Systems biology analysis of protein-drug interactions.
Drugs induce global perturbations at the molecular machinery level because their cognate targets are involved in multiple biological functions or because of off-target effects. The analysis or the prediction of such systems level consequences of drug treatment therefore requires the application of systems biology concepts and methods. In this review, we first summarize the methods of chemical proteomics that can measure unbiased and proteome-wide drug protein target spectra, which is an obvious necessity to perform a global analysis. We then focus on the introduction of computational methods and tools to relate such target spectra to global models such as pathways and networks of protein-protein interactions, and to integrate them with existing protein functional annotations. In particular, we discuss how drug treatment can be mapped onto likely affected biological functions, how this can help identifying drug mechanisms of action, and how such mappings can be exploited to predict potential side effects and to suggest new indications for existing compounds.
Research Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM), Jacques Colinge, Vienna, Austria. jcolinge@cemm.oeaw.ac.at
Jacques
J
Colinge
Uwe
U
Rix
Keiryn L
KL
Bennett
Giulio
G
Superti-Furga
D004347:Drug Interactions; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D057285:Precision Medicine; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics; D049490:Systems Biology
D004364:Pharmaceutical Preparations; D011506:Proteins