Drug target mining and analysis of the Chinese tree shrew for pharmacological testing

PLoS One. 2014 Aug 8;9(8):e104191. doi: 10.1371/journal.pone.0104191. eCollection 2014.

Abstract

The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • China
  • Drug Delivery Systems / methods
  • Drug Discovery / methods*
  • Gene Expression Profiling
  • Humans
  • Mice
  • Models, Animal*
  • Molecular Sequence Annotation
  • Pharmaceutical Preparations / metabolism*
  • Proteins / metabolism*
  • Tupaiidae*

Substances

  • Pharmaceutical Preparations
  • Proteins

Grant support

This work was supported by grants from the Chinese Academy of Sciences (KSCX2-EW-R-11 and KSCX2-EW-J-23), the National 863 project of China (No. 2012AA021801, 2012AA022402 ), and the Key Research Program of the Chinese Academy of Sciences (KJZD-EW-L03). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.