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Title: A Blood Transcriptional Diagnostic Assay for Septicemic Melioidosis      
dateReleased:
06-04-2015
description:
Melioidosis, caused by Gram negative bacteria Burkholderia pseudomallei, is a major type of community-acquired septicemia in Southeast Asia and Northern Australia with high mortality and morbidity rate. More accurate and rapid diagnosis is needed for improving the management of septicemic melioidosis. We previously identified 37-gene candidate signature to distinguish septicemic melioidosis from sepsis due to other pathogens. The aims of this current study were to independently validate our previous biomarker and consolidate gene selection from each of our microarray data set for establishing a targeted assay for the differential diagnosis of melioidosis. Blood samples were collected from patients who presented with severe inflammatory response syndromes from 3 provincial hospitals in Northeast of Thailand during September 2009 and November 2011. Only culture-confirmed sepsis were included in the study (n=166). We generated a new microarray dataset comprising of 29 patients with septicemic melioidosis and 54 patients with sepsis due to other pathogens. Validation of the 37-gene signature using this new dataset demonstrated the prediction accuracy of approximately 80% for detecting type of sepsis. In order to develop a nanoliter-scale high throughput PCR technology, we further identified additional gene signature from this new microarray dataset and by revisiting our published data. Altogether 85 genes including 6 housekeeping genes were selected. Using multi-steps iteration approach we could reduce the number of biomarkers to 12 genes while the performance is comparable to that of the full panel. The high performance (accuracy >70%) of this 12-gene signature could be validated in a second independent set of samples. The 12-gene panel identified by our study provides high performance for the differential diagnosis of septicemic melioidosis. This finding will be useful for improving the management of septicemic melioidosis in term of diagnosis, treatment and follow up. Total RNA from whole blood obtained from patients with sepsis caused by B.pseudomallei (n=29) or other pathogens (n=54) and uninfected controls (28 healthy and 27 subjects with type 2 diabetes mellitus) were collected. In order to validate the published signature, microarray data were generated from these samples. This dataset was also used for an independent selection of signature for septicemic melioidosis. The same RNA samples were used for validation by a high throughput real-time PCR technique, Fluidigm.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-69528
refinement:
raw
alternateIdentifiers:
69528
keywords:
functional genomics
dateModified:
06-05-2015
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-10558
name:
Illumina HumanHT-12 V4.0 expression beadchip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-69528/E-GEOD-69528.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-69528/E-GEOD-69528.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69528
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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