Summary of Study ST002909

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001809. The data can be accessed directly via it's Project DOI: 10.21228/M8W71R This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002909
Study TitlePlasma metabolomics reveals distinct biological and diagnostic signatures for melioidosis
Study SummaryRationale: The global burden of sepsis is greatest in low-resource settings. Melioidosis, infection with the Gram-negative bacterium Burkholderia pseudomallei, is a frequent cause of fatal sepsis in endemic tropical regions such as Southeast Asia. Objectives: To investigate whether plasma metabolomics would identify biological pathways specific to melioidosis and yield clinically meaningful biomarkers. Methods: Using a comprehensive approach, differential enrichment of plasma metabolites and pathways was systematically evaluated in individuals selected from a prospective cohort of patients hospitalized in rural Thailand with infection. Statistical and bioinformatics methods were used to distinguish metabolomic features and processes specific to melioidosis patients, and between fatal and non-fatal cases. Measurements and Main Results: Metabolomic profiling and pathway enrichment analysis of plasma samples of melioidosis (n=175) and non-melioidosis infections (n=75) revealed a distinct immuno-metabolic state among patients with melioidosis, as suggested by excessive tryptophan catabolism in the kynurenine pathway and significantly increased levels of sphingomyelins and ceramide species. We derived a 12-metabolite classifier to distinguish melioidosis from other infections, yielding an area under the receiver operating characteristic curve of 0.87 in a second validation set of patients. Melioidosis non-survivors (n=94) had a significantly disturbed metabolome compared to survivors (n=81) with increased leucine, isoleucine and valine metabolism, and elevated circulating free fatty acids and acylcarnitines. A limited 8-metabolite panel showed promise as an early prognosticator of mortality in melioidosis. Conclusions: Melioidosis induces a distinct metabolomic state that can be examined to distinguish underlying pathophysiological mechanisms associated with death. A twelve-metabolite signature accurately differentiates melioidosis from other infections and may have diagnostic applications.
Institute
University of Washington
Last NameGharib
First NameSina
AddressCenter for Lung Biology, 850 Republican St. Seattle WA 98109
Emailsagharib@uw.edu
Phone206-221-0630
Submit Date2023-10-03
Analysis Type DetailOther
Release Date2023-10-17
Release Version1
Sina Gharib Sina Gharib
https://dx.doi.org/10.21228/M8W71R
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001809
Project DOI:doi: 10.21228/M8W71R
Project Title:Plasma metabolomics reveals distinct biological and diagnostic signatures for melioidosis
Project Summary:Rationale: The global burden of sepsis is greatest in low-resource settings. Melioidosis, infection with the Gram-negative bacterium Burkholderia pseudomallei, is a frequent cause of fatal sepsis in endemic tropical regions such as Southeast Asia. Objectives: To investigate whether plasma metabolomics would identify biological pathways specific to melioidosis and yield clinically meaningful biomarkers. Methods: Using a comprehensive approach, differential enrichment of plasma metabolites and pathways was systematically evaluated in individuals selected from a prospective cohort of patients hospitalized in rural Thailand with infection. Statistical and bioinformatics methods were used to distinguish metabolomic features and processes specific to melioidosis patients, and between fatal and non-fatal cases. Measurements and Main Results: Metabolomic profiling and pathway enrichment analysis of plasma samples of melioidosis (n=175) and non-melioidosis infections (n=75) revealed a distinct immuno-metabolic state among patients with melioidosis, as suggested by excessive tryptophan catabolism in the kynurenine pathway and significantly increased levels of sphingomyelins and ceramide species. We derived a 12-metabolite classifier to distinguish melioidosis from other infections, yielding an area under the receiver operating characteristic curve of 0.87 in a second validation set of patients. Melioidosis non-survivors (n=94) had a significantly disturbed metabolome compared to survivors (n=81) with increased leucine, isoleucine and valine metabolism, and elevated circulating free fatty acids and acylcarnitines. A limited 8-metabolite panel showed promise as an early prognosticator of mortality in melioidosis. Conclusions: Melioidosis induces a distinct metabolomic state that can be examined to distinguish underlying pathophysiological mechanisms associated with death. A twelve-metabolite signature accurately differentiates melioidosis from other infections and may have diagnostic applications.
Institute:University of Washington
Department:Medicine
Last Name:Gharib
First Name:Sina
Address:Center for Lung Biology, 850 Republican St, Seattle WA 98109
Email:sagharib@uw.edu
Phone:206-221-0630
Funding Source:NIH (R01HL113382, R01AI137111, R01GM114029, R21AI173435) and the Wellcome Trust (090219/Z/09/Z, 101103/Z/13/Z)
Contributors:Lu Xia, T. Eoin West

Subject:

Subject ID:SU003022
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Gender:Male and female

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Group
SA31599135control
SA31599234control
SA31599336control
SA31599437control
SA31599538control
SA31599633control
SA31599732control
SA31599828control
SA31599929control
SA31600030control
SA31600131control
SA31600239control
SA31600340control
SA31600447control
SA31600549control
SA31600650control
SA3160071control
SA31600846control
SA31600945control
SA31601041control
SA31601142control
SA31601243control
SA31601344control
SA31601427control
SA31601548control
SA3160168control
SA3160177control
SA31601810control
SA31601911control
SA31602012control
SA3160216control
SA3160222control
SA31602326control
SA3160243control
SA3160254control
SA3160265control
SA31602713control
SA3160289control
SA31602922control
SA31603021control
SA31603123control
SA31603214control
SA31603325control
SA31603420control
SA31603524control
SA31603615control
SA31603719control
SA31603817control
SA31603916control
SA31604018control
SA316041286culture neg
SA316042285culture neg
SA316043287culture neg
SA316044288culture neg
SA316045284culture neg
SA316046281culture neg
SA316047289culture neg
SA316048279culture neg
SA316049280culture neg
SA316050282culture neg
SA316051283culture neg
SA316052291culture neg
SA316053297culture neg
SA316054290culture neg
SA316055299culture neg
SA316056300culture neg
SA316057296culture neg
SA316058298culture neg
SA316059295culture neg
SA316060292culture neg
SA316061293culture neg
SA316062294culture neg
SA316063246ecoli
SA316064247ecoli
SA316065237ecoli
SA316066238ecoli
SA316067239ecoli
SA316068241ecoli
SA316069236ecoli
SA316070242ecoli
SA316071243ecoli
SA316072244ecoli
SA316073245ecoli
SA316074230ecoli
SA316075228ecoli
SA316076227ecoli
SA316077226ecoli
SA316078240ecoli
SA316079229ecoli
SA316080231ecoli
SA316081234ecoli
SA316082233ecoli
SA316083232ecoli
SA316084235ecoli
SA316085268klebs
SA316086274klebs
SA316087273klebs
SA316088275klebs
SA316089276klebs
SA316090278klebs
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Collection:

Collection ID:CO003015
Collection Summary:Subjects at least 18 years of age admitted to Sunpasitthiprasong Hospital in Ubon Ratchathani, Thailand with suspected community-acquired infection were sequentially and prospectively enrolled within 24 hours of admission into the “Ubon-Sepsis” parent study from 2013 through 2017. Plasma samples were obtained from all participants at the time of enrollment.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR003031
Treatment Summary:N/A

Sample Preparation:

Sampleprep ID:SP003028
Sampleprep Summary:Metabolon standard protocol

Combined analysis:

Analysis ID AN004775 AN004776 AN004777 AN004778
Analysis type MS MS MS MS
Chromatography type Reversed phase Reversed phase Reversed phase HILIC
Chromatography system Waters Acquity Waters Acquity Waters Acquity Waters Acquity
Column Waters Acquity BEH C18 (100 x 2mm, 1.7um) Waters Acquity BEH C18 (100 x 2mm, 1.7um) Waters Acquity BEH C18 (100 x 2mm, 1.7um) Waters Acquity BEH Amide (150 x 2.1mm, 1.7um)
MS Type ESI ESI ESI ESI
MS instrument type Orbitrap Orbitrap Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE POSITIVE NEGATIVE NEGATIVE
Units Peak Area Peak Area Peak Area Peak area

Chromatography:

Chromatography ID:CH003607
Chromatography Summary:Low pH polar (LC/MS Pos early)
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (100 x 2mm, 1.7um)
Column Temperature:40-50
Flow Gradient:Linear gradient from 5% B to 80% B over 3.35 minutes
Flow Rate:0.35 mL/min
Solvent A:100% water; 0.1% formic acid; 0.05% PFPA, pH ~2.5
Solvent B:100% methanol; 0.1% formic acid; 0.05% PFPA, pH ~2.5
Chromatography Type:Reversed phase
  
Chromatography ID:CH003608
Chromatography Summary:Low pH Lipophilic (LC/MS Pos late)
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (100 x 2mm, 1.7um)
Column Temperature:40-50
Flow Gradient:Linear gradient from 40% B to 99.5% B over 1.0 minute, hold 99.5% B for 2.4 minutes.
Flow Rate:0.60 mL/min
Solvent A:100% water; 0.1% formic acid; 0.05% PFPA, pH ~2.5
Solvent B:50% methanol/50% acetonitrile; 0.1% formic acid; 0.05% PFPA, pH ~2.5
Chromatography Type:Reversed phase
  
Chromatography ID:CH003609
Chromatography Summary:High pH (LC/MS Neg)
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (100 x 2mm, 1.7um)
Column Temperature:40-50
Flow Gradient:Linear gradient from 0.5 to 70% B over 4.0 minutes, then rapid gradient to 99% B in 0.5 minutes.
Flow Rate:0.35 mL/min
Solvent A:100% water; 6.5 mM ammonium bicarbonate, pH 8
Solvent B:95% methanol/5% water; 6.5 mM ammonium bicarbonate
Chromatography Type:Reversed phase
  
Chromatography ID:CH003610
Chromatography Summary:HILIC (LC/MS Polar Neg)
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH Amide (150 x 2.1mm, 1.7um)
Column Temperature:40-50
Flow Gradient:Linear gradient from 5% B to 50% B in 3.5 minutes, then linear gradient from 50% B to 95% B in 2 minutes.
Flow Rate:0.50 mL/min
Solvent A:15% water/5% methanol/80% acetonitrile; 10 mM ammonium formate, (effective pH 10.16 with NH4OH)
Solvent B:50% water/50% acetonitrile; 10 mM ammonium formate, (effective pH 10.60 with NH4OH)
Chromatography Type:HILIC

MS:

MS ID:MS004521
Analysis ID:AN004775
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Metabolon (LC/MS Pos early)
Ion Mode:POSITIVE
  
MS ID:MS004522
Analysis ID:AN004776
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Metabolon (LC/MS Pos late)
Ion Mode:POSITIVE
  
MS ID:MS004523
Analysis ID:AN004777
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Metabolon (LC/MS Neg)
Ion Mode:NEGATIVE
  
MS ID:MS004524
Analysis ID:AN004778
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Metabolon (LC/MS Polar)
Ion Mode:NEGATIVE
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