. (2024). <i>Genetic information and biological optimization</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:15020\">https://doi.org/10.15479/at:ista:15020</a>","ama":"Hledik M. Genetic information and biological optimization. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:15020\">10.15479/at:ista:15020</a>"},"article_processing_charge":"No","ddc":["576","519"],"alternative_title":["ISTA Thesis"],"OA_place":"publisher","doi":"10.15479/at:ista:15020","status":"public","day":"23","publisher":"Institute of Science and Technology Austria","type":"dissertation","date_updated":"2026-04-07T12:59:25Z","oa_version":"Published Version","year":"2024","project":[{"name":"International IST Doctoral Program","call_identifier":"H2020","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"grant_number":"RGP0034/2018","_id":"2665AAFE-B435-11E9-9278-68D0E5697425","name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?"},{"_id":"bd6958e0-d553-11ed-ba76-86eba6a76c00","grant_number":"101055327","name":"Understanding the evolution of continuous genomes"}],"date_published":"2024-02-23T00:00:00Z","has_accepted_license":"1","page":"158","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","acknowledged_ssus":[{"_id":"ScienComp"}],"supervisor":[{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas H","last_name":"Barton","full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240"},{"full_name":"Tkačik, Gašper","last_name":"Tkačik","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"}],"abstract":[{"lang":"eng","text":"This thesis consists of four distinct pieces of work within theoretical biology, with two themes in common: the concept of optimization in biological systems, and the use of information-theoretic tools to quantify biological stochasticity and statistical uncertainty.\r\nChapter 2 develops a statistical framework for studying biological systems which we believe to be optimized for a particular utility function, such as retinal neurons conveying information about visual stimuli. We formalize such beliefs as maximum-entropy Bayesian priors, constrained by the expected utility. We explore how such priors aid inference of system parameters with limited data and enable optimality hypothesis testing: is the utility higher than by chance?\r\nChapter 3 examines the ultimate biological optimization process: evolution by natural selection. As some individuals survive and reproduce more successfully than others, populations evolve towards fitter genotypes and phenotypes. We formalize this as accumulation of genetic information, and use population genetics theory to study how much such information can be accumulated per generation and maintained in the face of random mutation and genetic drift. We identify the population size and fitness variance as the key quantities that control information accumulation and maintenance.\r\nChapter 4 reuses the concept of genetic information from Chapter 3, but from a different perspective: we ask how much genetic information organisms actually need, in particular in the context of gene regulation. For example, how much information is needed to bind transcription factors at correct locations within the genome? Population genetics provides us with a refined answer: with an increasing population size, populations achieve higher fitness by maintaining more genetic information. Moreover, regulatory parameters experience selection pressure to optimize the fitness-information trade-off, i.e. minimize the information needed for a given fitness. This provides an evolutionary derivation of the optimization priors introduced in Chapter 2.\r\nChapter 5 proves an upper bound on mutual information between a signal and a communication channel output (such as neural activity). Mutual information is an important utility measure for biological systems, but its practical use can be difficult due to the large dimensionality of many biological channels. Sometimes, a lower bound on mutual information is computed by replacing the high-dimensional channel outputs with decodes (signal estimates). Our result provides a corresponding upper bound, provided that the decodes are the maximum posterior estimates of the signal."}],"publication_status":"published","degree_awarded":"PhD","corr_author":"1","language":[{"iso":"eng"}],"date_created":"2024-02-23T14:02:04Z","department":[{"_id":"GradSch"},{"_id":"NiBa"},{"_id":"GaTk"}],"publication_identifier":{"issn":["2663-337X"]},"oa":1,"file":[{"checksum":"b2d3da47c98d481577a4baf68944fe41","content_type":"application/pdf","date_updated":"2024-02-23T13:50:53Z","file_name":"hledik thesis pdfa 2b.pdf","creator":"mhledik","date_created":"2024-02-23T13:50:53Z","file_id":"15021","file_size":7102089,"access_level":"open_access","relation":"main_file","success":1},{"access_level":"closed","relation":"source_file","content_type":"application/zip","checksum":"eda9b9430da2610fee7ce1c1419a479a","date_updated":"2024-02-23T14:20:16Z","creator":"mhledik","file_name":"hledik thesis source.zip","file_id":"15022","date_created":"2024-02-23T13:50:54Z","file_size":14014790}],"ec_funded":1,"author":[{"first_name":"Michal","id":"4171253A-F248-11E8-B48F-1D18A9856A87","full_name":"Hledik, Michal","last_name":"Hledik"}],"keyword":["Theoretical biology","Optimality","Evolution","Information"],"file_date_updated":"2024-02-23T14:20:16Z"},{"acknowledgement":"We thank Ksenia Khudiakova, Wiktor Młynarski, Sean Stankowski, and two anonymous reviewers for discussions and comments on the manuscript. G.T. and M.H. acknowledge funding from the Human Frontier Science Program Grant RGP0032/2018. N.B. acknowledges funding from ERC Grant 250152 “Information and Evolution.”","file":[{"success":1,"access_level":"open_access","relation":"main_file","creator":"dernst","file_name":"2022_PNAS_Hledik.pdf","file_id":"12091","date_created":"2022-09-12T08:08:12Z","file_size":2165752,"checksum":"6dec51f6567da9039982a571508a8e4d","content_type":"application/pdf","date_updated":"2022-09-12T08:08:12Z"}],"pmid":1,"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"oa":1,"scopus_import":"1","file_date_updated":"2022-09-12T08:08:12Z","author":[{"first_name":"Michal","id":"4171253A-F248-11E8-B48F-1D18A9856A87","full_name":"Hledik, Michal","last_name":"Hledik"},{"last_name":"Barton","full_name":"Barton, Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas H","orcid":"0000-0002-8548-5240"},{"orcid":"1","last_name":"Tkačik","full_name":"Tkačik, Gašper","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"publication":"Proceedings of the National Academy of Sciences of the United States of America","ec_funded":1,"isi":1,"intvolume":"       119","volume":119,"quality_controlled":"1","abstract":[{"text":"Selection accumulates information in the genome—it guides stochastically evolving populations toward states (genotype frequencies) that would be unlikely under neutrality. This can be quantified as the Kullback–Leibler (KL) divergence between the actual distribution of genotype frequencies and the corresponding neutral distribution. First, we show that this population-level information sets an upper bound on the information at the level of genotype and phenotype, limiting how precisely they can be specified by selection. Next, we study how the accumulation and maintenance of information is limited by the cost of selection, measured as the genetic load or the relative fitness variance, both of which we connect to the control-theoretic KL cost of control. The information accumulation rate is upper bounded by the population size times the cost of selection. This bound is very general, and applies across models (Wright–Fisher, Moran, diffusion) and to arbitrary forms of selection, mutation, and recombination. Finally, the cost of maintaining information depends on how it is encoded: Specifying a single allele out of two is expensive, but one bit encoded among many weakly specified loci (as in a polygenic trait) is cheap.","lang":"eng"}],"article_number":"e2123152119","publication_status":"published","external_id":{"pmid":["36037343"],"isi":["000889278400014"]},"department":[{"_id":"NiBa"},{"_id":"GaTk"}],"date_created":"2022-09-11T22:01:55Z","language":[{"iso":"eng"}],"corr_author":"1","status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publisher":"National Academy of Sciences","day":"29","type":"journal_article","issue":"36","date_published":"2022-08-29T00:00:00Z","project":[{"call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation","grant_number":"250152","_id":"25B07788-B435-11E9-9278-68D0E5697425"},{"grant_number":"RGP0034/2018","_id":"2665AAFE-B435-11E9-9278-68D0E5697425","name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?"}],"has_accepted_license":"1","oa_version":"Published Version","year":"2022","date_updated":"2026-04-07T12:59:24Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"12081","title":"Accumulation and maintenance of information in evolution","month":"08","article_processing_charge":"No","citation":{"ieee":"M. Hledik, N. H. Barton, and G. Tkačik, “Accumulation and maintenance of information in evolution,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 119, no. 36. National Academy of Sciences, 2022.","short":"M. Hledik, N.H. Barton, G. Tkačik, Proceedings of the National Academy of Sciences of the United States of America 119 (2022).","mla":"Hledik, Michal, et al. “Accumulation and Maintenance of Information in Evolution.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 119, no. 36, e2123152119, National Academy of Sciences, 2022, doi:<a href=\"https://doi.org/10.1073/pnas.2123152119\">10.1073/pnas.2123152119</a>.","chicago":"Hledik, Michal, Nicholas H Barton, and Gašper Tkačik. “Accumulation and Maintenance of Information in Evolution.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2022. <a href=\"https://doi.org/10.1073/pnas.2123152119\">https://doi.org/10.1073/pnas.2123152119</a>.","ista":"Hledik M, Barton NH, Tkačik G. 2022. Accumulation and maintenance of information in evolution. Proceedings of the National Academy of Sciences of the United States of America. 119(36), e2123152119.","ama":"Hledik M, Barton NH, Tkačik G. Accumulation and maintenance of information in evolution. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2022;119(36). doi:<a href=\"https://doi.org/10.1073/pnas.2123152119\">10.1073/pnas.2123152119</a>","apa":"Hledik, M., Barton, N. H., &#38; Tkačik, G. (2022). Accumulation and maintenance of information in evolution. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2123152119\">https://doi.org/10.1073/pnas.2123152119</a>"},"related_material":{"record":[{"id":"15020","status":"public","relation":"dissertation_contains"}]},"ddc":["570"],"doi":"10.1073/pnas.2123152119","article_type":"original"},{"volume":16,"quality_controlled":"1","article_number":"e0255267","abstract":[{"text":"Aims: Mass antigen testing programs have been challenged because of an alleged insufficient specificity, leading to a large number of false positives. The objective of this study is to derive a lower bound of the specificity of the SD Biosensor Standard Q Ag-Test in large scale practical use.\r\nMethods: Based on county data from the nationwide tests for SARS-CoV-2 in Slovakia between 31.10.–1.11. 2020 we calculate a lower confidence bound for the specificity. As positive test results were not systematically verified by PCR tests, we base the lower bound on a worst case assumption, assuming all positives to be false positives.\r\nResults: 3,625,332 persons from 79 counties were tested. The lowest positivity rate was observed in the county of Rožňava where 100 out of 34307 (0.29%) tests were positive. This implies a test specificity of at least 99.6% (97.5% one-sided lower confidence bound, adjusted for multiplicity).\r\nConclusion: The obtained lower bound suggests a higher specificity compared to earlier studies in spite of the underlying worst case assumption and the application in a mass testing setting. The actual specificity is expected to exceed 99.6% if the prevalence in the respective regions was non-negligible at the time of testing. To our knowledge, this estimate constitutes the first bound obtained from large scale practical use of an antigen test.","lang":"eng"}],"publication_status":"published","date_created":"2021-08-08T22:01:26Z","department":[{"_id":"NiBa"}],"external_id":{"isi":["000685248200095"],"pmid":["34324553"]},"language":[{"iso":"eng"}],"pmid":1,"acknowledgement":"We would like to thank Alfred Uhl, Richard Kollár and Katarína Bod’ová for very helpful comments. We also thank Matej Mišík for discussion and information regarding the Slovak testing data and Ag-Test used.","file":[{"file_id":"9835","date_created":"2021-08-09T11:52:14Z","creator":"asandaue","file_name":"2021_PLoSONE_Hledík.pdf","file_size":773921,"checksum":"ae4df60eb62f4491278588548d0c1f93","content_type":"application/pdf","date_updated":"2021-08-09T11:52:14Z","success":1,"relation":"main_file","access_level":"open_access"}],"oa":1,"publication_identifier":{"eissn":["1932-6203"]},"author":[{"first_name":"Michal","id":"4171253A-F248-11E8-B48F-1D18A9856A87","last_name":"Hledik","full_name":"Hledik, Michal"},{"orcid":"0000-0003-0951-3112","id":"3BBFB084-F248-11E8-B48F-1D18A9856A87","first_name":"Jitka","full_name":"Polechova, Jitka","last_name":"Polechova"},{"last_name":"Beiglböck","full_name":"Beiglböck, Mathias","first_name":"Mathias"},{"first_name":"Anna Nele","full_name":"Herdina, Anna Nele","last_name":"Herdina"},{"first_name":"Robert","last_name":"Strassl","full_name":"Strassl, Robert"},{"last_name":"Posch","full_name":"Posch, Martin","first_name":"Martin"}],"publication":"PLoS ONE","scopus_import":"1","file_date_updated":"2021-08-09T11:52:14Z","intvolume":"        16","isi":1,"_id":"9816","month":"07","title":"Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program","article_processing_charge":"Yes","citation":{"apa":"Hledik, M., Polechova, J., Beiglböck, M., Herdina, A. N., Strassl, R., &#38; Posch, M. (2021). Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program. <i>PLoS ONE</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pone.0255267\">https://doi.org/10.1371/journal.pone.0255267</a>","ama":"Hledik M, Polechova J, Beiglböck M, Herdina AN, Strassl R, Posch M. Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program. <i>PLoS ONE</i>. 2021;16(7). doi:<a href=\"https://doi.org/10.1371/journal.pone.0255267\">10.1371/journal.pone.0255267</a>","ista":"Hledik M, Polechova J, Beiglböck M, Herdina AN, Strassl R, Posch M. 2021. Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program. PLoS ONE. 16(7), e0255267.","chicago":"Hledik, Michal, Jitka Polechova, Mathias Beiglböck, Anna Nele Herdina, Robert Strassl, and Martin Posch. “Analysis of the Specificity of a COVID-19 Antigen Test in the Slovak Mass Testing Program.” <i>PLoS ONE</i>. Public Library of Science, 2021. <a href=\"https://doi.org/10.1371/journal.pone.0255267\">https://doi.org/10.1371/journal.pone.0255267</a>.","short":"M. Hledik, J. Polechova, M. Beiglböck, A.N. Herdina, R. Strassl, M. Posch, PLoS ONE 16 (2021).","mla":"Hledik, Michal, et al. “Analysis of the Specificity of a COVID-19 Antigen Test in the Slovak Mass Testing Program.” <i>PLoS ONE</i>, vol. 16, no. 7, e0255267, Public Library of Science, 2021, doi:<a href=\"https://doi.org/10.1371/journal.pone.0255267\">10.1371/journal.pone.0255267</a>.","ieee":"M. Hledik, J. Polechova, M. Beiglböck, A. N. Herdina, R. Strassl, and M. Posch, “Analysis of the specificity of a COVID-19 antigen test in the Slovak mass testing program,” <i>PLoS ONE</i>, vol. 16, no. 7. Public Library of Science, 2021."},"ddc":["610"],"article_type":"original","doi":"10.1371/journal.pone.0255267","status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"issue":"7","publisher":"Public Library of Science","day":"29","type":"journal_article","date_published":"2021-07-29T00:00:00Z","has_accepted_license":"1","date_updated":"2023-08-10T14:26:32Z","year":"2021","oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"author":[{"last_name":"Mlynarski","full_name":"Mlynarski, Wiktor F","first_name":"Wiktor F","id":"358A453A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hledik","full_name":"Hledik, Michal","id":"4171253A-F248-11E8-B48F-1D18A9856A87","first_name":"Michal"},{"orcid":"0000-0002-1287-3779","last_name":"Sokolowski","full_name":"Sokolowski, Thomas R","id":"3E999752-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas R"},{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455"}],"publication":"Neuron","scopus_import":"1","ec_funded":1,"intvolume":"       109","isi":1,"acknowledgement":"The authors thank Dario Ringach for providing the V1 receptive fields and Olivier Marre for providing the retinal receptive fields. W.M. was funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411. M.H. was funded in part by Human Frontiers Science grant no. HFSP RGP0032/2018.","pmid":1,"oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/848374"}],"publication_status":"published","external_id":{"isi":["000637809600006"],"pmid":["33592180"]},"department":[{"_id":"GaTk"}],"date_created":"2020-02-28T11:00:12Z","language":[{"iso":"eng"}],"corr_author":"1","volume":109,"quality_controlled":"1","abstract":[{"lang":"eng","text":"Normative theories and statistical inference provide complementary approaches for the study of biological systems. A normative theory postulates that organisms have adapted to efficiently solve essential tasks, and proceeds to mathematically work out testable consequences of such optimality; parameters that maximize the hypothesized organismal function can be derived ab initio, without reference to experimental data. In contrast, statistical inference focuses on efficient utilization of data to learn model parameters, without reference to any a priori notion of biological function, utility, or fitness. Traditionally, these two approaches were developed independently and applied separately. Here we unify them in a coherent Bayesian framework that embeds a normative theory into a family of maximum-entropy “optimization priors.” This family defines a smooth interpolation between a data-rich inference regime (characteristic of “bottom-up” statistical models), and a data-limited ab inito prediction regime (characteristic of “top-down” normative theory). We demonstrate the applicability of our framework using data from the visual cortex, and argue that the flexibility it affords is essential to address a number of fundamental challenges relating to inference and prediction in complex, high-dimensional biological problems."}],"date_published":"2021-04-07T00:00:00Z","project":[{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425"}],"oa_version":"Preprint","year":"2021","date_updated":"2026-04-07T12:59:24Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","page":"1227-1241.e5","status":"public","publisher":"Cell Press","day":"07","type":"journal_article","issue":"7","doi":"10.1016/j.neuron.2021.01.020","_id":"7553","title":"Statistical analysis and optimality of neural systems","month":"04","article_processing_charge":"No","citation":{"ieee":"W. F. Mlynarski, M. Hledik, T. R. Sokolowski, and G. Tkačik, “Statistical analysis and optimality of neural systems,” <i>Neuron</i>, vol. 109, no. 7. Cell Press, p. 1227–1241.e5, 2021.","mla":"Mlynarski, Wiktor F., et al. “Statistical Analysis and Optimality of Neural Systems.” <i>Neuron</i>, vol. 109, no. 7, Cell Press, 2021, p. 1227–1241.e5, doi:<a href=\"https://doi.org/10.1016/j.neuron.2021.01.020\">10.1016/j.neuron.2021.01.020</a>.","short":"W.F. Mlynarski, M. Hledik, T.R. Sokolowski, G. Tkačik, Neuron 109 (2021) 1227–1241.e5.","chicago":"Mlynarski, Wiktor F, Michal Hledik, Thomas R Sokolowski, and Gašper Tkačik. “Statistical Analysis and Optimality of Neural Systems.” <i>Neuron</i>. Cell Press, 2021. <a href=\"https://doi.org/10.1016/j.neuron.2021.01.020\">https://doi.org/10.1016/j.neuron.2021.01.020</a>.","ista":"Mlynarski WF, Hledik M, Sokolowski TR, Tkačik G. 2021. Statistical analysis and optimality of neural systems. Neuron. 109(7), 1227–1241.e5.","ama":"Mlynarski WF, Hledik M, Sokolowski TR, Tkačik G. Statistical analysis and optimality of neural systems. <i>Neuron</i>. 2021;109(7):1227-1241.e5. doi:<a href=\"https://doi.org/10.1016/j.neuron.2021.01.020\">10.1016/j.neuron.2021.01.020</a>","apa":"Mlynarski, W. F., Hledik, M., Sokolowski, T. R., &#38; Tkačik, G. (2021). Statistical analysis and optimality of neural systems. <i>Neuron</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.neuron.2021.01.020\">https://doi.org/10.1016/j.neuron.2021.01.020</a>"},"related_material":{"record":[{"id":"15020","status":"public","relation":"dissertation_contains"}],"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/can-evolution-be-predicted/"}]}},{"external_id":{"isi":["000540384500015"],"arxiv":["1812.01475"]},"department":[{"_id":"GaTk"}],"date_created":"2020-03-22T23:00:47Z","language":[{"iso":"eng"}],"publication_status":"published","abstract":[{"lang":"eng","text":"We derive a tight lower bound on equivocation (conditional entropy), or equivalently a tight upper bound on mutual information between a signal variable and channel outputs. The bound is in terms of the joint distribution of the signals and maximum a posteriori decodes (most probable signals given channel output). As part of our derivation, we describe the key properties of the distribution of signals, channel outputs and decodes, that minimizes equivocation and maximizes mutual information. This work addresses a problem in data analysis, where mutual information between signals and decodes is sometimes used to lower bound the mutual information between signals and channel outputs. Our result provides a corresponding upper bound."}],"article_number":"8989292","quality_controlled":"1","publication":"IEEE Information Theory Workshop, ITW 2019","scopus_import":"1","author":[{"last_name":"Hledik","full_name":"Hledik, Michal","id":"4171253A-F248-11E8-B48F-1D18A9856A87","first_name":"Michal"},{"id":"3E999752-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas R","last_name":"Sokolowski","full_name":"Sokolowski, Thomas R","orcid":"0000-0002-1287-3779"},{"orcid":"0000-0002-6699-1455","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","last_name":"Tkačik"}],"ec_funded":1,"isi":1,"main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1812.01475"}],"publication_identifier":{"isbn":["9781538669006"]},"oa":1,"doi":"10.1109/ITW44776.2019.8989292","arxiv":1,"article_processing_charge":"No","conference":{"end_date":"2019-08-28","location":"Visby, Sweden","start_date":"2019-08-25","name":"Information Theory Workshop"},"citation":{"ieee":"M. Hledik, T. R. Sokolowski, and G. Tkačik, “A tight upper bound on mutual information,” in <i>IEEE Information Theory Workshop, ITW 2019</i>, Visby, Sweden, 2019.","short":"M. Hledik, T.R. Sokolowski, G. Tkačik, in:, IEEE Information Theory Workshop, ITW 2019, IEEE, 2019.","mla":"Hledik, Michal, et al. “A Tight Upper Bound on Mutual Information.” <i>IEEE Information Theory Workshop, ITW 2019</i>, 8989292, IEEE, 2019, doi:<a href=\"https://doi.org/10.1109/ITW44776.2019.8989292\">10.1109/ITW44776.2019.8989292</a>.","ista":"Hledik M, Sokolowski TR, Tkačik G. 2019. A tight upper bound on mutual information. IEEE Information Theory Workshop, ITW 2019. Information Theory Workshop, 8989292.","chicago":"Hledik, Michal, Thomas R Sokolowski, and Gašper Tkačik. “A Tight Upper Bound on Mutual Information.” In <i>IEEE Information Theory Workshop, ITW 2019</i>. IEEE, 2019. <a href=\"https://doi.org/10.1109/ITW44776.2019.8989292\">https://doi.org/10.1109/ITW44776.2019.8989292</a>.","apa":"Hledik, M., Sokolowski, T. R., &#38; Tkačik, G. (2019). A tight upper bound on mutual information. In <i>IEEE Information Theory Workshop, ITW 2019</i>. Visby, Sweden: IEEE. <a href=\"https://doi.org/10.1109/ITW44776.2019.8989292\">https://doi.org/10.1109/ITW44776.2019.8989292</a>","ama":"Hledik M, Sokolowski TR, Tkačik G. A tight upper bound on mutual information. In: <i>IEEE Information Theory Workshop, ITW 2019</i>. IEEE; 2019. doi:<a href=\"https://doi.org/10.1109/ITW44776.2019.8989292\">10.1109/ITW44776.2019.8989292</a>"},"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"15020"}]},"_id":"7606","title":"A tight upper bound on mutual information","month":"08","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","project":[{"name":"International IST Doctoral Program","call_identifier":"H2020","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"date_published":"2019-08-01T00:00:00Z","oa_version":"Preprint","year":"2019","date_updated":"2026-04-07T12:59:24Z","publisher":"IEEE","type":"conference","day":"01","status":"public"}]