A network paradigm predicts drug synergistic effects using downstream protein-protein interactions.

ABSTRACT: In some cases, drug combinations affect adverse outcome phenotypes by binding the same protein; however, drug-binding proteins are associated through protein-protein interaction (PPI) networks within the cell, suggesting that drug phenotypes may result from long-range network effects. We first used PPI network analysis to classify drugs based on proteins downstream of their targets and next predicted drug combination effects where drugs shared network proteins but had distinct binding proteins (e.g., targets, enzymes, or transporters). By classifying drugs using their downstream proteins, we had an 80.7% sensitivity for predicting rare drug combination effects documented in gold-standard datasets. We further measured the effect of predicted drug combinations on adverse outcome phenotypes u

SUBMITTER: Wilson JL 

PROVIDER: S-EPMC9662203 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature