Development of a chemogenomics library for phenotypic screening.

Area of Science:

• Pharmacology
• Computational Biology
• Drug Discovery

Background:

• Phenotypic drug discovery (PDD) is a valuable approach for identifying novel therapeutics but requires target identification and mechanism deconvolution.
• Cell-based phenotypic screening, particularly high-content imaging assays like Cell Painting, generates rich morphological data.
• Integrating diverse biological data is crucial for advancing PDD.

Purpose of the Study:

• To develop a system pharmacology network integrating drug-target-pathway-disease relationships and morphological profiles.
• To create a chemogenomic library of 5000 small molecules for target identification and mechanism deconvolution in PDD.
• To provide a platform that assists in understanding phenotypic assays.

Main Methods:

• Developed a system pharmacology network by integrating drug-target-pathway-disease relationships.
• Incorporated morphological profiles from Cell Painting high-throughput phenotypic profiling assays.
• Constructed a chemogenomic library of 5000 diverse small molecules targeting various biological effects and diseases.

Main Results:

• Successfully integrated multi-omics data into a comprehensive system pharmacology network.
• Established a chemogenomic library of 5000 small molecules, enabling diverse target coverage.
• Demonstrated the platform's utility through illustrative examples in target identification and mechanism deconvolution.

Conclusions:

• The developed system pharmacology network and chemogenomic library offer a powerful platform for phenotypic drug discovery.
• This integrated approach facilitates target identification and mechanism deconvolution for phenotypic assays.
• The platform has the potential to accelerate the development of novel and safe drugs.