MEScan

MEScan performs genome-scale mutual exclusivity analysis of cancer mutations to detect mutually exclusive gene alterations and help distinguish driver from passenger mutations.

Key Features:

• Statistical Rigor: Incorporates a statistical test for mutual exclusivity that adjusts for background mutation rates and the impact of highly mutated genes.
• Computational Efficiency: Operates at least two orders of magnitude faster than most existing methods, enabling genome-wide analyses.
• False Discovery Rate Control: Implements a multi-step procedure to control false discovery rates during genome-wide screening.
• Genome-Wide Capability: Performs comprehensive analysis across the entire genome rather than being limited to pre-selected gene sets.

Scientific Applications:

• Discovery of mutually exclusive gene sets: Applied to cancer cohorts, including ovarian cancer data from The Cancer Genome Atlas (TCGA), to identify biologically meaningful mutually exclusive gene sets.
• Distinguishing driver and passenger mutations: Helps prioritize candidate driver mutations by identifying mutually exclusive alteration patterns indicative of functional redundancies.
• Insight into driver relationships and therapeutic targets: Reveals relationships among driver mutations that can inform molecular mechanisms and aid identification of potential therapeutic targets.

Methodology:

Data preparation of mutation data (e.g., TCGA), application of a fast statistical test for mutual exclusivity that accounts for background mutation rates and highly mutated genes, and a multi-step genome-wide screening procedure controlling the false discovery rate.