Summary of Study ST000813

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 PR000576. The data can be accessed directly via it's Project DOI: 10.21228/M86X1F 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 IDST000813
Study TitleInsights into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) phenotypes through comprehensive metabolomics (part IV)
Study TypeObservational
Study SummaryThe pathogenesis of ME/CFS, a disease characterized by unexplained debilitating fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, lymphadenopathy and irritable bowel syndrome (IBS), is poorly understood. There are no validated diagnostic tests or interventions to mitigate disease. Here we report association modeling, biomarker discovery, biochemical enrichment analysis and topological network visualization of plasma metabolomic, fecal bacterial metagenomic and clinical data from 50 ME/CFS patients and 50 healthy controls. Through targeted and untargeted metabolomics analyses we confirm earlier reports of specific alterations in plasma levels of choline, carnitine and complex lipid metabolism in ME/CFS. We also demonstrate that patients with ME/CFS and IBS have a unique metabolomic profile that includes increased plasma levels of ceramide, a waxy lipid implicated in suppression of electron transport, insulin and leptin resistance and apoptosis. Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC=0.836) than either metagenomic (cross-validated AUC=0.745) or metabolomic (cross-validated AUC=0.820) analysis alone. Our findings may provide insights into the pathogenesis of ME/CFS and ME/CFS subtypes, and suggest pathways for the development of diagnostic and therapeutic strategies.
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 Date2017-07-19
Study CommentsKey: MECFS: 1 in this column indicates case, while 0 indicates control IBS: 1 in this column indicates the patient does have disease, 0 indicates free of IBS
PublicationsInsights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics. Scientific Reports volume 8, Article number: 10056 (2018). Dorottya Nagy-Szakal, Dinesh K. Barupal, Bohyun Lee, Xiaoyu Che, Brent L. Williams, Ellie J. R. Kahn, Joy E. Ukaigwe, Lucinda Bateman, Nancy G. Klimas, Anthony L. Komaroff, Susan Levine, Jose G. Montoya, Daniel L. Peterson, Bruce Levin, Mady Hornig, Oliver Fiehn & W. Ian Lipkin.
Raw Data AvailableYes
Raw Data File Type(s)cdf
Analysis Type DetailGC-MS
Release Date2018-08-16
Release Version1
Release Comments2017-10-03 - request from Oliver to keep study embargoed; embargo date updated from 2017-07-30 to 2018-04-03 by Dawn
Oliver Fiehn Oliver Fiehn
https://dx.doi.org/10.21228/M86X1F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000576
Project DOI:doi: 10.21228/M86X1F
Project Title:Insights into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) phenotypes through comprehensive metabolomics
Project Summary:The pathogenesis of ME/CFS, a disease characterized by unexplained debilitating fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, lymphadenopathy and irritable bowel syndrome (IBS), is poorly understood. There are no validated diagnostic tests or interventions to mitigate disease. Here we report association modeling, biomarker discovery, biochemical enrichment analysis and topological network visualization of plasma metabolomic, fecal bacterial metagenomic and clinical data from 50 ME/CFS patients and 50 healthy controls.
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
Publications:Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics. Scientific Reports volume 8, Article number: 10056 (2018). Dorottya Nagy-Szakal, Dinesh K. Barupal, Bohyun Lee, Xiaoyu Che, Brent L. Williams, Ellie J. R. Kahn, Joy E. Ukaigwe, Lucinda Bateman, Nancy G. Klimas, Anthony L. Komaroff, Susan Levine, Jose G. Montoya, Daniel L. Peterson, Bruce Levin, Mady Hornig, Oliver Fiehn & W. Ian Lipkin.

Subject:

Subject ID:SU000838
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Human

Factors:

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

mb_sample_id local_sample_id CaseStatus MECFS IBS
SA045002ESP-1255_096Case 1 -
SA045003ESP-0423_033Case 1 -
SA045004ESP-0605_047Case 1 -
SA045005ESP-0865_067Case 1 -
SA045006ESP-1138_088Case 1 -
SA045007ESP-0813_063Case 1 -
SA045008ESP-0124_010Case 1 -
SA045009ESP-0462_036Case 1 -
SA045010ESP-0514_040Case 1 -
SA045011ESP-1151_089Case 1 -
SA045012ESP-0592_046Case 1 -
SA045013ESP-0761_059Case 1 -
SA045014ESP-0891_069Case 1 -
SA045015ESP-1203_093Case 1 -
SA045016ESP-0800_062Case 1 -
SA045017ESP-0332_026Case 1 -
SA045018ESP-0072_006Case 1 -
SA045019ESP-0644_050Case 1 -
SA045020ESP-0189_015Case 1 -
SA045021ESP-0956_074Case 1 -
SA045022ESP-0137_011Case 1 -
SA045023ESP-1164_090Case 1 -
SA045024ESP-0904_070Case 1 -
SA045025ESP-0306_024Case 1 -
SA045026ESP-0657_051Case 1 -
SA045027ESP-0982_076Case 1 -
SA045028ESP-0280_022Case 1 -
SA045029ESP-0046_004Case 1 -
SA045030ESP-0033_003Case 1 -
SA045031ESP-0696_054Case 1 1
SA045032ESP-0683_053Case 1 1
SA045033ESP-1047_081Case 1 1
SA045034ESP-1034_080Case 1 1
SA045035ESP-0943_073Case 1 1
SA045036ESP-0878_068Case 1 1
SA045037ESP-0826_064Case 1 1
SA045038ESP-0007_001Case 1 1
SA045039ESP-0748_058Case 1 1
SA045040ESP-0709_055Case 1 1
SA045041ESP-0488_038Case 1 1
SA045042ESP-0215_017Case 1 1
SA045043ESP-0228_018Case 1 1
SA045044ESP-0241_019Case 1 1
SA045045ESP-0345_027Case 1 1
SA045046ESP-0995_077Case 1 1
SA045047ESP-0501_039Case 1 1
SA045048ESP-1125_087Case 1 1
SA045049ESP-0566_044Case 1 1
SA045050ESP-0085_007Case 1 1
SA045051ESP-0020_002Case 1 1
SA045052ESP-1307_100Control - -
SA045053ESP-1021_079Control - -
SA045054ESP-1008_078Control - -
SA045055ESP-1294_099Control - -
SA045056ESP-1268_097Control - -
SA045057ESP-1086_084Control - -
SA045058ESP-1099_085Control - -
SA045059ESP-1190_092Control - -
SA045060ESP-1177_091Control - -
SA045061ESP-1073_083Control - -
SA045062ESP-1216_094Control - -
SA045063ESP-1060_082Control - -
SA045064ESP-1112_086Control - -
SA045065ESP-1229_095Control - -
SA045066ESP-1281_098Control - -
SA045067ESP-0722_056Control - -
SA045068ESP-0358_028Control - -
SA045069ESP-0319_025Control - -
SA045070ESP-0293_023Control - -
SA045071ESP-0371_029Control - -
SA045072ESP-0384_030Control - -
SA045073ESP-0410_032Control - -
SA045074ESP-0397_031Control - -
SA045075ESP-0267_021Control - -
SA045076ESP-0254_020Control - -
SA045077ESP-0111_009Control - -
SA045078ESP-0098_008Control - -
SA045079ESP-0059_005Control - -
SA045080ESP-0150_012Control - -
SA045081ESP-0163_013Control - -
SA045082ESP-0202_016Control - -
SA045083ESP-0176_014Control - -
SA045084ESP-0436_034Control - -
SA045085ESP-0449_035Control - -
SA045086ESP-0787_061Control - -
SA045087ESP-0774_060Control - -
SA045088ESP-0735_057Control - -
SA045089ESP-0839_065Control - -
SA045090ESP-0852_066Control - -
SA045091ESP-0930_072Control - -
SA045092ESP-0917_071Control - -
SA045093ESP-0670_052Control - -
SA045094ESP-0631_049Control - -
SA045095ESP-0527_041Control - -
SA045096ESP-0475_037Control - -
SA045097ESP-0540_042Control - -
SA045098ESP-0553_043Control - -
SA045099ESP-0618_048Control - -
SA045100ESP-0579_045Control - -
SA045101ESP-0969_075Control - -
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Collection:

Collection ID:CO000832
Collection Summary:Subjects included 50 cases and 50 controls from the Chronic Fatigue Initiative (CFI) Cohort (28) recruited at 4 sites across the US who met the 1994 CDC Fukuda and/or Canadian consensus criteria for ME/CFS.
Sample Type:Blood
Blood Serum Or Plasma:Plasma

Treatment:

Treatment ID:TR000852
Treatment Summary:Subjects included 50 cases and 50 controls from the Chronic Fatigue Initiative (CFI) Cohort (28) recruited at 4 sites across the US who met the 1994 CDC Fukuda and/or Canadian consensus criteria for ME/CFS.

Sample Preparation:

Sampleprep ID:SP000845
Sampleprep Summary:1.Thaw each 20 μL plasma aliquot at room temperature (see Aliquoting TEDDY samples SOP). Once thawed (~10min) place liquid 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, splitting into two aliquots of 350 μL, keeping one at –20°C for backup 11. Dry samples to complete dryness in the speed vacuum concentration system
Sampleprep Protocol Filename:SP_SOP_Extraction_of_plasma.pdf

Combined analysis:

Analysis ID AN001286
Analysis type MS
Chromatography type GC
Chromatography system Leco Pegasus III GC
Column Restek Rtx-5Sil (30m 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:CH000902
Instrument Name:Leco Pegasus III GC
Column Name:Restek Rtx-5Sil (30m 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
Randomization Order:Excel generated
Chromatography Type:GC

MS:

MS ID:MS001179
Analysis ID:AN001286
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
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