Summary of study ST000910

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 IDST000910
Study TitleInsights into the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) through metabolomic profiling of cerebrospinal fluid (part I)
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).cdf
Analysis Type DetailGC-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:SU000948
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
SA053406170608aOEsa21_1MECFS FEMALE
SA053407170607aOEsa01_1MECFS FEMALE
SA053408170606aOEsa24_2MECFS FEMALE
SA053409170607aOEsa28_1MECFS FEMALE
SA053410170607aOEsa38_1MECFS FEMALE
SA053411170607aOEsa20_1MECFS FEMALE
SA053412170606aOEsa42_1MECFS FEMALE
SA053413170606aOEsa21_3MECFS FEMALE
SA053414170608aOEsa15_1MECFS FEMALE
SA053415170607aOEsa04_1MECFS FEMALE
SA053416170608aOEsa06_1MECFS FEMALE
SA053417170608aOEsa03_1MECFS FEMALE
SA053418170608aOEsa11_1MECFS FEMALE
SA053419170607aOEsa31_1MECFS FEMALE
SA053420170607aOEsa13_1MECFS FEMALE
SA053421170607aOEsa37_1MECFS FEMALE
SA053422170607aOEsa46_1MECFS FEMALE
SA053423170607aOEsa10_1MECFS FEMALE
SA053424170606aOEsa27_2MECFS FEMALE
SA053425170606aOEsa38_1MECFS FEMALE
SA053426170608aOEsa22_1MECFS FEMALE
SA053427170606aOEsa10_3MECFS MALE
SA053428170607aOEsa36_1MECFS MALE
SA053429170606aOEsa07_3MECFS MALE
SA053430170606aOEsa37_1MECFS MALE
SA053431170607aOEsa19_1MECFS MALE
SA053432170606aOEsa47_1MECFS MALE
SA053433170608aOEsa18_1MECFS MALE
SA053434170606aOEsa25_2MECFS MALE
SA053435170606aOEsa22_2MECFS MALE
SA053436170606aOEsa29_2MECFS MALE
SA053437170606aOEsa18_3MECFS MALE
SA053438170607aOEsa24_1MS FEMALE
SA053439170607aOEsa18_1MS FEMALE
SA053440170606aOEsa40_1MS FEMALE
SA053441170607aOEsa22_1MS FEMALE
SA053442170607aOEsa35_1MS FEMALE
SA053443170607aOEsa30_1MS FEMALE
SA053444170607aOEsa26_1MS FEMALE
SA053445170606aOEsa09_3MS FEMALE
SA053446170608aOEsa05_1MS FEMALE
SA053447170606aOEsa17_3MS FEMALE
SA053448170606aOEsa02_3MS FEMALE
SA053449170606aOEsa04_3MS FEMALE
SA053450170607aOEsa27_1MS FEMALE
SA053451170606aOEsa01_3MS FEMALE
SA053452170607aOEsa05_1MS FEMALE
SA053453170606aOEsa20_3MS FEMALE
SA053454170606aOEsa33_1MS FEMALE
SA053455170606aOEsa32_1MS FEMALE
SA053456170608aOEsa12_1MS FEMALE
SA053457170606aOEsa11_3MS FEMALE
SA053458170607aOEsa50_1MS FEMALE
SA053459170606aOEsa36_1MS FEMALE
SA053460170608aOEsa07_1MS FEMALE
SA053461170607aOEsa40_1MS FEMALE
SA053462170607aOEsa14_1MS FEMALE
SA053463170608aOEsa16_1MS FEMALE
SA053464170607aOEsa23_1MS FEMALE
SA053465170607aOEsa48_1MS FEMALE
SA053466170606aOEsa41_1MS MALE
SA053467170607aOEsa42_1MS MALE
SA053468170607aOEsa41_1MS MALE
SA053469170606aOEsa35_1MS MALE
SA053470170606aOEsa50_1MS MALE
SA053471170607aOEsa49_1MS MALE
SA053472170606aOEsa03_3MS MALE
SA053473170607aOEsa32_1MS MALE
SA053474170607aOEsa17_1MS MALE
SA053475170606aOEsa14_3MS MALE
SA053476170607aOEsa29_1MS MALE
SA053477170607aOEsa08_1MS MALE
SA053478170607aOEsa07_1ND FEMALE
SA053479170606aOEsa49_1ND FEMALE
SA053480170608aOEsa01_1ND FEMALE
SA053481170606aOEsa46_1ND FEMALE
SA053482170607aOEsa06_1ND FEMALE
SA053483170608aOEsa02_1ND FEMALE
SA053484170607aOEsa25_1ND FEMALE
SA053485170608aOEsa13_1ND FEMALE
SA053486170608aOEsa09_1ND FEMALE
SA053487170608aOEsa19_1ND FEMALE
SA053488170608aOEsa10_1ND FEMALE
SA053489170607aOEsa43_1ND FEMALE
SA053490170606aOEsa34_1ND FEMALE
SA053491170606aOEsa15_3ND MALE
SA053492170606aOEsa12_3ND MALE
SA053493170607aOEsa16_1ND MALE
SA053494170607aOEsa39_1ND MALE
SA053495170607aOEsa09_1ND MALE
SA053496170606aOEsa48_1ND MALE

Collection:

Collection ID:CO000942
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:TR000962
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:SP000955
Sampleprep Summary:1) Aliquot 20 uL into 2 sample sets one for GC and one for LC analysis 2) Add 1 mL of 3:3:2 extraction solvent to ach tube 3) Vortex 10 sec 4) Shake 5 min 5) Centrifuge at 14000 RCF for 2 min 6) Aliquot 450 uL of supernatant into two sets of tubes saving one set for backup 7) Pipet the rest of sample into falcon tube 8) Dry down samples saving 1 set of backups 9) Aliquot 2 mL of the pooled samples from the falcon tube into 2 mL tubes then centrifuge again 10) Aliquot 450 uL of the pooled samples from the falcon tube into 1.5 mL tubes to dry down 11) Place pooled samples in centrivap to dry

Combined analysis:

Analysis ID AN001480
Analysis type MS
Chromatography type GC
Chromatography system Leco Pegasus III GC
Column Restek Rtx-5Sil MS (30 x 0.25mm, 0.25um)
MS Type EI
MS instrument type GC-TOF
MS instrument name Leco Pegasus III GC TOF
Ion Mode POSITIVE
Units Counts

Chromatography:

Chromatography ID:CH001038
Methods Filename:Data_Dictionary_Fiehn_laboratory_GCTOF_MS_primary_metabolism_10-15-2013_general.pdf
Chromatography Comments:Excel generated
Instrument Name:Leco Pegasus III GC
Column Name:Restek Rtx-5Sil MS (30 x 0.25mm, 0.25um)
Column Pressure:7.7 PSI (initial condition)
Column Temperature:50 - 330°C
Flow Rate:1 ml/min
Injection Temperature:50°C ramped to 250°C by 12°C/s
Sample Injection:0.5µl
Oven Temperature:50°C for 1 min, then ramped at 20°C/min to 330°C, held constant for 5 min
Transferline Temperature:230°C
Washing Buffer:Ethyl Acetate
Sample Loop Size:30 m length x 0.25 mm internal diameter
Chromatography Type:GC

MS:

MS ID:MS001364
Analysis ID:AN001480
Instrument Name:Leco Pegasus III GC TOF
Instrument Type:GC-TOF
MS Type:EI
Ion Mode:POSITIVE
Ion Source Temperature:250°C
Ionization Energy:70eV
Mass Accuracy:Nominal
Source Temperature:250°C
Scan Range Moverz:85-500
Scanning Cycle:17 Hz
Scanning Range:80-500 Da
Skimmer Voltage:1850 V
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