Swiss-PO 2025: Advancing Cancer Mutation and Structural Analysis for Precision Oncology With the Latest Release.

Abstract

The rapid expansion of precision oncology has led to a marked increase in the number of identified oncodriver genes and associated variants. This surge has elevated the frequency of mutations with unknown functional impact, highlighting the growing need for molecular modeling tools such as Swiss-PO to support variant interpretation for both clinical and research contexts. Swiss-PO was expanded and redesigned to integrate large-scale oncogenomic data with structure-based and sequence-based analytical tools. The platform combines data of oncodriver genes, multiple sequence alignment (MSA) for conservation analysis across orthologs and gene families, experimental and predicted three-dimensional (3D) structures prediction visualization to assess impacts of mutations. Additional modules include a BRAF kinase mutation classification model and a dedicated webpage for ligands targeting proteins, and unified integration with external databases to enable multidimensional analyses. The updated Swiss-PO platform integrates data for nearly 1,500 oncodriver genes, encompassing more than 3 million mutations and post-translational modification annotations, over 26,000 experimental and predicted 3D protein structures, more than 4,000 MSAs , and information on over 200,000 protein ligands. In addition, the platform includes a BRAF kinase mutation class predictor to support therapeutic decision-making, establishing Swiss-PO as one of the most comprehensive publicly available resources for precision oncology. With these enhancements, Swiss-PO strengthens its role as a powerful and versatile resource for oncologists, bioinformaticians, and molecular biologists engaged in the interpretation of cancer-associated mutations and the advancement of precision medicine. The website is available at Swiss-PO.