Identification of pediatric septic shock subclasses based on genome-wide expression profiling

Show simple item record Wong, Hector R Cvijanovich, Natalie Lin, Richard Allen, Geoffrey L Thomas, Neal J Willson, Douglas F Freishtat, Robert J Anas, Nick Meyer, Keith Checchia, Paul A Monaco, Marie Odoms, Kelli Shanley, Thomas P 2010-11-04T19:20:23Z 2010-11-04T19:20:23Z 2009-07-22
dc.description.abstract Abstract Background Septic shock is a heterogeneous syndrome within which probably exist several biological subclasses. Discovery and identification of septic shock subclasses could provide the foundation for the design of more specifically targeted therapies. Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling. Methods Genome-wide expression profiling was conducted using whole blood-derived RNA from 98 children with septic shock, followed by a series of bioinformatic approaches targeted at subclass discovery and characterization. Results Three putative subclasses (subclasses A, B, and C) were initially identified based on an empiric, discovery-oriented expression filter and unsupervised hierarchical clustering. Statistical comparison of the three putative subclasses (analysis of variance, Bonferonni correction, P < 0.05) identified 6,934 differentially regulated genes. K-means clustering of these 6,934 genes generated 10 coordinately regulated gene clusters corresponding to multiple signaling and metabolic pathways, all of which were differentially regulated across the three subclasses. Leave one out cross-validation procedures indentified 100 genes having the strongest predictive values for subclass identification. Forty-four of these 100 genes corresponded to signaling pathways relevant to the adaptive immune system and glucocorticoid receptor signaling, the majority of which were repressed in subclass A patients. Subclass A patients were also characterized by repression of genes corresponding to zinc-related biology. Phenotypic analyses revealed that subclass A patients were younger, had a higher illness severity, and a higher mortality rate than patients in subclasses B and C. Conclusion Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.
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dc.title Identification of pediatric septic shock subclasses based on genome-wide expression profiling
dc.type Journal Article
dc.language.rfc3066 en
dc.description.version Peer Reviewed
dc.rights.holder Wong et al.; licensee BioMed Central Ltd. 2010-11-04T19:20:23Z
dc.owningcollname Interdisciplinary and Peer-Reviewed
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