{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:02:34Z","timestamp":1776272554850,"version":"3.50.1"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":49,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Moffitt\u2019s Biostatistics and Bioinformatics Shared Resources at the H. Lee Moffitt Cancer Center & Research Institute"},{"name":"NCI-designated Comprehensive Cancer Center","award":["P30-CA076292"],"award-info":[{"award-number":["P30-CA076292"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Spatial transcriptomic (ST) technologies, such as GeoMx Digital Spatial Profiler, are increasingly utilized to investigate the role of diverse tumor microenvironment components, particularly in relation to cancer progression, treatment response, and therapeutic resistance. However, in many ST studies, the spatial information obtained from immunofluorescence imaging is primarily used for identifying regions of interest (ROIs) rather than as an integral part of downstream transcriptomic data analysis and interpretation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We developed ROICellTrack, a deep learning-based framework that better integrates cellular imaging with spatial transcriptomic profiling. By analyzing 56 ROIs from urothelial carcinoma of the bladder and upper tract urothelial carcinoma, ROICellTrack identified distinct cancer\u2013immune cell mixtures, characterized by specific transcriptomic and morphological signatures and receptor\u2013ligand interactions linked to tumor content and immune infiltrations. Our findings demonstrate the value of integrating imaging with transcriptomics to analyze spatial omics data, improving our understanding of tumor heterogeneity and its relevance to personalized and targeted therapies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>ROICellTrack is publicly available at https:\/\/github.com\/wanglab1\/ROICellTrack.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf152","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T03:02:36Z","timestamp":1744167756000},"source":"Crossref","is-referenced-by-count":2,"title":["ROICellTrack: a deep learning framework for integrating cellular imaging modalities in subcellular spatial transcriptomic profiling of tumor tissues"],"prefix":"10.1093","volume":"41","author":[{"given":"Xiaofei","family":"Song","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute , Tampa, FL 33612,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute , Tampa, FL 33612,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos M","family":"Moran-Segura","sequence":"additional","affiliation":[{"name":"Department of Pathology, H. Lee Moffitt Cancer Center & Research Institute , Tampa, FL 33612,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzhi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, H. Lee Moffitt Cancer Center & Research Institute , Tampa, FL 33612,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute , Tampa, FL 33612,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua T","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute , Tampa, FL 33612,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aram","family":"Vosoughi","sequence":"additional","affiliation":[{"name":"Department of Pathology, H. Lee Moffitt Cancer Center & Research Institute , Tampa, FL 33612,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G Daniel","family":"Grass","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute , Tampa, FL 33612,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Oncology, Moffitt Cancer Center , Tampa, FL 33612,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5775-408X","authenticated-orcid":false,"given":"Xuefeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute , Tampa, FL 33612,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"2025052712065606600_btaf152-B1","doi-asserted-by":"crossref","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci Rep"},{"key":"2025052712065606600_btaf152-B2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41592-019-0667-5","article-title":"NicheNet: modeling intercellular communication by linking ligands to target genes","volume":"17","author":"Browaeys","year":"2020","journal-title":"Nat Methods"},{"key":"2025052712065606600_btaf152-B3","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/s41467-022-28020-5","article-title":"Advances in mixed cell deconvolution enable quantification of cell types in spatial transcriptomic data","volume":"13","author":"Danaher","year":"2022","journal-title":"Nat Commun"},{"key":"2025052712065606600_btaf152-B4","doi-asserted-by":"crossref","first-page":"vbad130","DOI":"10.1093\/bioadv\/vbad130","article-title":"CCPlotR: an R package for the visualization of cell\u2013cell interactions","volume":"3","author":"Ennis","year":"2023","journal-title":"Bioinform Adv"},{"key":"2025052712065606600_btaf152-B5","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s42003-024-06426-9","article-title":"Digital spatial profiling of the microenvironment of muscle invasive bladder cancer","volume":"7","author":"Eyers","year":"2024","journal-title":"Commun Biol"},{"key":"2025052712065606600_btaf152-B6","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1038\/s41467-023-37822-0","article-title":"Spatial analysis with SPIAT and spaSim to characterize and simulate tissue microenvironments","volume":"14","author":"Feng","year":"2023","journal-title":"Nat Commun"},{"key":"2025052712065606600_btaf152-B7","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41592-023-02166-6","article-title":"Challenges and perspectives in computational deconvolution of genomics data","volume":"21","author":"Garmire","year":"2024","journal-title":"Nat Methods"},{"key":"2025052712065606600_btaf152-B8","doi-asserted-by":"crossref","first-page":"8353","DOI":"10.1038\/s41467-023-43458-x","article-title":"High resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis","volume":"14","author":"Janesick","year":"2023","journal-title":"Nat Commun"},{"key":"2025052712065606600_btaf152-B9","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1038\/s41467-023-37168-7","article-title":"A comprehensive benchmarking with practical guidelines for cellular deconvolution of spatial transcriptomics","volume":"14","author":"Li","year":"2023","journal-title":"Nat Commun"},{"key":"2025052712065606600_btaf152-B10","first-page":"110","author":"Li","year":"2025"},{"key":"2025052712065606600_btaf152-B11","doi-asserted-by":"crossref","first-page":"e11830","DOI":"10.1097\/MD.0000000000011830","article-title":"DHCR24 predicts poor clinicopathological features of patients with bladder cancer: a STROBE-compliant study","volume":"97","author":"Liu","year":"2018","journal-title":"Medicine"},{"key":"2025052712065606600_btaf152-B12","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1006\/geno.2002.6755","article-title":"Identification of EPSTI1, a novel gene induced by epithelial\u2013stromal interaction in human breast cancer","volume":"79","author":"Nielsen","year":"2002","journal-title":"Genomics"},{"key":"2025052712065606600_btaf152-B13","author":"Oliveira","year":"2024"},{"key":"2025052712065606600_btaf152-B14","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1038\/s41592-022-01663-4","article-title":"Cellpose 2.0: how to train your own model","volume":"19","author":"Pachitariu","year":"2022","journal-title":"Nat Methods"},{"key":"2025052712065606600_btaf152-B15","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1038\/s41467-019-10873-y","article-title":"Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling","volume":"10","author":"Robinson","year":"2019","journal-title":"Nat Commun"},{"key":"2025052712065606600_btaf152-B16","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41592-020-01018-x","article-title":"Cellpose: a generalist algorithm for cellular segmentation","volume":"18","author":"Stringer","year":"2021","journal-title":"Nat Methods"},{"key":"2025052712065606600_btaf152-B17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.iotech.2019.05.001","article-title":"A user\u2019s perspective on GeoMxTM digital spatial profiling","volume":"1","author":"Van","year":"2019","journal-title":"Immuno-Oncol Technol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaf152\/62892643\/btaf152.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/41\/5\/btaf152\/62892643\/btaf152.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/41\/5\/btaf152\/62892643\/btaf152.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T16:07:05Z","timestamp":1748362025000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btaf152\/8108826"}},"subtitle":[],"editor":[{"given":"Christina","family":"Kendziorski","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,8]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5,6]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaf152","relation":{},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,5]]},"published":{"date-parts":[[2025,4,8]]},"article-number":"btaf152"}}