{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:01:20Z","timestamp":1785438080476,"version":"3.56.0"},"posted":{"date-parts":[[2025,5,13]]},"group-title":"Bioinformatics","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["UH3CA268202"],"award-info":[{"award-number":["UH3CA268202"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Integrating spatially-resolved transcriptomics (SRT) across biological samples is essential for understanding dynamic changes in tissue architecture and cell-cell interactions\n                  <jats:italic>in situ<\/jats:italic>\n                  . While tools exist for multisample single-cell RNA-seq, methods tailored to multisample SRT remain limited. Here, we introduce P\n                  <jats:sc>opari<\/jats:sc>\n                  , a probabilistic graphical model for factor-based decomposition of multisample SRT that captures condition-specific changes in spatial organization. P\n                  <jats:sc>opari<\/jats:sc>\n                  jointly learns spatial metagenes \u2013 linear gene expression programs \u2013 and their spatial affinities across samples. Its key innovations include a differential prior to regularize spatial accordance and spatial downsampling to enable multiresolution, hierarchical analysis. Simulations show P\n                  <jats:sc>opari<\/jats:sc>\n                  outperforms existing methods on multisample and multi-resolution spatial metrics. Applications to real datasets uncover spatial metagene dynamics, spatial accordance, and cell identities. In mouse brain (STARmap PLUS), P\n                  <jats:sc>opari<\/jats:sc>\n                  identifies spatial metagenes linked to AD; in thymus (Slide-TCR-seq), it captures increasing colocalization of V(D)J recombination and T cell proliferation; and in ovarian cancer (CosMx), it reveals sample-specific malignant-immune interactions. Overall, P\n                  <jats:sc>opari<\/jats:sc>\n                  provides a general, interpretable framework for analyzing variation in multisample SRT.\n                <\/jats:p>","DOI":"10.1101\/2025.05.08.652741","type":"posted-content","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T02:30:16Z","timestamp":1747189816000},"source":"Crossref","is-referenced-by-count":4,"title":["Popari: Modeling multisample variation in spatial transcriptomics"],"prefix":"10.64898","author":[{"given":"Shahul","family":"Alam","sequence":"first","affiliation":[{"name":"Ray and Stephanie Lane Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Ray and Stephanie Lane Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellie","family":"Haber","sequence":"additional","affiliation":[{"name":"Machine Learning Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Chidester","sequence":"additional","affiliation":[{"name":"Ray and Stephanie Lane Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Liu","sequence":"additional","affiliation":[{"name":"Biophysics Program, Harvard University, Boston, MA 02115, USA"},{"name":"Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"},{"name":"Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2308-3649","authenticated-orcid":false,"given":"Fei","family":"Chen","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"},{"name":"Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4202-5834","authenticated-orcid":false,"given":"Jian","family":"Ma","sequence":"additional","affiliation":[{"name":"Ray and Stephanie Lane Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041121403884000_2025.05.08.652741v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00580-2"},{"key":"2026041121403884000_2025.05.08.652741v1.2","doi-asserted-by":"crossref","unstructured":"Palla, G. , Fischer, D. 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