Historeceptomics: Integrating a drug’s multiple targets (polypharmacology) with their expression pattern in human tissues

Abstract

Historeceptomics is a new, integrative informatics approach to describing the mechanism of action of drugs in a holistic, in vivo context. The approach is based on leveraging emerging big data sources in genomics and chemistry to incorporate tissue specificity into mechanism of action descriptions. New insights into drug mechanism of action, drug repurposing, and prediction of adverse effects may be possible, including the design and development of multi-target drugs or drug combinations. The critical elements still under development include: (1) defining the tissue ensemble associated with specific human diseases, (2) appreciating the pattern or partitioning of the expression of drug targets (receptors) across and outside of these ensembles, and (3) informatics methods to integrate direct drug-receptor data with receptor expression data in tissues. Maturation of this field may enable the complementary field of tissue-targeted drug delivery, enabling novel concepts in drug design and development for unmet medical needs.