GTExome: Modeling commonly expressed missense mutations in the human genome

Area of Science:

• Genomics
• Proteomics
• Bioinformatics

Background:

• Missense mutations are common genetic variations affecting protein function.
• Understanding mutation consequences requires integrating genomic and expression data.
• The Genotype-Tissue Expression (GTEx) project provides valuable tissue-specific gene expression data.

Purpose of the Study:

• To introduce GTExome, a web application for identifying, classifying, and modeling missense mutations in human proteins.
• To enable the assessment of mutation impacts on protein structure and function by integrating genomic and GTEx data.
• To facilitate the creation and visualization of mutated protein models for further study.

Main Methods:

• GTExome integrates genomic mutation data with tissue-specific expression data from the GTEx project.
• The tool analyzes missense mutations for potential structural and functional consequences (e.g., bond disruption, charge changes, binding pocket alterations).
• Users can model mutated proteins using experimental or predicted structures and the Fast and Accurate Side-chain Protein Repacking (FASPR) algorithm.

Main Results:

• GTExome successfully models a large set of common missense mutations (9,666) across various human tissues.
• The tool provides detailed information on mutation impacts, including structural changes and binding pocket characteristics.
• Confidence scores are available for AlphaFold-modeled proteins.

Conclusions:

• GTExome is an effective open-source tool for modeling missense mutations in human proteins.
• The application facilitates research into protein-protein and protein-drug interactions by providing structural insights into mutations.
• GTExome is freely accessible, promoting wider use in genomic and proteomic research.