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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 HumanHT-12 v3
39 Samples Loaded: 39
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
GSM365197 I027 64 E. coli Not Hispanic or Latino F
GSM365198 I028 81 Corynebacterium spp. Not Hispanic or Latino F
GSM365199 I029 74 Staphylococcus aureus Not Hispanic or Latino F
GSM365200 I031 48 Enterococcus spp Not Hispanic or Latino M
GSM365201 I032 54 Enterococcus faecium Not Hispanic or Latino F
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Average Normalized
Raw Signal
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All fields are editable except the "Sample ID" column. To edit a cell, click within the cell. To edit a "date" cell, click on the calendar icon. To cancel an edit, press the ESC key.

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

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