SUMMARY: Synthetic lethality is a state when simultaneous loss of two genes is lethal to a cancer cell, while the loss of the individual genes is not. We developed an R package DiscoverSL to predict and visualize synthetic lethality in cancers using multi-omic cancer data. Mutation, copy number alteration and gene expression data from The Cancer Genome Atlas project were combined to develop a multi-parametric Random Forest classifier. The effects of selectively targeting the predicted synthetic lethal genes is tested in silico using shRNA and drug screening data from cancer cell line databases. The clinical outcome in patients with mutation in primary gene and over/under-expression in the synthetic lethal gene is evaluated using Kaplan-Meier analysis. The method helps to identify new therapeutic approaches by exploiting the concept of synthetic lethality. AVAILABILITY AND IMPLEMENTATION: DiscoverSL package with user manual and sample workflow is available for download from github url: https://github.com/shaoli86/DiscoverSL/releases/tag/V1.0 under GNU GPL-3. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. Published by Oxford University Press 2018.
SUMMARY: Synthetic lethality is a state when simultaneous loss of two genes is lethal to a cancer cell, while the loss of the individual genes is not. We developed an R package DiscoverSL to predict and visualize synthetic lethality in cancers using multi-omic cancer data. Mutation, copy number alteration and gene expression data from The Cancer Genome Atlas project were combined to develop a multi-parametric Random Forest classifier. The effects of selectively targeting the predicted synthetic lethal genes is tested in silico using shRNA and drug screening data from cancer cell line databases. The clinical outcome in patients with mutation in primary gene and over/under-expression in the synthetic lethal gene is evaluated using Kaplan-Meier analysis. The method helps to identify new therapeutic approaches by exploiting the concept of synthetic lethality. AVAILABILITY AND IMPLEMENTATION: DiscoverSL package with user manual and sample workflow is available for download from github url: https://github.com/shaoli86/DiscoverSL/releases/tag/V1.0 under GNU GPL-3. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. Published by Oxford University Press 2018.
Authors: Salvatore Benfatto; Özdemirhan Serçin; Francesca R Dejure; Amir Abdollahi; Frank T Zenke; Balca R Mardin Journal: Mol Cancer Date: 2021-08-28 Impact factor: 27.401