TY - JOUR T1 - Harvesting Candidate Genes Responsible for Serious Adverse Drug Reactions from a Chemical-Protein Interactome A1 - Yang, Lun A1 - Chen, Jian A1 - He, Lin Y1 - 2009/07/24 N2 - Author Summary Why do tragedies caused by Vioxx or Avandia only happen to certain individuals? The unexpected bindings among drugs and human proteins might play important roles in such serious adverse drug reactions (SADRs). To mine these unexpected chemical-protein interactions, 162 drug molecules known to cause SADRs are ‘hybridized’ onto 845 proteins to construct a chemical-protein interaction matrix, from which two aspects of the information, the binding strength and the binding conformation, are disclosed. Followed by the data-mining strategies, the unexpected bindings that mediate SADRs are identified. For example, abacavir is found to bind to the antigen presentation groove of MHC I molecule in patients carrying the B*5701 allele but not B*5703, which explains why HLA-B*5701, not B*5703, is the risk allele of abacavir hypersensitivity. This research could explain to the public that SADR happens when some of the innocent proteins are attacked by drugs unexpectedly, and variances in certain people's genome make their proteins more sensitive to the drug. By pre-therapy screening, the susceptible people could be protected. Furthermore, new drugs or modified drugs will be designed to avoid these patient-specific unintended bindings, in a step toward realizing personalized medicine. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 5 IS - 7 UR - https://doi.org/10.1371/journal.pcbi.1000441 SP - e1000441 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1000441 ER -