{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T21:00:53Z","timestamp":1775768453180,"version":"3.50.1"},"posted":{"date-parts":[[2026,4,7]]},"group-title":"Bioinformatics","reference-count":92,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NLM","award":["R01 LM012373"],"award-info":[{"award-number":["R01 LM012373"]}]},{"name":"NIH","award":["R03 OD039978"],"award-info":[{"award-number":["R03 OD039978"]}]},{"name":"NIH","award":["P01CA093900"],"award-info":[{"award-number":["P01CA093900"]}]},{"name":"The Royal Thai government"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Drug repurposing offers a scalable route to accelerate therapeutic discovery, yet existing approaches based on single-cell RNA sequencing (scRNA-seq) often overlook spatial tissue context, limiting their ability to capture microenvironment-dependent drug responses. Here we present\n                  <jats:bold>STDrug<\/jats:bold>\n                  , a spatially informed computational framework that integrates spatial transcriptomics, graph-based modeling, and multimodal learning to enable patient-specific therapeutic prioritization. STDrug identifies and aligns disease and control spatial domains using graph convolutional networks and coherent point drift, and prioritizes candidate drugs through an integrative scoring scheme combining tumor-reversible gene signatures, perturbation-based reversal scores, and knowledge-guided gene weighting within a machine learning framework. By modeling spatial domain interactions alongside predicted drug efficacy and toxicity, STDrug generates robust patient-level drug scores. Across hepatocellular carcinoma and prostate cancer datasets, STDrug outperforms existing single-cell and spatial transcriptomics\u2013based drug repurposing methods, achieving signficantly improved predictive accuracy (AUCs=0.81-0.82) across patients. Validation using large-scale electronic health records and in vitro assays further supports the translational relevance of top-ranked candidates. Taking together, STDrug establishes a generalizable framework for incorporating spatial omics into therapeutic discovery, advancing spatially informed and personalized drug repurposing.\n                <\/jats:p>","DOI":"10.64898\/2026.04.03.715101","type":"posted-content","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T19:30:18Z","timestamp":1775590218000},"source":"Crossref","is-referenced-by-count":0,"title":["STDrug enables spatially informed personalized drug repurposing from spatial transcriptomics"],"prefix":"10.64898","author":[{"given":"Yiwen","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thatchayut","family":"Unjitwattana","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 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