Summary of Study ST000802
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
| Study ID | ST000802 |
| Study Title | Insights into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) phenotypes through comprehensive metabolomics (part III)) |
| Study Type | Observational |
| Study 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. 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 |
| Department | Genome and Biomedical Sciences Facility |
| Laboratory | WCMC Metabolomics Core |
| Last Name | Fiehn |
| First Name | Oliver |
| Address | 1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616 |
| ofiehn@ucdavis.edu | |
| Phone | (530) 754-8258 |
| Submit Date | 2017-07-19 |
| Study Comments | Key: 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 |
| 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. |
| Raw Data Available | Yes |
| Raw Data File Type(s) | wiff |
| Analysis Type Detail | LC-MS |
| Release Date | 2018-08-16 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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: | SU000827 |
| 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 |
|---|---|---|
| SA044110 | ESP-0891 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044111 | ESP-0189 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044112 | ESP-0345 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044113 | ESP-0332 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044114 | ESP-0228 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044115 | ESP-0280 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044116 | ESP-0865 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044117 | ESP-0683 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044118 | ESP-0137 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044119 | ESP-0566 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044120 | ESP-0514 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044121 | ESP-0501 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044122 | ESP-0592 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044123 | ESP-1047 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044124 | ESP-0995 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044125 | ESP-0124 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044126 | ESP-0605 | Case | SEX:Female | AGE_DICH:20_50 |
| SA044127 | ESP-0007 | Case | SEX:Female | AGE_DICH:over50 |
| SA044128 | ESP-0709 | Case | SEX:Female | AGE_DICH:over50 |
| SA044129 | ESP-0696 | Case | SEX:Female | AGE_DICH:over50 |
| SA044130 | ESP-0748 | Case | SEX:Female | AGE_DICH:over50 |
| SA044131 | ESP-0878 | Case | SEX:Female | AGE_DICH:over50 |
| SA044132 | ESP-1125 | Case | SEX:Female | AGE_DICH:over50 |
| SA044133 | ESP-1138 | Case | SEX:Female | AGE_DICH:over50 |
| SA044134 | ESP-1151 | Case | SEX:Female | AGE_DICH:over50 |
| SA044135 | ESP-1164 | Case | SEX:Female | AGE_DICH:over50 |
| SA044136 | ESP-1034 | Case | SEX:Female | AGE_DICH:over50 |
| SA044137 | ESP-0982 | Case | SEX:Female | AGE_DICH:over50 |
| SA044138 | ESP-0800 | Case | SEX:Female | AGE_DICH:over50 |
| SA044139 | ESP-0488 | Case | SEX:Female | AGE_DICH:over50 |
| SA044140 | ESP-0943 | Case | SEX:Female | AGE_DICH:over50 |
| SA044141 | ESP-0956 | Case | SEX:Female | AGE_DICH:over50 |
| SA044142 | ESP-0761 | Case | SEX:Female | AGE_DICH:over50 |
| SA044143 | ESP-0657 | Case | SEX:Female | AGE_DICH:over50 |
| SA044144 | ESP-0241 | Case | SEX:Female | AGE_DICH:over50 |
| SA044145 | ESP-0085 | Case | SEX:Female | AGE_DICH:over50 |
| SA044146 | ESP-0046 | Case | SEX:Female | AGE_DICH:over50 |
| SA044147 | ESP-0020 | Case | SEX:Female | AGE_DICH:over50 |
| SA044148 | ESP-0306 | Case | SEX:Female | AGE_DICH:over50 |
| SA044149 | ESP-0215 | Case | SEX:Female | AGE_DICH:over50 |
| SA044150 | ESP-0423 | Case | SEX:Female | AGE_DICH:over50 |
| SA044151 | ESP-1203 | Case | SEX:Male | AGE_DICH:20_50 |
| SA044152 | ESP-1255 | Case | SEX:Male | AGE_DICH:over50 |
| SA044153 | ESP-0826 | Case | SEX:Male | AGE_DICH:over50 |
| SA044154 | ESP-0813 | Case | SEX:Male | AGE_DICH:over50 |
| SA044155 | ESP-0072 | Case | SEX:Male | AGE_DICH:over50 |
| SA044156 | ESP-0033 | Case | SEX:Male | AGE_DICH:over50 |
| SA044157 | ESP-0644 | Case | SEX:Male | AGE_DICH:over50 |
| SA044158 | ESP-0462 | Case | SEX:Male | AGE_DICH:over50 |
| SA044159 | ESP-0904 | Case | SEX:Male | AGE_DICH:over50 |
| SA044160 | ESP-0098 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044161 | ESP-0111 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044162 | ESP-0254 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044163 | ESP-0176 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044164 | ESP-0202 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044165 | ESP-0774 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044166 | ESP-0852 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044167 | ESP-0059 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044168 | ESP-1294 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044169 | ESP-1021 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044170 | ESP-0579 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044171 | ESP-0410 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044172 | ESP-0553 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044173 | ESP-1268 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044174 | ESP-0618 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044175 | ESP-1190 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044176 | ESP-0319 | Control | SEX:Female | AGE_DICH:20_50 |
| SA044177 | ESP-1060 | Control | SEX:Female | AGE_DICH:over50 |
| SA044178 | ESP-0436 | Control | SEX:Female | AGE_DICH:over50 |
| SA044179 | ESP-1177 | Control | SEX:Female | AGE_DICH:over50 |
| SA044180 | ESP-0449 | Control | SEX:Female | AGE_DICH:over50 |
| SA044181 | ESP-1086 | Control | SEX:Female | AGE_DICH:over50 |
| SA044182 | ESP-1112 | Control | SEX:Female | AGE_DICH:over50 |
| SA044183 | ESP-0475 | Control | SEX:Female | AGE_DICH:over50 |
| SA044184 | ESP-1099 | Control | SEX:Female | AGE_DICH:over50 |
| SA044185 | ESP-1229 | Control | SEX:Female | AGE_DICH:over50 |
| SA044186 | ESP-0917 | Control | SEX:Female | AGE_DICH:over50 |
| SA044187 | ESP-0722 | Control | SEX:Female | AGE_DICH:over50 |
| SA044188 | ESP-1008 | Control | SEX:Female | AGE_DICH:over50 |
| SA044189 | ESP-0293 | Control | SEX:Female | AGE_DICH:over50 |
| SA044190 | ESP-0527 | Control | SEX:Female | AGE_DICH:over50 |
| SA044191 | ESP-0358 | Control | SEX:Female | AGE_DICH:over50 |
| SA044192 | ESP-0371 | Control | SEX:Female | AGE_DICH:over50 |
| SA044193 | ESP-0670 | Control | SEX:Female | AGE_DICH:over50 |
| SA044194 | ESP-0267 | Control | SEX:Female | AGE_DICH:over50 |
| SA044195 | ESP-0787 | Control | SEX:Female | AGE_DICH:over50 |
| SA044196 | ESP-0397 | Control | SEX:Female | AGE_DICH:over50 |
| SA044197 | ESP-0969 | Control | SEX:Female | AGE_DICH:over50 |
| SA044198 | ESP-0930 | Control | SEX:Female | AGE_DICH:over50 |
| SA044199 | ESP-0384 | Control | SEX:Female | AGE_DICH:over50 |
| SA044200 | ESP-0839 | Control | SEX:Female | AGE_DICH:over50 |
| SA044201 | ESP-1281 | Control | SEX:Male | AGE_DICH:20_50 |
| SA044202 | ESP-1073 | Control | SEX:Male | AGE_DICH:20_50 |
| SA044203 | ESP-1307 | Control | SEX:Male | AGE_DICH:20_50 |
| SA044204 | ESP-0631 | Control | SEX:Male | AGE_DICH:over50 |
| SA044205 | ESP-0735 | Control | SEX:Male | AGE_DICH:over50 |
| SA044206 | ESP-0150 | Control | SEX:Male | AGE_DICH:over50 |
| SA044207 | ESP-0163 | Control | SEX:Male | AGE_DICH:over50 |
| SA044208 | ESP-0540 | Control | SEX:Male | AGE_DICH:over50 |
| SA044209 | ESP-1216 | Control | SEX:Male | AGE_DICH:over50 |
| Showing results 1 to 100 of 100 |
Collection:
| Collection ID: | CO000821 |
| 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: | TR000841 |
| 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: | SP000834 |
| 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 | AN001274 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | Waters Acquity |
| Column | Waters Acquity BEH C18 (150 x 2.1mm,1.7um) |
| MS Type | ESI |
| MS instrument type | Triple quadrupole |
| MS instrument name | ABI Sciex API 4000 QTrap |
| Ion Mode | NEGATIVE |
| Units | Concentration (nM) |
Chromatography:
| Chromatography ID: | CH000890 |
| Instrument Name: | Waters Acquity |
| Column Name: | Waters Acquity BEH C18 (150 x 2.1mm,1.7um) |
| Column Temperature: | 60 °C |
| Flow Gradient: | 0 min 25% (B), 1 min 40% (B), 1-2.5 min 42% (B), 2.5-4.5 50% (B), 4.5-10.5 65% (B), 10.5-12.5 75% (B), 12.5-14 85% (B), 14-14.5 95% (B), 14.5-15 25% (B), 15-16 25% (B) |
| Flow Rate: | 0.25 uL |
| Sample Injection: | 5 µL |
| Solvent A: | 100% water; 0.1% acetic acid |
| Solvent B: | 90% acetonitrile/ 10% isopropanol |
| Analytical Time: | 16 min |
| Washing Buffer: | Ethyl Acetate |
| Weak Wash Solvent Name: | 20% methanol, 10% isopropanol |
| Weak Wash Volume: | 600 µL |
| Strong Wash Solvent Name: | 50:50 Acetonitrile:Methanol |
| Strong Wash Volume: | 600 µL |
| Sample Loop Size: | 17 µL |
| Randomization Order: | Excel generated |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS001167 |
| Analysis ID: | AN001274 |
| Instrument Name: | ABI Sciex API 4000 QTrap |
| Instrument Type: | Triple quadrupole |
| MS Type: | ESI |
| Ion Mode: | NEGATIVE |
