SPgen integrates protein sequences, functional annotations, transcriptomic profiles, and spatial information to learn transferable representations that enable inference beyond experimentally profiled proteins, and accurately reconstructs measured spatial patterns, reduces measurement noise, and enables proteome-wide spatial prediction.
Abstract
Spatial proteomics (SP) measures the spatial distribution of proteins within tissues, providing important insights into tissue function, disease, and therapeutic response. However, current SP technologies profile only a small fraction of the proteome and are limited by cost and measurement noise. Recent AI approaches enable predicting spatial protein expression from transcriptomic or histopathological data, but are typically restricted to paired datasets covering only tens of proteins, limiting their ability to generalize beyond experimentally measured protein panels. Here we present SPgen, a multi-modal foundation-model framework for proteome-wide spatial protein prediction. SPgen integrates protein sequences, functional annotations, transcriptomic profiles, and spatial information to learn transferable representations that enable inference beyond experimentally profiled proteins. Across diverse spatial proteomics datasets, SPgen accurately reconstructs measured spatial patterns, reduces measurement noise, and enables proteome-wide spatial prediction.
Spatial transcriptomics now profiles patient cohorts at single-cell resolution, enabling analysis of disease-associated cell organization in situ. However, discovering such spatial biomarkers remains challenging because relevant structures occur at unknown scales and cell-or niche-level annotations are rarely available...
Hoeyoung Kim, Donghee Kim, Sangwook Jung et al.· bioRxiv· 0 citations
Sequencing-based spatial omics platforms provide scalable and unbiased profiling of transcriptomic, epigenomic, and isoform-resolved signals, but their spatial resolution remains limited because each capture unit aggregates molecular information from multiple cells. Existing computational enhancement methods reconstruc...
It is argued that the most credible translational goal is not to infer every transcript from H&E, but to identify biologically coherent spatial states with reproducible morphological correlates that can be validated across independent platforms and cohorts before being mapped across large archival collections.
Mohammad Amin Rezania, Haechan Yi, Jae-Il Choi et al.· Cancer research and treatmen...· 0 citations
Single-cell and spatial transcriptomic studies often lack sufficient sample size to compute robust statistical associations between a sample-level phenotype and cell types or spatial locations. In contrast, lower resolution methods such as bulk gene expression profiling have been applied at scale in large, annotated da...
Brooks A. Benard, Chinmay K. Lalgudi, Armon Azizi et al.· bioRxiv· 1 citation
Abstract Spatial transcriptomics enables high-resolution profiling of gene expression within intact tissue architecture, providing new opportunities to study the spatial organization of tissue structures and cell types. However, identifying spatial domains that are reproducible across samples and individuals remains ch...
Shi-Wei Fu, Han Li, Wei Vivian Li· Briefings in Bioinformatics· 0 citations
Spatial transcriptomics is increasingly used to infer cellular phenotypes, molecular interactions, and functional tissue organization from RNA, although most of these biological processes are ultimately mediated by proteins. Here, we directly tested the interchangeability of spatial RNA and protein measurements using p...
Sergi Cervilla, D. Grases, Noelia Montesdeoca et al.· bioRxiv· 0 citations
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