Abstract
Swiss-PO is a new web tool to map gene mutations on the 3D structure of corresponding proteins and to intuitively assess the structural implications of protein variants for precision oncology. Swiss-PO is constructed around a manually curated database of 3D structures, variant annotations, and sequence alignments, for a list of 50 genes taken from the Ion AmpliSeqTM Custom Cancer Hotspot Panel. The website was designed to guide users in the choice of the most appropriate structure to analyze regarding the mutated residue, the role of the protein domain it belongs to, or the drug that could be selected to treat the patient. The importance of the mutated residue for the structure and activity of the protein can be assessed based on the molecular interactions exchanged with neighbor residues in 3D within the same protein or between different biomacromolecules, its conservation in orthologs, or the known effect of reported mutations in its 3D or sequence-based vicinity. Swiss-PO is available free of charge or login at https://www.swiss-po.ch.
Highlights
Facilitated access to next-generation sequencing (NGS) has triggered the development of precision oncology programs around the world for tumors escaping standard therapies[1]
Knowledge regarding the experimentally determined impact of known mutations on protein structure and activity was retrieved from the CKB CORE database, with the exception of proteins DDR2, EGFR, and PIK3CA whose data were generously provided by The Jackson Laboratory from the CKB BOOST database
These data were supplemented by variant annotations provided by the Swiss-Prot group of the SIB Swiss Institute of Bioinformatics
Summary
Facilitated access to next-generation sequencing (NGS) has triggered the development of precision oncology programs around the world for tumors escaping standard therapies[1]. The number of nonsynonymous somatic mutations found in tumors varies greatly[2,3], but gene panels covering between 50 and 500 genes typically yield several dozen variants to be analyzed. As integration of all this information is essential, live discussions in preparation or during the MTB represent an important added value as it allows challenging and contextualizing results. To address these important aspects, we have designed Swiss-PO, the first interactive tool to assess the structural implications of protein variants for precision oncology
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