1. Meta-analysis of molecular response of kidney to ischemia reperfusion injury for the identification of new candidate genes
- Author
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Dmitry N. Grigoryev, Hamid Rabb, Daniel P. Heruth, Shui Qing Ye, Dilyara Cheranova, Peixin Huang, and Li Q. Zhang
- Subjects
Male ,Nephrology ,Candidate gene ,medicine.medical_specialty ,Microarray ,Swine ,Bioinformatics ,Computational biology ,Kidney ,Mice ,Species Specificity ,Internal medicine ,Prevalence ,Animals ,Humans ,Medicine ,Gene ,Kidney transplantation ,urogenital system ,business.industry ,Microarray analysis techniques ,Proteins ,Kidney metabolism ,medicine.disease ,Rats ,Meta-analysis ,medicine.anatomical_structure ,Technical Advance ,Reperfusion Injury ,Immunology ,Female ,business ,Ischemia reperfusion injury - Abstract
Background Accumulated to-date microarray data on ischemia reperfusion injury (IRI) of kidney represent a powerful source for identifying new targets and mechanisms of kidney IRI. In this study, we conducted a meta-analysis of gene expression profiles of kidney IRI in human, pig, rat, and mouse models, using a new scoring method to correct for the bias of overrepresented species. The gene expression profiles were obtained from the public repositories for 24 different models. After filtering against inclusion criteria 21 experimental settings were selected for meta-analysis and were represented by 11 rat models, 6 mouse models, and 2 models each for pig and human, with a total of 150 samples. Meta-analysis was conducted using expression-based genome-wide association study (eGWAS). The eGWAS results were corrected for a rodent species bias using a new weighted scoring algorithm, which favors genes with unidirectional change in expression in all tested species. Results Our meta-analysis corrected for a species bias, identified 46 upregulated and 1 downregulated genes, of which 26 (55%) were known to be associated with kidney IRI or kidney transplantation, including LCN2, CCL2, CXCL1, HMOX1, ICAM1, ANXA1, and TIMP1, which justified our approach. Pathway analysis of our candidates identified “Acute renal failure panel” as the most implicated pathway, which further validates our new method. Among new IRI candidates were 10 novel (
- Published
- 2013