Summary of Study ST000912

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 PR000631. The data can be accessed directly via it's Project DOI: 10.21228/M83T1G 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 IDST000912
Study TitleInsights into the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) through metabolomic profiling of cerebrospinal fluid (part III)
Study SummaryMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling illness characterized by six months or more of unexplained profound fatigue with post-exertional malaise, sleep abnormalities, cognitive dysfunction and autonomic disturbances. Focusing on the pathogenesis of central nervous system abnormalities in ME/CFS, we pursued metabolomics analysis of cerebrospinal fluid (CSF) in 32 ME/CFS cases, 40 subjects with multiple sclerosis (MS), another fatiguing illness, and 19 healthy subjects with no neurological disease (ND). MS/ND subjects were frequency matched for age and sex to ME/CFS subjects. Three untargeted metabolomic assays for primary metabolites, biogenic amines and complex lipids were performed with gas chromatography time-of-flight (GC-TOF) and liquid chromatography–tandem mass spectrometry (LC-MS/MS) yielding profiles for 525 known metabolites. Mannose was a cardinal biomarker in ME/CFS subjects with reduced levels in ME/CFS compared to both MS and ND subjects. Levels of acetylcarnitine were reduced in ME/CFS vs. MS subjects. The predictive power of metabolomic analysis for diagnosis of ME/CFS vs. ND was higher (cross-validated AUC 0.875; 95% CI: 0.726~0.949) than with cytokine analysis alone (cross-validated AUC 0.865; 95% CI: 0.673~0.952) and improved with integration of both metabolomics and cytokine analyses (cross-validated AUC 0.916; 95% CI: 0.791~0.969). Our findings confirm the biological basis of ME/CFS, and may enable new methods for diagnosis and insight into cognitive and autonomic disturbances in this syndrome.
Institute
University of California, Davis
DepartmentGenome and Biomedical Sciences Facility
LaboratoryWCMC Metabolomics Core
Last NameFiehn
First NameOliver
Address1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Emailofiehn@ucdavis.edu
Phone(530) 754-8258
Submit Date2017-12-11
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2020-06-03
Release Version1
Oliver Fiehn Oliver Fiehn
https://dx.doi.org/10.21228/M83T1G
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000631
Project DOI:doi: 10.21228/M83T1G
Project Title:Insights into the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) through metabolomic profiling of cerebrospinal fluid
Project Summary:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling illness characterized by six months or more of unexplained profound fatigue with post-exertional malaise, sleep abnormalities, cognitive dysfunction and autonomic disturbances. Focusing on the pathogenesis of central nervous system abnormalities in ME/CFS, we pursued metabolomics analysis of cerebrospinal fluid (CSF) in 32 ME/CFS cases, 40 subjects with multiple sclerosis (MS), another fatiguing illness, and 19 healthy subjects with no neurological disease (ND). MS/ND subjects were frequency matched for age and sex to ME/CFS subjects. Three untargeted metabolomic assays for primary metabolites, biogenic amines and complex lipids were performed with gas chromatography time-of-flight (GC-TOF) and liquid chromatography–tandem mass spectrometry (LC-MS/MS) yielding profiles for 525 known metabolites. Mannose was a cardinal biomarker in ME/CFS subjects with reduced levels in ME/CFS compared to both MS and ND subjects. Levels of acetylcarnitine were reduced in ME/CFS vs. MS subjects. The predictive power of metabolomic analysis for diagnosis of ME/CFS vs. ND was higher (cross-validated AUC 0.875; 95% CI: 0.726~0.949) than with cytokine analysis alone (cross-validated AUC 0.865; 95% CI: 0.673~0.952) and improved with integration of both metabolomics and cytokine analyses (cross-validated AUC 0.916; 95% CI: 0.791~0.969). Our findings confirm the biological basis of ME/CFS, and may enable new methods for diagnosis and insight into cognitive and autonomic disturbances in this syndrome.
Institute:Columbia University
Department:Center for Infection and Immunity, Mailman School of Public Health
Last Name:Lipkin
First Name:Ian
Address:722 West 168th Street, Room 1703a, New York, NY USA 10032
Email:wil2001@columbia.edu
Phone:212-342-9044

Subject:

Subject ID:SU000950
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

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

mb_sample_id local_sample_id Diagnosis Sex
SA053588Lipkin019_negCSH_DPCSF3671_034.dMECFS FEMALE
SA053589Lipkin048_negCSH_DPCSF7598_086.dMECFS FEMALE
SA053590Lipkin069_negCSH_DPCSF3712_009.dMECFS FEMALE
SA053591Lipkin081_negCSH_DPCSF7638_068.dMECFS FEMALE
SA053592Lipkin120_negCSH_DPCSF3152_084.dMECFS FEMALE
SA053593Lipkin028_negCSH_DPCSF8065_085.dMECFS FEMALE
SA053594Lipkin100_negCSH_DPCSF6448_016.dMECFS FEMALE
SA053595Lipkin016_negCSH_DPCSF3752_069.dMECFS FEMALE
SA053596Lipkin097_negCSH_DPCSF4353_065.dMECFS FEMALE
SA053597Lipkin004_negCSH_DPCSF6529_083.dMECFS FEMALE
SA053598Lipkin044_negCSH_DPCSF6143_067.dMECFS FEMALE
SA053599Lipkin078_negCSH_DPCSF5981_073.dMECFS FEMALE
SA053600Lipkin076_negCSH_DPCSF5502_070.dMECFS FEMALE
SA053601Lipkin093_negCSH_DPCSF7263_094.dMECFS FEMALE
SA053602Lipkin064_negCSH_DPCSF5421_088.dMECFS FEMALE
SA053603Lipkin003_negCSH_DPCSF2216_007.dMECFS FEMALE
SA053604Lipkin105_negCSH_DPCSF7944_046.dMECFS FEMALE
SA053605Lipkin109_negCSH_DPCSF1870_082.dMECFS FEMALE
SA053606Lipkin010_negCSH_DPCSF9145_018.dMECFS FEMALE
SA053607Lipkin096_negCSH_DPCSF9226_039.dMECFS FEMALE
SA053608Lipkin080_negCSH_DPCSF8371_014.dMECFS FEMALE
SA053609Lipkin074_negCSH_DPCSF1495_036.dMECFS MALE
SA053610Lipkin041_negCSH_DPCSF6765_032.dMECFS MALE
SA053611Lipkin077_negCSH_DPCSF7476_001.dMECFS MALE
SA053612Lipkin071_negCSH_DPCSF1576_044.dMECFS MALE
SA053613Lipkin107_negCSH_DPCSF9012_005.dMECFS MALE
SA053614Lipkin072_negCSH_DPCSF7863_071.dMECFS MALE
SA053615Lipkin001_negCSH_DPCSF0426_003.dMECFS MALE
SA053616Lipkin066_negCSH_DPCSF2603_048.dMECFS MALE
SA053617Lipkin103_negCSH_DPCSF9826_042.dMECFS MALE
SA053618Lipkin110_negCSH_DPCSF2938_066.dMECFS MALE
SA053619Lipkin037_negCSH_DPCSF3285_072.dMECFS MALE
SA053620Lipkin011_negCSH_DPCSF6890_090.dMS FEMALE
SA053621Lipkin101_negCSH_DPCSF9292_037.dMS FEMALE
SA053622Lipkin075_negCSH_DPCSF9627_092.dMS FEMALE
SA053623Lipkin106_negCSH_DPCSF6902_103.dMS FEMALE
SA053624Lipkin023_negCSH_DPCSF9506_013.dMS FEMALE
SA053625Lipkin099_negCSH_DPCSF6688_062.dMS FEMALE
SA053626Lipkin068_negCSH_DPCSF8824_081.dMS FEMALE
SA053627Lipkin030_negCSH_DPCSF7877_079.dMS FEMALE
SA053628Lipkin053_negCSH_DPCSF7970_102.dMS FEMALE
SA053629Lipkin117_negCSH_DPCSF8397_025.dMS FEMALE
SA053630Lipkin032_negCSH_DPCSF8478_008.dMS FEMALE
SA053631Lipkin091_negCSH_DPCSF8692_015.dMS FEMALE
SA053632Lipkin090_negCSH_DPCSF7410_043.dMS FEMALE
SA053633Lipkin094_negCSH_DPCSF8183_080.dMS FEMALE
SA053634Lipkin029_negCSH_DPCSF7318_087.dMS FEMALE
SA053635Lipkin057_negCSH_DPCSF6088_055.dMS FEMALE
SA053636Lipkin046_negCSH_DPCSF1896_029.dMS FEMALE
SA053637Lipkin087_negCSH_DPCSF3686_093.dMS FEMALE
SA053638Lipkin119_negCSH_DPCSF4165_101.dMS FEMALE
SA053639Lipkin007_negCSH_DPCSF4592_121.dMS FEMALE
SA053640Lipkin014_negCSH_DPCSF1815_122.dMS FEMALE
SA053641Lipkin027_negCSH_DPCSF1041_058.dMS FEMALE
SA053642Lipkin089_negCSH_DPCSF0614_035.dMS FEMALE
SA053643Lipkin042_negCSH_DPCSF0747_027.dMS FEMALE
SA053644Lipkin104_negCSH_DPCSF0868_089.dMS FEMALE
SA053645Lipkin049_negCSH_DPCSF4633_104.dMS FEMALE
SA053646Lipkin063_negCSH_DPCSF3137_060.dMS FEMALE
SA053647Lipkin052_negCSH_DPCSF5274_054.dMS FEMALE
SA053648Lipkin118_negCSH_DPCSF1174_023.dMS MALE
SA053649Lipkin065_negCSH_DPCSF8732_075.dMS MALE
SA053650Lipkin033_negCSH_DPCSF5395_077.dMS MALE
SA053651Lipkin035_negCSH_DPCSF5447_011.dMS MALE
SA053652Lipkin031_negCSH_DPCSF4927_074.dMS MALE
SA053653Lipkin067_negCSH_DPCSF6728_056.dMS MALE
SA053654Lipkin102_negCSH_DPCSF0909_078.dMS MALE
SA053655Lipkin018_negCSH_DPCSF9719_033.dMS MALE
SA053656Lipkin020_negCSH_DPCSF2029_041.dMS MALE
SA053657Lipkin086_negCSH_DPCSF7329_006.dMS MALE
SA053658Lipkin050_negCSH_DPCSF7664_076.dMS MALE
SA053659Lipkin045_negCSH_DPCSF7023_091.dMS MALE
SA053660Lipkin036_negCSH_DPCSF6128_115.dND FEMALE
SA053661Lipkin024_negCSH_DPCSF0106_108.dND FEMALE
SA053662Lipkin034_negCSH_DPCSF0828_031.dND FEMALE
SA053663Lipkin098_negCSH_DPCSF7115_106.dND FEMALE
SA053664Lipkin005_negCSH_DPCSF7756_002.dND FEMALE
SA053665Lipkin116_negCSH_DPCSF6769_051.dND FEMALE
SA053666Lipkin113_negCSH_DPCSF6555_107.dND FEMALE
SA053667Lipkin056_negCSH_DPCSF0146_105.dND FEMALE
SA053668Lipkin108_negCSH_DPCSF2710_064.dND FEMALE
SA053669Lipkin039_negCSH_DPCSF3310_047.dND FEMALE
SA053670Lipkin009_negCSH_DPCSF9332_017.dND FEMALE
SA053671Lipkin114_negCSH_DPCSF7797_045.dND FEMALE
SA053672Lipkin084_negCSH_DPCSF1281_053.dND FEMALE
SA053673Lipkin055_negCSH_DPCSF1215_019.dND MALE
SA053674Lipkin059_negCSH_DPCSF2924_118.dND MALE
SA053675Lipkin038_negCSH_DPCSF2750_120.dND MALE
SA053676Lipkin092_negCSH_DPCSF2110_119.dND MALE
SA053677Lipkin043_negCSH_DPCSF8865_117.dND MALE
SA053678Lipkin051_negCSH_DPCSF3605_116.dND MALE
Showing results 1 to 91 of 91

Collection:

Collection ID:CO000944
Collection Summary:CSF samples obtained from lumbar punctures were retrieved from bio-repositories at Sierra Internal Medicine (SIM) and Wisconsin Viral Research Group (WVRG). These biobank specimens were collected over time and maintained at -80°C.
Sample Type:CSF

Treatment:

Treatment ID:TR000964
Treatment Summary:3 groups: 32 ME/CFS cases (11 men, 21 women) 59 comparator/control subjects (18 men, 41 women), including: 40 subjects with multiple sclerosis (MS) 19 subjects with non-infectious/non-inflammatory conditions (ND)

Sample Preparation:

Sampleprep ID:SP000957
Sampleprep Summary:1) Thaw each 100 μL CSF aliquot at room temperature (see Aliquoting TEDDY samples SOP). Once thawed (~10min) place CSF plasma samples on ice. 2) Add 225 μL cold “MeOH with QC mix” (see SOP “QC mix for LC-MS lipid analysis”). Keep MeOH on ice during extraction 3) Vortex each sample for 10s, keeping the rest on ice during all the extraction. 4) Add 750 μL of cold MTBE with 22:1 CE, keep MTBE on ice during extraction 5) Vortex for 10s 6) Shake for 6min at 4°C in the orbital mixer. 7) Add 188 μL room temperature LC/MS grade water. 8) Vortex for 20 s 9) Centrifuge for 2 min @ 14,000 rcf (12300 rpm) 10) Remove supernatant (upper phase), splitting into two aliquots of 300 μL, keeping one at –20°C for backup 11) Dry samples to complete dryness in the speed vacuum concentration system

Combined analysis:

Analysis ID AN001482
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 6530
Column Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6530 QTOF
Ion Mode NEGATIVE
Units Counts

Chromatography:

Chromatography ID:CH001040
Methods Filename:Data_Dictionary_Fiehn_laboratory_CSH_QTOF_lipidomics_05-29-2014.pdf
Instrument Name:Agilent 6530
Column Name:Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
Column Pressure:450-850 bar
Column Temperature:65 C
Flow Gradient:15% B to 99% B
Flow Rate:0.6 mL/min
Injection Temperature:4 C
Internal Standard:See data dictionary
Retention Time:See data dictionary
Sample Injection:5.0 uL
Solvent A:60% acetonitrile/40% water; 10mM formic acid; 10mM ammonium formate
Solvent B:90% isopropanol/10% acetonitrile; 10mM formic acid; 10mM ammonium formate
Analytical Time:13 min
Capillary Voltage:3500 eV
Oven Temperature:50°C for 1 min, then ramped at 20°C/min to 330°C, held constant for 5 min
Time Program:15 min
Washing Buffer:Ethyl Acetate
Weak Wash Solvent Name:Isopropanol
Strong Wash Solvent Name:Isopropanol
Target Sample Temperature:Autosampler temp 4 C
Sample Loop Size:30 m length x 0.25 mm internal diameter
Randomization Order:Excel generated
Chromatography Type:Reversed phase

MS:

MS ID:MS001366
Analysis ID:AN001482
Instrument Name:Agilent 6530 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:NEGATIVE
Capillary Voltage:3500 eV
Collision Energy:40 eV
Collision Gas:Nitrogen
Dry Gas Flow:13 L/min
Dry Gas Temp:200 C
Fragment Voltage:175 eV
Fragmentation Method:Auto MS/MS
Ion Source Temperature:325 C
Ion Spray Voltage:1000
Ionization:Neg
Mass Accuracy:Accurate
Reagent Gas:Nitrogen
Source Temperature:325 C
Dataformat:.d
Desolvation Gas Flow:11 L/min
Desolvation Temperature:350 C
Nebulizer:35 psig
Octpole Voltage:750 eV
Resolution Setting:Extended Dyamic Range
Scan Range Moverz:60-1700 Da
Scanning Cycle:2 Hz
Scanning Range:60-1700 Da
Skimmer Voltage:65
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