GEMap: A comprehensive gene essentiality map for drug discovery

Area of Science:

• Genomics
• Drug Discovery
• Computational Biology

Background:

• Gene essentiality mapping identifies therapeutic vulnerabilities in cancer.
• Existing platforms lack integration between CRISPR functional genomics and drug discovery.

Purpose of the Study:

• To develop GEMap, a novel platform integrating CRISPR-Cas9 essentiality profiles with multi-omics and drug data.
• To enable exploration of gene dependency, target prioritization, and drug discovery for precision oncology.

Main Methods:

• Combined genome-wide CRISPR-Cas9 essentiality screens (1912 screens, 1135 cell lines) with multi-omics data and drug profiles (20,000+ compounds).
• Developed functionalities for exploring multimodal gene data, prioritizing context-specific targets, and discovering tailored treatments.

Main Results:

• GEMap allows exploration of gene dependency, expression, CNV, and mutation data across cancer cell lines and tissues.
• The platform facilitates prioritization of context-specific therapeutic targets, exemplified by KRAS mutant cancers.
• GEMap enables discovery of drug candidates by integrating large-scale drug perturbation and target data.

Conclusions:

• GEMap is the first platform to bridge CRISPR genetic dependencies with pharmacological responses and biological networks.
• It establishes an open-access paradigm for accelerating precision oncology, particularly against undruggable targets.
• The platform is available at https://web.biotcm.net/GEMap/ for broader research use.