The rapid expansion of precision oncology has led to a substantial increase in identified oncodriver genes and associated variants. This growth has also increased the number of mutations with unknown functional impact, highlighting the need for molecular modeling tools to support variant interpretation. Swiss-PO has been expanded and redesigned to integrate large-scale oncogenomic data with structure- and sequence-based analytical tools. The platform combines oncodriver gene data with multiple sequence alignments (MSAs) for conservation analysis across orthologs and gene families, as well as visualization of experimental and predicted three-dimensional (3D) protein structures to assess the potential effects of mutations. Additional modules include a BRAF kinase mutation classification model and a dedicated page for ligands targeting proteins, alongside integrated links to external databases to enable multidimensional analyses.

The updated Swiss-PO platform integrates data for nearly 1,500 oncodriver genes, covering 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. The platform also includes a BRAF kinase mutation class predictor to support therapeutic decision-making. With these enhancements, Swiss-PO provides a comprehensive resource for oncologists, bioinformaticians, and molecular biologists involved in interpreting cancer-associated mutations and advancing precision medicine. The website is available at https://swiss-po.ch/

Co-authors: Olivier Michielin, Vincent Zoete