Summary of Study ST000913

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 IDST000913
Study TitleInsights into the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) through metabolomic profiling of cerebrospinal fluid (part IV)
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 Date2017-12-12
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2018-08-27
Release Version1
Oliver Fiehn Oliver Fiehn
https://dx.doi.org/10.21228/M83T1G
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

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:SU000951
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
SA053679Lipkin019_posHILIC_DPCSF3671_034.dMECFS FEMALE
SA053680Lipkin048_posHILIC_DPCSF7598_086.dMECFS FEMALE
SA053681Lipkin069_posHILIC_DPCSF3712_009.dMECFS FEMALE
SA053682Lipkin081_posHILIC_DPCSF7638_068.dMECFS FEMALE
SA053683Lipkin120_posHILIC_DPCSF3152_084.dMECFS FEMALE
SA053684Lipkin028_posHILIC_DPCSF8065_085_2.dMECFS FEMALE
SA053685Lipkin100_posHILIC_DPCSF6448_016.dMECFS FEMALE
SA053686Lipkin016_posHILIC_DPCSF3752_069.dMECFS FEMALE
SA053687Lipkin097_posHILIC_DPCSF4353_065.dMECFS FEMALE
SA053688Lipkin004_posHILIC_DPCSF6529_083_2.dMECFS FEMALE
SA053689Lipkin044_posHILIC_DPCSF6143_067.dMECFS FEMALE
SA053690Lipkin078_posHILIC_DPCSF5981_073.dMECFS FEMALE
SA053691Lipkin076_posHILIC_DPCSF5502_070.dMECFS FEMALE
SA053692Lipkin093_posHILIC_DPCSF7263_094.dMECFS FEMALE
SA053693Lipkin064_posHILIC_DPCSF5421_088.dMECFS FEMALE
SA053694Lipkin003_posHILIC_DPCSF2216_007.dMECFS FEMALE
SA053695Lipkin105_posHILIC_DPCSF7944_046.dMECFS FEMALE
SA053696Lipkin109_posHILIC_DPCSF1870_082.dMECFS FEMALE
SA053697Lipkin010_posHILIC_DPCSF9145_018.dMECFS FEMALE
SA053698Lipkin096_posHILIC_DPCSF9226_039.dMECFS FEMALE
SA053699Lipkin080_posHILIC_DPCSF8371_014.dMECFS FEMALE
SA053700Lipkin074_posHILIC_DPCSF1495_036.dMECFS MALE
SA053701Lipkin041_posHILIC_DPCSF6765_032.dMECFS MALE
SA053702Lipkin077_posHILIC_DPCSF7476_001_2.dMECFS MALE
SA053703Lipkin071_posHILIC_DPCSF1576_044.dMECFS MALE
SA053704Lipkin107_posHILIC_DPCSF9012_005.dMECFS MALE
SA053705Lipkin072_posHILIC_DPCSF7863_071.dMECFS MALE
SA053706Lipkin001_posHILIC_DPCSF0426_003.dMECFS MALE
SA053707Lipkin066_posHILIC_DPCSF2603_048.dMECFS MALE
SA053708Lipkin103_posHILIC_DPCSF9826_042.dMECFS MALE
SA053709Lipkin110_posHILIC_DPCSF2938_066.dMECFS MALE
SA053710Lipkin037_posHILIC_DPCSF3285_072.dMECFS MALE
SA053711Lipkin011_posHILIC_DPCSF6890_090.dMS FEMALE
SA053712Lipkin101_posHILIC_DPCSF9292_037.dMS FEMALE
SA053713Lipkin075_posHILIC_DPCSF9627_092.dMS FEMALE
SA053714Lipkin106_posHILIC_DPCSF6902_103.dMS FEMALE
SA053715Lipkin023_posHILIC_DPCSF9506_013.dMS FEMALE
SA053716Lipkin099_posHILIC_DPCSF6688_062.dMS FEMALE
SA053717Lipkin068_posHILIC_DPCSF8824_081.dMS FEMALE
SA053718Lipkin030_posHILIC_DPCSF7877_079.dMS FEMALE
SA053719Lipkin053_posHILIC_DPCSF7970_102_2.dMS FEMALE
SA053720Lipkin117_posHILIC_DPCSF8397_025.dMS FEMALE
SA053721Lipkin032_posHILIC_DPCSF8478_008.dMS FEMALE
SA053722Lipkin091_posHILIC_DPCSF8692_015.dMS FEMALE
SA053723Lipkin090_posHILIC_DPCSF7410_043.dMS FEMALE
SA053724Lipkin094_posHILIC_DPCSF8183_080.dMS FEMALE
SA053725Lipkin029_posHILIC_DPCSF7318_087.dMS FEMALE
SA053726Lipkin057_posHILIC_DPCSF6088_055.dMS FEMALE
SA053727Lipkin046_posHILIC_DPCSF1896_029.dMS FEMALE
SA053728Lipkin087_posHILIC_DPCSF3686_093.dMS FEMALE
SA053729Lipkin119_posHILIC_DPCSF4165_101.dMS FEMALE
SA053730Lipkin007_posHILIC_DPCSF4592_121.dMS FEMALE
SA053731Lipkin014_posHILIC_DPCSF1815_122.dMS FEMALE
SA053732Lipkin027_posHILIC_DPCSF1041_058.dMS FEMALE
SA053733Lipkin089_posHILIC_DPCSF0614_035.dMS FEMALE
SA053734Lipkin042_posHILIC_DPCSF0747_027.dMS FEMALE
SA053735Lipkin104_posHILIC_DPCSF0868_089.dMS FEMALE
SA053736Lipkin049_posHILIC_DPCSF4633_104.dMS FEMALE
SA053737Lipkin063_posHILIC_DPCSF3137_060.dMS FEMALE
SA053738Lipkin052_posHILIC_DPCSF5274_054.dMS FEMALE
SA053739Lipkin118_posHILIC_DPCSF1174_023.dMS MALE
SA053740Lipkin065_posHILIC_DPCSF8732_075.dMS MALE
SA053741Lipkin033_posHILIC_DPCSF5395_077.dMS MALE
SA053742Lipkin035_posHILIC_DPCSF5447_011.dMS MALE
SA053743Lipkin031_posHILIC_DPCSF4927_074.dMS MALE
SA053744Lipkin067_posHILIC_DPCSF6728_056.dMS MALE
SA053745Lipkin102_posHILIC_DPCSF0909_078.dMS MALE
SA053746Lipkin018_posHILIC_DPCSF9719_033.dMS MALE
SA053747Lipkin020_posHILIC_DPCSF2029_041.dMS MALE
SA053748Lipkin086_posHILIC_DPCSF7329_006.dMS MALE
SA053749Lipkin050_posHILIC_DPCSF7664_076.dMS MALE
SA053750Lipkin045_posHILIC_DPCSF7023_091.dMS MALE
SA053751Lipkin036_posHILIC_DPCSF6128_115.dND FEMALE
SA053752Lipkin024_posHILIC_DPCSF0106_108.dND FEMALE
SA053753Lipkin034_posHILIC_DPCSF0828_031.dND FEMALE
SA053754Lipkin098_posHILIC_DPCSF7115_106_2.dND FEMALE
SA053755Lipkin005_posHILIC_DPCSF7756_002.dND FEMALE
SA053756Lipkin116_posHILIC_DPCSF6769_051.dND FEMALE
SA053757Lipkin113_posHILIC_DPCSF6555_107_2.dND FEMALE
SA053758Lipkin056_posHILIC_DPCSF0146_105.dND FEMALE
SA053759Lipkin108_posHILIC_DPCSF2710_064.dND FEMALE
SA053760Lipkin039_posHILIC_DPCSF3310_047.dND FEMALE
SA053761Lipkin009_posHILIC_DPCSF9332_017.dND FEMALE
SA053762Lipkin114_posHILIC_DPCSF7797_045.dND FEMALE
SA053763Lipkin084_posHILIC_DPCSF1281_053.dND FEMALE
SA053764Lipkin055_posHILIC_DPCSF1215_019.dND MALE
SA053765Lipkin059_posHILIC_DPCSF2924_118.dND MALE
SA053766Lipkin038_posHILIC_DPCSF2750_120_2.dND MALE
SA053767Lipkin092_posHILIC_DPCSF2110_119.dND MALE
SA053768Lipkin043_posHILIC_DPCSF8865_117.dND MALE
SA053769Lipkin051_posHILIC_DPCSF3605_116.dND MALE
Showing results 1 to 91 of 91

Collection:

Collection ID:CO000945
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:TR000965
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:SP000958
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) 11) Aliquot the remaining aqueous phase into two separate tubes 125 uL per tube, keeping one at -20°C for backup 12) Dry samples to complete dryness in the speed vacuum concentration system

Combined analysis:

Analysis ID AN001483
Analysis type MS
Chromatography type HILIC
Chromatography system Agilent 6530
Column Waters Acquity BEH C18 (100 x 2mm,1.7um)
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6530 QTOF
Ion Mode POSITIVE
Units Counts

Chromatography:

Chromatography ID:CH001041
Instrument Name:Agilent 6530
Column Name:Waters Acquity BEH C18 (100 x 2mm,1.7um)
Column Pressure:200-700 bar
Column Temperature:40 C
Flow Gradient:0 min 100% (B), 0-2 min 100% (B), 2-7 min 70% (B), 7.7-9 min 40% (B), 9.5-10.25 min 30% (B), 10.25- 12.75 min 100% (B), 16.75 min 100% (B)
Flow Rate:0.4 mL/min
Injection Temperature:4 C
Internal Standard:See data dictionary
Retention Time:See data dictionary
Sample Injection:3 μL
Analytical Time:14 min
Capillary Voltage:4500 eV
Time Program:16.75 min
Weak Wash Solvent Name:1:1 ACN:H2O
Strong Wash Solvent Name:Same
Target Sample Temperature:Autosampler temp 4 C
Randomization Order:Excel generated
Chromatography Type:HILIC

MS:

MS ID:MS001367
Analysis ID:AN001483
Instrument Name:Agilent 6530 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:POSITIVE
Capillary Voltage:3500 eV
Collision Energy:45 eV
Collision Gas:Nitrogen
Dry Gas Flow:8L/min
Dry Gas Temp:325 C
Fragment Voltage:120 eV
Fragmentation Method:Auto MS/MS
Ion Source Temperature:325 C
Ion Spray Voltage:1000
Ionization:Pos
Precursor Type:Intact Molecule
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
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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