Summary of Study ST000911

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.

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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 IDST000911
Study TitleInsights into the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) through metabolomic profiling of cerebrospinal fluid (part II)
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 Date2018-08-27
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:SU000949
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
SA053497Lipkin019_posCSH_DPCSF3671_034.dMECFS FEMALE
SA053498Lipkin048_posCSH_DPCSF7598_086.dMECFS FEMALE
SA053499Lipkin069_posCSH_DPCSF3712_009.dMECFS FEMALE
SA053500Lipkin081_posCSH_DPCSF7638_068.dMECFS FEMALE
SA053501Lipkin120_posCSH_DPCSF3152_084.dMECFS FEMALE
SA053502Lipkin028_posCSH_DPCSF8065_085.dMECFS FEMALE
SA053503Lipkin100_posCSH_DPCSF6448_016_2.dMECFS FEMALE
SA053504Lipkin016_posCSH_DPCSF3752_069.dMECFS FEMALE
SA053505Lipkin097_posCSH_DPCSF4353_065.dMECFS FEMALE
SA053506Lipkin004_posCSH_DPCSF6529_083.dMECFS FEMALE
SA053507Lipkin044_posCSH_DPCSF6143_067.dMECFS FEMALE
SA053508Lipkin078_posCSH_DPCSF5981_073.dMECFS FEMALE
SA053509Lipkin076_posCSH_DPCSF5502_070_2.dMECFS FEMALE
SA053510Lipkin093_posCSH_DPCSF7263_094.dMECFS FEMALE
SA053511Lipkin064_posCSH_DPCSF5421_088.dMECFS FEMALE
SA053512Lipkin003_posCSH_DPCSF2216_007.dMECFS FEMALE
SA053513Lipkin105_posCSH_DPCSF7944_046.dMECFS FEMALE
SA053514Lipkin109_posCSH_DPCSF1870_082.dMECFS FEMALE
SA053515Lipkin010_posCSH_DPCSF9145_018.dMECFS FEMALE
SA053516Lipkin096_posCSH_DPCSF9226_039.dMECFS FEMALE
SA053517Lipkin080_posCSH_DPCSF8371_014.dMECFS FEMALE
SA053518Lipkin074_posCSH_DPCSF1495_036.dMECFS MALE
SA053519Lipkin041_posCSH_DPCSF6765_032.dMECFS MALE
SA053520Lipkin077_posCSH_DPCSF7476_001.dMECFS MALE
SA053521Lipkin071_posCSH_DPCSF1576_044.dMECFS MALE
SA053522Lipkin107_posCSH_DPCSF9012_005_3.dMECFS MALE
SA053523Lipkin072_posCSH_DPCSF7863_071.dMECFS MALE
SA053524Lipkin001_posCSH_DPCSF0426_003.dMECFS MALE
SA053525Lipkin066_posCSH_DPCSF2603_048.dMECFS MALE
SA053526Lipkin103_posCSH_DPCSF9826_2_BU.dMECFS MALE
SA053527Lipkin110_posCSH_DPCSF2938_066.dMECFS MALE
SA053528Lipkin037_posCSH_DPCSF3285_072.dMECFS MALE
SA053529Lipkin011_posCSH_DPCSF6890_090.dMS FEMALE
SA053530Lipkin101_posCSH_DPCSF9292_037.dMS FEMALE
SA053531Lipkin075_posCSH_DPCSF9627_092.dMS FEMALE
SA053532Lipkin106_posCSH_DPCSF6902_103.dMS FEMALE
SA053533Lipkin023_posCSH_DPCSF9506_013.dMS FEMALE
SA053534Lipkin099_posCSH_DPCSF6688_062.dMS FEMALE
SA053535Lipkin068_posCSH_DPCSF8824_081.dMS FEMALE
SA053536Lipkin030_posCSH_DPCSF7877_079.dMS FEMALE
SA053537Lipkin053_posCSH_DPCSF7970_102.dMS FEMALE
SA053538Lipkin117_posCSH_DPCSF8397_025.dMS FEMALE
SA053539Lipkin032_posCSH_DPCSF8478_008.dMS FEMALE
SA053540Lipkin091_posCSH_DPCSF8692_015_2.dMS FEMALE
SA053541Lipkin090_posCSH_DPCSF7410_043.dMS FEMALE
SA053542Lipkin094_posCSH_DPCSF8183_080.dMS FEMALE
SA053543Lipkin029_posCSH_DPCSF7318_087.dMS FEMALE
SA053544Lipkin057_posCSH_DPCSF6088_055.dMS FEMALE
SA053545Lipkin046_posCSH_DPCSF1896_029.dMS FEMALE
SA053546Lipkin087_posCSH_DPCSF3686_093.dMS FEMALE
SA053547Lipkin119_posCSH_DPCSF4165_101.dMS FEMALE
SA053548Lipkin007_posCSH_DPCSF4592_121.dMS FEMALE
SA053549Lipkin014_posCSH_DPCSF1815_122.dMS FEMALE
SA053550Lipkin027_posCSH_DPCSF1041_058.dMS FEMALE
SA053551Lipkin089_posCSH_DPCSF0614_035_2.dMS FEMALE
SA053552Lipkin042_posCSH_DPCSF0747_027.dMS FEMALE
SA053553Lipkin104_posCSH_DPCSF0868_089_3.dMS FEMALE
SA053554Lipkin049_posCSH_DPCSF4633_104.dMS FEMALE
SA053555Lipkin063_posCSH_DPCSF3137_060.dMS FEMALE
SA053556Lipkin052_posCSH_DPCSF5274_054.dMS FEMALE
SA053557Lipkin118_posCSH_DPCSF1174_023.dMS MALE
SA053558Lipkin065_posCSH_DPCSF8732_075.dMS MALE
SA053559Lipkin033_posCSH_DPCSF5395_077.dMS MALE
SA053560Lipkin035_posCSH_DPCSF5447_011_2.dMS MALE
SA053561Lipkin031_posCSH_DPCSF4927_074.dMS MALE
SA053562Lipkin067_posCSH_DPCSF6728_056.dMS MALE
SA053563Lipkin102_posCSH_DPCSF0909_078.dMS MALE
SA053564Lipkin018_posCSH_DPCSF9719_033.dMS MALE
SA053565Lipkin020_posCSH_DPCSF2029_041.dMS MALE
SA053566Lipkin086_posCSH_DPCSF7329_006.dMS MALE
SA053567Lipkin050_posCSH_DPCSF7664_076.dMS MALE
SA053568Lipkin045_posCSH_DPCSF7023_091.dMS MALE
SA053569Lipkin036_posCSH_DPCSF6128_115.dND FEMALE
SA053570Lipkin024_posCSH_DPCSF0106_108.dND FEMALE
SA053571Lipkin034_posCSH_DPCSF0828_031.dND FEMALE
SA053572Lipkin098_posCSH_DPCSF7115_106.dND FEMALE
SA053573Lipkin005_posCSH_DPCSF7756_002.dND FEMALE
SA053574Lipkin116_posCSH_DPCSF6769_051.dND FEMALE
SA053575Lipkin113_posCSH_DPCSF6555_107.dND FEMALE
SA053576Lipkin056_posCSH_DPCSF0146_105.dND FEMALE
SA053577Lipkin108_posCSH_DPCSF2710_064.dND FEMALE
SA053578Lipkin039_posCSH_DPCSF3310_047.dND FEMALE
SA053579Lipkin009_posCSH_DPCSF9332_017.dND FEMALE
SA053580Lipkin114_posCSH_DPCSF7797_045.dND FEMALE
SA053581Lipkin084_posCSH_DPCSF1281_053.dND FEMALE
SA053582Lipkin055_posCSH_DPCSF1215_019.dND MALE
SA053583Lipkin059_posCSH_DPCSF2924_118.dND MALE
SA053584Lipkin038_posCSH_DPCSF2750_120.dND MALE
SA053585Lipkin092_posCSH_DPCSF2110_119.dND MALE
SA053586Lipkin043_posCSH_DPCSF8865_117.dND MALE
SA053587Lipkin051_posCSH_DPCSF3605_116.dND MALE
Showing results 1 to 91 of 91

Collection:

Collection ID:CO000943
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:TR000963
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:SP000956
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 AN001481
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 POSITIVE
Units Counts

Chromatography:

Chromatography ID:CH001039
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:1.67 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:MS001365
Analysis ID:AN001481
Instrument Name:Agilent 6530 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:POSITIVE
Capillary Voltage:3500 eV
Collision Energy:25 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
Ionization Energy:70eV
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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