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Drug Discovery in a Multidimensional World: Systems, Patterns, and Networks

  • Joel T. Dudley
  • Eric Schadt
  • Marina Sirota
  • Atul J. Butte
  • Euan AshleyEmail author
Article

Abstract

Despite great strides in revealing and understanding the physiological and molecular bases of cardiovascular disease, efforts to translate this understanding into needed therapeutic interventions continue to lag far behind the initial discoveries. Although pharmaceutical companies continue to increase investments into research and development, the number of drugs gaining federal approval is in decline. Many factors underlie these trends, and a vast number of technological and scientific innovations are being sought through efforts to reinvigorate drug discovery pipelines. Recent advances in molecular profiling technologies and development of sophisticated computational approaches for analyzing these data are providing new, systems-oriented approaches towards drug discovery. Unlike the traditional approach to drug discovery which is typified by a one-drug-one-target mindset, systems-oriented approaches to drug discovery leverage the parallelism and high-dimensionality of the molecular data to construct more comprehensive molecular models that aim to model broader bimolecular systems. These models offer a means to explore complex molecular states (e.g., disease) where thousands to millions of molecular entities comprising multiple molecular data types (e.g., proteomics and gene expression) can be evaluated simultaneously as components of a cohesive biomolecular system. In this paper, we discuss emerging approaches towards systems-oriented drug discovery and contrast these efforts with the traditional, unidimensional approach to drug discovery. We also highlight several applications of these system-oriented approaches across various aspects of drug discovery, including target discovery, drug repositioning and drug toxicity. When available, specific applications to cardiovascular drug discovery are highlighted and discussed.

Keywords

Genomics Drug Discovery Systems Biology 

Notes

Acknowledgments

JTD is supported by the NLM Biomedical Informatics Training Grant (T15 LM007033) to Stanford University. AJB is supported by funding from the National Library of Medicine (R01 LM009719).

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Joel T. Dudley
    • 1
    • 2
    • 3
  • Eric Schadt
    • 4
    • 5
  • Marina Sirota
    • 1
    • 2
    • 3
  • Atul J. Butte
    • 2
    • 3
  • Euan Ashley
    • 6
    Email author
  1. 1.Program in Biomedical InformaticsStanford University School of MedicineStanfordUSA
  2. 2.Department of PediatricsStanford University School of MedicineStanfordUSA
  3. 3.Lucile Packard Children’s HospitalPalo AltoUSA
  4. 4.Pacific BiosciencesMenlo ParkUSA
  5. 5.Sage BionetworksPalo AltoUSA
  6. 6.Division of Cardiovascular MedicineStanford University School of MedicineStanfordUSA

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