{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T04:24:25Z","timestamp":1774067065040,"version":"3.50.1"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFF1205000"],"award-info":[{"award-number":["2023YFF1205000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62172369"],"award-info":[{"award-number":["62172369"]}],"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":["42107148"],"award-info":[{"award-number":["42107148"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>The analysis of RNA isoforms using long-read single-cell RNA sequencing (scRNA-seq) represents a frontier in gene expression research, offering deeper insights beyond traditional gene-level analysis. However, specialized analytical methods tailored for this advanced technology remain scarce, underscoring the urgent need for novel tools to match the rapid pace of its development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we present IsoDiffR, a robust tool designed to identify RNA isoforms with expression patterns that differ from their corresponding genes or major isoforms across cell types, enabling both pairwise and multicell-type comparisons. Using IsoDiffR, we conducted benchmark tests using simulated data and analyzed long-read scRNA-seq data from the corneal limbus of Macaca fascicularis and the human frontal cortex, uncovering previously unrecognized cell-type-specific isoforms that were not detectable using conventional approaches. Additionally, we explored the structural and functional properties of these isoforms, from their nucleotide sequences to their corresponding protein isoforms, revealing their potential biological roles. Our findings offer new perspectives on gene expression regulation at the single-cell level and provide a methodological framework for future investigations of isoform-specific functions in diverse biological contexts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The R package is available on https:\/\/github.com\/Eveqian98\/IsoDiffR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf664","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T13:05:43Z","timestamp":1765458343000},"source":"Crossref","is-referenced-by-count":1,"title":["Analyzing cell-type-specific isoform expression using IsoDiffR and long-read single-cell RNA sequencing"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0540-7036","authenticated-orcid":false,"given":"Hu","family":"Chen","sequence":"first","affiliation":[{"name":"College of Life Science and Medicine, Zhejiang Sci-Tech University , Hangzhou 310018,","place":["China"]},{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases , Guangzhou 510060,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8465-1137","authenticated-orcid":false,"given":"Ye","family":"Qian","sequence":"additional","affiliation":[{"name":"College of Life Science and Medicine, Zhejiang Sci-Tech University , Hangzhou 310018,","place":["China"]},{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases , Guangzhou 510060,","place":["China"]}]},{"given":"Qi","family":"Dai","sequence":"additional","affiliation":[{"name":"College of Life Science and Medicine, Zhejiang Sci-Tech University , Hangzhou 310018,","place":["China"]}]},{"given":"Ying-Feng","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases , Guangzhou 510060,","place":["China"]}]},{"given":"Zhen-Cang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Taizhou Central Hospital (Taizhou University Hospital) , Taizhou, Zhejiang 318000,","place":["China"]}]},{"given":"Zhuo-Xing","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases , Guangzhou 510060,","place":["China"]}]}],"member":"286","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"2026012113571740500_btaf664-B1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"2026012113571740500_btaf664-B2","volume-title":"Blood","author":"Allen"},{"key":"2026012113571740500_btaf664-B3","first-page":"95:S259","volume-title":"Acta 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