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Clinical

Study subjects were either stratified in age groups (default setting) or in controls, survivors, and non-survivors

Purpose

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.

Hypothesis

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Experimental 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.

Experimental Variables

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Controls

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Methods

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Additional Information

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Microarray
Affymetrix HG-U133_Plus_2
103 Samples Loaded: 103
Human (Homo sapiens)
Neonatal , Whole Blood , Pediatric
Sepsis
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample Title tissue Age (years) Disease state outcome
GSM647527 Septic Shock_biological rep1 Whole Blood 2 septic shock patient Survivor
GSM647528 Septic Shock_biological rep2 Whole Blood 0.5 septic shock patient Survivor
GSM647529 Septic Shock_biological rep3 Whole Blood 1.9 septic shock patient Survivor
GSM647530 Septic Shock_biological rep4 Whole Blood 2 septic shock patient Survivor
GSM647531 Septic Shock_biological rep5 Whole Blood 1.3 septic shock patient Survivor
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File

GSE26378 modified.csv
Sample Set Spreadsheet
GSE26378 modified.csv
Sample Set Spreadsheet
GSE26378_modified1.csv
Sample Set Spreadsheet
Raw Signal
Raw Signal
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Samples Viewer / Editor

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Sample ID !Sample Title Tissue Age (years) Disease state Outcome Group name
GSM647527
Septic Shock_biological rep1
Whole Blood
2
septic shock patient
Survivor
toddler
GSM647528
Septic Shock_biological rep2
Whole Blood
0.5
septic shock patient
Survivor
infant
GSM647529
Septic Shock_biological rep3
Whole Blood
1.9
septic shock patient
Survivor
toddler
GSM647530
Septic Shock_biological rep4
Whole Blood
2
septic shock patient
Survivor
toddler
GSM647531
Septic Shock_biological rep5
Whole Blood
1.3
septic shock patient
Survivor
toddler
GSM647532
Septic Shock_biological rep6
Whole Blood
3.8
septic shock patient
Survivor
children 3 yrs and above
GSM647533
Control_biological rep1
Whole Blood
1.1
normal control
Survivor
toddler control
GSM647534
Control_biological rep2
Whole Blood
7.6
normal control
Survivor
children control
GSM647535
Septic Shock_biological rep7
Whole Blood
9.6
septic shock patient
Nonsurvivor
children 3 yrs and above
GSM647536
Control_biological rep3
Whole Blood
1.3
normal control
Survivor
toddler control
GSM647537
Control_biological rep4
Whole Blood
0.5
normal control
Survivor
infant control
GSM647538
Control_biological rep5
Whole Blood
5
normal control
Survivor
children control
GSM647539
Control_biological rep6
Whole Blood
9
normal control
Survivor
children control
GSM647540
Septic Shock_biological rep8
Whole Blood
1.1
septic shock patient
Survivor
toddler
GSM647541
Septic Shock_biological rep9
Whole Blood
0.7
septic shock patient
Survivor
infant
GSM647542
Septic Shock_biological rep10
Whole Blood
8.3
septic shock patient
Survivor
children 3 yrs and above
GSM647543
Septic Shock_biological rep11
Whole Blood
8.9
septic shock patient
Survivor
children 3 yrs and above
GSM647544
Septic Shock_biological rep12
Whole Blood
4
septic shock patient
Survivor
children 3 yrs and above
GSM647545
Septic Shock_biological rep13
Whole Blood
0.6
septic shock patient
Nonsurvivor
infant
GSM647546
Septic Shock_biological rep14
Whole Blood
1.2
septic shock patient
Survivor
toddler
GSM647547
Septic Shock_biological rep15
Whole Blood
0.1
septic shock patient
Survivor
infant
GSM647548
Septic Shock_biological rep16
Whole Blood
6.6
septic shock patient
Survivor
children 3 yrs and above
GSM647549
Septic Shock_biological rep17
Whole Blood
0.8
septic shock patient
Nonsurvivor
infant
GSM647550
Septic Shock_biological rep18
Whole Blood
0.4
septic shock patient
Nonsurvivor
infant
GSM647551
Septic Shock_biological rep19
Whole Blood
5.9
septic shock patient
Survivor
children 3 yrs and above
GSM647552
Septic Shock_biological rep20
Whole Blood
0.1
septic shock patient
Survivor
infant
GSM647553
Septic Shock_biological rep21
Whole Blood
0.1
septic shock patient
Survivor
infant
GSM647554
Septic Shock_biological rep22
Whole Blood
6.5
septic shock patient
Survivor
children 3 yrs and above
GSM647555
Septic Shock_biological rep23
Whole Blood
8
septic shock patient
Survivor
children 3 yrs and above
GSM647556
Septic Shock_biological rep24
Whole Blood
3.9
septic shock patient
Survivor
children 3 yrs and above
GSM647557
Septic Shock_biological rep25
Whole Blood
1.7
septic shock patient
Survivor
toddler
GSM647558
Septic Shock_biological rep26
Whole Blood
5
septic shock patient
Survivor
children 3 yrs and above
GSM647559
Septic Shock_biological rep27
Whole Blood
8.5
septic shock patient
Survivor
children 3 yrs and above
GSM647560
Septic Shock_biological rep28
Whole Blood
0.3
septic shock patient
Nonsurvivor
infant
GSM647561
Septic Shock_biological rep29
Whole Blood
0.8
septic shock patient
Survivor
infant
GSM647562
Septic Shock_biological rep30
Whole Blood
9.3
septic shock patient
Survivor
children 3 yrs and above
GSM647563
Septic Shock_biological rep31
Whole Blood
9.5
septic shock patient
Nonsurvivor
children 3 yrs and above
GSM647564
Septic Shock_biological rep32
Whole Blood
9.7
septic shock patient
Survivor
children 3 yrs and above
GSM647565
Septic Shock_biological rep33
Whole Blood
0.1
septic shock patient
Survivor
infant
GSM647566
Control_biological rep7
Whole Blood
8.7
normal control
Survivor
children control
GSM647567
Septic Shock_biological rep34
Whole Blood
1.7
septic shock patient
Survivor
toddler
GSM647568
Septic Shock_biological rep35
Whole Blood
1.4
septic shock patient
Survivor
toddler
GSM647569
Septic Shock_biological rep36
Whole Blood
0.1
septic shock patient
Nonsurvivor
infant
GSM647570
Septic Shock_biological rep37
Whole Blood
1.2
septic shock patient
Survivor
toddler
GSM647571
Septic Shock_biological rep38
Whole Blood
7
septic shock patient
Survivor
children 3 yrs and above
GSM647572
Septic Shock_biological rep39
Whole Blood
4.4
septic shock patient
Survivor
children 3 yrs and above
GSM647573
Septic Shock_biological rep40
Whole Blood
1
septic shock patient
Survivor
toddler
GSM647574
Septic Shock_biological rep41
Whole Blood
0.1
septic shock patient
Nonsurvivor
infant
GSM647575
Control_biological rep8
Whole Blood
2
normal control
Survivor
toddler control
GSM647576
Septic Shock_biological rep42
Whole Blood
1
septic shock patient
Survivor
toddler
GSM647577
Septic Shock_biological rep43
Whole Blood
0.1
septic shock patient
Nonsurvivor
infant
GSM647578
Septic Shock_biological rep44
Whole Blood
4.4
septic shock patient
Survivor
children 3 yrs and above
GSM647579
Septic Shock_biological rep45
Whole Blood
0.8
septic shock patient
Survivor
infant
GSM647580
Septic Shock_biological rep46
Whole Blood
0.2
septic shock patient
Survivor
infant
GSM647581
Septic Shock_biological rep47
Whole Blood
4.2
septic shock patient
Survivor
children 3 yrs and above
GSM647582
Septic Shock_biological rep48
Whole Blood
5.2
septic shock patient
Nonsurvivor
children 3 yrs and above
GSM647583
Septic Shock_biological rep49
Whole Blood
1.6
septic shock patient
Survivor
toddler
GSM647584
Septic Shock_biological rep50
Whole Blood
8
septic shock patient
Survivor
children 3 yrs and above
GSM647585
Septic Shock_biological rep51
Whole Blood
9.3
septic shock patient
Survivor
children 3 yrs and above
GSM647586
Septic Shock_biological rep52
Whole Blood
8.6
septic shock patient
Survivor
children 3 yrs and above
GSM647587
Septic Shock_biological rep53
Whole Blood
9.3
septic shock patient
Survivor
children 3 yrs and above
GSM647588
Septic Shock_biological rep54
Whole Blood
9
septic shock patient
Survivor
children 3 yrs and above
GSM647589
Control_biological rep9
Whole Blood
7.4
normal control
Survivor
children control
GSM647590
Control_biological rep10
Whole Blood
4.4
normal control
Survivor
children control
GSM647591
Septic Shock_biological rep55
Whole Blood
4.2
septic shock patient
Nonsurvivor
children 3 yrs and above
GSM647592
Septic Shock_biological rep56
Whole Blood
1.9
septic shock patient
Survivor
toddler
GSM647593
Septic Shock_biological rep57
Whole Blood
1
septic shock patient
Survivor
toddler
GSM647594
Septic Shock_biological rep58
Whole Blood
2.4
septic shock patient
Survivor
toddler
GSM647595
Septic Shock_biological rep59
Whole Blood
1.2
septic shock patient
Survivor
toddler
GSM647596
Septic Shock_biological rep60
Whole Blood
7.7
septic shock patient
Survivor
children 3 yrs and above
GSM647597
Septic Shock_biological rep61
Whole Blood
0.7
septic shock patient
Survivor
infant
GSM647598
Septic Shock_biological rep62
Whole Blood
0.8
septic shock patient
Survivor
infant
GSM647599
Septic Shock_biological rep63
Whole Blood
3.6
septic shock patient
Survivor
children 3 yrs and above
GSM647600
Septic Shock_biological rep64
Whole Blood
2.4
septic shock patient
Survivor
toddler
GSM647601
Septic Shock_biological rep65
Whole Blood
5.6
septic shock patient
Survivor
children 3 yrs and above
GSM647602
Septic Shock_biological rep66
Whole Blood
9.8
septic shock patient
Survivor
children 3 yrs and above
GSM647603
Septic Shock_biological rep67
Whole Blood
2.8
septic shock patient
Survivor
toddler
GSM647604
Control_biological rep11
Whole Blood
9.6
normal control
Survivor
children control
GSM647605
Control_biological rep12
Whole Blood
4.6
normal control
Survivor
children control
GSM647606
Control_biological rep13
Whole Blood
1.2
normal control
Survivor
toddler control
GSM647607
Control_biological rep14
Whole Blood
2.3
normal control
Survivor
toddler control
GSM647608
Control_biological rep15
Whole Blood
2.9
normal control
Survivor
toddler control
GSM647609
Septic Shock_biological rep68
Whole Blood
9.3
septic shock patient
Survivor
children 3 yrs and above
GSM647610
Septic Shock_biological rep69
Whole Blood
2
septic shock patient
Survivor
toddler
GSM647611
Septic Shock_biological rep70
Whole Blood
5.3
septic shock patient
Survivor
children 3 yrs and above
GSM647612
Septic Shock_biological rep71
Whole Blood
3.7
septic shock patient
Survivor
children 3 yrs and above
GSM647613
Septic Shock_biological rep72
Whole Blood
0.8
septic shock patient
Survivor
infant
GSM647614
Septic Shock_biological rep73
Whole Blood
3
septic shock patient
Survivor
children 3 yrs and above
GSM647615
Septic Shock_biological rep74
Whole Blood
1.3
septic shock patient
Survivor
toddler
GSM647616
Septic Shock_biological rep75
Whole Blood
0.5
septic shock patient
Survivor
infant
GSM647617
Septic Shock_biological rep76
Whole Blood
0.6
septic shock patient
Nonsurvivor
infant
GSM647618
Septic Shock_biological rep77
Whole Blood
5.2
septic shock patient
Survivor
children 3 yrs and above
GSM647619
Septic Shock_biological rep78
Whole Blood
0.3
septic shock patient
Survivor
infant
GSM647620
Septic Shock_biological rep79
Whole Blood
9.1
septic shock patient
Survivor
children 3 yrs and above
GSM647621
Control_biological rep16
Whole Blood
1
normal control
Survivor
toddler control
GSM647622
Control_biological rep17
Whole Blood
2.9
normal control
Survivor
toddler control
GSM647623
Control_biological rep18
Whole Blood
4.2
normal control
Survivor
children control
GSM647624
Control_biological rep19
Whole Blood
2.2
normal control
Survivor
toddler control
GSM647625
Control_biological rep20
Whole Blood
2.9
normal control
Survivor
toddler control
GSM647626
Control_biological rep21
Whole Blood
0.5
normal control
Survivor
infant control
GSM647627
Septic Shock_biological rep80
Whole Blood
6.5
septic shock patient
Survivor
children 3 yrs and above
GSM647628
Septic Shock_biological rep81
Whole Blood
8.7
septic shock patient
Survivor
children 3 yrs and above
GSM647629
Septic Shock_biological rep82
Whole Blood
2.4
septic shock patient
Survivor
toddler

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