%0 Journal Article %A Tal Lorberbaum %A Kevin J. Sampson %A Raymond L. Woosley %A Robert S. Kass %A Nicholas P. Tatonetti %T Data science identifies novel drug interactions that prolong the QT interval %D 2015 %R 10.1101/024745 %J bioRxiv %P 024745 %X Drug-induced prolongation of the QT interval on the electrocardiogram (long QT syndrome, LQTS) can lead to a potentially fatal ventricular arrhythmia called torsades de pointes (TdP). 180 drugs with both cardiac and non-cardiac indications have been found to increase risk for TdP, but drug-drug interactions contributing to LQTS (QT-DDIs) remain poorly characterized. Traditional methods for mining observational healthcare data are poorly equipped to detect QT- DDI signals due to low reporting numbers and a lack of direct evidence for LQTS. In this study we present an integrative data science pipeline that addresses these limitations by identifying latent signals for QT-DDIs in the FDA’s Adverse Event Reporting System and retrospectively validating these predictions using electrocardiogram data in electronic health records. We present 26 novel QT-DDIs flagged using this method that warrant further investigation.Key Points- Drug-induced long QT syndrome (LQTS) can lead to potentially fatal arrhythmias (torsades de pointes, TdP). Drug-drug interactions that prolong the QT interval (QT- DDIs) can be clinically significant but remain poorly characterized.- Observational health data (such as adverse event spontaneous reporting systems and electronic health records) offer an opportunity to mine for new QT-DDIs, but when used individually these datasets have a number of limitations that prevent identification of true signals.- We present an integrative data science approach that combines mining for latent QT- DDI signals in the FDA Adverse Event Reporting System and retrospective analysis of electrocardiogram lab results in electronic health records at Columbia University Medical Center to identify 26 novel QT-DDIs. %U https://www.biorxiv.org/content/biorxiv/early/2015/08/17/024745.full.pdf