Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis

Rungnapa Pankla, Surachat Buddhisa, Matthew Berry, Derek M. Blankenship, Gregory J. Bancroft, Jacques Banchereau, Ganjana Lertmemongkolchai, Damien J. Chaussabel

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Background: Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, a Gram-negative bacillus classified by the National Institute of Allergy and Infectious Diseases (NIAID) as a category B priority agent. Septicemia is the most common presentation of the disease with a 40% mortality rate even with appropriate treatments. Better diagnostic tests are therefore needed to improve therapeutic efficacy and survival rates.Results: We have used microarray technology to generate genome-wide transcriptional profiles (>48,000 transcripts) from the whole blood of 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% accuracy in a training set. This finding was confirmed in 2 independent validation sets, which gave high prediction accuracies of 78% and 80%, respectively. This signature was significantly enriched in genes coding for products involved in the MHC class II antigen processing and presentation pathway.Conclusions: Blood transcriptional patterns 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.

Original languageEnglish
Article number127
JournalGenome Biology
Volume10
Issue number11
DOIs
Publication statusPublished - 10 Nov 2009
Externally publishedYes

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Melioidosis
sepsis (infection)
biomarker
biomarkers
Sepsis
genomics
Biomarkers
blood
infectious disease
gene
pathogen
allergy
infectious diseases
Antigen Presentation
prediction
antigen
Burkholderia pseudomallei
genome
National Institute of Allergy and Infectious Diseases (U.S.)
microarray technology

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Cell Biology
  • Genetics

Cite this

Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis. / Pankla, Rungnapa; Buddhisa, Surachat; Berry, Matthew; Blankenship, Derek M.; Bancroft, Gregory J.; Banchereau, Jacques; Lertmemongkolchai, Ganjana; Chaussabel, Damien J.

In: Genome Biology, Vol. 10, No. 11, 127, 10.11.2009.

Research output: Contribution to journalArticle

Pankla, R, Buddhisa, S, Berry, M, Blankenship, DM, Bancroft, GJ, Banchereau, J, Lertmemongkolchai, G & Chaussabel, DJ 2009, 'Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis', Genome Biology, vol. 10, no. 11, 127. https://doi.org/10.1186/gb-2009-10-11-r127
Pankla, Rungnapa ; Buddhisa, Surachat ; Berry, Matthew ; Blankenship, Derek M. ; Bancroft, Gregory J. ; Banchereau, Jacques ; Lertmemongkolchai, Ganjana ; Chaussabel, Damien J. / Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis. In: Genome Biology. 2009 ; Vol. 10, No. 11.
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N2 - Background: Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, a Gram-negative bacillus classified by the National Institute of Allergy and Infectious Diseases (NIAID) as a category B priority agent. Septicemia is the most common presentation of the disease with a 40% mortality rate even with appropriate treatments. Better diagnostic tests are therefore needed to improve therapeutic efficacy and survival rates.Results: We have used microarray technology to generate genome-wide transcriptional profiles (>48,000 transcripts) from the whole blood of 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% accuracy in a training set. This finding was confirmed in 2 independent validation sets, which gave high prediction accuracies of 78% and 80%, respectively. This signature was significantly enriched in genes coding for products involved in the MHC class II antigen processing and presentation pathway.Conclusions: Blood transcriptional patterns 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.

AB - Background: Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, a Gram-negative bacillus classified by the National Institute of Allergy and Infectious Diseases (NIAID) as a category B priority agent. Septicemia is the most common presentation of the disease with a 40% mortality rate even with appropriate treatments. Better diagnostic tests are therefore needed to improve therapeutic efficacy and survival rates.Results: We have used microarray technology to generate genome-wide transcriptional profiles (>48,000 transcripts) from the whole blood of 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% accuracy in a training set. This finding was confirmed in 2 independent validation sets, which gave high prediction accuracies of 78% and 80%, respectively. This signature was significantly enriched in genes coding for products involved in the MHC class II antigen processing and presentation pathway.Conclusions: Blood transcriptional patterns 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.

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