Defining the optimal animal model for translational research using gene set enrichment analysis.
The mouse is the main model organism used to study the functions of human genes because most biological processes in the mouse are highly conserved in humans. Recent reports that compared identical transcriptomic datasets of human inflammatory diseases with datasets from mouse models using traditional gene-to-gene comparison techniques resulted in contradictory conclusions regarding the relevance of animal models for translational research. To reduce susceptibility to biased interpretation, all genes of interest for the biological question under investigation should be considered. Thus, standardized approaches for systematic data analysis are needed. We analyzed the same datasets using gene set enrichment analysis focusing on pathways assigned to inflammatory processes in either humans or mice. The analyses revealed a moderate overlap between all human and mouse datasets, with average positive and negative predictive values of 48 and 57% significant correlations. Subgroups of the septic mouse models (i.e., Staphylococcus aureus injection) correlated very well with most human studies. These findings support the applicability of targeted strategies to identify the optimal animal model and protocol to improve the success of translational research.
Department of Experimental Toxicology and ZEBET, German Federal Institute for Risk Assessment (BfR), Berlin, Germany.
Christopher
C
Weidner
Department of Experimental Toxicology and ZEBET, German Federal Institute for Risk Assessment (BfR), Berlin, Germany.
Matthias
M
Steinfath
Department of Experimental Toxicology and ZEBET, German Federal Institute for Risk Assessment (BfR), Berlin, Germany.
Elisa
E
Opitz
Department of Experimental Toxicology and ZEBET, German Federal Institute for Risk Assessment (BfR), Berlin, Germany.
Michael
M
Oelgeschläger
Department of Experimental Toxicology and ZEBET, German Federal Institute for Risk Assessment (BfR), Berlin, Germany Department of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany gilbert.schoenfelder@bfr.bund.de.
Gilbert
0000-0001-6134-1990
G
Schönfelder
D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D051379:Mice; D018805:Sepsis / Q000235:genetics / Q000473:pathology; D049490:Systems Biology / Q000379:methods*; D057170:Translational Research, Biomedical / Q000379:methods*
GSEA; animal model; inflammation; transcriptomics; translational research