Englander Institute for Precision Medicine

Fast mutual exclusivity algorithm nominates potential synthetic lethal gene pairs through brute force matrix product computations.

TitleFast mutual exclusivity algorithm nominates potential synthetic lethal gene pairs through brute force matrix product computations.
Publication TypeJournal Article
Year of Publication2021
AuthorsFedrizzi T, Ciani Y, Lorenzin F, Cantore T, Gasperini P, Demichelis F
JournalComput Struct Biotechnol J
Volume19
Pagination4394-4403
Date Published2021
ISSN2001-0370
Abstract

Mutual Exclusivity analysis of genomic aberrations contributes to the exploration of potential synthetic lethal (SL) relationships thus guiding the nomination of specific cancer cells vulnerabilities. When multiple classes of genomic aberrations and large cohorts of patients are interrogated, exhaustive genome-wide analyses are not computationally feasible with commonly used approaches. Here we present Fast Mutual Exclusivity (FaME), an algorithm based on matrix multiplication that employs a logarithm-based implementation of the Fisher's exact test to achieve fast computation of genome-wide mutual exclusivity tests; we show that brute force testing for mutual exclusivity of hundreds of millions of aberrations combinations can be performed in few minutes. We applied FaME to allele-specific data from whole exome experiments of 27 TCGA studies cohorts, detecting both mutual exclusivity of point mutations, as well as allele-specific copy number signals that span sets of contiguous cytobands. We next focused on a case study involving the loss of tumor suppressors and druggable genes while exploiting an integrated analysis of both public cell lines loss of function screens data and patients' transcriptomic profiles. FaME algorithm implementation as well as allele-specific analysis output are publicly available at https://github.com/demichelislab/FaME.

DOI10.1016/j.csbj.2021.08.001
Alternate JournalComput Struct Biotechnol J
PubMed ID34429855
PubMed Central IDPMC8369001
Grant List648670 / ERC_ / European Research Council / International

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