{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:09:42Z","timestamp":1783591782567,"version":"3.55.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Inter-Disciplinary Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>The rapid accumulation of high-throughput sequence data demands the development of effective and efficient data-driven computational methods to functionally annotate proteins. However, most current approaches used for functional annotation simply focus on the use of protein-level information but ignore inter-relationships among annotations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we established PFresGO, an attention-based deep-learning approach that incorporates hierarchical structures in Gene Ontology (GO) graphs and advances in natural language processing algorithms for the functional annotation of proteins. PFresGO employs a self-attention operation to capture the inter-relationships of GO terms, updates its embedding accordingly and uses a cross-attention operation to project protein representations and GO embedding into a common latent space to identify global protein sequence patterns and local functional residues. We demonstrate that PFresGO consistently achieves superior performance across GO categories when compared with \u2018state-of-the-art\u2019 methods. Importantly, we show that PFresGO can identify functionally important residues in protein sequences by assessing the distribution of attention weightings. PFresGO should serve as an effective tool for the accurate functional annotation of proteins and functional domains within proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>PFresGO is available for academic purposes at https:\/\/github.com\/BioColLab\/PFresGO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btad094","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T13:45:12Z","timestamp":1676555112000},"source":"Crossref","is-referenced-by-count":46,"title":["PFresGO: an attention mechanism-based deep-learning approach for protein annotation by integrating gene ontology inter-relationships"],"prefix":"10.1093","volume":"39","author":[{"given":"Tong","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1847-754X","authenticated-orcid":false,"given":"Chen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4423-1690","authenticated-orcid":false,"given":"Robin B","family":"Gasser","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, Melbourne Veterinary School, The University of Melbourne , Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony W","family":"Purcell","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9763-797X","authenticated-orcid":false,"given":"Tatsuya","family":"Akutsu","sequence":"additional","affiliation":[{"name":"Bioinformatics Center, Institute for Chemical Research, Kyoto University , Uji 611-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey I","family":"Webb","sequence":"additional","affiliation":[{"name":"Monash Data Futures Institute, Monash University , Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2989-308X","authenticated-orcid":false,"given":"Seiya","family":"Imoto","sequence":"additional","affiliation":[{"name":"Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku , Tokyo 108-8639, Japan"},{"name":"Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Bunkyo-ku , Tokyo 113-8657, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8031-9086","authenticated-orcid":false,"given":"Jiangning","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Melbourne, VIC 3800, Australia"},{"name":"Bioinformatics Center, Institute for Chemical Research, Kyoto University , Uji 611-0011, Japan"},{"name":"Monash Data Futures Institute, Monash University , Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"2023030207415950100_","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/nar\/28.1.304","article-title":"The ENZYME database in 2000","volume":"28","author":"Bairoch","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"2023030207415950100_","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0025-5564(03)00096-8","article-title":"Protein function classification via support vector machine approach","volume":"185","author":"Cai","year":"2003","journal-title":"Math. 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