Randomized Spatial PCA (RASP): a computationally efficient method for dimensionality reduction of high-resolution spatial transcriptomics data 

Randomized Spatial PCA (RASP): a computationally efficient method for dimensionality reduction of high-resolution spatial transcriptomics data | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Randomized Spatial PCA (RASP): a computationally efficient method for dimensionality reduction of high-resolution spatial transcriptomics data Ian K. Gingerich, Brittany A. Goods, H. Robert Frost This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6050441/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Spatial transcriptomics (ST) provides critical insights into the spatial organization of gene expression, enabling researchers to unravel the intricate relationship between cellular environments and biological function. Identifying spatial domains within tissues is key to understanding tissue architecture and mechanisms underlying development and disease progression. Here, we present Randomized Spatial PCA (RASP), a novel spatially-aware dimensionality reduction method for ST data. RASP is designed to be orders-of-magnitude faster than existing techniques, scale to datasets with 100,000+ locations, support flexible integration of non-transcriptomic covariates, and reconstruct de-noised, spatially-smoothed gene expression values. It employs a randomized two-stage PCA framework with sparse matrix operations and configurable spatial smoothing. RASP was compared to BASS, GraphST, SEDR, SpatialPCA, and STAGATE using diverse ST datasets (10x Visium, Stereo-Seq, MERFISH, 10x Xenium) on human and mouse tissues. RASP demonstrates comparable or superior tissue domain detection with substantial improvements in computational speed, enhancing exploration of high-resolution subcellular datasets. Full Text Additional Declarations No competing interests reported. Supplementary Files RASPsuppliment.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6050441","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":417418614,"identity":"4c62534e-da8a-4c35-8649-70d508d50201","order_by":0,"name":"Ian K. 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