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. 2021 Mar 18;5(1):19.
doi: 10.1038/s41698-021-00156-5.

Swiss-PO: a new tool to analyze the impact of mutations on protein three-dimensional structures for precision oncology

Fanny S Krebs #  1 , Vincent Zoete #  2   3 , Maxence Trottet  1   4 , Timothée Pouchon  4 , Christophe Bovigny  4 , Olivier Michielin  5   6   7
Affiliations

Swiss-PO: a new tool to analyze the impact of mutations on protein three-dimensional structures for precision oncology

Fanny S Krebs et al. NPJ Precis Oncol. .

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.

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Conflict of interest statement

V.Z. is consultant for Cellestia Biotech. O.M. is the beneficiary of research funding from Merck Sharp & Dohme, Bristol-Myers Squibb, and Roche and/or is consultant or participated to advisory boards for Novartis, Merck Sharp & Dohme, Bristol-Myers Squibb, Amgen, Roche, and GlaxoSmithKline. F.S.K., M.T., T.P., and C.B. declare no competing interest.

Figures

Fig. 1
Fig. 1. Databases preparation.
a Sequence database preparation. b 3D-structure database preparation. (1) 3D structures were fetched from the PDB using their unique human UniProt code and parsed based on their chains. (2) Correction and control of the composition of each chain. (3) Final controls including visualization and ranking of the structures.
Fig. 2
Fig. 2. General structure of the website.
Definition and position of the four panels.
Fig. 3
Fig. 3. The selection panel.
a Description of the selection panel. b Description of the structure list table.
Fig. 4
Fig. 4. Variant panel description.
The panel provides information regarding known variants. In the current version, the data was taken from the CKB Core and the Swiss-Prot databases.
Fig. 5
Fig. 5. 3D-structure and sequence alignment panels.
a 3D-structure panel. b Multiple sequence alignment panel.
See this image and copyright information in PMC

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