{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:05:54Z","timestamp":1789635954774,"version":"4.0.0"},"reference-count":28,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Over-representation analysis (ORA) is widely used to interpret selected-gene lists, including differentially expressed genes and cell-type marker genes. Unlike ranked-list gene-set enrichment analysis (GSEA), ORA tests whether selected genes are over-represented in predefined gene sets under an explicit background. Repeated analysis of large gene-set libraries, however, can be computationally costly. GPU-accelerated methods such as rapidGSEA mainly target ranked-list GSEA and do not address repeated exact-ORA processing. We developed paraORA to accelerate repeated ORA by preparing a gene-set library once and reusing its compressed representation across queries. In the GPU-exact path, overlap counting, exact hypergeometric testing, Benjamini\u2013Hochberg correction, and odds-ratio calculation are performed on the GPU. Across 425 numerical validation cases on three GPU models, paraORA agreed with CPU-reference results within the prespecified tolerance while preserving statistical decisions and rankings. On an RTX 4090, the CPU\/GPU runtime ratio for the complete in-memory workflow increased from 1.89 for one query to 60.10 for 100 queries against 141,002 gene sets, including one-time preparation but excluding file writing. In a separate complete file-to-file benchmark, GPU-exact was 2.55-fold faster than CPU execution. An exploratory limma reanalysis showed direction-specific Hallmark enrichment. paraORA is available as a web service and an open-source package.<\/jats:p>","DOI":"10.3390\/biology15181641","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:03:17Z","timestamp":1789632197000},"page":"1641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["paraORA: GPU-Accelerated Exact Over-Representation Analysis for Repeated Queries of Large Gene-Set Libraries"],"prefix":"10.3390","volume":"15","author":[{"given":"Zheng","family":"Wu","sequence":"first","affiliation":[{"name":"School of Computer Science, Luoyang Institute of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Zejun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Electrical and Energy Engineering, Shanghai Dianji University, Shanghai 201306, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Wenqing","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Computer Science, Luoyang Institute of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9194-2282","authenticated-orcid":false,"given":"Jinlei","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Computer Science, Luoyang Institute of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7275-5599","authenticated-orcid":false,"given":"Zhichun","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Computer Science, Luoyang Institute of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6277-5467","authenticated-orcid":false,"given":"Guoqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Computer Science, Luoyang Institute of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Yunqing","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Computer Science, Luoyang Institute of Science and Technology, Luoyang 471000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3587","DOI":"10.1093\/bioinformatics\/bti565","article-title":"Ontological Analysis of Gene Expression Data: Current Tools, Limitations, and Open Problems","volume":"21","author":"Khatri","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and Integrative Analysis of Large Gene Lists Using DAVID Bioinformatics Resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. 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