FaME

FaME identifies mutual exclusivity and co-occurrence signals among genomic aberrations to enable discovery of synthetic lethal (SL) relationships and cancer-specific vulnerabilities.

Key Features:

• Efficient Computation: Implements an algorithm based on matrix multiplication and a logarithm-based implementation of Fisher's exact test to perform rapid genome-wide mutual exclusivity tests.
• Scalability: Processes hundreds of millions of aberration combinations in a few minutes to support exhaustive analyses across large datasets.
• Application to Diverse Data Types: Applied to allele-specific data from whole exome sequencing across 27 TCGA study cohorts, detecting mutual exclusivity among point mutations and allele-specific copy number signals that span contiguous cytobands.
• Integrated Analysis Capability: Enables combined analysis of public cell line loss of function screen data with patient transcriptomic profiles to identify interactions between tumor suppressor losses and druggable genes.

Scientific Applications:

• Exploration of Synthetic Lethality: Identifies mutually exclusive genomic aberrations to pinpoint synthetic lethal relationships for targeted cancer research.
• Genomic Aberration Analysis: Performs comprehensive genome-wide analyses across large cohorts and multiple classes of genomic aberrations.
• Research on Tumor Suppressors and Druggable Genes: Facilitates study of interactions between tumor suppressor gene losses and potential therapeutic targets to inform cancer biology and treatment strategies.

Methodology:

Performs mutual exclusivity testing using matrix multiplication combined with a logarithm-based implementation of Fisher's exact test.