{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:30:49Z","timestamp":1785407449750,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,3]]},"group-title":"Genomics","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01HG013185"],"award-info":[{"award-number":["R01HG013185"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01LM014592"],"award-info":[{"award-number":["R01LM014592"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U19NS135582"],"award-info":[{"award-number":["U19NS135582"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01HL171595"],"award-info":[{"award-number":["R01HL171595"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U01CA294518"],"award-info":[{"award-number":["U01CA294518"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Virtual spatial transcriptomics (ST) methods predict gene expression or cell types from histology images, extending molecular readouts beyond the limited regions or samples directly measured by ST platforms. However, the statistical reliability of these predictions remains unclear. Here, we present UTOPIA, a model-agnostic framework for multiscale confidence quantification in virtual ST. UTOPIA assigns statistically calibrated confidence scores to predictions across spatial resolutions and biological granularities, ranging from single genes to metagenes and from specific cell types to broader cell classes. UTOPIA controls false discovery rates for detecting genes, metagenes, or cell types while accounting for local tissue context. We show that prediction confidence depends critically on both spatial resolution and biological granularity, with reliable inference often emerging only at coarser, biologically meaningful scales. Across multiple ST platforms and in both in-sample and out-of-sample settings, UTOPIA enhances interpretability, prevents false biological conclusions, and enables more trustworthy downstream analyses of virtual ST.<\/jats:p>","DOI":"10.64898\/2026.03.01.708850","type":"posted-content","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T21:10:13Z","timestamp":1772572213000},"source":"Crossref","is-referenced-by-count":0,"title":["Multiscale confidence quantification for virtual spatial transcriptomics with UTOPIA"],"prefix":"10.64898","author":[{"given":"Kaitian","family":"Jin","sequence":"first","affiliation":[{"name":"Statistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Chen","sequence":"additional","affiliation":[{"name":"Statistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokang","family":"Yu","sequence":"additional","affiliation":[{"name":"Statistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musu","family":"Yuan","sequence":"additional","affiliation":[{"name":"Statistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, St. Jude Children\u2019s Research Hospital, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Dumoulin","sequence":"additional","affiliation":[{"name":"Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"},{"name":"Penn\/CHOP Kidney Innovation Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhe","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, UT MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linghua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, UT MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA"},{"name":"The James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"Institute for Data Science in Oncology, UT MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, Seoul Metropolitan Government-Seoul National University Baramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hyun","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA"},{"name":"Center for Computational Systems Biology, Vanderbilt University, Nashville, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Susztak","sequence":"additional","affiliation":[{"name":"Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"},{"name":"Penn\/CHOP Kidney Innovation Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimei","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Statistics and Data Science, University of Pennsylvania Wharton School of Business, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy R.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Statistics and Data Science, University of Pennsylvania Wharton School of Business, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8180-0621","authenticated-orcid":false,"given":"Mingyao","family":"Li","sequence":"additional","affiliation":[{"name":"Statistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"},{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.01.708850","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T02:35:22Z","timestamp":1772850922000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.01.708850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,3]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.03.01.708850","relation":{},"subject":[],"published":{"date-parts":[[2026,3,3]]},"subtype":"preprint"}}