Towards Structural Systems Pharmacology to Study Complex Diseases and Personalized Medicine

Lei Xie, Xiaoxia Ge, Hepan Tan, Li Xie, Yinliang Zhang, Thomas Hart, Xiaowei Yang, Philip E. Bourne

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Genome-Wide Association Studies (GWAS), whole genome sequencing, and high-throughput omics techniques have generated vast amounts of genotypic and molecular phenotypic data. However, these data have not yet been fully explored to improve the effectiveness and efficiency of drug discovery, which continues along a one-drug-one-target-one-disease paradigm. As a partial consequence, both the cost to launch a new drug and the attrition rate are increasing. Systems pharmacology and pharmacogenomics are emerging to exploit the available data and potentially reverse this trend, but, as we argue here, more is needed. To understand the impact of genetic, epigenetic, and environmental factors on drug action, we must study the structural energetics and dynamics of molecular interactions in the context of the whole human genome and interactome. Such an approach requires an integrative modeling framework for drug action that leverages advances in data-driven statistical modeling and mechanism-based multiscale modeling and transforms heterogeneous data from GWAS, high-throughput sequencing, structural genomics, functional genomics, and chemical genomics into unified knowledge. This is not a small task, but, as reviewed here, progress is being made towards the final goal of personalized medicines for the treatment of complex diseases.

Original languageEnglish (US)
Article numbere1003554
JournalPLoS Computational Biology
Volume10
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Pharmacology
Precision Medicine
pharmacology
Genomics
medicine
Medicine
Drugs
Genome
drug
Genes
Genome-Wide Association Study
drugs
genome
genomics
Pharmaceutical Preparations
Sequencing
High Throughput
Drug Design
Pharmacogenetics
Throughput

ASJC Scopus subject areas

  • Computational Theory and Mathematics
  • Modeling and Simulation
  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Molecular Biology
  • Ecology
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Towards Structural Systems Pharmacology to Study Complex Diseases and Personalized Medicine. / Xie, Lei; Ge, Xiaoxia; Tan, Hepan; Xie, Li; Zhang, Yinliang; Hart, Thomas; Yang, Xiaowei; Bourne, Philip E.

In: PLoS Computational Biology, Vol. 10, No. 5, e1003554, 2014.

Research output: Contribution to journalArticle

Xie, L, Ge, X, Tan, H, Xie, L, Zhang, Y, Hart, T, Yang, X & Bourne, PE 2014, 'Towards Structural Systems Pharmacology to Study Complex Diseases and Personalized Medicine', PLoS Computational Biology, vol. 10, no. 5, e1003554. https://doi.org/10.1371/journal.pcbi.1003554
Xie, Lei ; Ge, Xiaoxia ; Tan, Hepan ; Xie, Li ; Zhang, Yinliang ; Hart, Thomas ; Yang, Xiaowei ; Bourne, Philip E. / Towards Structural Systems Pharmacology to Study Complex Diseases and Personalized Medicine. In: PLoS Computational Biology. 2014 ; Vol. 10, No. 5.
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