CellSNVReg: a multidimensional resource for SNV-mediated regulatory perturbations in single-cell and spatial omics

Abstract Single nucleotide variants (SNVs) represent the most prevalent form of genetic variation and can perturb gene regulation, RNA processing, and protein function across multiple molecular layers, ultimately altering cellular functional states and contributing to disease development. Here, we present CellSNVReg (http://bio-bigdata.hrbmu.edu.cn/CellSNVReg/index.jsp), a comprehensive multidimensional resource systematically characterizing regulatory perturbations caused by SNVs at cell-type and spatial resolutions in humans. By integrating 4.6 million cellular profiles from scRNA-seq, spatial transcriptomics, and scATAC-seq across normal, tumor, and other disease tissues, CellSNVReg identifies an average of over 70 000 regulatory perturbations per sample across six dimensions: miRNA–target, transcription factor (TF)–target, enhancer–target, RBP–target, protein–protein interaction, and neoantigen generation, and further characterizes differential expression of perturbed target genes together with associated perturbation networks. For each perturbation, CellSNVReg provides qualitative annotations and quantitative scores to assess SNV perturbation impact, potentially facilitating prioritization of candidate driver SNVs in disease-relevant contexts. To assess downstream functional consequences, the platform links SNV-perturbed targets to alterations in cell functions, states, stemness, metabolism, cell–cell communication, and drug repurposing. In summary, CellSNVReg offers a high-resolution framework for dissecting the functional impact of SNVs across diverse regulatory layers, enabling exploration of the landscape of SNV-mediated regulatory disruptions and their phenotypic consequences in normal and disease contexts.