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BRIEF RESEARCH REPORT article

Front. Bioinform.

Sec. Genomic Analysis

Volume 5 - 2025 | doi: 10.3389/fbinf.2025.1634042

DIAMOND2GO: Rapid Gene Ontology assignment and enrichment detection for functional genomics

Provisionally accepted
  • 1Medical Research Council Centre for Medical Mycology at the University of Exeter, Exeter, United Kingdom
  • 2University of Exeter, Exeter, United Kingdom

The final, formatted version of the article will be published soon.

DIAMOND2GO (D2GO) is a high-speed toolset for assigning Gene Ontology (GO) terms to genes or proteins based on sequence similarity. Leveraging the ultrafast alignment capabilities of DIAMOND, which is 100 to 20,000 times faster than BLAST, D2GO enables rapid functional annotation of large-scale datasets. D2GO maps GO terms from pre-annotated sequences in the NCBI non-redundant database to query sequences. During benchmarking, D2GO assigned over 2 million GO terms to 98% of 130,184 predicted human protein isoforms in under 13 minutes on a standard laptop. In addition to annotation, D2GO includes an enrichment analysis tool, allowing users to identify significantly overrepresented GO terms between subsets of sequences. We compared D2GO against two widely used tools, Blast2GO and EggNOG-mapper, and observed substantial differences in the number and type of annotations produced. These discrepancies reflect varying sensitivities and specificities across tools and suggest that using multiple methods in tandem may improve overall annotation coverage. D2GO is open-source and freely available under the MIT license at: https://github.com/rhysf/DIAMOND2GO

Keywords: Functional Genomics, Software, Diamond, gene ontology, Enrichment analyses

Received: 23 May 2025; Accepted: 24 Jul 2025.

Copyright: © 2025 Golden, Studholme and Farrer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Rhys Alexander Farrer, Medical Research Council Centre for Medical Mycology at the University of Exeter, Exeter, United Kingdom

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