Spatial profiling of proteins and protein interactions facilitates understanding of cell functions within tissues and is essential for studies in signaling, immunity, and cancer. We present spatial proximity sequencing (Sprox-seq) for simultaneous profiling of surface proteins, protein complexes, and mRNAs, recording the tissue location of each molecule. Sprox-seq profiled 32 proteins, 528 pairwise interactions, and thousands of mRNAs with spatial resolution across human tonsils and germinal centers. Mapping tissue-wide protein interactions recapitulated RNA-defined tissue architecture but also revealed higher interaction complexity in the light zone. Protein-interaction trajectories uncovered a B cell state transition distinct from that inferred by RNA. Integrated protein-complex and mRNA analysis related spatially enriched complexes with mitotic pathways. Sprox-seq captured cell-cell interactions, such as B cell-follicular dendritic cell interactions mediated by the receptor complex VLA-4-VCAM1. Sprox-seq provides a spatially resolved multi-modal view of cell states and an integrated study of protein and cellular interactions across tissues.
Huili Wang, Junjie Xia, P. Rahman et al.· Cell· 0 citations
Simple Summary Breast cancer treatment is guided by three molecular biomarkers—estrogen receptor (ER), progesterone receptor (PR), and HER2—typically measured by immunohistochemistry (IHC), a process that requires additional staining, time, and specialist review. Whole-slide image (WSI) foundation models are large pre-trained neural networks that summarize a digital biopsy into a compact representation, raising the possibility of inferring biomarker status directly from routinely stained H&E images. In this study, we compare two open-source pathology foundation models—TITAN and CHIEF—for ER, PR, and HER2 prediction on the publicly available TCGA-BRCA cohort, under a strict patient-level evaluation protocol with 10 random partitions and 95% confidence intervals. ER and PR predictions show robust discriminative performance under retrospective evaluation; HER2 prediction at the default decision threshold remains limited and motivates threshold-calibration and multimodal extensions. The findings are hypothesis-generating and motivate prospective external validation before any clinical use.
S. Atiya, Jiayou Liang, Kwaku Ofori-Atta et al.· Cancers· 0 citations
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