A compendium of human gene functions derived from evolutionary modelling

作者：Marc Feuermann, Huaiyu Mi, Pascale Gaudet, Anushya Muruganujan, Suzanna Lewis, Dustin Ebert, Tremayne Mushayahama, Suzi Aleksander, James P. Balhoff, Seth J Carbon, J. Michael Cherry, Harold Drabkin, Nomi L. Harris, David P. Hill, Raymond Lee, Colin Logie, Sierra A. Taylor Moxon, Chris Mungall, Paul W. Sternberg, Kimberly M. Van Auken, CACAO/EcoliWiki, Jolene Ramsey, Deborah A. Siegele, dictyBase, Rex L. Chisholm, Petra Fey, Evidence and Conclusion Ontology, Michelle Gwinn Giglio, Suvarna Nadendla, FlyBase, Giulia Antonazzo, Helen Attrill, Nicholas H. Brown, Phani V Garapati, Steven J Marygold, Functional Gene Annotation UCL, 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, Mouse Genome Informatics, Judith A. Blake, Karen Christie, Lori E Corbani, Mary Eileen Dolan, Li Ni, Dmitry M. Sitnikov, Cynthia L. Smith, PomBase, Manuel Lera-Ramírez, Kim Rutherford, Valerie Wood, Reactome, Peter D’Eustachio, Rat Genome Database, Wendy Demos, Jeff 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, Saccharomyces Genome Database, 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, Lennart Niels Cornelisse, Jaime de Juan‐Sanz, Hana L. Goldschmidt, Eckart Dieter 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 M. O'Connor, Rainer Pielot, Timothy P. Ryan, Carlo Sala, Morgan Sheng, Karl‐Heinz Smalla, August Benjamin Smit, Ruud F. G. Toonen, Jan R.T. van Weering, Matthijs Verhage, Chiara Verpelli, The Arabidopsis Information Resource (TAIR), Erika Bakker, Tanya Berardini, Leonore Reiser, Andrea H Auchincloss, Kristian B. Axelsen, Ghislaine Argoud‐Puy, Marie-Claude Blatter, Emmanuel Boutet, Lionel Breuza, Alan James 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 C. DENNY, Alexandr Ignatchenko, Rizwan Ishtiaq, Antonia Lock, Yvonne Lussi, Michele Magrane, Maria Jesus Martin, Sandra E. Orchard, Pedro Raposo, Elena Speretta, Nidhi Tyagi, Kate A. Warner, Rossana Zaru, WormBase, Juancarlos Chan, Stavros Diamantakis, Daniela Raciti, Xenbase, Malcolm E Fisher, Christina James‐Zorn, Virgilio G. Ponferrada, Aaron M. Zorn, Zebrafish Information Network (ZFIN), Sridhar Ramachandran, Leyla Ruzicka, Monte Westerfield, Paul D. Thomas · 发表于：Nature · 年份：2025 · DOI：10.1038/s41586-025-08592-0 · 被引用次数：41 · 研究领域：Bioinformatics and Genomic Networks、Biomedical Text Mining and Ontologies、Genomics and Phylogenetic Studies

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 re...