Advances in Protein Function Prediction from the Fifth CAFA Challenge.

Authors

M Clara De Paolis Kaluza, Rashika Ramola, Parnal Joshi, Damiano Piovesan, Walter Reade, Sandra Orchard, Maria J Martin, Alex Ignatchenko, Burkhard Rost, Christine A Orengo, Marc Robinson-Rechavi, Dannie Durand, Steven E Brenner, Casey S Greene, Sean D Mooney, Iddo Friedberg, Predrag Radivojac

Published in

bioRxiv : the preprint server for biology. Jun 10, 2026. Epub Jun 10, 2026.

Abstract

The Critical Assessment of Functional Annotation (CAFA) is a long-standing community effort to independently assess computational methods for protein function prediction, to highlight well-performing methodologies, to identify bottlenecks in the field, and to provide a forum for the dissemination of results and exchange of ideas. In its fifth round (CAFA5) of triennial challenges, a partnership with Kaggle Inc. facilitated participation from a large community of data scientists and computational biologists through a competitive prospective challenge on the crowdsourcing platform. In this work, we present an in-depth analysis of the submitted predictions and report improvements in accuracy over all methods from the previous CAFA challenges. We further introduce a new evaluation setting for proteins with pre-existing (incomplete) annotations and identify the need for methods that better leverage existing annotations to predict those that will be discovered later. Finally, we characterize the prospective evaluation framework by examining performance on a strict set of unpublished annotations and across intermediate database releases. Our results indicate that recent developments in the field, such as the availability of protein language models and accurately predicted 3D structures, as well as the growth of experimental annotations through biocuration, have all contributed to performance improvements.

PMID:
42094442
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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