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An emerging theme from large-scale genetic screens that identify genes essential for cell fitness is that essentiality of a given gene is highly context-specific. Identification of such contexts could be the key to defining gene function and also to develop novel therapeutic interventions. Here, we present Context-specific Essentiality Network-tools (CEN-tools), a website and python package, in which users can interrogate the essentiality of a gene from large-scale genome-scale CRISPR screens in a number of biological contexts including tissue of origin, mutation profiles, expression levels and drug responses. We show that CEN-tools is suitable for the systematic identification of genetic dependencies and for more targeted queries. The associations between genes and a given context are represented as dependency networks (CENs), and we demonstrate the utility of these networks in elucidating novel gene functions. In addition, we integrate the dependency networks with existing protein-protein interaction networks to reveal context-dependent essential cellular pathways in cancer cells. Together, we demonstrate the applicability of CEN-tools in aiding the current efforts to define the human cellular dependency map.

Original publication

DOI

10.15252/msb.20209698

Type

Journal article

Journal

Mol Syst Biol

Publication Date

10/2020

Volume

16

Keywords

CRISPR , NRAS-mutant melanoma, context-specific essentiality, networks, omics integration, CRISPR-Cas Systems, Cell Line, Tumor, Computational Biology, Gene Expression Regulation, Neoplastic, Gene Knockout Techniques, Gene Regulatory Networks, Genes, Essential, Humans, Melanoma, Metabolomics, Mutation, SOXE Transcription Factors, Serum Response Factor, Signal Transduction, Skin Neoplasms, Software