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Systematic analysis of the associations between adverse drug reactions and pathways

Xiaowen Chen1, Yanqiu Wang1, Pingping Wang1

  • 1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.

Biomed Research International
|October 24, 2015
PubMed

Insights

This study reveals how biological pathways link to adverse drug reactions (ADRs). Understanding these ADR-pathway connections helps predict and prevent drug failures during clinical trials.

Area of Science:

  • Pharmacology
  • Systems Biology
  • Computational Biology

Background:

  • Adverse drug reactions (ADRs) frequently cause drug candidate failure in clinical trials.
  • Investigating the biological pathways implicated in ADRs is critical for drug development.
  • Current understanding of ADR mechanisms and pathway associations requires systematic analysis.

Purpose of the Study:

  • To identify overrepresented combinations of ADRs and biological pathways.
  • To construct and analyze networks of ADRs and pathways for mechanistic insights.
  • To understand how drug perturbations affect biological systems and lead to ADRs.

Main Methods:

  • Large-scale analysis merging clinical data, pathway data, and drug-target relations.
  • Construction of an ADR-pathway network and an ADR-ADR network.
  • Network analysis incorporating scientific literature review and pathway-based similarity measures.

Main Results:

  • The method efficiently identified significant ADR-pathway associations.
  • Frequent ADRs were linked to a greater number of pathways compared to rare ADRs.
  • Environmental information processing pathways were most frequently associated with ADRs.
  • ADR classes predominantly interacted with other classes, indicating pleiotropic effects.
  • Drug effects on single pathways can impact multiple organs.

Conclusions:

  • This work provides a comprehensive view of ADR-pathway associations.
  • The findings enhance the understanding of ADR mechanisms.
  • The approach aids in predicting and mitigating drug-induced toxicity.

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