{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002909","ANALYSIS_ID":"AN004776","VERSION":"1","CREATED_ON":"October 3, 2023, 11:37 am"},

"PROJECT":{"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"},

"STUDY":{"STUDY_TITLE":"Plasma metabolomics reveals distinct biological and diagnostic signatures for melioidosis","STUDY_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","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"},

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"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"25","sex":"F","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"283",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"89","sex":"F","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"284",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"67","sex":"M","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"285",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"44","sex":"F","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"286",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"67","sex":"M","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"287",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"63","sex":"F","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"288",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"82","sex":"F","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"289",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"66","sex":"F","mortality":"dead"}
},
{
"Subject ID":"-",
"Sample ID":"290",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"79","sex":"M","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"291",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"39","sex":"M","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"292",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"65","sex":"F","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"293",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"77","sex":"F","mortality":"dead"}
},
{
"Subject ID":"-",
"Sample ID":"294",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"51","sex":"M","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"295",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"40","sex":"M","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"296",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"54","sex":"F","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"297",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"69","sex":"M","mortality":"dead"}
},
{
"Subject ID":"-",
"Sample ID":"298",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"53","sex":"F","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"299",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"23","sex":"F","mortality":"alive"}
},
{
"Subject ID":"-",
"Sample ID":"300",
"Factors":{"Group":"culture neg"},
"Additional sample data":{"age":"76","sex":"F","mortality":"dead"}
}
],
"COLLECTION":{"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_SUMMARY":"N/A"},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Metabolon standard protocol"},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_SUMMARY":"Low pH Lipophilic (LC/MS Pos late)","CHROMATOGRAPHY_TYPE":"Reversed phase","INSTRUMENT_NAME":"Waters Acquity","COLUMN_NAME":"Waters Acquity BEH C18 (100 x 2mm, 1.7um)","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","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","COLUMN_TEMPERATURE":"40-50"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS"},

"MS":{"INSTRUMENT_NAME":"Thermo Q Exactive Orbitrap","INSTRUMENT_TYPE":"Orbitrap","MS_TYPE":"Other","ION_MODE":"POSITIVE","MS_COMMENTS":"Metabolon (LC/MS Pos late)"},

"MS_METABOLITE_DATA":{
"Units":"Peak Area",

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}

}