#METABOLOMICS WORKBENCH cclish_20250406_182430 DATATRACK_ID:5820 STUDY_ID:ST003867 ANALYSIS_ID:AN006355 PROJECT_ID:PR002423
VERSION             	1
CREATED_ON             	April 9, 2025, 8:53 pm
#PROJECT
PR:PROJECT_TITLE                 	Fatty-acid oxidation is a metabolic hallmark of human proliferative retinopathy
PR:PROJECT_SUMMARY               	In this experiment, we used nontargeted metabolomics to measure metabolite
PR:PROJECT_SUMMARY               	profiles of vitreous humor from subjects with proliferative diabetic
PR:PROJECT_SUMMARY               	retinopathy. Vitreous samples were collected adjacent to leaky pathological
PR:PROJECT_SUMMARY               	neovascular tufts that characterize PR. Amongst the top 25 most significantly
PR:PROJECT_SUMMARY               	dysregulated metabolites, we observed an accumulation of acylcarnitines in human
PR:PROJECT_SUMMARY               	neovascular PR samples compared to control subjects with epiretinal membranes.
PR:INSTITUTE                     	Broad Institute of MIT and Harvard
PR:DEPARTMENT                    	Metabolomics Platform
PR:LAST_NAME                     	Clish
PR:FIRST_NAME                    	Clary
PR:ADDRESS                       	300 BineyStreet, Cambridge, MA, 02142, USA
PR:EMAIL                         	clary@broadinstitute.org
PR:PHONE                         	617-714-7654
PR:PUBLICATIONS                  	submitted
PR:CONTRIBUTORS                  	Gael Cagnone, Sheetal Pundir, Charlotte Betus, Tapan Agnihotri, Anli Ren, Jin
PR:CONTRIBUTORS                  	SungKim, Noémie-Rose Harvey, Emilie Heckel, Mei Xi Chen, Anu Situ, Perrine
PR:CONTRIBUTORS                  	Gaub, Nicholas Kim, Ashim Das, Severine Leclerc, Florian Wünnemann, Louis
PR:CONTRIBUTORS                  	Berillon, Gregor Andelfinger, Sergio Crespo-Garcia, Alexandre Dubrac, Flavio A.
PR:CONTRIBUTORS                  	Rezende, Clary B. Clish, Bruno Maranda, José Carlos Rivera, Lois E. H. Smith,
PR:CONTRIBUTORS                  	Przemyslaw Sapieha, JeanSébastien Joyal
#STUDY
ST:STUDY_TITLE                   	Fatty-acid oxidation is a metabolic hallmark of human proliferative retinopathy
ST:STUDY_TYPE                    	comparison of vitreous humor from subjects with proliferative diabetic
ST:STUDY_TYPE                    	retinopathy to epiretinal membrane (control)
ST:STUDY_SUMMARY                 	Healthy blood vessels supply neurons to preserve metabolic function. In blinding
ST:STUDY_SUMMARY                 	proliferative retinopathies (PRs), pathological neovascular tufts often emerge
ST:STUDY_SUMMARY                 	in lieu of needed physiological revascularization. Here we show that metabolic
ST:STUDY_SUMMARY                 	shifts in the neovascular niche define angiogenic fate. Fatty acid oxidation
ST:STUDY_SUMMARY                 	(FAO) metabolites accumulated in human and murine retinopathy samples.
ST:STUDY_SUMMARY                 	Neovascular tufts with a distinct single-cell transcriptional signature highly
ST:STUDY_SUMMARY                 	expressed FAO enzymes. The deletion of Sirt3, an FAO regulator, shifted the
ST:STUDY_SUMMARY                 	neovascular niche metabolism from FAO to glycolysis and suppressed tuft
ST:STUDY_SUMMARY                 	formation. This metabolic transition increased Vegf expression in astrocytes and
ST:STUDY_SUMMARY                 	reprogrammed pathological neovessels to a physiological phenotype, hastening
ST:STUDY_SUMMARY                 	vascular regeneration of the ischemic retina and improving vision. Hence,
ST:STUDY_SUMMARY                 	strategies to change the metabolic environment of vessels could promote a
ST:STUDY_SUMMARY                 	regenerative phenotype in vascular diseases. In this experiment, we used
ST:STUDY_SUMMARY                 	nontargeted metabolomics to measure metabolite profiles of vitreous humor from
ST:STUDY_SUMMARY                 	subjects with proliferative diabetic retinopathy. Vitreous samples were
ST:STUDY_SUMMARY                 	collected adjacent to leaky pathological neovascular tufts that characterize PR.
ST:STUDY_SUMMARY                 	Amongst the top 25 most significantly dysregulated metabolites, we observed an
ST:STUDY_SUMMARY                 	accumulation of acylcarnitines in human neovascular PR samples compared to
ST:STUDY_SUMMARY                 	control subjects with epiretinal membranes. Fatty acylcarnitines are by-products
ST:STUDY_SUMMARY                 	of fatty-acid beta-oxidation (FAO), the process of oxidizing fatty acids in
ST:STUDY_SUMMARY                 	mitochondria to produce acetyl-CoA (Fig. 1b). 5 of the 6 most enriched metabolic
ST:STUDY_SUMMARY                 	pathways in human PR pertained to FA metabolism, including long and short-chain
ST:STUDY_SUMMARY                 	saturated FAO pathways.
ST:INSTITUTE                     	Broad Institute of MIT and Harvard
ST:DEPARTMENT                    	Metabolomics Platform
ST:LAST_NAME                     	Clish
ST:FIRST_NAME                    	Clary
ST:ADDRESS                       	300 Binney Street, Cambridge, MA, 02142, USA
ST:EMAIL                         	clary@broadinstitute.org
ST:PHONE                         	617-714-7654
ST:NUM_GROUPS                    	2
ST:TOTAL_SUBJECTS                	15
ST:NUM_MALES                     	9
ST:NUM_FEMALES                   	6
#SUBJECT
SU:SUBJECT_TYPE                  	Human
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
SU:AGE_OR_AGE_RANGE              	35-84
SU:GENDER                        	Male and female
#SUBJECT_SAMPLE_FACTORS:         	SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data
SUBJECT_SAMPLE_FACTORS           	-	14	Sample source:Vitreous humor | Dianosis:Epiretinal membrane (ERM) | Disease Status:Control	Sex=F; Age=46; Eye Collected=OS; Past Medical History=-; Medications=none; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=-; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0006_JOY_VitHum_HIL-ERM-14.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0006_JOY_ERM_CMH-14.raw
SUBJECT_SAMPLE_FACTORS           	-	15	Sample source:Vitreous humor | Dianosis:Epiretinal membrane (ERM) | Disease Status:Control	Sex=F; Age=84; Eye Collected=OD; Past Medical History=Hypertension, Dyslipidemia; Medications=Warfarin, Fluoxetine; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=-; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0007_JOY_VitHum_HIL-ERM-15.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0007_JOY_ERM_CMH-15.raw
SUBJECT_SAMPLE_FACTORS           	-	16	Sample source:Vitreous humor | Dianosis:Epiretinal membrane (ERM) | Disease Status:Control	Sex=M; Age=78; Eye Collected=OS; Past Medical History=Hypertension, Dyslipidemia, Coronary artery disease, Gout, Diabetes Type 2, Atrial fibrillation; Medications=Warfarin; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=-; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0008_JOY_VitHum_HIL-ERM-16.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0008_JOY_ERM_CMH-16.raw
SUBJECT_SAMPLE_FACTORS           	-	108	Sample source:Vitreous humor | Dianosis:Epiretinal membrane (ERM) | Disease Status:Control	Sex=M; Age=57; Eye Collected=OS; Past Medical History=Hypertension; Medications=NifedipineIrbezartan/Hydrochlorothiazide, Acetaminophen; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=-; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0009_JOY_VitHum_HIL-ERM-108.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0009_JOY_ERM_CMH-108.raw
SUBJECT_SAMPLE_FACTORS           	-	136	Sample source:Vitreous humor | Dianosis:Epiretinal membrane (ERM) | Disease Status:Control	Sex=M; Age=68; Eye Collected=OD; Past Medical History=Diabetes Type 1; Medications=Formoterol/ budesonide, Rosuvastatin, Calcium/Vit D, Perindopril/Erbumine, Tamsulosine; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=excluded; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0010_JOY_VitHum_HIL-ERM-136.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0010_JOY_ERM_CMH-136.raw
SUBJECT_SAMPLE_FACTORS           	-	85	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage and tractional retinal detachments	Sex=M; Age=74; Eye Collected=OD; Past Medical History=Diabetes Type 2, Dyslipidemia, Hypertension, stroke, Coronary artery disease; Medications=Warfarin, Metformin, Glicazide, Acetaminophen, Gabapentin, Biocal-D forte, Alendronate, Atorvastatin, AAS, Furosemide; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=-; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0031_JOY_VitHum_HIL-DR-85.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0031_JOY_DR_CMH-85.raw
SUBJECT_SAMPLE_FACTORS           	-	126	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with neovascular glaucoma	Sex=F; Age=79; Eye Collected=OS; Past Medical History=Diabetes Type 2, Hemodialysis, Hypertension, Coronary artery disease; Medications=NA; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=excluded; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0032_JOY_VitHum_HIL-DR-126.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0032_JOY_DR_CMH-126.raw
SUBJECT_SAMPLE_FACTORS           	-	124	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage and tractional retinal detachments	Sex=M; Age=35; Eye Collected=OD; Past Medical History=Diabetes Type 2; Medications=NA; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=-; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0033_JOY_VitHum_HIL-DR-124.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0033_JOY_DR_CMH-124.raw
SUBJECT_SAMPLE_FACTORS           	-	86	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage	Sex=F; Age=78; Eye Collected=OD; Past Medical History=Diabetes Type 2, Dyslipidemia, Hypertension, Renal insufficiency; Medications=Metformin, Formoterol/budesonide, Escitalopram, Vit D; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=-; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0034_JOY_VitHum_HIL-DR-86.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0034_JOY_DR_CMH-86.raw
SUBJECT_SAMPLE_FACTORS           	-	142	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with tractional retinal detachments	Sex=M; Age=36; Eye Collected=OD; Past Medical History=Diabetes Type 2, Stroke, Renal insufficiency; Medications=NA; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=-; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0035_JOY_VitHum_HIL-DR-142.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0035_JOY_DR_CMH-142.raw
SUBJECT_SAMPLE_FACTORS           	-	153	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with macular edema and pre-retinal hemorrhage	Sex=M; Age=45; Eye Collected=OD; Past Medical History=Diabetes Type 2, Dyslipidemia, Hypertension; Medications=Insulin, Diltiazem, EzetimibeRosuvastatin, Perindopril/Erbumine/IndapamideMontelukast, EmpagliflozineSemaglutide, AAS, Metformin; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=excluded; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0036_JOY_VitHum_HIL-DR-153.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0036_JOY_DR_CMH-153.raw
SUBJECT_SAMPLE_FACTORS           	-	87	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage	Sex=F; Age=72; Eye Collected=OS; Past Medical History=Diabetes Type 2, Hypertension; Medications=Lyrica, Coumadin, Furosemide, Pantoprazol, Metformin, Dilaudil, Bisoprolol, Ferrous sulfate, Lorazepan; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=-; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0037_JOY_VitHum_HIL-DR-87.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0037_JOY_DR_CMH-87.raw
SUBJECT_SAMPLE_FACTORS           	-	144	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage and cataract	Sex=F; Age=81; Eye Collected=OD; Past Medical History=Diabetes Type 2, Hypertension, Irondeficiency anaemia, dyslipidemia; Medications=Adalat, AAS, Docusate sodium, Metoprolol, Novolin, Furosemide, Ferrous sulfate; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=excluded; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0038_JOY_VitHum_HIL-DR-144.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0038_JOY_DR_CMH-144.raw
SUBJECT_SAMPLE_FACTORS           	-	77	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage	Sex=M; Age=73; Eye Collected=OS; Past Medical History=Diabetes Type 2; Medications=AAS, Atorvastatin, Metoprolol, Amlodipine, Oxybutynin, Tamsulosine, Januvia, Novolin, Gliclazide, Lorazepan, Nitro; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=-; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0039_JOY_VitHum_HIL-DR-77.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0039_JOY_DR_CMH-77.raw
SUBJECT_SAMPLE_FACTORS           	-	76	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage	Sex=M; Age=80; Eye Collected=OS; Past Medical History=Diabetes Type 2, Hypertension, Coronary artery disease; Medications=NA; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=-; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0040_JOY_VitHum_HIL-DR-76.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0040_JOY_DR_CMH-76.raw
SUBJECT_SAMPLE_FACTORS           	-	QC01	Sample source:pooled vitreous QC | Dianosis:NA | Disease Status:NA	Sex=NA; Age=NA; Eye Collected=NA; Past Medical History=NA; Medications=NA; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=NA; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0000g_JOY_VitHum_HIL-PREFB01.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0000d_JOY_VitHum_CMH_JP01.raw
SUBJECT_SAMPLE_FACTORS           	-	QC02	Sample source:pooled vitreous QC | Dianosis:NA | Disease Status:NA	Sex=NA; Age=NA; Eye Collected=NA; Past Medical History=NA; Medications=NA; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=NA; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0020b_JOY_VitHum_HIL-PREFB02.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0020a_JOY_VitHum_CMH_JP02.raw
SUBJECT_SAMPLE_FACTORS           	-	QC03	Sample source:pooled vitreous QC | Dianosis:NA | Disease Status:NA	Sex=NA; Age=NA; Eye Collected=NA; Past Medical History=NA; Medications=NA; Flagged as outlier in MetaboAnalyst Random Forest analysis (excluded)=NA; RAW_FILE_NAME(HILIC-pos_raw_file_name)=0040b_JOY_VitHum_HIL-PREFB03.raw; RAW_FILE_NAME(HILIC-neg_raw_file_name)=0040a_JOY_VitHum_CMH_JP03.raw
#COLLECTION
CO:COLLECTION_SUMMARY            	The study conforms to the tenets of the Declaration of Helsinki, and approval of
CO:COLLECTION_SUMMARY            	the human clinical protocol and informed consent were obtained from the
CO:COLLECTION_SUMMARY            	Maisonneuve-Rosemont Hospital Ethics Committee (CER: 10059). All patients
CO:COLLECTION_SUMMARY            	previously diagnosed with proliferative diabetic retinopathy or epiretinal
CO:COLLECTION_SUMMARY            	membrane were followed clinically, and surgery was performed by a single
CO:COLLECTION_SUMMARY            	vitreoretinal surgeon when indicated by 'standard-of-care' guidelines. Informed
CO:COLLECTION_SUMMARY            	consent was obtained. Undiluted vitreous samples were aspirated in the region
CO:COLLECTION_SUMMARY            	adjacent to neovascular tufts or epiretinal membrane (control) and were frozen
CO:COLLECTION_SUMMARY            	on dry ice immediately after biopsy and stored at –80°C. All patients
CO:COLLECTION_SUMMARY            	received their first anti-VEGF injection after vitreous sampling; they did not
CO:COLLECTION_SUMMARY            	have prior anti-VEGF or photocoagulation treatment. Medication details are
CO:COLLECTION_SUMMARY            	provided in the metadata table, except for four deceased diabetic patients whose
CO:COLLECTION_SUMMARY            	records were no longer available (NA). Sex and gender factors were not analyzed
CO:COLLECTION_SUMMARY            	due to insufficient statistical power when disaggregated.
CO:COLLECTION_PROTOCOL_ID        	CER: 10059
CO:SAMPLE_TYPE                   	Vitreous humor
CO:STORAGE_CONDITIONS            	-80℃
#TREATMENT
TR:TREATMENT_SUMMARY             	No treatment was used in the study
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Samples were thawed on ice, vortexes, and aliquoted to prepare extracts for
SP:SAMPLEPREP_SUMMARY            	three different LC-MS methods: HILIC-pos: 10 µL of vitreous sample was
SP:SAMPLEPREP_SUMMARY            	extracted using 90 µL of acetonitrile/methanol/formic acid (74.9:24.9:0.2
SP:SAMPLEPREP_SUMMARY            	v/v/v) containing stable isotope-labeled internal standards (valine-d8,
SP:SAMPLEPREP_SUMMARY            	Sigma-Aldrich; St. Louis, MO; and phenylalanine-d8, Cambridge Isotope
SP:SAMPLEPREP_SUMMARY            	Laboratories; Andover, MA). The samples were centrifuged (10 min, 9,000 x g,
SP:SAMPLEPREP_SUMMARY            	4°C), and the supernatants were transferred to autosampler vials containing
SP:SAMPLEPREP_SUMMARY            	deactivated glass inserts. HILIC-neg: 30 µL of each vitreous sample was
SP:SAMPLEPREP_SUMMARY            	extracted using 120 µL of 80% methanol containing inosine-15N4, thymine-d4 and
SP:SAMPLEPREP_SUMMARY            	glycocholate-d4 internal standards (Cambridge Isotope Laboratories; Andover,
SP:SAMPLEPREP_SUMMARY            	MA). The samples were centrifuged (10 min, 9,000 x g, 4°C), and the
SP:SAMPLEPREP_SUMMARY            	supernatants were transferred to autosampler vials containing deactivated glass
SP:SAMPLEPREP_SUMMARY            	inserts.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	HILIC-pos: Hydrophilic interaction liquid chromatography (HILIC) analysis of
CH:CHROMATOGRAPHY_SUMMARY        	water soluble metabolites in the positive ionization mode
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Shimadzu Nexera X2
CH:COLUMN_NAME                   	Waters Atlantis HILIC (150 x 2.1mm,3um,100Å)
CH:SOLVENT_A                     	100% water; 0.1% formic acid; 10 mM ammonium formate
CH:SOLVENT_B                     	100% acetonitrile; 0.1% formic acid
CH:FLOW_GRADIENT                 	0-0.5 min, isocratic 95% B; 0.5-10.5 min, gradient to 40% B; 10.5-15 min,
CH:FLOW_GRADIENT                 	isocratic 40% B; 15-17 min, gradient to 95% B
CH:FLOW_RATE                     	250 uL/min
CH:COLUMN_TEMPERATURE            	30
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	POSITIVE
MS:MS_COMMENTS                   	MS analyses were carried out using electrospray ionization in the positive ion
MS:MS_COMMENTS                   	mode using full scan analysis over 70-800 m/z at 70,000 resolution and 3 Hz data
MS:MS_COMMENTS                   	acquisition rate. Other MS settings were: sheath gas 40, sweep gas 2, spray
MS:MS_COMMENTS                   	voltage 3.5 kV, capillary temperature 350°C, S-lens RF 40, heater temperature
MS:MS_COMMENTS                   	300°C, microscans 1, automatic gain control target 1e6, and maximum ion time
MS:MS_COMMENTS                   	250 ms. Raw data were processed using TraceFinder 3.3 software (Thermo Fisher
MS:MS_COMMENTS                   	Scientific; Waltham, MA) and Progenesis QI (Nonlinear Dynamics; Newcastle upon
MS:MS_COMMENTS                   	Tyne, UK). Metabolite identities were confirmed using authentic reference
MS:MS_COMMENTS                   	standards.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	peak area
MS_METABOLITE_DATA_START
Samples	QC01	14	15	16	108	136	QC02	85	126	124	86	142	153	87	144	77	76	QC03
Factors	Sample source:pooled vitreous QC | Dianosis:NA | Disease Status:NA	Sample source:Vitreous humor | Dianosis:Epiretinal membrane (ERM) | Disease Status:Control	Sample source:Vitreous humor | Dianosis:Epiretinal membrane (ERM) | Disease Status:Control	Sample source:Vitreous humor | Dianosis:Epiretinal membrane (ERM) | Disease Status:Control	Sample source:Vitreous humor | Dianosis:Epiretinal membrane (ERM) | Disease Status:Control	Sample source:Vitreous humor | Dianosis:Epiretinal membrane (ERM) | Disease Status:Control	Sample source:pooled vitreous QC | Dianosis:NA | Disease Status:NA	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage and tractional retinal detachments	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with neovascular glaucoma	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage and tractional retinal detachments	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with tractional retinal detachments	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with macular edema and pre-retinal hemorrhage	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage and cataract	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage	Sample source:Vitreous humor | Dianosis:Proliferative diabetic retinopathy (PDR) | Disease Status:Active with vitreous hemorrhage	Sample source:pooled vitreous QC | Dianosis:NA | Disease Status:NA
valine-d8	37590060	37583717	37463783	37329444	37919519	38490719	37112752	37171143	37448830	37130232	37106045	36636704	36535617	37292103	37678445	37109691	37618736	37317553
phenylalanine-d8	67584274	67591034	67807356	68052982	66999756	66040222	68452618	68347019	67834523	68423834	68469407	69378179	69580195	68121888	67422112	68462530	67528388	68074591
1,2,4-trimethylbenzene	15557	16140	15001	15362	15418	15682	16192	14088	16172	13256	13112	14622	14568	14529	17161	14125	13421	16121
bilirubin	66966	2052	2325	23186	3671	331711	69641		4923	58808	18126	94719	151579	96952	59621	59704	9900	65608
cytidine	14247	20745	2456	10987	35330	16466	12833	14497	18438	5284	11408	15622	6740	6052	5993	11141	6954	12162
guanine	2095	2534	1017	1001	3200	2800	1955	5214	3146	2656	2750	1761	1611	2033	2388	5688	3155	2144
hippurate	4275	501	972	2163	1296	7214	6769	12605	929	4681	14366	18240	4449	13269	133621	40485	16104	5873
hypoxanthine	196572	260766	108668	219554	228769	381517	191408	357276	312825	232823	270262	177209	168976	186249	196595	449994	306383	224856
inosine	5345	6407	5962	8512	3790	13297	6033	5233	16570	2745	8236	5123	2310	1953	3741	22129	6094	6892
1-methyladenosine	46907	51954	15175	40390	76618	62045	46652	52441	58180	38736	66107	67353	12980	59468	65555	41487	46184	45659
xanthine	11021	9314	4676	29520	10606	26841	11642	18079	10882	7263	10227	7144	5743	15027	7395	11114	15778	11509
glycine	416	244	255	290	217	280	476	770	263	1245	574	1879	715	482	430	348	288	494
alanine	8957	7142	4467	9642	4960	9993	9535	17429	10866	17024	19394	11781	7527	7264	11436	15271	12598	9466
serine	6514	7926	2979	5845	7383	10649	6448	9613	9280	10842	12320	7344	3621	7170	4227	6385	6479	6252
threonine	13936	15661	7204	12245	11113	20214	13127	23913	21008	22240	22916	11529	12033	9933	4388	15316	12558	13223
methionine	21241	19596	8708	18756	20767	25526	23481	40601	38650	57127	37334	26106	17806	19113	11928	23016	20771	22335
glutamate	461	495	2072	1317	142	159	458	836	273	616	811	782	400	278	349	362	331	444
asparagine	6341	6580	2405	4389	6980	9093	7670	13972	11640	11792	10020	13081	4364	5823	5983	8214	8411	7840
glutamine	590019	762266	186431	486392	730356	1077608	615800	709049	779631	1016354	867678	590522	254885	897674	660627	951797	791725	600908
histidine	130453	200833	64713	180998	159655	212528	138398	409652	318619	457631	453384	257225	81231	263602	160483	419680	304670	204593
arginine	1402714	1571206	588657	1268835	1746518	2203588	1241367	2045339	1724460	2770932	2468296	1250524	709901	1239553	1530057	2091307	1767551	1485763
lysine	276421	322685	84520	299215	337139	613981	270071	543931	407995	335607	338540	344061	105807	391551	185630	508679	364556	302675
valine	68510795	44950930	32297519	59414655	62243047	79040823	69529071	86272397	123852507	116441965	76938963	108567879	42977244	46924690	35902189	98840128	77712542	69949231
leucine	72032317	47312948	27478317	54718826	70561214	95431610	77137908	101157153	143445526	152542690	75220073	135124949	45993308	54847449	41951713	92100255	91947086	78392730
isoleucine	36340708	21188062	13559073	26873598	31192038	43248873	39018050	59438650	73744148	86690972	47462251	67014015	22250390	29502064	29600554	46571184	44403568	38242680
phenylalanine	73635515	57813745	44023040	71712157	63916388	68916003	78932660	121724602	138830015	129925745	123134729	111389941	60474196	59885760	50991075	93746309	69391413	77987692
tyrosine	20254598	22638963	10220437	21045014	22323689	23114790	21847249	20937970	35999110	33352438	38931856	19301415	16002871	15875970	12784109	21563655	25586106	22050475
tryptophan	15083105	10765481	8696213	15228175	12903491	19330570	16732548	20632629	23562746	24229748	21893108	15249651	12670287	10786227	6173359	18207347	16231936	17375242
proline	133918	42387	28986	58736	47207	103910	143955	238377	58004	704421	291671	418194	167368	226270	149576	246603	122386	139411
hydroxyproline	3841	729	1397	2809	674	3446	3981	8643	1871	11763	13529	7587	4836	3831	3838	7630	4463	3983
ornithine	17809	15012	5458	15748	14815	47634	16651	58171	28605	51065	45702	22331	9550	39050	18259	39426	42727	20569
citrulline	10815	7055	2140	5442	8699	15815	12077	25999	5640	25399	39743	33818	8862	19344	24082	42874	15147	11705
taurine	85745	98848	28433	78269	136269	165699	87259	88689	104562	88531	85278	117331	32450	128468	109124	64076	106450	88615
5-hydroxytryptophan		26			27	19	59	176	40	83	404	463	15	206	80	167	364	152
GABA	850	639	406	716	633	1470	822	988	1852	651	645	1111	462	839	207	1198	1512	767
dimethylglycine	2944	985	896	4200	1102	4581	3206	5804	1332	12235	6971	12323	2977	6205	3917	13123	6178	3226
ADMA	21908728	20114137	8656158	20675006	25539365	34986889	13058007	36924035	24877990	37192029	45083514	45343650	14127245	30975533	28670666	40906826	37947032	24105867
SDMA	40097529	32876647	10864728	29343120	33874330	64061986	33131243	80064243	34201208	59121113	143638357	137655524	18452264	44890164	77242920	74839496	72863986	45874665
NMMA	15422	14602	5214	18273	24329	35583	12450	19144	22658	23191	29837	32411	7179	21035	24121	32011	25973	18309
allantoin	3857	933	723	3027	1939	3646	4214	2304	821	6979	21713	19612	1329	9560	8881	14824	5216	4092
aminoisobutyric acid	1401745	1054503	722466	1167301	993963	2388759	1332981	1829051	2913925	1301268	1205959	1919276	805919	1455835	579023	2397593	2358818	1308436
methylguanidine	313	64	32	219	75	220	440	551	76	271	4100	5696	61	426	1622	873	816	474
kynurenic acid	1084	1162	418	631	1472	1296	840	1371	230	434	2467	3440	566	4636	807	3295	2185	1157
1-methylhistamine	4599405	2900183	366998	2004836	5532360	2745645	2086992	271475	4252944	837332	284214	1547064	137580	1195167	900844	629072	293661	2164712
histamine	659	1074	209	365	1402	889	549	259	705	667	237	94	167	564	155	470	343	669
N-carbamoyl-beta-alanine	1319	446	256	1250	1018	2924	1390	1653	1042	1494	1524	2140	589	2343	1893	2469	2206	1405
niacinamide	8465	10563	8039	8930	18574	7258	11447	9782	11382	13410	19504	8663	5478	9944	8040	16902	10778	7475
betaine	801793	470234	277450	1233777	680869	1241927	830403	1042876	627502	2586022	789915	1084728	747294	900339	684451	1354509	1381383	816766
choline	391278	258731	72921	426741	749479	443721	428500	431718	403170	732616	690237	582308	202239	509873	686504	317164	477403	418850
phosphocholine	8885	6419	3369	5587	4486	4070	9067	15839	9726	20647	39225	19246	6405	5721	5908	13193	11794	9005
alpha-glycerophosphocholine	134230	173605	31959	64669	316853	190201	144384	94643	204189	129329	94972	154887	42929	78612	157705	54058	96697	140023
acetylcholine	2169	240	196	1004	135	386	2279	1894	176	668	2819	34611	206	710	4218	3235	872	2249
creatine	910152	965010	311073	531342	1295816	907646	951814	907989	1415160	989262	964991	1007067	427520	957023	492547	853250	548852	901837
creatinine	2631017	1427182	715049	2245153	1738718	3382374	2816135	3581932	1772180	3401176	6134319	8148640	1241587	3007428	4299258	3512405	3059440	2733039
trimethylamine-N-oxide	58143	8583	24063	173925	16758	69699	62453	101850	31686	61175	425001	232321	28043	220279	125383	84620	124009	61092
adenosine	45665	9475	3787	11904	10941	20889	45396	70959	12633	54437	120776	37032	30286	27285	109532	180036	72939	48200
cytosine	1388	769	296	911	1193	1432	1430	2496	1327	973	8911	7189	445	3042	3222	2715	2313	1456
xanthosine	514551	447724	322698	298319	685307	933506	786580	1036632	749044	1236787	344441	901074	352226	638944	364326	221800	821679	816236
cotinine	10739	511	489	562	1975	404	10850	807	418	1331	14999	667	553707	893	615	24121	470	10899
pyroglutamic acid	1631	2440	1231	1732	2105	3653	2524	2774	2848	2827	3803	2833	1349	3553	2397	3771	2789	3178
1-methylnicotinamide	6564	6116	3608	9878	4531	16287	6659	7202	3468	6928	31387	9415	2188	13196	6637	10641	9991	6266
butyrobetaine	25188	10966	4913	19821	9825	39797	25843	59745	13520	59674	36072	134393	18277	43967	25403	54618	30474	26075
putrescine	468061	655267	105753	304864	376996	483125	400439	266998	593369	559630	360822	593725	268005	295888	427578	337425	389568	396849
methionine sulfoxide	557867	645352	476468	1208595	470622	518049	624460	552598	508603	1250444	1072766	1224037	288296	752708	697926	956438	702766	685884
carnitine	2692208	1583731	1006667	2315556	1680566	3796544	2832777	4532888	1875416	4998908	4628950	7386108	1870124	4946189	2511086	3916969	1989053	2760979
C2 carnitine	1772330	666298	455854	1264241	1031337	3238577	1826851	2545298	1131081	3206012	2568869	5066574	909316	3685164	1533628	2617450	1972361	1836026
C3 carnitine	165222	64326	55828	124665	114784	290979	167810	229309	144051	362586	180368	415248	68652	320049	89191	271261	149808	167012
C3-DC-CH3 carnitine	4498	3765	586	2766	4174	7369	4258	4331	4729	4148	12397	11929	1030	11491	9907	5525	4847	4828
C4 carnitine	78796	23063	19329	46713	55944	182711	79847	170099	41182	97885	180439	295041	24999	190602	65764	141904	85905	80363
C4-OH carnitine	11007	2132	2641	8091	4294	29714	11297	25870	5667	11716	21222	29652	6308	35579	9602	16863	22100	11337
C5 carnitine	71205	28087	27728	50013	54045	125141	74480	141824	56475	210626	89437	156340	30123	161065	87370	121696	63515	74171
C5:1 carnitine	9167	4124	2576	7051	12607	21357	9678	15249	9001	8657	14941	25210	2499	17632	11028	13421	6952	9783
C5-DC carnitine	15027	10321	1997	8914	12617	18330	15275	32750	7538	10324	45365	86794	9100	32360	18641	12890	16205	15138
C6 carnitine	4422	1378	491	1268	1348	11142	4346	13678	1422	3615	5211	27183	2122	19605	3671	7342	6619	4555
C8 carnitine	3722	522	27	765	468	4513	3393	9621	325	2416	2472	39272	2373	12545	2290	7832	6405	3727
C10 carnitine	7003	1023	367	1522	1118	6789	5705	17038	1145	4144	3911	43622	4773	22073	4909	10689	7695	5367
C12 carnitine	1072	248	26	410	258	1828	1087	6032	234	459	904	2666	1537	7616	1470	2490	838	1255
C12:1 carnitine	981	331	50	342	228	2229	998	3211	201	414	735	4927	1070	5552	791	2143	1133	934
C14 carnitine	831			174	119	985	483	3297	23	260	380	1100	767	2573	524	1208	206	427
C14:1 carnitine	433	86		203	59	1418	578	2806	148	381	306	3790	767	3564	348	1914	207	703
C14:2 carnitine	95216	21304	1326	46388	65661	282067	93652	280155	21070	80647	52318	370791	107835	383396	76517	215092	71618	87621
1-methylguanine	4286	6411	1554	3618	9377	7034	4859	9556	5258	5149	6121	9958	2780	8152	8232	7101	8088	5612
3-methoxytyramine	920	1702	883	387	154	564	916	141	388	442	36912	40	91	912	130	921	433	864
1-methylguanosine	3464	4299	1277	2583	5064	6759	3592	6796	3426	3765	3872	10110	2851	4801	5343	4548	6764	4116
1-methylhistidine	42841	13610	8797	29281	9792	70471	38704	69844	29460	51049	233436	419997	19505	75659	50344	85183	78756	47363
metoprolol	42910	14	28	148725	34		42323	435	161	15	62	18	41		631835	329981	35626	43302
methylthioadenosine	4454	3253	1152	2359	2169	5921	4249	1506	5757	1950	4295	13930	1108	3637	4641	2322	3148	5246
2'-O-methyladenosine	1095893	390181	207990	635338	521990	822371	1140057	2051836	692362	341597	4734475	6463800	238365	1414719	4907952	6298839	1151115	1072823
3-(N-acetyl-L-cystein-S-yl) acetaminophen	46103		8101	4771			44433	86475			122884	717033		80933				53668
3-methylhistamine	344317		48120	121304		602686	199796	172415	372120	276286	1121024	1185160	93973	199917	309588	787438	656013	233453
3-methylhistidine	40412	14615	8734	19556	10949	116178	34055	43952	57870	63263	278324	284616	25130	47217	71532	192974	151417	47412
3-methylxanthine	20053	7161	3518	10370	3681	38006	21736	5121	27023	39452	25564	13047	2584	7626	94055	9013	92060	20966
4-acetamidobutanoate	8496	4258	2275	4701	5417	8472	9350	12723	4082	8187	46108	61167	3297	14034	36393	13879	10118	9262
4-acetamidophenylglucuronide	48539880		14462533	4469863			47313105	127984169			644202112	570720134		133126625				50045490
4-Hydroxy-3-methylacetophenone	6812	5565	5206	5231	5124	5132	5245	3802	5625	4389	4848	5201	4108	4534	6072	3788	4504	4883
4-hydroxyhippurate	3694	429	257	1363	239	1232	5066	10354	130	13704	12359	31993	1919	4549	44515	16366	13503	4706
5-acetylamino-6-amino-3-methyluracil	2791	3228	1152	744	1262	3995	3205	3273	200	5732	22662	1539	1913	5144	20714	11627	12661	3141
5-hydroxymethy4-methyluracil	3687954	2283018	1023684	2646408	3080530	3663485	3432402	2798350	3016308	2315794	11624408	10539103	1200393	4593750	6919831	3320000	4584384	3238888
5-methylcytidine	3076	3678	291	1547	8095	4676	3320	2842	5415	1825	2613	4092	994	2372	2990	2517	2099	2837
5-methylcytosine	206	99	44	120	252	102	171	227	87	223	789	715	92	476	432	265	165	185
6,8-dihydroxypurine	2356	1252	835	1495	1246	6964	2224	3375	1137	1834	2221	5426	774	2615	2695	2180	1643	2071
7-Methylguanine	28068	24734	9669	21670	33822	36859	28163	36776	24580	24359	32418	91045	13044	25772	33263	30841	27243	30171
7-methylxanthine	11236	5854	1329	5750	3212	38087	11992	2100	23078	25123	6908	2769	1645	2367	24262	4893	29904	11774
acetaminophen glucuronide	311376		94864	28803		21	305270	846322			4332181	3880857	43	885124	25			330978
acetyl-galactosamine	6375	7170	2152	5501	14189	10573	7402	5000	9368	7443	2806	4405	2625	3524	11027	5247	8718	7160
adrenochrome	20580	20123	199419	67102	8774	10932	23200	3647	4694	80312	10066	38325	284335	13648	52575	26461	15459	30346
alpha-hydroxymetoprolol	19851		16	121866			20877							111	485822	200143	166443	19713
biliverdin	31000			3393		54263	144438	829984		736248	87590	30639	266187	32541	313265	804250	1849885	183097
caffeine	172528	44785	54419	230138	76561	75449	187223	50294	24807	199365	39035	621	30576	170502	1383176	47344	163782	181427
cortisol	8635	7651	1994	10100	11947	26322	9244	5962	10122	3451	8315	15374	4926	19273	13528	8231	4468	8319
cortisone	2584	4414	140	2842	6461	7520	2772	1157	4485	1808	1197	2493	1513	4664	2492	1092	1354	2470
cyclohexylamine	7589	7528	12820	9863	6290	5410	6800	5743	6297	4864	4156	4126	5704	5156	4907	4943	5868	7001
diacetylspermine	414			24		359	378	507	8	54	670	7074	54	443	540	329	443	482
2-aminooctanoic acid	378469	170830	200698	513383	320713	775407	433784	430458	1173709	1218213	494359	80179	148999	181452	299622	361637	400799	510449
DMGV	4765697	33699	296503	1575544	69316	1033070	4988678	7859231	127268	4479045	27961888	43026087	2843745	13389641	16242788	14130198	9168302	4782216
ectoine	684867	226366	96534	496936		447844	578668	1951802	371924	824592	1375764	3307377	384922		1402803	862523	1456958	554175
guanidoacetic acid	206	137	35	223	123	271	200	496	107	1006	367	436	313	119	119	279	231	191
homoarginine	23405	34667	9789	31281	56041	37075	19962	22860	39822	38351	15656	13694	11766	17330	16374	58559	24070	25216
hydroxycotinine	437				80		354	33		160	2668		20269	9		1306		357
imidazole propionate	585	273	107	402	67	279	624	724	124	911	2658	1073	120	1071	929	582	2137	628
imidazoleacetic acid	191426	115052	93403	828123	57864	129251	159081	378142	121257	359260	317170	417392	104968	223804	316174	273233	318357	172247
L-a-glutamyl-L-Lysine	185446	122004	54339	220615	144291	857447	154246	550502	175977	223667	317915	357564	77497	356027	138242	728038	378007	217004
linoleoyl ethanolamide	1756	1168	413	835	1389	2017	2384	1780	3190	466	582	1688	1298	836	2007	1372	891	3741
L-threo-Sphingosine	1395	1248	1094	1341	1255	1347	1562	1322	2033	1246	1135	1148	1356	1474	1493	1714	1636	1242
methyl N-methylanthranilate	585	1033	1034	852	1047	930	905	894	534	918	998	1014	848	943	1121	942	916	879
methylimidazole acetic acid	25446	2531	1419	9658	1086	17709	25221	77754	4168	6373	217561	299422	4398	4928	94412	37132	68743	27076
myristoleate	10768	17846	15404	14614	13892	16455	17020	12552	12515	14846	15814	13396	17886	18244	16093	14717	16085	12468
N1,N12-diacetylspermine	103316					102623	116630	135911			178355	1795610		101470	146374	83957	115881	123975
N1-acetylspermidine	6684614	5551227	1315189	4672210	6777874	9191258	7197845	10004007	7757498	6380000	9411646	24536259	3893206	6718683	6206791	10488661	10400813	6984589
N1-Methyl-2-pyridone-5-carboxamide	139714	93100	30820	131066	88396	183633	144815	105218	116763	268593	1235013	219440	28737	224790	163862	201325	186170	136596
N2,N2-dimethylguanosine	4076	2388	1437	3083	3483	3243	4406	12076	2391	3105	30664	56643	1711	8526	8418	10887	10075	4039
N4-acetylcytidine	20094	8916	2655	12067	26935	15909	21694	25696	21223	11724	60059	89739	4304	42332	68885	19849	27930	20980
N6-acetyllysine	1000	589	213	588	752	1594	1090	3322	458	859	1866	3828	688	2440	1783	1751	1681	1066
N-acetyalanine	5215	4627	1300	3738	6599	6865	5270	5374	4871	6418	8013	13716	2543	6982	8231	6158	5409	5147
N-acetylaspartic acid	59077	63609	17261	39563	153273	51089	68579	23799	111215	44609	25598	40828	11059	45400	63423	26806	29001	66017
N-acetylgalactosamine	2711725	3356940	971440	2284358	6076721	4554441	3224158	2625547	3998134	3070176	1884915	3266999	1212201	1937598	4539619	2354944	3949078	3282822
N-acetylhistamine	105	33	4	11	416	40	107	146	108	38	181	5		884	563	72	55	111
N-acetylhistidine	4442	3288	929	2745	3431	6394	4604	12393	2383	10778	20055	15268	3813	8837	10833	21368	7023	5008
N-acetylmethionine	1193	1003	206	643	2010	1539	1320	741	1404	1037	881	4211	370	1314	2425	1058	1479	1433
N-acetylornithine	1532	203	147	922	583	4233	1678	692	2958	1449	9633	6093	272	1324	6502	5720	2462	1562
N-acetylputrescine	5184	7789	1100	3817	7165	7357	5200	3781	6059	5383	6042	10596	2244	6293	8079	5308	3909	5367
N-acetylspermidine	15553	12869	3080	10674	15576	21289	16455	22961	17750	14700	21780	57588	8849	15348	14078	24207	24147	16159
N-alpha-acetylarginine	2855	2055	515	2520	2067	4938	3136	11617	914	8798	7400	10928	1706	7713	5337	6201	2899	2799
Ne,Ne dimethyllysine	20411	22465	3820	11948	11725	19970	16636	87250	31414	15587	191633	38230	17052	27303	31499	24331	100314	22487
N-ethylglycinexylidide	387	20	21	6	788	712	430	133	128	519	13	703	284			15	106	240
N-lauroylglycine	2559	2124	1505	1973	2713	2309	3251	3970	2725	3095	1989	7747	3530	2548	11253	4077	3142	3623
N-methylproline	8631318	2467759	520941	14564119	5771090	2079132	9715785	34293906	6680829	2517206	1698199	38727819		10988736	84787911	17090873	1885059	9544604
Pantothenol	2730	4338	2710	4299	3337	3830	13865	2988	5536	2366	3212	2064	2840	4405	9375	33713	5381	6316
phenylacetylglutamine	1092678	102469	132860	718698	157170	635117	1011416	3943005	220658	918735	3510322	8936535	526643	1813425	3757785	2159662	3080089	1127877
phytosphingosine	2499	2926	3507	7271	1868	3921	3073	5473	2302	2901	2438	1543	903	3191	3137	5314	2573	2691
piperine	5278	100	285	56210			5156	15904	694		6421	2809	1914	70242	584	24434	6663	5001
proline betaine	1071163	44111	16919	959302	409212	35627	1141385	1808790	679418	122230	2169751	6295385	20951	1441548	5548776	1334249	51970	1140745
pseudouridine	988428	566170	216201	554451	702144	1005115	1012293	1214373	782691	824803	2977924	3742100	317799	1223778	2144669	1177066	1354435	1010815
pterin	390	624	53	323	185	323	204	1816	124	608	1048	1097	43	564	382	847	849	517
pyridoxamine	23159	34377	10583	33864	35769	63328	20454	45045	39197	28252	28520	35847	11367	35263	17144	39788	32035	30229
S-methyl-L-cysteine-S-oxide	59771	54214	48617	48603	58727	53566	55019	36562	51223	45655	34252	45392	50893	33564	50537	28066	39039	54067
sphinganine	441	71	84	285	87	3628	633	776	186	132	346	3790	1792	90	112	427	406	632
trigonelline	31166	5773	13115	19643	7228	43550	30648	28487	8136	6513	62847	86000	1515	22138	206514	111636	105929	31631
trimethyllysine	62454	46820	15910	66400	64187	194303	59447	148223	57796	87733	182801	237043	55616	137334	146537	175155	117304	83104
urocanic acid	14793	12096	13373	19783	21024	17490	64631	22115	32334	14152	58571	21643	14530	35712	166750	62991	46269	53506
warfarin	8222		10315	199616			13848	398386						204643				13187
C16:0 LPC_B	19973	11502	10628	20115	10110	34270	19653	36734	9971	20569	20577	74227	22999	18660	14159	33097	12569	19927
C18:3 LPC	6805	4348	3175	8126	3527	12857	6454	15251	3946	7659	9268	26860	5938	7528	4730	13220	5124	6846
C18:2 LPC	84879	46162	67362	85692	55493	99118	67053	102962	57508	80469	85930	236008	69199	74299	79569	90859	75427	78456
C18:1 LPC	157566	93235	77240	150577	80748	361679	149645	269419	87829	131243	144114	555346	181784	172813	111954	216048	82259	145748
C18:0 LPC	4972	2900	2938	6817	2902	9122	5026	12211	2528	5468	6216	11887	6448	5439	3224	8369	3191	5318
C30:0 PC	5764	2100	459	4214	5955	8910	6208	48607	1552	1859	8959	7771	5752	27545	5927	8127	8678	6270
C34:3 PC	6670	2442	91	1750	5693	8284	8527	56586	3934	5682	17091	9889	8200	28379	6525	10181	11852	9007
C36:2 PC	107872	27116	15678	123248	30093	415933	112175	613037	13113	113884	132466	107718	75029	281837	103391	159304	109592	111661
C36:5 PE plasmalogen	3407		68	5111	1396	4935	2863	21845		6925	32235	11392	6391	23859	4216	7699	7773	3527
C38:6 PE plasmalogen	2912	124	71	4196	371	10550	3436	20582		4551	17670	4585	2957	17824	888	6485	6569	2659
C38:5 PE plasmalogen	7422	219	425	10613	3317	6742	6841	62327		14410	28035	14158	6636	49126	9341	15841	23965	7380
C40:7 PE plasmalogen	2047	164		2405	2480	5235	1691	14830	130	1740	5347	4147	1288	11596	1470	4539	2916	2481
sphingosine_A*	1692	3320	105528	19833	1471	1123	12280	4470	406982	285926	2580	19785	766	1587	3435	8018	77430	2172
sphingosine_B*	1374	2319	72675	13338	1113	475	9316	2653	311563	203346	1938	15677	466	1045	2183	4814	52630	1679
sphingosine_D*	2485	2270	2148	2153	2813	2413	2301	1964	2180	2598	2172	3144	2343	2979	2577	3053	2587	2875
C16:0 Ceramide (d18:1)		57	9682	916			151		23418	9630	60	748			78		4746	
C16:0 SM	15658	2937	1631	12673	3949	36547	14743	133088	841	12688	26641	24293	10997	78621	15171	34830	38673	14946
C18:1 SM	11435	2496	664	10629	4456	19439	11810	91702	985	8106	15042	17174	9298	55841	13545	17162	16872	10186
C18:0 SM	18356	5385	1924	17001	11200	28284	18352	121802	2152	13060	22237	34624	15945	104303	22084	37169	24694	19061
C20:0 SM	6683	362	468	6314	3048	13882	6161	38841	244	4445	7709	9985	5884	27525	6198	11139	5225	6054
C22:0 SM	304118			275483	50193	862228	249080	2190428		269511	353714	236174	195098	1217168	280472	521931	390755	272679
NH4_C34:2 DAG		276	257	365	345	87	501	2768	258	1423	1725	2435	959	2017	1881	2737	875	974
NH4_C36:3 DAG	567	113	57	2144	399	1379	1172	7832	58	2959	3609	4490	1457	3553	2425	4658	936	1915
NH4_C44:2 TAG	2000	2700	2386	2570	5599	2417	3087	7100	10464	3833	2784	3179	2697	2849	8616	5625	4869	4627
NH4_C44:1 TAG	6395	7953	6890	7437	15554	8453	9238	20961	23592	10203	7591	9174	8438	10911	24417	15933	10188	12448
NH4_C46:3 TAG	815	1490	1216	1170	3741	1100	2129	4939	7090	2383	1517	1849	1475	1863	5633	3098	2536	2468
NH4_C46:2 TAG	7788	10028	8845	8499	20519	10672	14134	28483	32940	13220	12023	12710	10249	13562	32325	19085	12783	14156
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	Compound_ID	MZ	RT	HMDB_ID (*representative)	mz_rt
valine-d8	TF30	126.1364	7.53	internal standard	126.1364_7.53
phenylalanine-d8	TF24	174.1364	6.84	internal standard	174.1364_6.84
1,2,4-trimethylbenzene	QI2938	121.1011	2.06	HMDB13733	121.1011_2.06
bilirubin	QI1097	585.2711	1.73	HMDB00054	585.2711_1.73
cytidine	QI6665	244.0929	5.95	HMDB00089	244.0929_5.95
guanine	QI6290	152.0568	5.48	HMDB00132	152.0568_5.48
hippurate	QI4206	180.0655	2.68	HMDB00714	180.0655_2.68
hypoxanthine	QI5959	137.0458	4.91	HMDB00157	137.0458_4.91
inosine	QI5976	269.0883	4.92	HMDB00195	269.0883_4.92
1-methyladenosine	QI8145	282.1198	7.81	HMDB03331	282.1198_7.81
xanthine	QI4990	153.0407	3.81	HMDB00292	153.0407_3.81
glycine	QI8293	76.0393	7.98	HMDB00123	76.0393_7.98
alanine	QI8212	90.0550	7.87	HMDB00161	90.055_7.87
serine	QI8096	106.0499	7.74	HMDB00187	106.0499_7.74
threonine	QI8097	120.0656	7.74	HMDB00167	120.0656_7.74
methionine	QI7578	150.0584	7.17	HMDB00696	150.0584_7.17
glutamate	QI7998	148.0605	7.67	HMDB00148	148.0605_7.67
asparagine	QI8327	133.0607	8.04	HMDB00168	133.0607_8.04
glutamine	QI8404	147.0764	8.10	HMDB00641	147.0764_8.1
histidine	QI9146	156.0769	9.56	HMDB00177	156.0769_9.56
arginine	QI9023	175.1190	9.28	HMDB00517	175.119_9.28
lysine	QI9113	147.1128	9.50	HMDB00182	147.1128_9.5
valine	TF29	118.0862	7.52	HMDB00883	118.0862_7.52
leucine	TF17	132.1018	7.09	HMDB00687	132.1018_7.09
isoleucine	TF15	132.1018	7.21	HMDB00172	132.1018_7.21
phenylalanine	TF23	166.0862	6.83	HMDB00159	166.0862_6.83
tyrosine	TF28	182.0811	6.90	HMDB00158	182.0811_6.9
tryptophan	TF27	205.0971	6.61	HMDB00929	205.0971_6.61
proline	QI8497	116.0706	8.21	HMDB00162	116.0706_8.21
hydroxyproline	QI8272	132.0655	7.97	HMDB00725	132.0655_7.97
ornithine	QI9085	133.0972	9.46	HMDB00214	133.0972_9.46
citrulline	QI8600	176.1030	8.42	HMDB00904	176.103_8.42
taurine	QI6824	126.0220	6.10	HMDB00251	126.022_6.1
5-hydroxytryptophan	QI7508	221.0920	7.05	HMDB00472	221.092_7.05
GABA	QI8086	104.0706	7.73	HMDB00112	104.0706_7.73
dimethylglycine	QI8704	104.0705	8.61	HMDB00092	104.0705_8.61
ADMA	TF7	203.1502	9.91	HMDB01539	203.1502_9.91
SDMA	TF26	203.1502	9.80	HMDB03334	203.1502_9.8
NMMA	QI9136	189.1346	9.52	HMDB29416	189.1346_9.52
allantoin	QI4864	159.0513	3.61	HMDB00462	159.0513_3.61
aminoisobutyric acid	TF2	104.0705	7.76	HMDB01906*	104.0705_7.76
methylguanidine	QI7438	74.0713	6.91	HMDB01522	74.0713_6.91
kynurenic acid	QI6176	190.0499	5.29	HMDB00715	190.0499_5.29
1-methylhistamine	TF1	126.1025	9.82	HMDB00898	126.1025_9.82
histamine	QI9057	112.0870	9.36	HMDB00870	112.087_9.36
N-carbamoyl-beta-alanine	QI5252	133.0608	4.20	HMDB00026	133.0608_4.2
niacinamide	QI5043	123.0553	3.88	HMDB01406	123.0553_3.88
betaine	QI8969	118.0862	9.07	HMDB00043	118.0862_9.07
choline	QI8593	104.1069	8.42	HMDB00097	104.1069_8.42
phosphocholine	QI2421	184.0734	11.94	HMDB01565	184.0734_11.94
alpha-glycerophosphocholine	QI2331	258.1103	10.51	HMDB00086	258.1103_10.51
acetylcholine	QI8232	146.1175	7.90	HMDB00895	146.1175_7.9
creatine	QI8565	132.0767	8.39	HMDB00064	132.0767_8.39
creatinine	QI7188	114.0662	6.58	HMDB00562	114.0662_6.58
trimethylamine-N-oxide	QI8508	76.0757	8.23	HMDB00925	76.0757_8.23
adenosine	QI6073	268.1041	5.08	HMDB00050	268.1041_5.08
cytosine	QI6976	112.0505	6.28	HMDB00630	112.0505_6.28
xanthosine	TF31	285.0830	4.31	HMDB00299	285.083_4.31
cotinine	QI6149	177.1023	5.23	HMDB01046	177.1023_5.23
pyroglutamic acid	QI7308	130.0499	6.77	HMDB00267	130.0499_6.77
1-methylnicotinamide	QI8556	137.0709	8.37	HMDB00699	137.0709_8.37
butyrobetaine	QI8930	146.1175	8.94	HMDB01161	146.1175_8.94
putrescine	TF25	89.1073	9.52	HMDB01414	89.1073_9.52
methionine sulfoxide	TF18	166.0532	8.74	HMDB02005	166.0532_8.74
carnitine	QI8956	162.1125	9.02	HMDB00062	162.1125_9.02
C2 carnitine	QI8894	204.1231	8.83	HMDB00201	204.1231_8.83
C3 carnitine	QI8623	218.1387	8.49	HMDB00824	218.1387_8.49
C3-DC-CH3 carnitine	QI8812	262.1287	8.71	HMDB13133	262.1287_8.71
C4 carnitine	QI8481	232.1544	8.18	HMDB02013	232.1544_8.18
C4-OH carnitine	QI8948	248.1493	8.98	HMDB13127	248.1493_8.98
C5 carnitine	QI8262	246.1701	7.94	HMDB00688	246.1701_7.94
C5:1 carnitine	QI8321	244.1544	8.02	HMDB02366	244.1544_8.02
C5-DC carnitine	QI8611	276.1443	8.47	HMDB13130	276.1443_8.47
C6 carnitine	QI8014	260.1858	7.68	HMDB00705	260.1858_7.68
C8 carnitine	QI7737	288.2170	7.43	HMDB00791	288.217_7.43
C10 carnitine	QI7632	316.2484	7.26	HMDB00651	316.2484_7.26
C12 carnitine	QI7512	344.2799	7.06	HMDB02250	344.2799_7.06
C12:1 carnitine	QI7526	342.2638	7.09	HMDB13326	342.2638_7.09
C14 carnitine	QI7433	372.3113	6.91	HMDB05066	372.3113_6.91
C14:1 carnitine	QI7441	370.2951	6.92	HMDB02014	370.2951_6.92
C14:2 carnitine	TF8	368.2795	6.98	HMDB13331	368.2795_6.98
1-methylguanine	QI6193	166.0724	5.31	HMDB03282	166.0724_5.31
3-methoxytyramine	QI7123	168.1020	6.50	HMDB00022	168.102_6.5
1-methylguanosine	QI6113	298.1148	5.15	HMDB01563	298.1148_5.15
1-methylhistidine	QI2330	170.0924	10.51	HMDB00001	170.0924_10.51
metoprolol	QI6960	268.1909	6.26	HMDB01932	268.1909_6.26
methylthioadenosine	QI5322	298.0971	4.31	HMDB01173	298.0971_4.31
2'-O-methyladenosine	TF3	282.1195	4.74	HMDB04326	282.1195_4.74
3-(N-acetyl-L-cystein-S-yl) acetaminophen	QI6065	313.0853	5.07	NA	313.0853_5.07
3-methylhistamine	TF4	126.1026	10.03	HMDB01861	126.1026_10.03
3-methylhistidine	QI2278	170.0924	10.04	HMDB00479	170.0924_10.04
3-methylxanthine	QI4729	167.0564	3.43	HMDB01886	167.0564_3.43
4-acetamidobutanoate	QI4813	146.0812	3.55	HMDB03681	146.0812_3.55
4-acetamidophenylglucuronide	TF5	328.1025	5.56	HMDB10316	328.1025_5.56
4-Hydroxy-3-methylacetophenone	QI2800	151.0754	2.05	HMDB59824	151.0754_2.05
4-hydroxyhippurate	QI4255	196.0604	2.73	HMDB13678	196.0604_2.73
5-acetylamino-6-amino-3-methyluracil	QI6207	199.0826	5.34	HMDB04400	199.0826_5.34
5-hydroxymethy4-methyluracil	TF6	157.0608	3.69	HMDB00544	157.0608_3.69
5-methylcytidine	QI6830	258.1087	6.10	HMDB00982	258.1087_6.1
5-methylcytosine	QI7065	126.0662	6.41	HMDB02894	126.0662_6.41
6,8-dihydroxypurine	QI5388	153.0408	4.38	HMDB01182	153.0408_4.38
7-Methylguanine	QI6584	166.0723	5.86	HMDB00897	166.0723_5.86
7-methylxanthine	QI4975	167.0564	3.78	HMDB01991	167.0564_3.78
acetaminophen glucuronide	QI6352	328.1027	5.56	HMDB10316	328.1027_5.56
acetyl-galactosamine	QI6316	222.0973	5.49	HMDB00212	222.0973_5.49
adrenochrome	QI5843	180.0656	4.79	HMDB12884	180.0656_4.79
alpha-hydroxymetoprolol	QI7201	284.1858	6.61	NA	284.1858_6.61
biliverdin	QI2923	583.2555	2.05	HMDB01008	583.2555_2.05
caffeine	QI4494	195.0877	2.98	HMDB01847	195.0877_2.98
cortisol	QI3264	363.2166	2.06	HMDB00063	363.2166_2.06
cortisone	QI3259	361.2006	2.06	HMDB02802	361.2006_2.06
cyclohexylamine	QI7168	100.1120	6.55	HMDB31404	100.112_6.55
diacetylspermine	QI2344	287.2441	10.61	HMDB41876	287.2441_10.61
2-aminooctanoic acid	TF12	160.1331	6.53	HMDB00991	160.1331_6.53
DMGV	TF32	202.1185	8.32	NA	202.1185_8.32
ectoine	TF13	143.0815	9.01	NA	143.0815_9.01
guanidoacetic acid	QI8250	118.0611	7.93	HMDB00128	118.0611_7.93
homoarginine	QI9054	189.1346	9.33	HMDB00670*	189.1346_9.33
hydroxycotinine	QI6101	193.0976	5.14	HMDB01390	193.0976_5.14
imidazole propionate	QI7878	141.0659	7.54	HMDB02271	141.0659_7.54
imidazoleacetic acid	TF14	127.0501	8.23	HMDB02024	127.0501_8.23
L-a-glutamyl-L-Lysine	TF16	276.1555	9.79	HMDB04207	276.1555_9.79
linoleoyl ethanolamide	QI3209	324.2897	2.06	HMDB12252	324.2897_2.06
L-threo-Sphingosine	QI6580	300.2896	5.85	NA	300.2896_5.85
methyl N-methylanthranilate	QI1627	166.0863	1.85	HMDB34169	166.0863_1.85
methylimidazole acetic acid	QI8942	141.0658	8.97	HMDB02820	141.0658_8.97
myristoleate	QI1460	227.2005	1.81	HMDB02000	227.2005_1.81
N1,N12-diacetylspermine	TF19	287.2442	10.61	HMDB02172	287.2442_10.61
N1-acetylspermidine	TF20	188.1757	10.01	HMDB01276	188.1757_10.01
N1-Methyl-2-pyridone-5-carboxamide	QI5404	153.0659	4.39	HMDB04193	153.0659_4.39
N2,N2-dimethylguanosine	QI6269	312.1302	5.45	HMDB04824	312.1302_5.45
N4-acetylcytidine	QI5345	286.1034	4.33	HMDB05923	286.1034_4.33
N6-acetyllysine	QI8619	189.1234	8.49	HMDB00206*	189.1234_8.49
N-acetyalanine	QI5057	132.0655	3.90	HMDB00766*	132.0655_3.9
N-acetylaspartic acid	QI5495	176.0554	4.52	HMDB00812	176.0554_4.52
N-acetylgalactosamine	TF21	222.0970	5.48	HMDB00853	222.097_5.48
N-acetylhistamine	QI8189	154.0976	7.87	HMDB13253	154.0976_7.87
N-acetylhistidine	QI8602	198.0849	8.42	HMDB32055	198.0849_8.42
N-acetylmethionine	QI4822	192.0689	3.56	HMDB11745	192.0689_3.56
N-acetylornithine	QI8629	175.1077	8.50	HMDB03357	175.1077_8.5
N-acetylputrescine	QI8342	131.1178	8.06	HMDB02064	131.1178_8.06
N-acetylspermidine	QI2275	188.1758	10.02	HMDB01276*	188.1758_10.02
N-alpha-acetylarginine	QI8514	217.1295	8.27	HMDB04620*	217.1295_8.27
Ne,Ne dimethyllysine	QI2313	175.1441	10.41	HMDB13287	175.1441_10.41
N-ethylglycinexylidide	QI6987	207.1491	6.30	NA	207.1491_6.3
N-lauroylglycine	QI3884	258.2064	2.45	HMDB13272	258.2064_2.45
N-methylproline	TF22	130.0862	8.73	NA	130.0862_8.73
Pantothenol	QI5074	206.1387	3.91	HMDB04231	206.1387_3.91
phenylacetylglutamine	QI5645	265.1184	4.64	HMDB06344	265.1184_4.64
phytosphingosine	QI6668	318.3005	5.95	HMDB04610	318.3005_5.95
piperine	QI2715	286.1440	2.03	HMDB29377	286.144_2.03
proline betaine	QI9067	144.1019	9.38	HMDB04827	144.1019_9.38
pseudouridine	QI5273	245.0769	4.23	HMDB00767	245.0769_4.23
pterin	QI5950	164.0567	4.90	HMDB00802	164.0567_4.9
pyridoxamine	QI9116	169.0948	9.50	HMDB01431	169.0948_9.5
S-methyl-L-cysteine-S-oxide	QI8741	152.0383	8.67	NA	152.0383_8.67
sphinganine	QI6689	302.3052	5.97	HMDB00269	302.3052_5.97
trigonelline	QI8940	138.0550	8.97	HMDB00875	138.055_8.97
trimethyllysine	QI2394	189.1598	11.41	NA	189.1598_11.41
urocanic acid	QI5587	139.0502	4.60	HMDB00301	139.0502_4.6
warfarin	QI1382	309.1123	1.79	HMDB01935	309.1123_1.79
C16:0 LPC_B	QI8203	496.3400	7.87	HMDB10382	496.34_7.87
C18:3 LPC	QI8205	518.3222	7.87	HMDB10387*	518.3222_7.87
C18:2 LPC	TF10	520.3398	7.84	HMDB10386*	520.3398_7.84
C18:1 LPC	TF9	522.3554	7.79	HMDB02815*	522.3554_7.79
C18:0 LPC	QI8103	524.3715	7.74	HMDB10384	524.3715_7.74
C30:0 PC	QI7338	706.5386	6.82	HMDB07869*	706.5386_6.82
C34:3 PC	QI7339	756.5517	6.82	HMDB08006*	756.5517_6.82
C36:2 PC	QI7255	786.6014	6.68	HMDB08039*	786.6014_6.68
C36:5 PE plasmalogen	QI6277	724.5275	5.46	HMDB11410*	724.5275_5.46
C38:6 PE plasmalogen	QI6265	750.5437	5.44	HMDB11387*	750.5437_5.44
C38:5 PE plasmalogen	QI6266	752.5593	5.44	HMDB11386*	752.5593_5.44
C40:7 PE plasmalogen	QI6256	776.5585	5.41	HMDB11394*	776.5585_5.41
sphingosine_A*	QI3174	300.2899	2.06	HMDB00252*	300.2899_2.06
sphingosine_B*	QI3964	300.2898	2.46	HMDB00252*	300.2898_2.46
sphingosine_D*	QI6887	300.2899	6.16	HMDB00252*	300.2899_6.16
C16:0 Ceramide (d18:1)	QI1031	538.5193	1.72	HMDB04949	538.5193_1.72
C16:0 SM	QI7679	703.5750	7.31	HMDB10169	703.575_7.31
C18:1 SM	QI7633	729.5911	7.26	HMDB12101*	729.5911_7.26
C18:0 SM	QI7634	731.6070	7.26	HMDB01348	731.607_7.26
C20:0 SM	QI7618	759.6384	7.22	HMDB12102	759.6384_7.22
C22:0 SM	TF11	787.6691	7.19	HMDB12103	787.6691_7.19
NH4_C34:2 DAG	QI731	610.5407	1.64	NA	610.5407_1.64
NH4_C36:3 DAG	QI713	636.5566	1.63	NA	636.5566_1.63
NH4_C44:2 TAG	QI607	764.6759	1.58	NA	764.6759_1.58
NH4_C44:1 TAG	QI608	766.6921	1.58	NA	766.6921_1.58
NH4_C46:3 TAG	QI612	790.6914	1.58	NA	790.6914_1.58
NH4_C46:2 TAG	QI613	792.7078	1.58	NA	792.7078_1.58
METABOLITES_END
#END