Core Gene Essentiality

Data supporting core essentiality of a target

Overview

Core essential target genes are unlikely to tolerate inhibition and are susceptible to causing adverse events if modulated. This is crucial safety information for drug discovery scientists looking to develop inhibition strategies.

To support target prioritisation with an extra focus on target safety, the Open Targets Platform includes key information on target core essentiality in the context of 28 tissues assayed in the DepMap portal. In this project and its ancillary projects (e.g. Achilles), cell fitness is measured after the inhibition of individual genes across a number of cell lines. As a result, a gene is catalogued as core essential if the majority of cell lines die after inhibition/knockout. Although in cancer, this experiment represents a good proxy of whether loss of function is tolerated across a diverse set of tissues.

Essentiality assessment: The Chronos dependency score is based on data from a cell depletion assay. A lower Chronos score indicates a higher likelihood that the gene of interest is essential in a given cell line. A score of 0 indicates a gene is not essential; correspondingly -1 is comparable to the median of all pan-essential genes.

Together with a DepMap target annotation widget, essential target genes are annotated with a `Core essential gene` chip on the target page.

Data source

DepMap Portal

The goal of the Dependency Map (DepMap) portal is to empower the research community to make discoveries related to cancer vulnerabilities by providing open access to key cancer dependencies analytical and visualisation tools.

Publications

When using this data please remember to acknowledge the sources:

Pacini C, Dempster JM, Boyle I, Gonçalves E, Najgebauer H, Karakoc E, van der Meer D, Barthorpe A, Lightfoot H, Jaaks P, McFarland JM, Garnett MJ, Tsherniak A, Iorio F. Integrated cross-study datasets of genetic dependencies in cancer. Nat Commun. 2021 Mar 12;12(1):1661. doi: 10.1038/s41467-021-21898-7. PMID: 33712601; PMCID: PMC7955067.

See all relevant DepMap publications.