The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

Naihui Zhou, Yuxiang Jiang, Timothy R. Bergquist, Alexandra J. Lee, Balint Z. Kacsoh, Alex W. Crocker, Kimberley A. Lewis, George Georghiou, Huy N. Nguyen, Md Nafiz Hamid, Larry Davis, Tunca Dogan, Volkan Atalay, Ahmet S. Rifaioglu, Alperen Dalklran, Rengul Cetin Atalay, Chengxin Zhang, Rebecca L. Hurto, Peter L. Freddolino, Yang ZhangPrajwal Bhat, Fran Supek, José M. Fernández, Branislava Gemovic, Vladimir R. Perovic, Radoslav S. Davidović, Neven Sumonja, Nevena Veljkovic, Ehsaneddin Asgari, Mohammad R.K. Mofrad, Giuseppe Profiti, Castrense Savojardo, Pier Luigi Martelli, Rita Casadio, Florian Boecker, Heiko Schoof, Indika Kahanda, Natalie Thurlby, Alice C. McHardy, Alexandre Renaux, Rabie Saidi, Julian Gough, Alex A. Freitas, Magdalena Antczak, Fabio Fabris, Mark N. Wass, Jie Hou, Jianlin Cheng, Zheng Wang, Alfonso E. Romero, Alberto Paccanaro, Haixuan Yang, Tatyana Goldberg, Chenguang Zhao, Liisa Holm, Petri Törönen, Alan J. Medlar, Elaine Zosa, Itamar Borukhov, Ilya Novikov, Angela Wilkins, Olivier Lichtarge, Po Han Chi, Wei Cheng Tseng, Michal Linial, Peter W. Rose, Christophe Dessimoz, Vedrana Vidulin, Saso Dzeroski, Ian Sillitoe, Sayoni Das, Jonathan Gill Lees, David T. Jones, Cen Wan, Domenico Cozzetto, Rui Fa, Mateo Torres, Alex Warwick Vesztrocy, Jose Manuel Rodriguez, Michael L. Tress, Marco Frasca, Marco Notaro, Giuliano Grossi, Alessandro Petrini, Matteo Re, Giorgio Valentini, Marco Mesiti, Daniel B. Roche, Jonas Reeb, David W. Ritchie, Sabeur Aridhi, Seyed Ziaeddin Alborzi, Marie Dominique Devignes, Da Chen Emily Koo, Richard Bonneau, Vladimir Gligorijević, Meet Barot, Hai Fang, Stefano Toppo, Enrico Lavezzo, Marco Falda, Michele Berselli, Silvio C.E. Tosatto, Marco Carraro, Damiano Piovesan, Hafeez Ur Rehman, Qizhong Mao, Shanshan Zhang, Slobodan Vucetic, Gage S. Black, Dane Jo, Erica Suh, Jonathan B. Dayton, Dallas J. Larsen, Ashton R. Omdahl, Liam J. McGuffin, Danielle A. Brackenridge, Patricia C. Babbitt, Jeffrey M. Yunes, Paolo Fontana, Feng Zhang, Shanfeng Zhu, Ronghui You, Zihan Zhang, Suyang Dai, Shuwei Yao, Weidong Tian, Renzhi Cao, Caleb Chandler, Miguel Amezola, Devon Johnson, Jia Ming Chang, Wen Hung Liao, Yi Wei Liu, Stefano Pascarelli, Yotam Frank, Robert Hoehndorf, Maxat Kulmanov, Imane Boudellioua, Gianfranco Politano, Stefano Di Carlo, Alfredo Benso, Kai Hakala, Filip Ginter, Farrokh Mehryary, Suwisa Kaewphan, Jari Björne, Hans Moen, Martti E.E. Tolvanen, Tapio Salakoski, Daisuke Kihara, Aashish Jain, Tomislav Šmuc, Adrian Altenhoff, Asa Ben-Hur, Burkhard Rost, Steven E. Brenner, Christine A. Orengo, Constance J. Jeffery, Giovanni Bosco, Deborah A. Hogan, Maria J. Martin, Claire O'Donovan, Sean D. Mooney, Casey S. Greene, Predrag Radivojac, Iddo Friedberg

Research output: Contribution to journalArticlepeer-review


Background: The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results: Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-Term memory. Conclusion: We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.

Original languageEnglish (US)
Article number244
JournalGenome biology
Issue number1
StatePublished - Nov 19 2019


  • Biofilm
  • Community challenge
  • Critical assessment
  • Long-Term memory
  • Protein function prediction

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology


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