HUME: large-scale detection of causal genetic factors of adverse drug reactions.

Abstract

Adverse drug reactions are one of the major factors that affect the wellbeing of patients and financial costs of healthcare systems. Genetic variations of patients have been shown to be a key factor in the occurrence and severity of many ADRs. However, the large number of confounding drugs and genetic biomarkers for each adverse reaction case demands a method that evaluates all potential genetic causes of ADRs simultaneously. To address this challenge, we propose HUME, a multi-phase algorithm that recommends genetic factors for ADRs that are causally supported by the patient record data. HUME consists of the construction of a network from co-prevalence between significant genetic biomarkers and ADRs, a link score phase for predicting candidate relations based on the Adamic-Adar measure, and a causal refinement phase based on multiple hypothesis testing of quasi experimental designs for evaluating evidence and counter evidence of candidate relations in the patient records. Supplementary data are available at Bioinformatics online.