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Clinical

Genomic Transcriptional Profiling Identifies a Blood Biomarker Signature for the Diagnosis of Septicemic Melioidosis - GSE13015 - GPL6106

Purpose

Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, a gram-negative bacillus classified by the NIAID as a category B priority agent. Septicemia is the most common presentation of the disease with 40% mortality rate even with appropriate treatments. Faster diagnostic procedures are required to improve therapeutic response and survival rates. We have used microarray technology to generate genome-wide transcriptional profiles (>48,000 transcripts) of whole blood obtained from patients with septicemic melioidosis (n=32), patients with sepsis caused by other pathogens (n=31), and uninfected controls (n=29). Unsupervised analyses demonstrated the existence of a whole blood transcriptional signature distinguishing patients with sepsis from control subjects. The majority of changes observed were common to both septicemic melioidosis and sepsis caused by other infections, including genes related to inflammation, interferon-related genes, neutrophils, cytotoxic cells, and T cells. Finally, class prediction analysis identified a 37 transcript candidate diagnostic signature that distinguished melioidosis from sepsis caused by other organisms with 100% and 78% accuracy in training and independent test sets, respectively. This finding was confirmed by the independent validation set, which showed 80% prediction accuracy. This signature was highly enriched in genes coding for products involved in the MHC Class II antigen processing and presentation pathway. Transcriptional patterns of whole blood RNA distinguish patients with septicemic melioidosis from patients with sepsis caused by other pathogens. Once confirmed in a large scale trial this diagnostic signature might constitute the basis of a differential diagnostic assay.

Hypothesis

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Experimental Design

Whole blood obtained from patients with sepsis caused by B.pseudomallei or other pathogens were collected. mRNA Expression level of each patient was determined and compared to mRNA expression level from uninfected control including patient who had recovered from melioidosis, patient diagnosed type 2 diabetes, and healthy donors suing microarray analysis.

Experimental Variables

Septicemic Melioidosis (2021 ICD-10-CM code* = A24.1)

Controls

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Methods

The data were analysed using BeadStudio version 1.5.1.3 using the average chip normalization method.

Additional Information

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13015

Microarray
Illumina Human-6 v2
67 Samples Loaded: 67
Human (Homo sapiens)
Whole Blood
Septicemic Melioidosis
Tempus Spin Isolation Kit
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample Title Age Ethnicity Gender Illness
GSM326090 M016 39 Not Hispanic or Latino M Sepsis/Melioidosis
GSM326091 M017 52 Not Hispanic or Latino F Sepsis/Melioidosis
GSM326092 I016 61 Not Hispanic or Latino F Sepsis/Other infections
GSM326093 I017 50 Not Hispanic or Latino M Sepsis/Other infections
GSM326094 R007 55 Not Hispanic or Latino F Control/Recovery
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File
sampleset4000129_sampleannotations_v1.csv
Sample Set Spreadsheet
sampleset4000129_sampleannotations_v1.csv
Sample Set Spreadsheet
Average Normalized
Raw Signal
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Samples Viewer / Editor

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Sample ID !Sample Title Age Ethnicity Gender Illness Race Treatment Pathogen Illness V1
GSM326090
M016
39
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftazidime, Bactrim, Doxycycline
B.pseudomallei
Sepsis/Melioidosis
GSM326091
M017
52
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Norfloxacin, Ceftazolin
B.pseudomallei
Sepsis/Melioidosis
GSM326092
I016
61
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftazidime,Bactrim,Sulperazole
Staphylococcus coagulase negative
Sepsis/Other infections
GSM326093
I017
50
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Ceftriaxone, Ceftazidime, Doxycycline,Cloxacillin
Staphylococcus coagulase negative
Sepsis/Other infections
GSM326094
R007
55
Not Hispanic or Latino
F
Control/Recovery
Asian
N/A
N/A
Control
GSM326095
DM007
48
Not Hispanic or Latino
F
Control/type 2 diabetes
Asian
N/A
N/A
Control
GSM326096
H001
37
Not Hispanic or Latino
F
Control/healthy
Asian
N/A
N/A
Control
GSM326097
M020
61
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftriaxone,Doxycycline, Ceftazidime
B.pseudomallei
Sepsis/Melioidosis
GSM326098
I019
58
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Cloxacillin, Ceftazidime
Staphylococcus aureus
Sepsis/Other infections
GSM326099
R008
39
Not Hispanic or Latino
M
Control/Recovery
Asian
N/A
N/A
Control
GSM326100
R009
41
Not Hispanic or Latino
M
Control/Recovery
Asian
N/A
N/A
Control
GSM326101
M022
18
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftazidime, Cactrim
B.pseudomallei
Sepsis/Melioidosis
GSM326102
M023
63
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Bactrim, Ceftazidime
B.pseudomallei
Sepsis/Melioidosis
GSM326103
I020
66
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftazidime,Ceftriaxone
Staphylococcus coagulase negative
Sepsis/Other infections
GSM326104
I021
54
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftazidime,Cloxacilin
Enterococcus spp.
Sepsis/Other infections
GSM326105
M024
44
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Meropenem
B.pseudomallei
Sepsis/Melioidosis
GSM326106
M025
57
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftazidime
B.pseudomallei
Sepsis/Melioidosis
GSM326107
I022
37
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Ceftriaxone, Ceftazidime
Staphylococcus coagulase negative
Sepsis/Other infections
GSM326108
I023
70
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Doxycycline,Ceftazidime
E.coli
Sepsis/Other infections
GSM326109
R010
64
Not Hispanic or Latino
M
Control/Recovery
Asian
N/A
N/A
Control
GSM326110
M021
56
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Ceftriaxone, Ceftazidime
B.pseudomallei
Sepsis/Melioidosis
GSM326111
I018
57
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Vancomycin
Staphylococcus coagulase negative
Sepsis/Other infections
GSM326112
H002
35
Not Hispanic or Latino
F
Control/healthy
Asian
N/A
N/A
Control
GSM326113
DM008
50
Not Hispanic or Latino
F
Control/type 2 diabetes
Asian
N/A
N/A
Control
GSM326114
M026
48
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftazidime, Doxycycline, Bactrim
B.pseudomallei
Sepsis/Melioidosis
GSM326115
M027
44
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftriaxone, Ceftazidime, Meropenem
B.pseudomallei
Sepsis/Melioidosis
GSM326116
I024
56
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Meropenem,Ceftazidime
Staphylococcus coagulase negative
Sepsis/Other infections
GSM326117
I025
50
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Ceftriaxone, Meropenem
S.pneumoniae
Sepsis/Other infections
GSM326118
I026
57
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Ceftriaxone, Ceftazidime, Bactrim
K.pneumoniae
Sepsis/Other infections
GSM326119
H004
43
Not Hispanic or Latino
F
Control/healthy
Asian
N/A
N/A
Control
GSM326120
M028
70
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftazidime, levofloxacin, Bactrim
B.pseudomallei
Sepsis/Melioidosis
GSM326121
M029
50
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftriaxone, Ceftazidime
B.pseudomallei
Sepsis/Melioidosis
GSM326122
M030
44
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftazidime, Ceftriazone
B.pseudomallei
Sepsis/Melioidosis
GSM326161
I001
52
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Ceftriaxone
Streptococcus non A,B
Sepsis/Other infections
GSM326162
I002
52
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftriaxone,Bactrim
Acinetobactor baumannii
Sepsis/Other infections
GSM326163
M001
68
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftazidime, Bactrim
B.pseudomallei
Sepsis/Melioidosis
GSM326164
M002
43
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Ceftriaxone, Ceftazidime
B.pseudomallei
Sepsis/Melioidosis
GSM326165
R001
41
Not Hispanic or Latino
F
Control/Recovery
Asian
N/A
N/A
Control
GSM326166
M003
55
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftazidime
B.pseudomallei
Sepsis/Melioidosis
GSM326167
DM002
55
Not Hispanic or Latino
F
Control/type 2 diabetes
Asian
N/A
N/A
Control
GSM326168
I004
45
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Cloxacillin, Ceftriaxone
Salmonella serotype B
Sepsis/Other infections
GSM326169
DM003
68
Not Hispanic or Latino
F
Control/type 2 diabetes
Asian
N/A
N/A
Control
GSM326170
I006
37
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Ceftriaxone, Sulperazone, Bactrim
C.albicans
Sepsis/Other infections
GSM326171
I007
73
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
N/A
Corynebacterium spp.
Sepsis/Other infections
GSM326172
M006
46
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftriaxone
B.pseudomallei
Sepsis/Melioidosis
GSM326173
M007
50
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftazidime, Tazocin
B.pseudomallei
Sepsis/Melioidosis
GSM326174
R003
42
Not Hispanic or Latino
F
Control/Recovery
Asian
N/A
N/A
Control
GSM326175
DM004
39
Not Hispanic or Latino
M
Control/type 2 diabetes
Asian
N/A
N/A
Control
GSM326176
I008
70
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Bactrim, Ceftazidime
E.coli
Sepsis/Other infections
GSM326177
M008
70
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Ceftazidime, Bactrim
B.pseudomallei
Sepsis/Melioidosis
GSM326178
I009
52
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftazidime, Cloxacillin
Staphylococcus aureus
Sepsis/Other infections
GSM326179
M009
48
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Sulperazone
B.pseudomallei
Sepsis/Melioidosis
GSM326180
M010
48
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftriaxone, Ceftazidime, Doxycycline
B.pseudomallei
Sepsis/Melioidosis
GSM326181
I010
72
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftriaxone
E.coli
Sepsis/Other infections
GSM326182
I011
38
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
N/A
E.coli
Sepsis/Other infections
GSM326183
R004
48
Not Hispanic or Latino
M
Control/Recovery
Asian
N/A
N/A
Control
GSM326184
M012
56
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Sulperazone, Bactrim,Cetazidime
B.pseudomallei
Sepsis/Melioidosis
GSM326185
I012
69
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftazidime
C.albicans
Sepsis/Other infections
GSM326186
I013
74
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftazidime, Clarithromycin
Corynebacterium spp.
Sepsis/Other infections
GSM326187
DM005
41
Not Hispanic or Latino
F
Control/type 2 diabetes
Asian
N/A
N/A
Control
GSM326188
R005
56
Not Hispanic or Latino
M
Control/Recovery
Asian
N/A
N/A
Control
GSM326189
DM006
48
Not Hispanic or Latino
F
Control/type 2 diabetes
Asian
N/A
N/A
Control
GSM326190
R006
41
Not Hispanic or Latino
M
Control/Recovery
Asian
N/A
N/A
Control
GSM326191
M014
65
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Cloxacilin,Ceftazidime
B.pseudomallei
Sepsis/Melioidosis
GSM326192
M015
41
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Bactrim, Ceftazidime
B.pseudomallei
Sepsis/Melioidosis
GSM326193
I014
54
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftriaxone, Ceftazidime, Levofloxacin
Salmonella spp.
Sepsis/Other infections
GSM326194
I015
41
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Ceftazidime
C.albicans
Sepsis/Other infections

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