E-GEOD-47970 - Cross-species gene expression analysis of species-specific differences in preclinical assessment of pharmaceutical compounds (human)
Released on 30 April 2014, last updated on 14 July 2015
Significant qualitative and quantitative differences exist between humans and the animal models used in research. 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 difference using a cross-species methodology by investigating species specific differences of the peroxisome proliferator activator receptor (PPAR) alpha in rat and human. Human primary hepatocytes were treated with 30 uM, 100 uM EMD and 0.1% DMSO as vehicle control. All samples were incubated at 24hr and 72hr intervals before RNA extractions and hybridization onto Affymetrix human microarrays.
transcription profiling by array
John Okyere <firstname.lastname@example.org>, D Dzidzienyo, G Ball, J Okyere, J Oppon, L Sharma
Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds. Okyere J, Oppon E, Dzidzienyo D, Sharma L, Ball G.