Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds

John Okyere, Ekow Oppon, Daniel Dzidzienyo, Lav Sharma, Graham Ball

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Animals are frequently used as model systems for determination of safety and efficacy in pharmaceutical research and development. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this cross-species methodology by investigating species specific differences of the peroxisome proliferator-activator receptor (PPAR) α response in rat and human.

Original languageEnglish
Article numbere96853
JournalPLoS ONE
Volume9
Issue number5
DOIs
Publication statusPublished - 13 May 2014
Externally publishedYes

Fingerprint

Dive into the research topics of 'Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds'. Together they form a unique fingerprint.

Cite this