{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T19:54:48Z","timestamp":1774036488421,"version":"3.50.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:p>DIAMOND2GO (D2GO) is a high-speed toolset for assigning Gene Ontology (GO) terms to genes or proteins based on sequence similarity. Leveraging the ultra-fast 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 min on a standard laptop. In addition to annotation, D2GO includes an enrichment analysis tool that allows 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 <jats:ext-link>https:\/\/github.com\/rhysf\/DIAMOND2GO<\/jats:ext-link>.<\/jats:p>","DOI":"10.3389\/fbinf.2025.1634042","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T05:29:03Z","timestamp":1755235743000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["DIAMOND2GO: rapid Gene Ontology assignment and enrichment detection for functional genomics"],"prefix":"10.3389","volume":"5","author":[{"given":"Christopher","family":"Golden","sequence":"first","affiliation":[]},{"given":"David J.","family":"Studholme","sequence":"additional","affiliation":[]},{"given":"Rhys A.","family":"Farrer","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"iyad031","DOI":"10.1093\/genetics\/iyad031","article-title":"The gene ontology knowledgebase in 2023","volume":"224","author":"Aleksander","year":"2023","journal-title":"Genetics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1093\/nar\/28.1.45","article-title":"The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000","volume":"28","author":"Bairoch","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"B4","unstructured":"BioBam\n          \n          \n          2024"},{"key":"B5","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nmeth.3176","article-title":"Fast and sensitive protein alignment using DIAMOND","volume":"12","author":"Buchfink","year":"2015","journal-title":"Nat. Methods."},{"key":"B6","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1093\/bioinformatics\/btn615","article-title":"AmiGO: online access to ontology and annotation data","volume":"25","author":"Carbon","year":"2009","journal-title":"Bioinformatics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3674","DOI":"10.1093\/bioinformatics\/bti610","article-title":"Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research","volume":"21","author":"Conesa","year":"2005","journal-title":"Bioinformatics"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e0198216","DOI":"10.1371\/journal.pone.0198216","article-title":"Predicting human protein function with multi-task deep neural networks","volume":"13","author":"Fa","year":"2018","journal-title":"PLOS ONE"},{"key":"B9","doi-asserted-by":"publisher","first-page":"D222","DOI":"10.1093\/nar\/gkt1223","article-title":"Pfam: the protein families database","volume":"42","author":"Finn","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1093\/bib\/bbr042","article-title":"Phylogenetic-based propagation of functional annotations within the gene ontology consortium","volume":"12","author":"Gaudet","year":"2011","journal-title":"Briefings Bioinforma."},{"key":"B11","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s12859-015-0611-3","article-title":"InteractiVenn: a web-based tool for the analysis of sets through venn diagrams","volume":"16","author":"Heberle","year":"2015","journal-title":"BMC Bioinforma."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1093\/molbev\/msx148","article-title":"Fast genome-wide functional annotation through orthology assignment by eggNOG-Mapper","volume":"34","author":"Huerta-Cepas","year":"2017","journal-title":"Mol. Biol. Evol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"D211","DOI":"10.1093\/nar\/gkn785","article-title":"InterPro: the integrative protein signature database","volume":"37","author":"Hunter","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1038\/nature03001","article-title":"Finishing the euchromatic sequence of the human genome","volume":"431","year":"2004","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.ajhg.2009.09.003","article-title":"Clinical diagnostics in human genetics with semantic similarity searches in ontologies","volume":"85","author":"K\u00f6hler","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/35057062","article-title":"Initial sequencing and analysis of the human genome","volume":"409","author":"Lander","year":"2001","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1109\/eScience.2008.62","article-title":"CloudBLAST: combining MapReduce and virtualization on distributed resources for bioinformatics applications","volume-title":"2008 IEEE fourth international conference on eScience","author":"Matsunaga","year":"2008"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e12931","DOI":"10.7717\/peerj.12931","article-title":"Wei2GO: weighted sequence similarity-based protein function prediction","volume":"10","author":"Reijnders","year":"2022","journal-title":"PeerJ"},{"key":"B20","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s13059-019-1715-2","article-title":"Next-generation genome annotation: we still struggle to get it right","volume":"20","author":"Salzberg","year":"2019","journal-title":"Genome Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"619","DOI":"10.6000\/1927-5129.2015.11.83","article-title":"Gene ontology tools: a comparative study","volume":"11","author":"Shahzad","year":"2015","journal-title":"J. basic Appl. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"110185","DOI":"10.1016\/j.compbiomed.2025.110185","article-title":"GOReverseLookup: a gene ontology reverse lookup tool","volume":"191","author":"\u0160korjanc","year":"2025","journal-title":"Comput. Biol. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1038\/nbt1346","article-title":"The OBO foundry: coordinated evolution of ontologies to support biomedical data integration","volume":"25","author":"Smith","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"9440","DOI":"10.1073\/pnas.1530509100","article-title":"Statistical significance for genomewide studies","volume":"100","author":"Storey","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B25","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/pro.4218","article-title":"PANTHER: making genome-scale phylogenetics accessible to all","volume":"31","author":"Thomas","year":"2022","journal-title":"Protein Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1038\/s41588-019-0500-1","article-title":"Gene ontology causal activity modeling (GO-CAM) moves beyond GO annotations to structured descriptions of biological functions and systems","volume":"51","author":"Thomas","year":"2019","journal-title":"Nat. Genet."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e2212633120","DOI":"10.1073\/pnas.2212633120","article-title":"Two-speed genome evolution drives pathogenicity in fungal pathogens of animals","volume":"120","author":"Wacker","year":"2023","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1093\/bioinformatics\/bty130","article-title":"GOLabeler: improving sequence-based large-scale protein function prediction by learning to rank","volume":"34","author":"You","year":"2018","journal-title":"Bioinforma. Oxf. Engl."},{"key":"B29","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1186\/s13059-019-1835-8","article-title":"The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens","volume":"20","author":"Zhou","year":"2019","journal-title":"Genome Biol."}],"container-title":["Frontiers in Bioinformatics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2025.1634042\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T05:29:05Z","timestamp":1755235745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2025.1634042\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,15]]},"references-count":29,"alternative-id":["10.3389\/fbinf.2025.1634042"],"URL":"https:\/\/doi.org\/10.3389\/fbinf.2025.1634042","relation":{},"ISSN":["2673-7647"],"issn-type":[{"value":"2673-7647","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,15]]},"article-number":"1634042"}}