Biochemistry & Molecular Pharmacology
Gene Therapy Center
Algebraic Geometry | Life Sciences | Medicine and Health Sciences | Microarrays | Multivariate Analysis | Statistical Methodology
Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury, a common problem worldwide associated with significant morbidity and mortality. We have recently examined the role of microRNAs (miRs) in renal IRI using expression profiling. Here we conducted mathematical analyses to determine if differential expression of miRs can be used to define a biomarker of renal IRI. Principal component analysis (PCA) was combined with spherical geometry to determine whether samples that underwent renal injury as a result of IRI can be distinguished from controls based on alterations in miR expression using our data set consisting of time series measuring 571 miRs. Using PCA, we examined whether changes in miR expression in the kidney following IRI have a distinct direction when compared to controls based on the trajectory of the first three principal components (PCs) for our time series. We then used Monte Carlo methods and spherical geometry to assess the statistical significance of these directions. We hypothesized that if IRI and control samples exhibit distinct directions, then miR expression can be used as a biomarker of injury. Our data reveal that the pattern of miR expression in the kidney following IRI has a distinct direction based on the trajectory of the first three PCs and can be distinguished from changes observed in sham controls. Analyses of samples from immunodeficient mice indicated that the changes in miR expression observed following IRI were lymphocyte independent, and therefore represent a kidney intrinsic response to injury. Together, these data strongly support the notion that IRI results in distinct changes in miR expression that can be used as a biomarker of injury.
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Copyright: © 2011 Shapiro et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
Shapiro MD, Bagley J, Latz J, Godwin JG, Ge X, et al. (2011) MicroRNA Expression Data Reveals a Signature of Kidney Damage following Ischemia Reperfusion Injury. PLoS ONE 6(8): e23011. doi:10.1371/journal.pone.0023011. Link to article on publisher's website
Shapiro, Michael D.; Bagley, Jessamyn; Latz, Jeff; Godwin, Jonathan G.; Ge, Xupeng; Tullius, Stefan G.; and Iacomini, John, "MicroRNA Expression Data Reveals a Signature of Kidney Damage following Ischemia Reperfusion Injury" (2011). GSBS Student Publications. 1756.