Targeting trypanosomes: how chemogenomics and artificial intelligence can guide drug discovery.

Trypanosomatids are protozoan parasites that cause human and animal neglected diseases. Despite global efforts, effective treatments are still much needed. Phenotypic screens have provided several chemical leads for drug discovery, but the mechanism of action for many of these chemicals is currently unknown. Recently, chemogenomic screens assessing the susceptibility or resistance of parasites carrying genome-wide modifications started to define the mechanism of action of drugs at large scale. In this review, we discuss how genomics is being used for drug discovery in trypanosomatids, how integration of chemical and genomics data from these and other organisms has guided prioritisations of candidate therapeutic targets and additional chemical starting points, and how these data can fuel the expansion of drug discovery pipelines into the era of artificial intelligence.

TDR Targets 6: driving drug discovery for human pathogens through intensive chemogenomic data integration.

The volume of biological, chemical and functional data deposited in the public domain is growing rapidly, thanks to next generation sequencing and highly-automated screening technologies. These datasets represent invaluable resources for drug discovery, particularly for less studied neglected disease pathogens. To leverage these datasets, smart and intensive data integration is required to guide computational inferences across diverse organisms. The TDR Targets chemogenomics resource integrates genomic data from human pathogens and model organisms along with information on bioactive compounds and their annotated activities. This report highlights the latest updates on the available data and functionality in TDR Targets 6. Based on chemogenomic network models providing links between inhibitors and targets, the database now incorporates network-driven target prioritizations, and novel visualizations of network subgraphs displaying chemical- and target-similarity neighborhoods along with associated target-compound bioactivity links. Available data can be browsed and queried through a new user interface, that allow users to perform prioritizations of protein targets and chemical inhibitors. As such, TDR Targets now facilitates the investigation of drug repurposing against pathogen targets, which can potentially help in identifying candidate targets for bioactive compounds with previously unknown targets. TDR Targets is available at https://tdrtargets.org.