PheWAS-Based Systems Genetics Methods for Anti-Breast Cancer Drug Discovery

Genes (Basel). 2019 Feb 18;10(2):154. doi: 10.3390/genes10020154.

Abstract

Breast cancer is a high-risk disease worldwide. For such complex diseases that are induced by multiple pathogenic genes, determining how to establish an effective drug discovery strategy is a challenge. In recent years, a large amount of genetic data has accumulated, particularly in the genome-wide identification of disorder genes. However, understanding how to use these data efficiently for pathogenesis elucidation and drug discovery is still a problem because the gene⁻disease links that are identified by high-throughput techniques such as phenome-wide association studies (PheWASs) are usually too weak to have biological significance. Systems genetics is a thriving area of study that aims to understand genetic interactions on a genome-wide scale. In this study, we aimed to establish two effective strategies for identifying breast cancer genes based on the systems genetics algorithm. As a result, we found that the GeneRank-based strategy, which combines the prognostic phenotype-based gene-dependent network with the phenotypic-related PheWAS data, can promote the identification of breast cancer genes and the discovery of anti-breast cancer drugs.

Keywords: PheWAS; breast cancer; drug discovery; systems genetics.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Drug Discovery / methods*
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Genome-Wide Association Study / methods*
  • Humans
  • Pharmacogenomic Variants*

Substances

  • Antineoplastic Agents