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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 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 3 putative subclasses (ANOVA, 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 3 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. Conclusions: Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.

Hypothesis

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Experimental Design

Expression data from 98 children with septic shock and 32 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 to derive expression-based subclasses of patients using discovery oriented expression and statistical filters, followed by unsupervised hierarchical clustering.

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
130 Samples Loaded: 130
Human (Homo sapiens)
Whole Blood , Neonatal , Pediatric
Sepsis
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample Title tissue group Age (years) Disease state
GSM648590 Septic Shock_biological rep1 01-0013 whole blood A 9.4 septic shock patient
GSM648591 Septic Shock_biological rep2 01-0014 whole blood C 3 septic shock patient
GSM648592 Septic Shock_biological rep3 01-0019 whole blood C 2.1 septic shock patient
GSM648593 Septic Shock_biological rep4 01-0021 whole blood B 1.9 septic shock patient
GSM648594 Septic Shock_biological rep5 01-0024 whole blood B 0.8 septic shock patient
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File

GSE26440 modified.csv
Sample Set Spreadsheet
Raw Signal
Raw Signal
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Clinical Datasource
Links

Samples Viewer / Editor

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Sample ID !Sample Title Tissue Group Age (years) Disease state Group 1 Group 2 Outcome Group name
GSM648590
Septic Shock_biological rep1 01-0013
whole blood
A
9.4
septic shock patient
children
children-septic shock patient
Nonsurvivor
children 3 yrs and older
GSM648591
Septic Shock_biological rep2 01-0014
whole blood
C
3
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648592
Septic Shock_biological rep3 01-0019
whole blood
C
2.1
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648593
Septic Shock_biological rep4 01-0021
whole blood
B
1.9
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648594
Septic Shock_biological rep5 01-0024
whole blood
B
0.8
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648595
Septic Shock_biological rep6 01-0025
whole blood
A
0.3
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648596
Septic Shock_biological rep7 01-0026
whole blood
A
9.1
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648597
Septic Shock_biological rep8 01-0030
whole blood
C
0.6
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648598
Septic Shock_biological rep9 01-0033A
whole blood
B
2.6
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648599
Septic Shock_biological rep10 01-0045A
whole blood
B
8.8
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648600
Septic Shock_biological rep11 01-0049A
whole blood
B
0.9
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648601
Septic Shock_biological rep12 01-0051A
whole blood
B
4.5
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648602
Septic Shock_biological rep13 01-0052A
whole blood
B
2
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648603
Septic Shock_biological rep14 01-0053A
whole blood
C
0.5
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648604
Septic Shock_biological rep15 01-0064
whole blood
B
2.4
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648605
Septic Shock_biological rep16 01-0068
whole blood
A
0.1
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648606
Septic Shock_biological rep17 01-0069
whole blood
C
0.8
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648607
Septic Shock_biological rep18 01-0071
whole blood
C
2.7
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648608
Septic Shock_biological rep19 01-0072
whole blood
B
6.8
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648609
Septic Shock_biological rep20 01-0073
whole blood
B
7.1
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648610
Septic Shock_biological rep21 01-0074
whole blood
B
7.3
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648611
Septic Shock_biological rep22 01-0077
whole blood
C
4.4
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648612
Septic Shock_biological rep23 01-0078
whole blood
C
2.8
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648613
Septic Shock_biological rep24 01-0079
whole blood
C
0.3
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648614
Septic Shock_biological rep25 01-0080
whole blood
B
3
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648615
Septic Shock_biological rep26 01-0007A
whole blood
A
3.7
septic shock patient
children
children-septic shock patient
Nonsurvivor
children 3 yrs and older
GSM648616
Septic Shock_biological rep27 01-0034A
whole blood
C
2.7
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648617
Septic Shock_biological rep28 01-0036A
whole blood
C
2.7
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648618
Septic Shock_biological rep29 01-0044A
whole blood
A
0.1
septic shock patient
infant
infant-septic shock patient
Nonsurvivor
infant
GSM648619
Septic Shock_biological rep30 01-0047
whole blood
C
0.7
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648620
Septic Shock_biological rep31 01-0058A
whole blood
A
0
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648621
Septic Shock_biological rep32 01-0059A
whole blood
B
1.6
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648622
Septic Shock_biological rep33 01-0060A
whole blood
B
1.1
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648623
Septic Shock_biological rep34 01-0061A
whole blood
B
1.9
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648624
Septic Shock_biological rep35 01-0062A
whole blood
B
2.2
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648625
Septic Shock_biological rep36 05-0007
whole blood
B
4.2
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648626
Septic Shock_biological rep37 01-0066A
whole blood
C
2.3
septic shock patient
toddler
toddler-septic shock patient
Nonsurvivor
toddler
GSM648627
Septic Shock_biological rep38 01-0070
whole blood
C
7.2
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648628
Septic Shock_biological rep39 01-0086
whole blood
C
0
septic shock patient
infant
infant-septic shock patient
Nonsurvivor
infant
GSM648629
Septic Shock_biological rep40 01-0088
whole blood
B
2.8
septic shock patient
toddler
toddler-septic shock patient
Nonsurvivor
toddler
GSM648630
Control_biological rep1 01-0104
whole blood
n/a
3.3
normal control
children
children-normal control
n/a
children control
GSM648631
Control_biological rep2 01-0105
whole blood
n/a
0.9
normal control
infant
infant-normal control
n/a
infant control
GSM648632
Control_biological rep3 01-0106
whole blood
n/a
5.3
normal control
children
children-normal control
n/a
children control
GSM648633
Septic Shock_biological rep41 02-0001
whole blood
B
7.3
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648634
Septic Shock_biological rep42 02-0002A
whole blood
B
5.7
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648635
Septic Shock_biological rep43 04-0003
whole blood
A
0.9
septic shock patient
infant
infant-septic shock patient
Nonsurvivor
infant
GSM648636
Septic Shock_biological rep44 04-0005
whole blood
B
1.6
septic shock patient
toddler
toddler-septic shock patient
Nonsurvivor
toddler
GSM648637
Control_biological rep4 04-0010C
whole blood
n/a
0
normal control
infant
infant-normal control
n/a
infant control
GSM648638
Control_biological rep5 04-0010
whole blood
n/a
0
normal control
infant
infant-normal control
Survivor
infant control
GSM648639
Control_biological rep6 04-0011C
whole blood
n/a
2.9
normal control
toddler
toddler-normal control
n/a
toddler control
GSM648640
Control_biological rep7 04-0011
whole blood
n/a
2.9
normal control
toddler
toddler-normal control
Survivor
toddler control
GSM648641
Control_biological rep8 04-0015
whole blood
n/a
0
normal control
infant
infant-normal control
n/a
infant control
GSM648642
Septic Shock_biological rep45 05-0003
whole blood
A
7.3
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648643
Septic Shock_biological rep46 05-0006
whole blood
A
2.3
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648644
Septic Shock_biological rep47 05-0008
whole blood
B
9
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648645
Septic Shock_biological rep48 05-0010
whole blood
A
0.2
septic shock patient
infant
infant-septic shock patient
Nonsurvivor
infant
GSM648646
Septic Shock_biological rep49 05-0011
whole blood
A
0
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648647
Septic Shock_biological rep50 06-0001
whole blood
A
0.3
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648648
Septic Shock_biological rep51 06-0003
whole blood
B
2.5
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648649
Septic Shock_biological rep52 06-0004
whole blood
A
0
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648650
Septic Shock_biological rep53 06-0006
whole blood
A
2.2
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648651
Septic Shock_biological rep54 06-0009A
whole blood
B
5.1
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648652
Septic Shock_biological rep55 07-0002
whole blood
B
10.9
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648653
Septic Shock_biological rep56 07-0006A
whole blood
B
6
septic shock patient
children
children-septic shock patient
Nonsurvivor
children 3 yrs and older
GSM648654
Septic Shock_biological rep57 07-0004
whole blood
C
0.7
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648655
Septic Shock_biological rep58 09-0001
whole blood
B
1.9
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648656
Septic Shock_biological rep59 09-0002
whole blood
A
2.3
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648657
Septic Shock_biological rep60 10-0001
whole blood
B
5.3
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648658
Septic Shock_biological rep61 10-0012
whole blood
B
10.8
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648659
Septic Shock_biological rep62 10-0017
whole blood
B
7.5
septic shock patient
children
children-septic shock patient
Nonsurvivor
children 3 yrs and older
GSM648660
Septic Shock_biological rep63 10-0020
whole blood
B
2.9
septic shock patient
toddler
toddler-septic shock patient
Nonsurvivor
toddler
GSM648661
Septic Shock_biological rep64 10-0003
whole blood
B
1.4
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648662
Septic Shock_biological rep65 10-0005
whole blood
B
7.8
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648663
Septic Shock_biological rep66 10-0009
whole blood
C
1.9
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648664
Septic Shock_biological rep67 10-0018
whole blood
B
1.5
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648665
Septic Shock_biological rep68 10-0019
whole blood
B
6.1
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648666
Septic Shock_biological rep69 10-0021A
whole blood
B
8.9
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648667
Septic Shock_biological rep70 11-0001
whole blood
A
1.8
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648668
Control_biological rep9 11-0008
whole blood
n/a
3.7
normal control
children
children-normal control
Survivor
children control
GSM648669
Control_biological rep10 11-0009
whole blood
n/a
0.7
normal control
infant
infant-normal control
Survivor
infant control
GSM648670
Septic Shock_biological rep71 11-0010
whole blood
C
1.4
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648671
Control_biological rep11 11-0011
whole blood
n/a
0.9
normal control
infant
infant-normal control
Survivor
infant control
GSM648672
Control_biological rep12 11-0012
whole blood
n/a
0
normal control
infant
infant-normal control
Survivor
infant control
GSM648673
Control_biological rep13 11-0013
whole blood
n/a
6.8
normal control
children
children-normal control
Survivor
children control
GSM648674
Control_biological rep14 11-0014
whole blood
n/a
0
normal control
infant
infant-normal control
Survivor
infant control
GSM648675
Septic Shock_biological rep72 11-0017
whole blood
A
0
septic shock patient
infant
infant-septic shock patient
Nonsurvivor
infant
GSM648676
Control_biological rep15 11-0018
whole blood
n/a
5.9
normal control
children
children-normal control
Survivor
children control
GSM648677
Control_biological rep16 11-0019
whole blood
n/a
9.7
normal control
children
children-normal control
Survivor
children control
GSM648678
Control_biological rep17 11-0020
whole blood
n/a
0.2
normal control
infant
infant-normal control
Survivor
infant control
GSM648679
Control_biological rep18 11-0027
whole blood
n/a
0.3
normal control
infant
infant-normal control
Survivor
infant control
GSM648680
Septic Shock_biological rep73 11-0029
whole blood
B
6.3
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648681
Control_biological rep19 11-0037
whole blood
n/a
0.3
normal control
infant
infant-normal control
Survivor
infant control
GSM648682
Septic Shock_biological rep74 11-0054A
whole blood
A
0.1
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648683
Septic Shock_biological rep75 11-0002
whole blood
B
1.3
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648684
Septic Shock_biological rep76 11-0007
whole blood
B
8
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648685
Septic Shock_biological rep77 11-0035
whole blood
B
1.7
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648686
Control_biological rep20 11-0036
whole blood
n/a
0.2
normal control
infant
infant-normal control
n/a
infant control
GSM648687
Control_biological rep21 11-0052C
whole blood
n/a
6
normal control
children
children-normal control
n/a
children control
GSM648688
Control_biological rep22 11-0052
whole blood
n/a
6
normal control
children
children-normal control
Survivor
children control
GSM648689
Control_biological rep23 11-0077
whole blood
n/a
1.9
normal control
toddler
toddler-normal control
n/a
toddler control
GSM648690
Control_biological rep24 11-0078
whole blood
n/a
0.7
normal control
infant
infant-normal control
n/a
infant control
GSM648691
Control_biological rep25 11-0080
whole blood
n/a
1.5
normal control
toddler
toddler-normal control
n/a
toddler control
GSM648692
Control_biological rep26 11-0081
whole blood
n/a
3
normal control
children
children-normal control
n/a
children control
GSM648693
Control_biological rep27 11-0082
whole blood
n/a
1.2
normal control
toddler
toddler-normal control
n/a
toddler control
GSM648694
Control_biological rep28 11-0083
whole blood
n/a
5.1
normal control
children
children-normal control
n/a
children control
GSM648695
Septic Shock_biological rep78 12-0002A
whole blood
A
1.4
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648696
Septic Shock_biological rep79 13-0002A
whole blood
A
7
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648697
Septic Shock_biological rep80 14-0002A
whole blood
B
5.9
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648698
Septic Shock_biological rep81 14-0004A
whole blood
A
0.1
septic shock patient
infant
infant-septic shock patient
Nonsurvivor
infant
GSM648699
Control_biological rep29 15-0001
whole blood
n/a
2
normal control
toddler
toddler-normal control
Survivor
toddler control
GSM648700
Control_biological rep30 15-0002
whole blood
n/a
1.8
normal control
toddler
toddler-normal control
Survivor
toddler control
GSM648701
Control_biological rep31 15-0003
whole blood
n/a
3.8
normal control
children
children-normal control
Survivor
children control
GSM648702
Septic Shock_biological rep82 15-0004
whole blood
B
1
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648703
Control_biological rep32 15-0005
whole blood
n/a
0
normal control
infant
infant-normal control
Survivor
infant control
GSM648704
Septic Shock_biological rep83 15-0007
whole blood
A
0.3
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648705
Septic Shock_biological rep84 15-0008
whole blood
A
9.4
septic shock patient
children
children-septic shock patient
Nonsurvivor
children 3 yrs and older
GSM648706
Septic Shock_biological rep85 15-0017
whole blood
A
0.3
septic shock patient
infant
infant-septic shock patient
Survivor
infant
GSM648707
Septic Shock_biological rep86 15-0011A
whole blood
C
1.5
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648708
Septic Shock_biological rep87 15-0012A
whole blood
A
0
septic shock patient
infant
infant-septic shock patient
Nonsurvivor
infant
GSM648709
Septic Shock_biological rep88 17-0001A
whole blood
B
8.2
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648710
Septic Shock_biological rep89 18-0002
whole blood
B
4.3
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older
GSM648711
Septic Shock_biological rep90 19-0001
whole blood
C
2
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648712
Septic Shock_biological rep91 19-0005
whole blood
C
2
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648713
Septic Shock_biological rep92 20-0002
whole blood
C
2
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648714
Septic Shock_biological rep93 20-0003
whole blood
C
2
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648715
Septic Shock_biological rep94 04-0004
whole blood
A
2.4
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648716
Septic Shock_biological rep95 21-0001
whole blood
C
2
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648717
Septic Shock_biological rep96 21-0003
whole blood
C
2
septic shock patient
toddler
toddler-septic shock patient
Survivor
toddler
GSM648718
Septic Shock_biological rep97 26-260611
whole blood
A
7.4
septic shock patient
children
children-septic shock patient
Nonsurvivor
children 3 yrs and older
GSM648719
Septic Shock_biological rep98 25-070603
whole blood
B
10
septic shock patient
children
children-septic shock patient
Survivor
children 3 yrs and older

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