{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T01:12:47Z","timestamp":1770685967765,"version":"3.49.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2018YFC0910504"],"award-info":[{"award-number":["2018YFC0910504"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30ES017885"],"award-info":[{"award-number":["P30ES017885"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U24CA210967"],"award-info":[{"award-number":["U24CA210967"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61702555"],"award-info":[{"award-number":["61702555"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61702556"],"award-info":[{"award-number":["61702556"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61772557"],"award-info":[{"award-number":["61772557"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013314","name":"111 Project","doi-asserted-by":"publisher","award":["B18059"],"award-info":[{"award-number":["B18059"]}],"id":[{"id":"10.13039\/501100013314","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hunan Provincial Science and Technology Program","award":["2018WK4001"],"award-info":[{"award-number":["2018WK4001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>High resolution annotation of gene functions is a central goal in functional genomics. A single gene may produce multiple isoforms with different functions through alternative splicing. Conventional approaches, however, consider a gene as a single entity without differentiating these functionally different isoforms. Towards understanding gene functions at higher resolution, recent efforts have focused on predicting the functions of isoforms. However, the performance of existing methods is far from satisfactory mainly because of the lack of isoform-level functional annotation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We present IsoResolve, a novel approach for isoform function prediction, which leverages the information from gene function prediction models with domain adaptation (DA). IsoResolve treats gene-level and isoform-level features as source and target domains, respectively. It uses DA to project the two domains into a latent variable space in such a way that the latent variables from the two domains have similar distribution, which enables the gene domain information to be leveraged for isoform function prediction. We systematically evaluated the performance of IsoResolve in predicting functions. Compared with five state-of-the-art methods, IsoResolve achieved significantly better performance. IsoResolve was further validated by case studies of genes with isoform-level functional annotation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>IsoResolve is freely available at https:\/\/github.com\/genemine\/IsoResolve.<\/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\/btaa829","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T11:11:42Z","timestamp":1599649902000},"page":"522-530","source":"Crossref","is-referenced-by-count":15,"title":["IsoResolve: predicting splice isoform functions by integrating gene and isoform-level features with domain adaptation"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3438-739X","authenticated-orcid":false,"given":"Hong-Dong","family":"Li","sequence":"first","affiliation":[{"name":"Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and Engineering"}]},{"given":"Changhuo","family":"Yang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and Engineering"}]},{"given":"Zhimin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering, Central South University , Changsha, Hunan 410083, China"}]},{"given":"Mengyun","family":"Yang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and Engineering"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4593-9332","authenticated-orcid":false,"given":"Fang-Xiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Biomedical Engineering, University of Saskatchewan , Saskatoon, SK S7N5A9, Canada"}]},{"given":"Gilbert S","family":"Omenn","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology , Seattle, WA 98101, USA"},{"name":"University of Michigan Department of Computational Medicine & Bioinformatics, , Ann Arbor, MI 48109-2218, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1516-0480","authenticated-orcid":false,"given":"Jianxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and Engineering"}]}],"member":"286","published-online":{"date-parts":[[2020,9,23]]},"reference":[{"key":"2023051706070160600_btaa829-B1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/wics.51","article-title":"Partial least squares regression and projection on latent structure regression (PLS regression)","volume":"2","author":"Abdi","year":"2010","journal-title":"Wiley Interdiscip. Rev. Comput. Stat"},{"key":"2023051706070160600_btaa829-B2","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nrm.2017.27","article-title":"Alternative splicing as a regulator of development and tissue identity","volume":"18","author":"Baralle","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"2023051706070160600_btaa829-B3","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/bfgp\/els038","article-title":"Functional genomics in drosophila models of human disease","volume":"11","author":"Chen","year":"2012","journal-title":"Brief. Funct. Genomics"},{"key":"2023051706070160600_btaa829-B4","doi-asserted-by":"crossref","first-page":"i284","DOI":"10.1093\/bioinformatics\/btz367","article-title":"DIFFUSE: predicting isoform functions from sequences and expression profiles via deep learning","volume":"35","author":"Chen","year":"2019","journal-title":"Bioinformatics"},{"key":"2023051706070160600_btaa829-B5","doi-asserted-by":"crossref","first-page":"e10288","DOI":"10.7554\/eLife.10288","article-title":"An extensive program of periodic alternative splicing linked to cell cycle progression","volume":"5","author":"Dominguez","year":"2016","journal-title":"Elife"},{"key":"2023051706070160600_btaa829-B6","doi-asserted-by":"crossref","first-page":"e1003314","DOI":"10.1371\/journal.pcbi.1003314","article-title":"Systematically differentiating functions for alternatively spliced isoforms through integrating RNA-seq data","volume":"9","author":"Eksi","year":"2013","journal-title":"PLoS Comput. Biol"},{"key":"2023051706070160600_btaa829-B7","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/cem.1225","article-title":"Repeated double cross validation","volume":"23","author":"Filzmoser","year":"2009","journal-title":"J. Chemom"},{"key":"2023051706070160600_btaa829-B8","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1186\/gb-2008-9-s1-s3","article-title":"Predicting gene function in a hierarchical context with an ensemble of classifiers","volume":"9","author":"Guan","year":"2008","journal-title":"Genome Biol"},{"key":"2023051706070160600_btaa829-B9","doi-asserted-by":"crossref","first-page":"e1000991","DOI":"10.1371\/journal.pcbi.1000991","article-title":"Functional genomics complements quantitative genetics in identifying disease-gene associations","volume":"6","author":"Guan","year":"2010","journal-title":"PLoS Comput. Biol"},{"key":"2023051706070160600_btaa829-B10","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1093\/bioinformatics\/btm403","article-title":"Exploring the functional landscape of gene expression: directed search of large microarray compendia","volume":"23","author":"Hibbs","year":"2007","journal-title":"Bioinformatics"},{"key":"2023051706070160600_btaa829-B11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nrc2036","article-title":"Computational prediction of cancer-gene function","volume":"7","author":"Hu","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"2023051706070160600_btaa829-B12","doi-asserted-by":"crossref","first-page":"i197","DOI":"10.1093\/bioinformatics\/btg1026","article-title":"Predicting protein function from protein protein interaction data: a probabilistic approach","volume":"19","author":"Letovsky","year":"2003","journal-title":"Bioinformatics"},{"key":"2023051706070160600_btaa829-B13","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1093\/nar\/gkt1362","article-title":"High-resolution functional annotation of human transcriptome: predicting isoform functions by a novel multiple instance-based label propagation method","volume":"42","author":"Li","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2023051706070160600_btaa829-B14","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.neucom.2020.03.006","article-title":"Enhancing the feature representation of multi-modal MRI data by combining multi-view information for MCI classification","volume":"400","author":"Liu","year":"2020","journal-title":"Neurocomputing"},{"key":"2023051706070160600_btaa829-B15","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.patrec.2020.07.005","article-title":"Improved ASD classification using dynamic functional connectivity and multi-task feature selection","volume":"138","author":"Liu","year":"2020","journal-title":"Pattern Recogn. Lett"},{"key":"2023051706070160600_btaa829-B16","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The genotype-tissue expression (GTEx) project","volume":"45","author":"Lonsdale","year":"2013","journal-title":"Nat. Genet"},{"key":"2023051706070160600_btaa829-B17","first-page":"345","author":"Luo","year":"2017"},{"key":"2023051706070160600_btaa829-B18","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41586-019-1195-2","article-title":"Single-cell transcriptomic analysis of Alzheimer\u2019s disease","volume":"570","author":"Mathys","year":"2019","journal-title":"Nature"},{"key":"2023051706070160600_btaa829-B19","doi-asserted-by":"crossref","first-page":"5503","DOI":"10.1021\/pr200772w","article-title":"Functional implications of structural predictions for alternative splice proteins expressed in her2\/neu\u2013induced breast cancers","volume":"10","author":"Menon","year":"2011","journal-title":"J. Proteom Res"},{"key":"2023051706070160600_btaa829-B20","doi-asserted-by":"crossref","first-page":"6693","DOI":"10.1021\/acs.analchem.8b00498","article-title":"Domain-invariant partial-least-squares regression","volume":"90","author":"Nikzad-Langerodi","year":"2018","journal-title":"Anal. Chem"},{"key":"2023051706070160600_btaa829-B21","doi-asserted-by":"crossref","first-page":"22540","DOI":"10.1074\/jbc.M503092200","article-title":"Alternative splicing switches the divalent cation selectivity of Trpm3 channels","volume":"280","author":"Oberwinkler","year":"2005","journal-title":"J. Biol. Chem"},{"key":"2023051706070160600_btaa829-B22","first-page":"e50653","article-title":"The duplicated genes database: identification and functional annotation of colocalised duplicated genes across genomes","volume":"7","author":"Ouedraogo","year":"2012","journal-title":"PLoS Comput. Biol"},{"key":"2023051706070160600_btaa829-B23","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/ng.259","article-title":"Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing","volume":"40","author":"Pan","year":"2008","journal-title":"Nat. Genet"},{"key":"2023051706070160600_btaa829-B24","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1021\/acs.jproteome.5b00883","article-title":"Genome-wide functional annotation of human protein-coding splice variants using multiple instance learning","volume":"15","author":"Panwar","year":"2016","journal-title":"J. Proteom Res"},{"key":"2023051706070160600_btaa829-B25","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.inffus.2016.10.001","article-title":"Exploiting the ensemble paradigm for stable feature selection: a case study on high-dimensional genomic data","volume":"35","author":"Pes","year":"2017","journal-title":"Inf. Fusion"},{"key":"2023051706070160600_btaa829-B26","doi-asserted-by":"crossref","first-page":"e0118432","DOI":"10.1371\/journal.pone.0118432","article-title":"The precision-recall plot is more informative than the ROC plot when evaluating binary classifiers on imbalanced datasets","volume":"10","author":"Saito","year":"2015","journal-title":"PLoS One"},{"key":"2023051706070160600_btaa829-B27","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1471-2105-11-2","article-title":"Predicting gene function using hierarchical multi-label decision tree ensembles","volume":"11","author":"Schietgat","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2023051706070160600_btaa829-B28","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nature11378","article-title":"Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics","volume":"490","author":"Schmitz","year":"2012","journal-title":"Nature"},{"key":"2023051706070160600_btaa829-B29","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1471-2229-11-82","article-title":"Assessing the contribution of alternative splicing to proteome diversity in Arabidopsis Thaliana using proteomics data","volume":"11","author":"Severing","year":"2011","journal-title":"BMC Plant Biol"},{"key":"2023051706070160600_btaa829-B30","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1093\/bioinformatics\/bty1017","article-title":"DeepIsoFun: a deep domain adaptation approach to predict isoform functions","volume":"35","author":"Shaw","year":"2019","journal-title":"Bioinformatics"},{"key":"2023051706070160600_btaa829-B31","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.molcel.2017.06.003","article-title":"Single-cell alternative splicing analysis with expedition reveals splicing dynamics during neuron differentiation","volume":"67","author":"Song","year":"2017","journal-title":"Mol. Cell"},{"key":"2023051706070160600_btaa829-B32","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/nprot.2012.016","article-title":"Differential gene and transcript expression analysis of RNA-seq experiments with Tophat and Cufflinks","volume":"7","author":"Trapnell","year":"2012","journal-title":"Nat. Protoc"},{"key":"2023051706070160600_btaa829-B33","doi-asserted-by":"crossref","first-page":"5794","DOI":"10.1158\/1078-0432.CCR-06-0725","article-title":"Overexpression of caspase-3s splice variant in locally advanced breast carcinoma is associated with poor response to neoadjuvant chemotherapy","volume":"12","author":"Vegran","year":"2006","journal-title":"Clin. Cancer Res"},{"key":"2023051706070160600_btaa829-B34","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1093\/bioinformatics\/btz847","article-title":"Differentiating isoform functions with collaborative matrix factorization","volume":"36","author":"Wang","year":"2020","journal-title":"Bioinformatics"},{"key":"2023051706070160600_btaa829-B35","doi-asserted-by":"crossref","first-page":"108840","DOI":"10.1016\/j.jneumeth.2020.108840","article-title":"AIMAFE: autism spectrum disorder identification with multi-atlas deep feature representation and ensemble learning","volume":"343","author":"Wang","year":"2020","journal-title":"J. Neurosci. Methods"},{"key":"2023051706070160600_btaa829-B36","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1038\/s41467-018-04559-0","article-title":"Precise temporal regulation of alternative splicing during neural development","volume":"9","author":"Weyn-Vanhentenryck","year":"2018","journal-title":"Nat. Commun"},{"key":"2023051706070160600_btaa829-B37","article-title":"A gene rank based approach for single cell similarity assessment and clustering","author":"Xu","year":"2019","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform"},{"key":"2023051706070160600_btaa829-B38","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nmeth.3213","article-title":"The I-TASSER Suite: protein structure and function prediction","volume":"12","author":"Yang","year":"2015","journal-title":"Nat. Methods"},{"key":"2023051706070160600_btaa829-B39","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2016.01.029","article-title":"Widespread expansion of protein interaction capabilities by alternative splicing","volume":"164","author":"Yang","year":"2016","journal-title":"Cell"},{"key":"2023051706070160600_btaa829-B40","doi-asserted-by":"crossref","first-page":"W379","DOI":"10.1093\/nar\/gkz388","article-title":"NetGO: improving large-scale protein function prediction with massive network information","volume":"47","author":"You","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023051706070160600_btaa829-B41","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1093\/bioinformatics\/btz535","article-title":"Isoform function prediction based on bi-random walks on a heterogeneous network","volume":"36","author":"Yu","year":"2020","journal-title":"Bioinformatics"},{"key":"2023051706070160600_btaa829-B42","doi-asserted-by":"crossref","DOI":"10.1016\/j.inffus.2020.06.012","article-title":"Attributed heterogeneous network fusion via collaborative matrix tri-factorization","author":"Yu","year":"2020","journal-title":"Inf. Fus"},{"key":"2023051706070160600_btaa829-B43","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.ygeno.2018.02.008","article-title":"Gene function prediction based on gene ontology hierarchy preserving hashing","volume":"111","author":"Zhao","year":"2019","journal-title":"Genomics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaa829\/34686217\/btaa829.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/4\/522\/50359764\/btaa829.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/4\/522\/50359764\/btaa829.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T02:32:32Z","timestamp":1696645952000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/37\/4\/522\/5910547"}},"subtitle":[],"editor":[{"given":"Inanc","family":"Birol","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2020,9,23]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaa829","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,2,15]]},"published":{"date-parts":[[2020,9,23]]}}}