POPARI: Modeling multisample variation in spatial transcriptomics.
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Abstract | Integrating spatially-resolved transcriptomics (SRT) across biological samples is essential for understanding dynamic changes in tissue architecture and cell-cell interactions . While tools exist for multisample single-cell RNA-seq, methods tailored to multisample SRT remain limited. Here, we introduce Popari, a probabilistic graphical model for factor-based decomposition of multisample SRT that captures condition-specific changes in spatial organization. Popari jointly learns spatial metagenes - linear gene expression programs - 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 Popari 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), Popari 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, Popari provides a general, interpretable framework for analyzing variation in multisample SRT. |
Year of Publication | 2025
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Journal | bioRxiv : the preprint server for biology
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Date Published | 05/2025
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ISSN | 2692-8205
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DOI | 10.1101/2025.05.08.652741
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PubMed ID | 40462963
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