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Series GSE26378 Query DataSets for GSE26378
Status Public on Jan 13, 2011
Title Expression data from validation cohort of children with septic shock
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Background: Septic shock heterogeneity has important implications for the conduct of clinical trials and individual patient management. We previously addressed this heterogeneity by indentifying 3 putative subclasses of children with septic shock based on a 100-gene expression signature corresponding to adaptive immunity and glucocorticoid receptor signaling. Herein we attempted to prospectively validate the existence of these gene expression-based subclasses in a validation cohort. Methods: Gene expression mosaics were generated from the 100 class-defining genes for 82 individual patients in the validation cohort. Patients were classified into 1 of 3 subclasses (“A”, “B”, or “C”) based on color and pattern similarity relative to reference mosaics generated from the original derivation cohort. Separate classifications were conducted by 21 individual clinicians and a computer-based algorithm. After subclassification the clinical database was mined for clinical phenotyping. Results: In the final consensus subclassification generated by clinicians, subclass A patients had a higher illness severity, as measured by illness severity scores and maximal organ failure, relative to subclasses B and C. The k coefficient across all possible inter-evaluator comparisons was 0.633. Similar observations were made based on the computer-generated subclassification. Patients in subclass A were also characterized by repression of a large number of genes having functional annotations related to zinc biology. Conclusions: We have validated the existence of subclasses of children with septic shock based on a biologically relevant, 100-gene expression signature. The subclasses can be indentified by clinicians without formal bioinformatics training, at a clinically relevant time point, and have clinically relevant phenotypic differences.
 
Overall design Expression data from 82 children with septic shock and 21 normal controls were generated using whole blood-derived RNA samples representing the first 24 hours of admission to the pediatric intensive care unit. The controls were used for normalization. Subsequently, we used the expression data from 100 class defining genes to validate the existence of pediatric septic shock subclasses having phenotypic differences.
 
Contributor(s) Wong HR
Citation(s) 21738952, 26376786, 24650276
Submission date Dec 30, 2010
Last update date Aug 16, 2019
Contact name Hector R Wong
E-mail(s) hector.wong@cchmc.org
Phone 513-636-4259
Fax 513-636-4267
Organization name Cincinnati Children's Hospital Medical Center
Department Pediatrics
Street address 3333 Burnet Avenue
City Cincinnati
State/province OH
ZIP/Postal code 45229
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (103)
GSM647527 Septic Shock_biological rep1
GSM647528 Septic Shock_biological rep2
GSM647529 Septic Shock_biological rep3
Relations
BioProject PRJNA136605

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE26378_RAW.tar 482.1 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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