VarXOmics: A Versatile Web Server for Genomic Data Querying, Analysis, and Variant Prioritization With Multi-omics Insights

• VarXOmics is an integrated and versatile web server for genomic data querying, variant analysis, and prioritization. • It consolidates multi-omics datasets of eQTL, pQTL, GWAS, MR, and pharmacogenomics information to provide holistic insights into the diverse effects of genetic variation. • It facilitates the identification of potential disease-causing variants and causal genes by integrating multi-omics evidence into the prioritization. • It enables functional interpretations through gene set enrichment analysis and reveals interactions across multiple biological layers via network analysis, thereby supporting the elucidation of underlying disease pathogenesis. Numerous web-based tools have been developed to support large-scale genomics research, whereas challenges remain due to their limited functionality. Therefore, we developed VarXOmics, an end-to-end, versatile web server for querying variants and genes, streamlining germline variant analysis, prioritizing variants with multi-omics insights, and providing interactive visualizations. The utility of VarXOmics was demonstrated by analyzing multiple small variants of the whole-genome sequencing data from a breast cancer patient. It prioritized BRCA2 c.3751dup as the most likely pathogenic variant, and highlighted disease associations with cell cycle regulation, DNA repair pathways, and type 2 diabetes through multi-omics evidence, gene set enrichment, and network analysis. Overall, VarXOmics serves as a practical genomics platform for researchers and clinicians. It shows potential in identifying pathogenic variants and causal genes, uncovering the molecular mechanisms of disease pathogenesis, providing valuable references for clinical decision-making and therapeutic strategies, thus advancing precision medicine. VarXOmics is publicly available at https://www.phenomeportal.org/varxomics .