Summary of Study ST003788

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 PR002365. The data can be accessed directly via it's Project DOI: 10.21228/M8XN97 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.

Study ID	ST003788
Study Title	Pre-treatment untargeted cerebrospinal fluid metabolomic profiling in tuberculous meningitis reveals multiple pathways associated with mortality
Study Summary	Background Dysregulation of cerebrospinal fluid (CSF) tryptophan metabolism contributes to the high mortality of tuberculous meningitis (TBM). We aimed to identify novel metabolic pathways associated with TBM mortality through untargeted metabolome-wide analysis. Methods We measured 619 metabolites using untargeted liquid chromatography-mass spectrometry in pre-treatment CSF from adults with TBM from Indonesia (n=388; 34 HIV-positive) and Vietnam (n=679; 250 HIV-positive). Sixty-day mortality was modelled using Cox regression, adjusting for age and HIV-status. Metabolites were ranked in a screening subset (n=194, Indonesia), and validated in the same cohort (n=194) and externally (n=679, Vietnam). Secondary analysis included variable selection, clustering to classify associated metabolites into subgroups, comparison with non-infectious controls, and correlation with patient characteristics, CSF cytokines, CSF protein, and serum metabolite concentrations. Findings Sixty-day mortality was 21.6% and was associated with the concentration of ten CSF metabolites, including tryptophan. The strongest association was with 3-hydroxyoctanoate (FA 8:0;3OH), part of a cluster of hydroxylated fatty acids, further including hydroxy-isocaproate (FA 6:0;OH), hydroxyisobutyrate (FA 4:0;OH), and C4-OH-carnitine. These fatty acids correlated weakly with CSF TNF-α, IL-6, leukocyte counts, bacterial load and CSF protein. Mediation analysis showed that the variation in fatty acids was linked directly to mortality rather than through disease severity. Conclusion We identified and validated nine new metabolites associated with TBM mortality, independent of HIV-status, disease severity, and tryptophan. These metabolites suggest that altered fatty acid beta-oxidation is linked to TBM associated mortality. Interventions targeting cerebral fatty acid metabolism may improve survival from TBM.
Institute	Broad Institute of MIT and Harvard
Last Name	Avila-Pacheco
First Name	Julian
Address	415 Main Street
Email	jravilap@broadinstitute.org
Phone	(617) 714-1729
Submit Date	2025-03-03
Analysis Type Detail	LC-MS
Release Date	2025-05-23
Release Version	1

Select appropriate tab below to view additional metadata details:

Project:

Project ID:	PR002365
Project DOI:	doi: 10.21228/M8XN97
Project Title:	Pre-treatment untargeted cerebrospinal fluid metabolomic profiling in tuberculous meningitis reveals multiple pathways associated with mortality
Project Type:	Metabolomic profiling of cerebrospinal fluid metabolomic in tuberculous meningitis.
Project Summary:	Background Dysregulation of cerebrospinal fluid (CSF) tryptophan metabolism contributes to the high mortality of tuberculous meningitis (TBM). We aimed to identify novel metabolic pathways associated with TBM mortality through untargeted metabolome-wide analysis. Methods We measured 619 metabolites using untargeted liquid chromatography-mass spectrometry in pre-treatment CSF from adults with TBM from Indonesia (n=388; 34 HIV-positive) and Vietnam (n=679; 250 HIV-positive). Sixty-day mortality was modelled using Cox regression, adjusting for age and HIV-status. Metabolites were ranked in a screening subset (n=194, Indonesia), and validated in the same cohort (n=194) and externally (n=679, Vietnam). Secondary analysis included variable selection, clustering to classify associated metabolites into subgroups, comparison with non-infectious controls, and correlation with patient characteristics, CSF cytokines, CSF protein, and serum metabolite concentrations. Findings Sixty-day mortality was 21.6% and was associated with the concentration of ten CSF metabolites, including tryptophan. The strongest association was with 3-hydroxyoctanoate (FA 8:0;3OH), part of a cluster of hydroxylated fatty acids, further including hydroxy-isocaproate (FA 6:0;OH), hydroxyisobutyrate (FA 4:0;OH), and C4-OH-carnitine. These fatty acids correlated weakly with CSF TNF-α, IL-6, leukocyte counts, bacterial load and CSF protein. Mediation analysis showed that the variation in fatty acids was linked directly to mortality rather than through disease severity. Conclusion We identified and validated nine new metabolites associated with TBM mortality, independent of HIV-status, disease severity, and tryptophan. These metabolites suggest that altered fatty acid beta-oxidation is linked to TBM associated mortality. Interventions targeting cerebral fatty acid metabolism may improve survival from TBM.
Institute:	Broad Institute of MIT and Harvard
Last Name:	Avila-Pacheco
First Name:	Julian
Address:	415 Main Street
Email:	jravilap@broadinstitute.org
Phone:	+1 (617) 714-1729
Contributors:	Le Thanh Hoang Nhat, Kirsten CJ van Abeelen, Edwin Ardiansyah,, Julian Avila-Pacheco, Sofiati Dian, Gesa Carstens, Lara Schramke, Hoang Thanh Hai, Nguyen Tran Binh Minh, Thai Minh Triet, Amy Deik, Jesse Krejci, Jeff Pruyne, Lucas Dailey, Bachti Alisjahbana, Mihai G Netea, Riwanti Estiasari, Trinh Thi Bich Tram, Joseph Donovan, Dorothee Heemskerk, Tran Thi Hong Chau, Nguyen Duc Bang, Ahmad Rizal Ganiem, Raph L Hamers, Rovina Ruslami, Darma Imran, Kartika Maharani, Vinod Kumar, Reinout van Crevel, Guy Thwaites,, Clary B. Clish, Nguyen Thuy Thuong Thuong, Arjan van Laarhoven

Subject:

Subject ID:	SU004060
Subject Type:	Human
Subject Species:	Homo sapiens
Taxonomy ID:	9606
Age Or Age Range:	14-87

Factors:

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

mb_sample_id	local_sample_id	Sample source	cohort	sex	HIV	diagnosis	outcome_day_60
SA444418	IN_0293	CSF	Indonesia	Female	HIV-negative	Bacterial meningitis	Alive
SA444419	IN_0290	CSF	Indonesia	Female	HIV-negative	Bacterial meningitis	Alive
SA444420	IN_0296	CSF	Indonesia	Female	HIV-negative	Bacterial meningitis	Dead
SA444421	IN_0195	CSF	Indonesia	Female	HIV-negative	Bacterial meningitis	Follow-up < 60 days
SA444422	IN_0060	CSF	Indonesia	Female	HIV-negative	Bacterial meningitis	Follow-up < 60 days
SA444423	IN_0247	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Alive
SA444424	IN_0001	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Alive
SA444425	IN_0220	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Alive
SA444426	IN_0244	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Alive
SA444427	IN_0067	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Alive
SA444428	IN_0092	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Dead
SA444429	IN_0140	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Dead
SA444430	IN_0189	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Dead
SA444431	IN_0176	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Follow-up < 60 days
SA444432	IN_0087	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Follow-up < 60 days
SA444433	IN_0194	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Follow-up < 60 days
SA444434	IN_0080	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Follow-up < 60 days
SA444435	IN_0110	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Follow-up < 60 days
SA444436	IN_0090	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Follow-up < 60 days
SA444437	IN_0204	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Follow-up < 60 days
SA444438	IN_0207	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Follow-up < 60 days
SA444439	IN_0097	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Follow-up < 60 days
SA444440	IN_0234	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Follow-up < 60 days
SA444441	IN_0134	CSF	Indonesia	Female	HIV-negative	Non-infectious control	Follow-up < 60 days
SA444442	IN_0252	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444443	IN_0355	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444444	IN_0356	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444445	IN_0357	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444446	IN_0023	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444447	IN_0091	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444448	IN_0088	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444449	IN_0366	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444450	IN_0359	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444451	IN_0245	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444452	IN_0365	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444453	IN_0345	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444454	IN_0369	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444455	IN_0239	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444456	IN_0371	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444457	IN_0372	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444458	IN_0237	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444459	IN_0287	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444460	IN_0228	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444461	IN_0378	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444462	IN_0346	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444463	IN_0338	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444464	IN_0086	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444465	IN_0278	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444466	IN_0268	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444467	IN_0308	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444468	IN_0273	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444469	IN_0274	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444470	IN_0304	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444471	IN_0035	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444472	IN_0299	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444473	IN_0263	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444474	IN_0281	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444475	IN_0038	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444476	IN_0295	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444477	IN_0284	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444478	IN_0285	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444479	IN_0289	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444480	IN_0311	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444481	IN_0314	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444482	IN_0343	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444483	IN_0026	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444484	IN_0259	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444485	IN_0340	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444486	IN_0085	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444487	IN_0224	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444488	IN_0336	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444489	IN_0084	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444490	IN_0330	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444491	IN_0050	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444492	IN_0327	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444493	IN_0326	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444494	IN_0321	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444495	IN_0028	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444496	IN_0319	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444497	IN_0056	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444498	IN_0053	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444499	IN_0227	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444500	IN_0376	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444501	IN_0040	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444502	IN_0439	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444503	IN_0421	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444504	IN_0423	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444505	IN_0382	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444506	IN_0427	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444507	IN_0428	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444508	IN_0174	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444509	IN_0123	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444510	IN_0171	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444511	IN_0433	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444512	IN_0125	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444513	IN_0435	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444514	IN_0436	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444515	IN_0167	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444516	IN_0440	CSF	Indonesia	Female	HIV-negative	TBM	Alive
SA444517	IN_0415	CSF	Indonesia	Female	HIV-negative	TBM	Alive

Showing page 1 of 13 Results: 1 2 3 4 5 Next Last Showing results 1 to 100 of 1233

Collection:

Collection ID:	CO004053
Collection Summary:	According to routine care, all patients with suspected meningitis underwent lumbar puncture (spinal tap) before starting antimicrobial or corticosteroid treatment.
Sample Type:	Cerebrospinal fluid

Treatment:

Treatment ID:	TR004069
Treatment Summary:	CSF samples were processed according to in-house developed protocols and according to the “Standardized approaches for clinical sampling and endpoint ascertainment in tuberculous meningitis studies” (PMID: 32399496), with the exception that centrifugation speed has changed over time, ranging from 865-3000 x g, for 15 minutes. The resulting supernatants were stored at -80°C.

Sample Preparation:

Sampleprep ID:	SP004066
Sampleprep Summary:	LC–MS samples were prepared from CSF samples for each profiling method as follows: - HILIC-pos: CSF (10 μL) samples were extracted with the addition of nine volumes of 74.9:24.9:0.2 v/v/v acetonitrile/methanol/formic acid containing stable isotope-labeled internal standards (valine-d8, Isotec; and phenylalanine-d8, Cambridge Isotope Laboratories). The samples were centrifuged (10 min, 9,000g, 4°C), and the supernatants (10 μL)injected directly onto column. - C8-pos: CSF samples (10 μL) were extracted using 190 μL isopropanol containing 1-dodecanoyl-2-tridecanoyl-sn-glycero-3-phosphocholine as an internal standard (Avanti Polar Lipids; Alabaster, AL). After centrifugation (10 min, 9,000g, ambient temperature), supernatants (2 μl) were injected directly onto column. - C18-neg: CSF samples (30 μL) were extracted using 90 μl methanol containing 15R-15-methyl ProstaglandinA2,15R-15-methyl ProstaglandinF2α, 15S-15-methyl ProstaglandinD2, 15S-15-methyl Prostaglandin E1, and 15S-15-methyl Prostaglandin E2 as internal standards (Cayman Chemical Co.) and centrifuged (10 min, 9,000g, 4°C). The supernatants (10 μL) were injected onto column. - HILIC-neg: CSF samples (30 μL) were extracted with the addition of four volumes of 80% methanol containing inosine-15N4, thymine-d4 and glycocholate-d4 internal standards (Cambridge Isotope Laboratories). The samples were centrifuged (10 min, 9,000g, 4°C) and the supernatants 10 μL) were injected directly onto column.

Sampleprep ID:

SP004066

Sampleprep Summary:

LC–MS samples were prepared from CSF samples for each profiling method as follows: - HILIC-pos: CSF (10 μL) samples were extracted with the addition of nine volumes of 74.9:24.9:0.2 v/v/v acetonitrile/methanol/formic acid containing stable isotope-labeled internal standards (valine-d8, Isotec; and phenylalanine-d8, Cambridge Isotope Laboratories). The samples were centrifuged (10 min, 9,000g, 4°C), and the supernatants (10 μL)injected directly onto column. - C8-pos: CSF samples (10 μL) were extracted using 190 μL isopropanol containing 1-dodecanoyl-2-tridecanoyl-sn-glycero-3-phosphocholine as an internal standard (Avanti Polar Lipids; Alabaster, AL). After centrifugation (10 min, 9,000g, ambient temperature), supernatants (2 μl) were injected directly onto column. - C18-neg: CSF samples (30 μL) were extracted using 90 μl methanol containing 15R-15-methyl ProstaglandinA2,15R-15-methyl ProstaglandinF2α, 15S-15-methyl ProstaglandinD2, 15S-15-methyl Prostaglandin E1, and 15S-15-methyl Prostaglandin E2 as internal standards (Cayman Chemical Co.) and centrifuged (10 min, 9,000g, 4°C). The supernatants (10 μL) were injected onto column. - HILIC-neg: CSF samples (30 μL) were extracted with the addition of four volumes of 80% methanol containing inosine-15N4, thymine-d4 and glycocholate-d4 internal standards (Cambridge Isotope Laboratories). The samples were centrifuged (10 min, 9,000g, 4°C) and the supernatants 10 μL) were injected directly onto column.

Combined analysis:

Analysis ID	AN006443	AN006444	AN006445	AN006446
Analysis type	MS	MS	MS	MS
Chromatography type	HILIC	Reversed phase	HILIC	Reversed phase
Chromatography system	Shimadzu Nexera X2	Shimadzu Nexera X2	Shimadzu Nexera X2	Shimadzu Nexera X2
Column	Waters Atlantis HILIC (150 x 2.1mm, 3um)	Waters Acquity BEH C8 (100 x 2.1mm, 1.7um)	Phenomenex Luna NH2 (150 x 2.1mm, 3um)	Waters ACQUITY UPLC BEH C18 (150 x 1.7mm, 2.1um)
MS Type	ESI	ESI	ESI	ESI
MS instrument type	Orbitrap	Orbitrap	Orbitrap	Orbitrap
MS instrument name	Thermo Orbitrap ID-X Tribrid	Thermo Orbitrap ID-X Tribrid	Thermo Q Exactive Plus Orbitrap	Thermo Orbitrap ID-X Tribrid
Ion Mode	POSITIVE	POSITIVE	NEGATIVE	NEGATIVE
Units	Abudances	Abudances	Abudances	Abudances

Chromatography:

Chromatography ID:	CH004889
Instrument Name:	Shimadzu Nexera X2
Column Name:	Waters Atlantis HILIC (150 x 2.1mm, 3um)
Column Temperature:	30℃
Flow Gradient:	Isocratically with 5% mobile phase A for 1 minute followed by a linear gradient to 40% mobile phase B over 10 minutes
Flow Rate:	250 µL/min
Solvent A:	100% water; 10 mM Ammonium formate; 0.1% Formic acid
Solvent B:	100% acetonitrile; 0.1% Formic acid
Chromatography Type:	HILIC

Chromatography ID:	CH004890
Instrument Name:	Shimadzu Nexera X2
Column Name:	Waters Acquity BEH C8 (100 x 2.1mm, 1.7um)
Column Temperature:	40℃
Flow Gradient:	The column was eluted at a flow rate of 450 µL/min isocratically for 1 minute at 80% mobile phase A, followed by a linear gradient to 80% mobile-phase B over 2 minutes, a linear gradient to 100% mobile phase B over 7 minutes, and then 3 minutes at 100% mobile-phase B.
Flow Rate:	450 µL/min
Solvent A:	95% water/5% methanol; 10 mM Ammonium acetate; 0.1% Acetic acid
Solvent B:	100% methanol; 0.1% Acetic acid
Chromatography Type:	Reversed phase

Chromatography ID:	CH004891
Instrument Name:	Shimadzu Nexera X2
Column Name:	Phenomenex Luna NH2 (150 x 2.1mm, 3um)
Column Temperature:	30℃
Flow Gradient:	The column was eluted with initial conditions of 10% mobile phase A and 90% mobile phase B followed by a 10 min linear gradient to 100% mobile phase A.
Flow Rate:	400 µL/min
Solvent A:	100% water; 20 mM ammonium acetate; 20 mM ammonium hydroxide
Solvent B:	75% acetonitrile/25% methanol; 10 mM ammonium hydroxide
Chromatography Type:	HILIC

Chromatography ID:	CH004892
Instrument Name:	Shimadzu Nexera X2
Column Name:	Waters ACQUITY UPLC BEH C18 (150 x 1.7mm, 2.1um)
Column Temperature:	45℃
Flow Gradient:	The column was eluted isocratically at a flow rate of 450 µL/min with 20% mobile phase A for 3 minutes followed by a linear gradient to 100% mobile phase B over 12 minutes.
Flow Rate:	450 µL/min
Solvent A:	100% water; 0.01% formic acid
Solvent B:	100% acetonitrile; 0.01% acetic acid
Chromatography Type:	Reversed phase

MS:

MS ID:	MS006142
Analysis ID:	AN006443
Instrument Name:	Thermo Orbitrap ID-X Tribrid
Instrument Type:	Orbitrap
MS Type:	ESI
MS Comments:	Raw data were processed using TraceFinder 3.3 software (Thermo Fisher Scientific; Waltham, MA) and Progenesis QI (Nonlinear Dynamics; Newcastle upon Tyne, UK). Metabolite identities were confirmed using authentic reference standards or reference samples.
Ion Mode:	POSITIVE

MS ID:	MS006143
Analysis ID:	AN006444
Instrument Name:	Thermo Orbitrap ID-X Tribrid
Instrument Type:	Orbitrap
MS Type:	ESI
MS Comments:	Raw data were processed using TraceFinder 3.3 software (Thermo Fisher Scientific; Waltham, MA) and Progenesis QI (Nonlinear Dynamics; Newcastle upon Tyne, UK). Metabolite identities were confirmed using authentic reference standards or reference samples.
Ion Mode:	POSITIVE

MS ID:	MS006144
Analysis ID:	AN006445
Instrument Name:	Thermo Q Exactive Plus Orbitrap
Instrument Type:	Orbitrap
MS Type:	ESI
MS Comments:	Raw data were processed using TraceFinder 3.3 software (Thermo Fisher Scientific; Waltham, MA) and Progenesis QI (Nonlinear Dynamics; Newcastle upon Tyne, UK). Metabolite identities were confirmed using authentic reference standards or reference samples.
Ion Mode:	NEGATIVE

MS ID:	MS006145
Analysis ID:	AN006446
Instrument Name:	Thermo Orbitrap ID-X Tribrid
Instrument Type:	Orbitrap
MS Type:	ESI
MS Comments:	Raw data were processed using TraceFinder 3.3 software (Thermo Fisher Scientific; Waltham, MA) and Progenesis QI (Nonlinear Dynamics; Newcastle upon Tyne, UK). Metabolite identities were confirmed using authentic reference standards or reference samples.
Ion Mode:	NEGATIVE