A compendium of human gene functions derived from evolutionary modelling
Abstract
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.
Article Details
Authors (164)
Marc Feuermann
Huaiyu Mi
Pascale Gaudet
Anushya Muruganujan
Suzanna E. Lewis
Dustin Ebert
Tremayne Mushayahama
Suzanne A. Aleksander
James Balhoff
Seth Carbon
J. Michael Cherry
Harold J. Drabkin
Nomi L. Harris
David P. Hill
Raymond Lee
Colin Logie
Sierra Moxon
Christopher J. 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 V. Garapati
Steven Marygold
Saadullah H. Ahmed
Praoparn Asanitthong
Diana Luna Buitrago
Meltem N. Erdol
Matthew C. Gage
Siyao Huang
Mohamed Ali Kadhum
Kan Yan Chloe Li
Miao Long
Aleksandra Michalak
Angeline Pesala
Armalya Pritazahra
Shirin C. C. Saverimuttu
Renzhi Su
Qianhan Xu
Ruth C. Lovering
Judith Blake
Karen Christie
Lori Corbani
Mary E. Dolan
Li Ni
Dmitry Sitnikov
Cynthia Smith
Manuel Lera-Ramirez
Kim Rutherford
Valerie Wood
Peter D’Eustachio
Wendy M. 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 A. 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 A. Ryan
Carlo Sala
Morgan Sheng
Karl-Heinz Smalla
A. B. Smit
Ruud F. Toonen
Jan R. T. van Weering
Matthijs Verhage
Chiara Verpelli
Erika Bakker
Tanya Z. Berardini
Leonore Reiser
Andrea Auchincloss
Kristian 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
Maria J. Martin
Sandra Orchard
Pedro Raposo
Elena Speretta
Nidhi Tyagi
Kate Warner
Rossana Zaru
Juancarlos Chan
Stavros Diamantakis
Daniela Raciti
Malcolm Fisher
Christina James-Zorn
Virgilio Ponferrada
Aaron Zorn
Sridhar Ramachandran
Leyla Ruzicka
Monte Westerfield
Paul D. Thomas