{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T23:29:54Z","timestamp":1773790194064,"version":"3.50.1"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP230166"],"award-info":[{"award-number":["RP230166"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>The identification of tumor cells is pivotal for understanding tumor heterogeneity and the tumor microenvironment. Recent advances in spatially resolved transcriptomics (SRT) have revolutionized the way that transcriptomic profiles are characterized and have enabled the simultaneous quantification of transcript locations in intact tissue samples. SRT is a promising alternative method to study gene expression patterns in spatial domains. Nevertheless, the precise detection of tumor regions within intact tissue remains a great challenge. A common strategy for identifying tumor cells is via tumor-specific marker gene expression signatures, which are highly dependent on marker accuracy. Another effective approach is through aneuploid copy number alterations, as most types of cancer exhibit copy number abnormalities. Here, we introduce a novel computational method, called TUSCAN (TUmor Segmentation and Classification ANalysis in spatial transcriptomics), which constructs a spatial copy number variation profile to improve the accuracy of tumor region identification. TUSCAN combines gene information from SRT data and hematoxylin-and-eosin-staining image to annotate tumor sections and other benign tissues. We benchmark the performance of TUSCAN and several existing methods through the application to multiple datasets from different SRT platforms. We demonstrate that TUSCAN can effectively delineate tumor regions, with improved accuracy compared to other approaches. Additionally, the output of TUSCAN provides interpretable clonal evolution inferences that may lead to novel insights into disease development and potential druggable targets.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1014058","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T20:02:41Z","timestamp":1773777761000},"page":"e1014058","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["TUSCAN: Tumor segmentation and classification analysis in spatial transcriptomics"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5237-0351","authenticated-orcid":true,"given":"Chenxuan","family":"Zang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles C.","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaohong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8359-0533","authenticated-orcid":true,"given":"Ziyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"issue":"10","key":"pcbi.1014058.ref001","doi-asserted-by":"crossref","first-page":"11149","DOI":"10.1002\/cam4.5698","article-title":"Role of tumor microenvironment in cancer progression and therapeutic strategy","volume":"12","author":"Q Wang","year":"2023","journal-title":"Cancer Med"},{"key":"pcbi.1014058.ref002","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/0-387-26283-0_5","article-title":"The role of immune cells in the tumor microenvironment","volume":"130","author":"TL Whiteside","year":"2006","journal-title":"Cancer Treat Res"},{"issue":"9","key":"pcbi.1014058.ref003","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.3390\/cancers13092053","article-title":"The Role of tumor microenvironment in cancer metastasis: molecular mechanisms and therapeutic opportunities","volume":"13","author":"CM Neophytou","year":"2021","journal-title":"Cancers (Basel)"},{"key":"pcbi.1014058.ref004","doi-asserted-by":"crossref","first-page":"107753","DOI":"10.1016\/j.pharmthera.2020.107753","article-title":"Tumor microenvironment as a therapeutic target in cancer","volume":"221","author":"Y Xiao","year":"2021","journal-title":"Pharmacol Ther"},{"issue":"5","key":"pcbi.1014058.ref005","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/s41592-022-01409-2","article-title":"Museum of spatial transcriptomics","volume":"19","author":"L Moses","year":"2022","journal-title":"Nat Methods"},{"issue":"1","key":"pcbi.1014058.ref006","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13073-022-01075-1","article-title":"An introduction to spatial transcriptomics for biomedical research","volume":"14","author":"CG Williams","year":"2022","journal-title":"Genome Med"},{"issue":"9","key":"pcbi.1014058.ref007","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/s41588-021-00911-1","article-title":"A single-cell and spatially resolved atlas of human breast cancers","volume":"53","author":"SZ Wu","year":"2021","journal-title":"Nat Genet"},{"issue":"5","key":"pcbi.1014058.ref008","article-title":"Deciphering tumor ecosystems at super resolution from spatial transcriptomics with TESLA","volume":"14","author":"J Hu","year":"2023","journal-title":"Cell Syst"},{"issue":"6","key":"pcbi.1014058.ref009","first-page":"1871","article-title":"Detection of circulating breast tumor cells by differential expression of marker genes","volume":"8","author":"AJ Bosma","year":"2002","journal-title":"Clin Cancer Res"},{"issue":"1","key":"pcbi.1014058.ref010","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s13046-022-02476-1","article-title":"Heterogeneity of triple negative breast cancer: current advances in subtyping and treatment implications","volume":"41","author":"K Asleh","year":"2022","journal-title":"J Exp Clin Cancer Res"},{"issue":"2","key":"pcbi.1014058.ref011","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.3390\/ijms24021601","article-title":"Phenotype switching and the melanoma microenvironment; 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