Clinical connectivity map for drug repurposing: using laboratory tests to bridge drugs and diseases

Abstract

Drug repurposing has attracted increasing attention from both the pharmaceutical industry and the research community. Many existing computational drug repurposing methods rely on preclinical data (e.g., chemical structures, drug targets), resulting in translational problems for clinical trials. In this study, we propose a clinical connectivity map framework for drug repurposing by leveraging laboratory tests to analyze complementarity between drugs and diseases. We establish clinical drug effect vectors (i.e., drug-laboratory test associations) by applying a continuous self-controlled case series model on a longitudinal electronic health record data. We establish clinical disease sign vectors (i.e., disease-laboratory test associations) by applying a Wilcoxon rank sum test on a large-scale national survey data. Finally, we compute a repurposing possibility score for each drug-disease pair by applying a dot product-based scoring function on clinical disease sign vectors and clinical drug effect vectors. We comprehensively evaluate 392 drugs for 6 important chronic diseases (e.g., asthma, coronary heart disease, type 2 diabetes, etc.). We discover not only known associations between diseases and drugs but also many hidden drug-disease associations. Moreover, we are able to explain the predicted drug-disease associations via the corresponding complementarity between laboratory tests of drug effect vectors and disease sign vectors. The proposed clinical connectivity map framework uses laboratory tests from electronic clinical information to bridge drugs and diseases, which is explainable and has better translational power than existing computational methods. Experimental results demonstrate the effectiveness of the proposed framework and suggest that our method could help identify drug repurposing opportunities, which will benefit patients by offering more effective and safer treatments.