{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T15:10:23Z","timestamp":1789744223872,"version":"4.0.1"},"reference-count":42,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The rapid growth of high-throughput biology and genomics over the past two decades has helped catalogue many different aspects of gene function in diverse cell types and conditions. More recently, advances in artificial intelligence and deep learning have shown tremendous promise in making accurate predictions of functional genomics measurements. These advances make it tempting to equate experimental cataloguing and accurate prediction with the growth of our theoretical understanding of biological processes \u2013 an equivalence we believe is ultimately misleading.<\/jats:p>","DOI":"10.7554\/elife.112987","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:15:07Z","timestamp":1789125307000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.112987","source":"Crossref","is-referenced-by-count":0,"title":["The power of theory in the life sciences"],"prefix":"10.7554","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1611-5398","authenticated-orcid":true,"given":"Jacob L","family":"Fine","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"Donnelly Centre, University of Toronto","place":["Toronto, Canada"]},{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"Molecular Genetics, University of Toronto","place":["Toronto, Canada"]},{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"Genome Biology and Bioinformatics, University of Toronto","place":["Toronto, Canada"]},{"id":[{"id":"https:\/\/ror.org\/03kqdja62","id-type":"ROR","asserted-by":"publisher"}],"name":"Vector Institute","place":["Toronto, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1573-8864","authenticated-orcid":true,"given":"Finn","family":"Creeggan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wra1b14","id-type":"ROR","asserted-by":"publisher"}],"name":"Arc Institute","place":["Palo Alto, United States"]},{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"Montreal Neurological Institute-Hospital, McGill University","place":["Montr\u00e9al, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0451-3276","authenticated-orcid":true,"given":"Joshua","family":"Gertsvolf","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wra1b14","id-type":"ROR","asserted-by":"publisher"}],"name":"Arc Institute","place":["Palo Alto, United States"]},{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"Montreal Neurological Institute-Hospital, McGill University","place":["Montr\u00e9al, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8855-9215","authenticated-orcid":true,"given":"Purav","family":"Gupta","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"Donnelly Centre, University of Toronto","place":["Toronto, Canada"]},{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"Molecular Genetics, University of Toronto","place":["Toronto, Canada"]},{"id":[{"id":"https:\/\/ror.org\/03kqdja62","id-type":"ROR","asserted-by":"publisher"}],"name":"Vector Institute","place":["Toronto, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5878-0973","authenticated-orcid":true,"given":"Adam MR","family":"Groh","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"Montreal Neurological Institute-Hospital, McGill University","place":["Montr\u00e9al, Canada"]},{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"Integrated Program in Neuroscience, McGill University","place":["Montr\u00e9al, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1101\/2025.06.26.661135","type":"preprint","article-title":"Predicting cellular responses to perturbation across diverse contexts with state","volume-title":"bioRxiv","author":"Adduri","year":"2025"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1038\/s41592-021-01252-x","type":"journal-article","article-title":"Effective gene expression prediction from sequence by integrating long-range interactions","volume":"18","author":"Avsec","year":"2021","journal-title":"Nature Methods"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.64898\/2026.01.30.702911","type":"preprint","article-title":"Science should be machine-readable","volume-title":"bioRxiv","author":"Booeshaghi","year":"2026"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1023\/A:1010933404324","type":"journal-article","article-title":"Random forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Machine Learning"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1038\/s41586-026-10176-5","type":"journal-article","article-title":"Genome modelling and design across all domains of life with Evo 2","volume":"652","author":"Brixi","year":"2026","journal-title":"Nature"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1126\/science.1204553","type":"journal-article","article-title":"Information transduction capacity of noisy biochemical signaling networks","volume":"334","author":"Cheong","year":"2011","journal-title":"Science"},{"key":"bib7","doi-asserted-by":"publisher","DOI":"10.64898\/2026.03.02.709176","type":"preprint","article-title":"Towards building a world model to simulate perturbation-induced cellular dynamics by AlphaCell","volume-title":"bioRxiv","author":"Chuai","year":"2026"},{"key":"bib8","volume-title":"On the Origin of Species","author":"Darwin","year":"1859","type":"book"},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.64898\/2026.02.04.703804","type":"preprint","article-title":"Virtual cells need context, not just scale","volume-title":"bioRxiv","author":"Dibaeinia","year":"2026"},{"key":"bib10","doi-asserted-by":"publisher","DOI":"10.31222\/osf.io\/ysv2u_v2","type":"preprint","article-title":"Against theory-motivated experimentation in science","volume-title":"MetaArXiv","author":"Dubova","year":"2022"},{"key":"bib11","doi-asserted-by":"publisher","DOI":"10.7208\/chicago\/9780226771137.001.0001","type":"book","volume-title":"Theory and Reality: An Introduction to the Philosophy of Science","author":"Godfrey-Smith","year":"2021"},{"key":"bib12","volume-title":"Philosophy of Natural Science","author":"Hempel","year":"1966","type":"book"},{"key":"bib13","volume-title":"The Statue Within: An Autobiography","author":"Jacob","year":"1988","type":"book"},{"key":"bib14","volume-title":"The Eighth Day of Creation: Makers of the Revolution in Biology","author":"Judson","year":"2011","type":"book"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.1515\/9781503617575","type":"book","volume-title":"Who Wrote the Book of Life? A History of the Genetic Code","author":"Kay","year":"2000"},{"key":"bib16","first-page":"410","type":"book-chapter","article-title":"Explanatory unification and the causal structure of the world","volume-title":"Scientific Explanation","author":"Kitcher","year":"1989"},{"key":"bib17","doi-asserted-by":"publisher","DOI":"10.1093\/oso\/9780195151787.001.0001","type":"book","volume-title":"In Mendel\u2019s Mirror: Philosophical Reflections on Biology","author":"Kitcher","year":"2003"},{"key":"bib18","volume-title":"The Structure of Scientific Revolutions","author":"Kuhn","year":"1962","type":"book"},{"key":"bib19","type":"preprint","article-title":"The inductive bias of convolutional neural networks: locality and weight sharing reshape implicit regularization","volume-title":"arXiv","author":"Liang","year":"2026","unstructured":"Liang T, Singh E, Parhi R, Cloninger A, Wang YX. 2026. The inductive bias of convolutional neural networks: locality and weight sharing reshape implicit regularization. arXiv. http:\/\/arxiv.org\/abs\/2603.04807."},{"key":"bib20","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1038\/s41588-024-02053-6","type":"journal-article","article-title":"Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation","volume":"57","author":"Linder","year":"2025","journal-title":"Nature Genetics"},{"key":"bib21","volume-title":"The Growth of Biological Thought: Diversity, Evolution, and Inheritance","author":"Mayr","year":"1982","type":"book"},{"key":"bib22","doi-asserted-by":"crossref","DOI":"10.1119\/1.1937571","type":"book","volume-title":"The Structure of Science: Problems in the Logic of Scientific Explanation","author":"Nagel","year":"1961"},{"key":"bib23","doi-asserted-by":"publisher","DOI":"10.1126\/science.ado9336","type":"journal-article","article-title":"Sequence modeling and design from molecular to genome scale with Evo","volume":"386","author":"Nguyen","year":"2024","journal-title":"Science"},{"key":"bib24","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-021-02480-z","type":"journal-article","article-title":"Biology must generate ideas as well as data","volume":"597","author":"Nurse","year":"2021","journal-title":"Nature"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/0004-3702(86)90072-X","type":"journal-article","article-title":"Fusion, propagation, and structuring in belief networks","volume":"29","author":"Pearl","year":"1986","journal-title":"Artificial Intelligence"},{"key":"bib26","volume-title":"The Logic of Scientific Discovery","author":"Popper","year":"1992","type":"book"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"6421","DOI":"10.1016\/j.cell.2024.10.029","type":"journal-article","article-title":"The cellular dogma","volume":"187","author":"Quake","year":"2024","journal-title":"Cell"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/0022-2836(86)90165-8","type":"journal-article","article-title":"Information content of binding sites on nucleotide sequences","volume":"188","author":"Schneider","year":"1986","journal-title":"Journal of Molecular Biology"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1109\/memb.2006.1578661","type":"journal-article","article-title":"Claude Shannon: biologist. The founder of information theory used biology to formulate the channel capacity","volume":"25","author":"Schneider","year":"2006","journal-title":"IEEE Engineering in Medicine and Biology Magazine"},{"key":"bib30","volume-title":"What Is Life? The Physical Aspect of the Living Cell","author":"Schr\u00f6dinger","year":"1944","type":"book"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1002\/j.1538-7305.1948.tb01338.x","type":"journal-article","article-title":"A mathematical theory of communication","volume":"27","author":"Shannon","year":"1948","journal-title":"Bell System Technical Journal"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1214\/10-STS330","type":"journal-article","article-title":"To Explain or to Predict?","volume":"25","author":"Shmueli","year":"2010","journal-title":"Statistical Science"},{"key":"bib33","doi-asserted-by":"publisher","DOI":"10.64898\/2026.02.11.705358","type":"preprint","article-title":"Parameter-free representations outperform single-cell foundation models on downstream benchmarks","volume-title":"bioRxiv","author":"Souza","year":"2026"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.64898\/2026.06.09.731197","type":"preprint","article-title":"Back to basics: observed statistics are sufficient to predict drug responses","volume-title":"bioRxiv","author":"Svensson","year":"2026"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.1088\/1361-6633\/ac7a4a","type":"journal-article","article-title":"Quantifying information of intracellular signaling: progress with machine learning","volume":"85","author":"Tang","year":"2022","journal-title":"Reports on Progress in Physics. Physical Society"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1038\/s41586-023-06139-9","type":"journal-article","article-title":"Transfer learning enables predictions in network biology","volume":"618","author":"Theodoris","year":"2023","journal-title":"Nature"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s12551-020-00665-w","type":"journal-article","article-title":"Application of information theory in systems biology","volume":"12","author":"Uda","year":"2020","journal-title":"Biophysical Reviews"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1706.03762","type":"preprint","article-title":"Attention is all you need","volume-title":"arXiv","author":"Vaswani","year":"2023"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1038\/s41586-023-06415-8","type":"journal-article","article-title":"De novo design of protein structure and function with RFdiffusion","volume":"620","author":"Watson","year":"2023","journal-title":"Nature"},{"key":"bib40","doi-asserted-by":"publisher","DOI":"10.1093\/0195155270.001.0001","type":"book","volume-title":"Making Things Happen: A Theory of Causal Explanation","author":"Woodward","year":"2003"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1800-6","type":"journal-article","article-title":"Night science","volume":"20","author":"Yanai","year":"2019","journal-title":"Genome Biology"},{"key":"bib42","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-02133-w","type":"journal-article","article-title":"A hypothesis is a liability","volume":"21","author":"Yanai","year":"2020","journal-title":"Genome Biology"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/112987\/elife-112987-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/112987\/elife-112987-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/112987","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:35:45Z","timestamp":1789742145000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/112987"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":42,"alternative-id":["10.7554\/eLife.112987"],"URL":"https:\/\/doi.org\/10.7554\/elife.112987","archive":["CLOCKSS"],"relation":{},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]},"article-number":"e112987"}}