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Clinical

Genomic Transcriptional Profiling Identifies a Blood Biomarker Signature for the Diagnosis of Septicemic Melioidosis - GSE13015 - GPL6947

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 3.1.3.0 using the average chip normalization method.

Additional Information

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

Microarray
Illumina HumanHT-12 v3
39 Samples Loaded: 39
Human (Homo sapiens)
Whole Blood
Septicemic Melioidosis
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample Title Age Ethnicity Gender Illness
GSM365197 I027 64 Not Hispanic or Latino F Sepsis/Other infections
GSM365198 I028 81 Not Hispanic or Latino F Sepsis/Other infections
GSM365199 I029 74 Not Hispanic or Latino F Sepsis/Other infections
GSM365200 I031 48 Not Hispanic or Latino M Sepsis/Other infections
GSM365201 I032 54 Not Hispanic or Latino F Sepsis/Other infections
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File
sampleset4000130_sampleannotations_v1_GSE13015_GPL6947.csv
Sample Set Spreadsheet
sampleset4000130_sampleannotations_v1_GSE13015_GPL6947.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
GSM365197
I027
64
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Fortum, Ceftriaxone
E. coli
Sepsis/Other infections
GSM365198
I028
81
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftriaxone, Fortum,Clindamycin
Corynebacterium spp.
Sepsis/Other infections
GSM365199
I029
74
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Fortum,Ceftriaxone,Tazocin
Staphylococcus aureus
Sepsis/Other infections
GSM365200
I031
48
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Fortum
Enterococcus spp
Sepsis/Other infections
GSM365201
I032
54
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Fortum, Tazocin
Enterococcus faecium
Sepsis/Other infections
GSM365202
I033
63
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Tazocin, Ceftriaxone, Fortum
E. coli
Sepsis/Other infections
GSM365203
I034
43
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Tazocin
Aeromonas hydrophila
Sepsis/Other infections
GSM365204
M031
49
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Fortum, Bactrim, Trazocin
B.pseudomallei
Sepsis/Melioidosis
GSM365205
M032
54
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Fortum , Doxycycline, Sulperazone
B.pseudomallei
Sepsis/Melioidosis
GSM365206
M033
44
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Fortum , Sulperazone, Bactrim, Ciprofloxacin
B.pseudomallei
Sepsis/Melioidosis
GSM365207
M034
40
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Fortum, Bactrim, Ceftazidime, Ceftriaxone
B.pseudomallei
Sepsis/Melioidosis
GSM365208
M035
56
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftriaxone, Ceftazidime, Fortum
B.pseudomallei
Sepsis/Melioidosis
GSM365209
M036
41
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Ceftriaxone, Ceftazidime
B.pseudomallei
Sepsis/Melioidosis
GSM365210
M037
42
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Bactrim, Fortum, Cloxacillin
B.pseudomallei
Sepsis/Melioidosis
GSM365211
M038
49
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Ceftriaxone, Fortum,Ceftazidime, Levofloxacin
B.pseudomallei
Sepsis/Melioidosis
GSM365212
H005
37
Not Hispanic or Latino
M
Control/healthy
Asian
 
 
Control
GSM365213
H006
35
Not Hispanic or Latino
M
Control/healthy
Asian
 
 
Control
GSM365214
H007
46
Not Hispanic or Latino
F
Control/healthy
Asian
 
 
Control
GSM365215
H008
67
Not Hispanic or Latino
M
Control/healthy
Asian
 
 
Control
GSM365216
H009
37
Not Hispanic or Latino
F
Control/healthy
Asian
 
 
Control
GSM365217
DM009
50
Not Hispanic or Latino
F
Control/type 2 diabetes
Asian
 
 
Control
GSM365218
DM010
50
Not Hispanic or Latino
F
Control/type 2 diabetes
Asian
 
 
Control
GSM365219
DM011
56
Not Hispanic or Latino
F
Control/type 2 diabetes
Asian
 
 
Control
GSM365220
DM012
57
Not Hispanic or Latino
F
Control/type 2 diabetes
Asian
 
 
Control
GSM365221
DM013
71
Not Hispanic or Latino
F
Control/type 2 diabetes
Asian
 
 
Control
GSM365229
Rerun_I014
54
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftriaxone, Ceftazidime, Levofloxacin
Salmonella spp.
Sepsis/Other infections
GSM365230
Rerun_M007
50
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftazidime, Tazocin
B.pseudomallei
Sepsis/Melioidosis
GSM365231
Rerun_M008
70
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Ceftazidime, Bactrim
B.pseudomallei
Sepsis/Melioidosis
GSM365232
Rerun_M009
48
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Sulperazone
B.pseudomallei
Sepsis/Melioidosis
GSM365233
Rerun_M012
56
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Sulperazone, Bactrim,Cetazidime
B.pseudomallei
Sepsis/Melioidosis
GSM365234
Rerun_M014
65
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Cloxacilin,Ceftazidime
B.pseudomallei
Sepsis/Melioidosis
GSM365235
Rerun_I009
52
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftazidime, Cloxacillin
Staphylococcus aureus
Sepsis/Other infections
GSM365236
Rerun_I010
72
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftriaxone
E.coli
Sepsis/Other infections
GSM365237
Rerun_I012
69
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Ceftazidime
C.albicans
Sepsis/Other infections
GSM365238
Rerun_M001
68
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftazidime, Bactrim
B.pseudomallei
Sepsis/Melioidosis
GSM365239
Rerun_M002
43
Not Hispanic or Latino
F
Sepsis/Melioidosis
Asian
Ceftriaxone, Ceftazidime
B.pseudomallei
Sepsis/Melioidosis
GSM365240
Rerun_M006
46
Not Hispanic or Latino
M
Sepsis/Melioidosis
Asian
Ceftriaxone
B.pseudomallei
Sepsis/Melioidosis
GSM365241
Rerun_I001
52
Not Hispanic or Latino
M
Sepsis/Other infections
Asian
Ceftriaxone
Streptococcus non A,B
Sepsis/Other infections
GSM365242
Rerun_I008
70
Not Hispanic or Latino
F
Sepsis/Other infections
Asian
Bactrim, Ceftazidime
E.coli
Sepsis/Other infections

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