Towards quantitative biology: integration of biological information to elucidate disease pathways and to guide drug discovery

Biotechnol Annu Rev. 2005:11:1-68. doi: 10.1016/S1387-2656(05)11001-1.

Abstract

Developing a new drug is a tedious and expensive undertaking. The recently developed high-throughput experimental technologies, summarised by the terms genomics, transcriptomics, proteomics and metabolomics provide for the first time ever the means to comprehensively monitor the molecular level of disease processes. The "-omics" technologies facilitate the systematic characterisation of a drug target's physiology, thereby helping to reduce the typically high attrition rates in discovery projects, and improving the overall efficiency of pharmaceutical research processes. Currently, the bottleneck for taking full advantage of the new experimental technologies are the rapidly growing volumes of automatically produced biological data. A lack of scalable database systems and computational tools for target discovery has been recognised as a major hurdle. In this review, an overview will be given on recent progress in computational biology that has an impact on drug discovery applications. The focus will be on novel in silico methods to reconstruct regulatory networks, signalling cascades, and metabolic pathways, with an emphasis on comparative genomics and microarray-based approaches. Promising methods, such as the mathematical simulation of pathway dynamics are discussed in the context of applications in discovery projects. The review concludes by exemplifying concrete data-driven studies in pharmaceutical research that demonstrate the value of integrated computational systems for drug target identification and validation, screening assay development, as well as drug candidate efficacy and toxicity evaluations.

Publication types

  • Review

MeSH terms

  • Animals
  • Biotechnology / methods
  • Biotechnology / trends
  • Drug Industry / methods
  • Drug Industry / trends
  • Genomics
  • Humans
  • Models, Biological
  • Proteomics
  • Systems Biology / methods*
  • Systems Biology / trends
  • Technology, Pharmaceutical / methods*
  • Technology, Pharmaceutical / trends