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Clinical

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

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

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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
Sepsis
Tempus Spin Isolation Kit
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample_title Age Pathogen Ethnicity Gender
GSM326090 M016 39 B.pseudomallei Not Hispanic or Latino M
GSM326091 M017 52 B.pseudomallei Not Hispanic or Latino F
GSM326092 I016 61 Staphylococcus coagulase negative Not Hispanic or Latino F
GSM326093 I017 50 Staphylococcus coagulase negative Not Hispanic or Latino M
GSM326094 R007 55 N/A Not Hispanic or Latino F
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File
Average Normalized
Raw Signal
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Samples Viewer / Editor

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

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