{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:03:57Z","timestamp":1790370237710,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"29","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371048"],"award-info":[{"award-number":["32371048"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Characterizing the cellular origin and disease\u2010driven dynamics of cfRNA is essential for integrating cfRNA profiling into clinical workflows and precision\u2010medicine strategies. Most cfRNA studies are restricted to bulk\u2010level analyses, which preclude detailed analysis of alterations in the cellular origins of cfRNA. Single\u2010cell RNA sequencing reveals cellular heterogeneity and communication, but its application to cfRNA is limited by diverse cellular origins, leaving a critical gap in understanding functional alterations in cfRNA biomarker\u2010originating cells. In this work, we propose CellFreeGMF, a tool designed to enable diagnosis classification of clinical samples, identify cfRNA biomarkers, and analyze the alterations in their originating cells based on graph matrix factorization. Furthermore, by utilizing cell\u2013cell communication analysis, CellFreeGMF investigates the functional alterations occurring in the cfRNA originating cells under disease conditions. We validate CellFreeGMF on diverse cell\u2010free RNA transcriptome clinical datasets. In the case of pancreatic ductal adenocarcinoma (PDAC), CellFreeGMF not only identified cfRNA biomarkers but also traced their cellular origins to myeloid and T\u2010cell populations. Further analysis revealed significant transcriptomic differences in these cell populations between disease and normal groups. Our user\u2010friendly CellFreeGMF toolkit (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/cellfreegmf.readthedocs.io\/\">https:\/\/cellfreegmf.readthedocs.io\/<\/jats:ext-link>\n                    ) enables identifying cfRNA biomarkers and elucidating pathophysiological changes in their originating cells.\n                  <\/jats:p>","DOI":"10.1002\/advs.74814","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T19:27:26Z","timestamp":1773343646000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Cell\u2010Free Transcriptomes to Single\u2010Cell Landscapes: Biomarker Discovery and Originating Cell Alteration Analysis via Graph Matrix Factorization"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8926-1615","authenticated-orcid":false,"given":"Wenxiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Shenzhen Clinical Research Center for Trauma treatment Shenzhen University General Hospital Shenzhen University  Shenzhen China"},{"name":"Guangdong Key Laboratory For Biomedical Measurements and Ultrasound Imaging National\u2010Regional Key Technology Engineering Laboratory For Medical Ultrasound School of Biomedical Engineering Shenzhen University Medical School  Shenzhen China"},{"name":"National Center for Trauma Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen Clinical Research Center for Trauma treatment Shenzhen University General Hospital Shenzhen University  Shenzhen China"},{"name":"Guangdong Key Laboratory For Biomedical Measurements and Ultrasound Imaging National\u2010Regional Key Technology Engineering Laboratory For Medical Ultrasound School of Biomedical Engineering Shenzhen University Medical School  Shenzhen China"},{"name":"National Center for Trauma Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology Xidian University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Clinical Research Center for Trauma treatment Shenzhen University General Hospital Shenzhen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8488-2228","authenticated-orcid":false,"given":"Junliang","family":"Shang","sequence":"additional","affiliation":[{"name":"School of Computer Science Qufu Normal University  Rizhao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Family Medicine Shenzhen University Medical School  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanwen","family":"Cheng","sequence":"additional","affiliation":[{"name":"National Center for Trauma Medicine  Beijing China"},{"name":"Department of Orthopedics and Trauma Peking University People's Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9901-1732","authenticated-orcid":false,"given":"Xiujuan","family":"Lei","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence and Computer Science Shaanxi Normal University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Kou","sequence":"additional","affiliation":[{"name":"National Center for Trauma 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