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Record W4407956796 · doi:10.1038/s41586-025-08592-0

A compendium of human gene functions derived from evolutionary modelling

2025· article· en· W4407956796 on OpenAlexaff
Marc Feuermann, Huaiyu Mi, Pascale Gaudet, Anushya Muruganujan, Suzanna Lewis, Dustin Ebert, Tremayne Mushayahama, Suzi Aleksander, James P. Balhoff, Seth Carbon, J. Michael Cherry, Harold Drabkin, Nomi L. Harris, David P. Hill, Raymond Lee, Colin Logie, Sierra Moxon, Chris Mungall, Paul W. Sternberg, Kimberly Van Auken, Jolene Ramsey, Deborah A. Siegele, Rex L. Chisholm, Petra Fey, Michelle Giglio, Suvarna Nadendla, Giulia Antonazzo, Helen Attrill, Nicholas H. Brown, Phani Garapati, Steven J Marygold, Saadullah H. Ahmed, Praoparn Asanitthong, Diana Luna Buitrago, Meltem N Erdol, Matthew Gage, SI-YAO HUANG, Mohamed Ali Kadhum, Kan Yan Chloe Li, Miao Long, Aleksandra Michalak, Angeline Pesala, Armalya Pritazahra, Shirin C C Saverimuttu, Renzhi Su, Qiang Xu, Ruth C. Lovering, Judith A. Blake, Karen Christie, Lori E Corbani, M. Eileen Dolan, Li Ni, Dmitry Sitnikov, Cynthia L. Smith, Manuel Lera-Ramírez, Kim Rutherford, Valerie Wood, Peter D’Eustachio, Wendy Demos, Jeffrey L De Pons, Melinda R. Dwinell, G. Thomas Hayman, Mary L. Kaldunski, Anne E. Kwitek, Stanley J. F. Laulederkind, Jennifer R. Smith, Marek Tutaj, Mahima Vedi, Shur‐Jen Wang, Stacia R. Engel, Kalpana Karra, Stuart R. Miyasato, Robert S Nash, Marek S. Skrzypek, Shuai Weng, Edith D. Wong, Tilmann Achsel, Maria Andres‐Alonso, Claudia Bagni, Àlex Bayés, Thomas Biederer, Nils Brose, John Jia En Chua, Marcelo P. Coba, L. Niels Cornelisse, Jaime de Juan‐Sanz, Hana L. Goldschmidt, Eckart D. Gundelfinger, Richard L. Huganir, Cordelia Imig, Reinhard Jahn, Hwajin Jung, Pascal S. Kaeser, Eunjoon Kim, Frank Koopmans, Michael R. Kreutz, Noa Lipstein, Harold D. MacGillavry, Peter S. McPherson, Vincent O’Connor, Rainer Pielot, Timothy P. Ryan, Carlo Sala, Morgan Sheng, Karl‐Heinz Smalla, August B. Smit, Ruud F. Toonen, Jan R.T. van Weering, Matthijs Verhage, Chiara Verpelli, Erika Bakker, Tanya Berardini, Leonore Reiser, Andrea H Auchincloss, Kristian B. Axelsen, Ghislaine Argoud‐Puy, Marie-Claude Blatter, Emmanuel Boutet, Lionel Breuza, Alan Bridge, Cristina Casals‐Casas, Elisabeth Coudert, Anne Estreicher, Maria Livia Famiglietti, Arnaud Gos, Nadine Gruaz-Gumowski, Chantal Hulo, Nevila Hyka‐Nouspikel, Florence Jungo, Philippe Le Mercier, Damien Lieberherr, Patrick Masson, Anne Morgat, Ivo Pedruzzi, Lucille Pourcel, Sylvain Poux, Catherine Rivoire, Shyamala Sundaram, Emily Bowler-Barnett, Hema Bye‐A‐Jee, Paul Denny, Alexandr Ignatchenko, Rizwan Ishtiaq, Antonia Lock, Yvonne Lussi, Michele Magrane, María Martin, Sandra Orchard, Pedro Raposo, Elena Speretta, Nidhi Tyagi, Kate Warner, Rossana Zaru, Juancarlos Chan, Stavros Diamantakis, Daniela Raciti, Malcolm E Fisher, Christina James‐Zorn, Virgilio Ponferrada, Aaron M. Zorn, Sridhar Ramachandran, Leyla Ruzicka, Monte Westerfield, Paul D. Thomas

Bibliographic record

VenueNature · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBioinformatics and Genomic Networks
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersBasic Energy SciencesNational Institute of Child Health and Human DevelopmentWellcome TrustNational Human Genome Research InstituteMedical Research CouncilNational Institutes of HealthNational Institute for Health and Care ResearchAustralian GovernmentNational Heart, Lung, and Blood InstituteStaatssekretariat für Bildung, Forschung und InnovationEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentU.S. Department of EnergyOffice of ScienceUniversity College London
KeywordsCompendiumGeneComputational biologyRepertoireHuman genomeSet (abstract data type)Representation (politics)Gene nomenclatureComputer scienceGenomeBiologyOntologyGenetics

Abstract

fetched live from OpenAlex

Abstract A comprehensive, computable representation of the functional repertoire of all macromolecules encoded within the human genome is a foundational resource for biology and biomedical research. The Gene Ontology Consortium has been working towards this goal by generating a structured body of information about gene functions, which now includes experimental findings reported in more than 175,000 publications for human genes and genes in experimentally tractable model organisms1,2. Here, we describe the results of a large, international effort to integrate all of these findings to create a representation of human gene functions that is as complete and accurate as possible. Specifically, we apply an expert-curated, explicit evolutionary modelling approach to all human protein-coding genes. This approach integrates available experimental information across families of related genes into models that reconstruct the gain and loss of functional characteristics over evolutionary time. The models and the resulting set of 68,667 integrated gene functions cover approximately 82% of human protein-coding genes. The functional repertoire reveals a marked preponderance of molecular regulatory functions, and the models provide insights into the evolutionary origins of human gene functions. We show that our set of descriptions of functions can improve the widely used genomic technique of Gene Ontology enrichment analysis. The experimental evidence for each functional characteristic is recorded, thereby enabling the scientific community to help review and improve the resource, which we have made publicly available.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.008
Threshold uncertainty score0.025

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0040.004
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0080.003

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.006
GPT teacher head0.231
Teacher spread0.224 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations34
Published2025
Admission routes1
Has abstractyes

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