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

Okyere, J., Oppon, E., Dzidzienyo, D., Sharma, L. and Ball, G. ORCID: 0000-0001-5828-7129, 2014. Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds. PLoS ONE, 9 (5), e96853. ISSN 1932-6203

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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 proliferatoractivator receptor (PPAR) a response in rat and human.

Item Type: Journal article
Publication Title: PLoS ONE
Creators: Okyere, J., Oppon, E., Dzidzienyo, D., Sharma, L. and Ball, G.
Publisher: PLoS (Public Library of Science)
Date: 2014
Volume: 9
Number: 5
ISSN: 1932-6203
Identifiers:
NumberType
10.1371/journal.pone.0096853DOI
Rights: Open access via the Creative Commons Attribution (CC BY) license
Divisions: Schools > School of Science and Technology
Depositing User: EPrints Services
Date Added: 09 Oct 2015 10:32
Last Modified: 09 Jun 2017 13:32
URI: http://irep.ntu.ac.uk/id/eprint/14356

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