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

Bioinformatics. 2018 Dec 15;34(24):4274-4283. doi: 10.1093/bioinformatics/bty475.

Abstract

Motivation: 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.

Results: 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 information: Supplementary data are available at Bioinformatics online.

MeSH terms

  • Algorithms*
  • Computational Biology / methods*
  • Drug-Related Side Effects and Adverse Reactions* / genetics
  • Genetic Markers* / genetics
  • Humans

Substances

  • Genetic Markers