Chemical genomics for studying parasite gene function and interaction

•Quantitative high-throughput screen (qHTS) of small molecules (SMs).•SMs as a tool for studying phenotypes and gene function.•Combination of SM screening and genome-wide approaches.•Target identification and pathway/network building.

With the development of new technologies in genome sequencing, gene expression profiling, genotyping, and high-throughput screening of chemical compound libraries, small molecules are playing increasingly important roles in studying gene expression regulation, gene–gene interaction, and gene function. Here we briefly review and discuss some recent advancements in drug target identification and phenotype characterization using combinations of high-throughput screening of small-molecule libraries and various genome-wide methods such as whole-genome sequencing, genome-wide association studies (GWAS), and genome-wide expression analysis. These approaches can be used to search for new drugs against parasite infections, to identify drug targets or drug resistance genes, and to infer gene function.