We describe an approach to early stage drug discovery that explicitly engages with the complexities of human biology. The combined computational and experimental approach is formulated on a conceptual framework in which network biology is used to bridge between individual molecular entities and the cellular phenotype that emerges when those entities interact in a network. Multiple aspects of early stage discovery are addressed including the data-driven elucidation of biological processes implicated in disease, target identification and validation, phenotypic discovery of active molecules and their mechanism of action, and extraction of genetic target support from human population genetics data. Validation is described via summary of a number of discovery projects and details from a project aimed at COVID-19 disease.
Keywords: Biological complexity; Drug discovery; GWAS; Human genetics; Network biology; Network perturbation; Phenotypic assays; Phenotypic screening; Statistical network models; Systems biology; Target identification; Target validation.
© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.