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

Autor:	Fedrizzi T; Department of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, Italy., Ciani Y; Department of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, Italy., Lorenzin F; Department of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, Italy., Cantore T; Department of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, Italy., Gasperini P; Department of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, Italy., Demichelis F; Department of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, Italy.; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10021, USA.; The Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
Jazyk:	angličtina
Zdroj:	Computational and structural biotechnology journal [Comput Struct Biotechnol J] 2021 Aug 05; Vol. 19, pp. 4394-4403. Date of Electronic Publication: 2021 Aug 05 (Print Publication: 2021).
DOI:	10.1016/j.csbj.2021.08.001
Abstrakt:	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. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2021 The Authors.)
Databáze:	MEDLINE
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