CG-TARGET

CG-TARGET (standing for Chemical Genetic Translation via A Reference Genetic nETwork) is a computational method to harness the potential of chemical-genetic interactions to understand chemical compounds' cellular modes of action. Chemical-genetic interactions occur when treating mutant cells with chemical compounds, which leads to unexpected phenotypes, revealing a rich tapestry of functional information that connects compounds to their effects on cellular functions. The method involves challenging an array of mutants with a compound and monitoring for fitness defects, thereby generating a chemical-genetic interaction profile. This profile offers a quantitative, unbiased description of the cellular function(s) affected by the compound.

One of CG-TARGET's unique strengths is its ability to integrate large-scale chemical-genetic interaction screening data with genetic interaction networks. Genetic interactions, often obtained from genome-wide double-mutant screens, provide critical insights into the functional relationships between genes. By integrating this information with chemical-genetic interaction data, CG-TARGET can predict the biological processes that are perturbed by compounds. This integrative approach represents a significant step forward in systematically evaluating the utility of genetic and chemical-genetic interaction networks for functional analysis.

CG-TARGET has also been validated experimentally, including by identifying compounds that inhibit tubulin polymerization and cell cycle progression. This demonstrates its practical application in the functional annotation of compounds in biological processes.