#METABOLOMICS WORKBENCH amuirchicago_20250225_104023 DATATRACK_ID:5676 STUDY_ID:ST003759 ANALYSIS_ID:AN006172 PROJECT_ID:PR002342
VERSION             	1
CREATED_ON             	February 28, 2025, 12:51 pm
#PROJECT
PR:PROJECT_TITLE                 	Analysis of metabolite levels in the circulation of pancreatic tumor bearing
PR:PROJECT_TITLE                 	mice with or without depletion of myeloid cells
PR:PROJECT_SUMMARY               	In this study, we assessed the impact of myeloid cells on the levels of
PR:PROJECT_SUMMARY               	circulating metabolites in the plasma of mice bearing tumors. To do so, murine
PR:PROJECT_SUMMARY               	pancreatic ductal adenocarcinoma (PDAC) cells were implanted into C57Bl6J
PR:PROJECT_SUMMARY               	CD11b-DTR host animals. Myeloid cells were then ablated with 25 ng/g diptheria
PR:PROJECT_SUMMARY               	toxin (DT). Serum from DT treated mice was collected for analysis. Additionally,
PR:PROJECT_SUMMARY               	serum was collected from PDAC bearing mice that were vehicle treated. This data
PR:PROJECT_SUMMARY               	allows for identification of how myeloid cells in tumor bearing mice contribute
PR:PROJECT_SUMMARY               	to levels of circulating metabolites.
PR:INSTITUTE                     	University of Chicago
PR:DEPARTMENT                    	Ben May Department for Cancer Research
PR:LAST_NAME                     	Muir
PR:FIRST_NAME                    	Alexander
PR:ADDRESS                       	929 E 57th St
PR:EMAIL                         	amuir@uchicago.edu
PR:PHONE                         	7738346506
#STUDY
ST:STUDY_TITLE                   	Analysis of metabolite levels in the circulation of pancreatic tumor bearing
ST:STUDY_TITLE                   	mice with or without depletion of myeloid cells
ST:STUDY_SUMMARY                 	In this study, we assessed the impact of myeloid cells on the levels of
ST:STUDY_SUMMARY                 	circulating metabolites in the plasma of mice bearing tumors. To do so, murine
ST:STUDY_SUMMARY                 	pancreatic ductal adenocarcinoma (PDAC) cells were implanted into C57Bl6J
ST:STUDY_SUMMARY                 	CD11b-DTR host animals. Myeloid cells were then ablated with 25 ng/kg diptheria
ST:STUDY_SUMMARY                 	toxin (DT). Serum from DT treated mice was collected for analysis. Additionally,
ST:STUDY_SUMMARY                 	serum was collected from PDAC bearing mice that were vehicle treated. This data
ST:STUDY_SUMMARY                 	allows for identification of how myeloid cells in tumor bearing mice contribute
ST:STUDY_SUMMARY                 	to levels of circulating metabolites.
ST:INSTITUTE                     	University of Chicago
ST:LAST_NAME                     	Muir
ST:FIRST_NAME                    	Alexander
ST:ADDRESS                       	929 E 57th St
ST:EMAIL                         	amuir@uchicago.edu
ST:PHONE                         	7738346506
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
#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           	-	serum_DT_1	Sample source:Blood serum | Treatment:Diptheria_toxin	RAW_FILE_NAME(Raw_data_file_name)=190723_QE2_AlexanderMuir_Job1623_35.raw
SUBJECT_SAMPLE_FACTORS           	-	serum_DT_2	Sample source:Blood serum | Treatment:Diptheria_toxin	RAW_FILE_NAME(Raw_data_file_name)=190723_QE2_AlexanderMuir_Job1623_36.raw
SUBJECT_SAMPLE_FACTORS           	-	serum_DT_3	Sample source:Blood serum | Treatment:Diptheria_toxin	RAW_FILE_NAME(Raw_data_file_name)=190723_QE2_AlexanderMuir_Job1623_37.raw
SUBJECT_SAMPLE_FACTORS           	-	serum_DT_4	Sample source:Blood serum | Treatment:Diptheria_toxin	RAW_FILE_NAME(Raw_data_file_name)=190723_QE2_AlexanderMuir_Job1623_38.raw
SUBJECT_SAMPLE_FACTORS           	-	serum_DT_5	Sample source:Blood serum | Treatment:Diptheria_toxin	RAW_FILE_NAME(Raw_data_file_name)=190723_QE2_AlexanderMuir_Job1623_39.raw
SUBJECT_SAMPLE_FACTORS           	-	serum_DT_6	Sample source:Blood serum | Treatment:Diptheria_toxin	RAW_FILE_NAME(Raw_data_file_name)=190723_QE2_AlexanderMuir_Job1623_40.raw
SUBJECT_SAMPLE_FACTORS           	-	serum_noDT_1	Sample source:Blood serum | Treatment:vehicle	RAW_FILE_NAME(Raw_data_file_name)=190723_QE2_AlexanderMuir_Job1623_47.raw
SUBJECT_SAMPLE_FACTORS           	-	serum_noDT_2	Sample source:Blood serum | Treatment:vehicle	RAW_FILE_NAME(Raw_data_file_name)=190723_QE2_AlexanderMuir_Job1623_48.raw
SUBJECT_SAMPLE_FACTORS           	-	serum_noDT_3	Sample source:Blood serum | Treatment:vehicle	RAW_FILE_NAME(Raw_data_file_name)=190723_QE2_AlexanderMuir_Job1623_49.raw
SUBJECT_SAMPLE_FACTORS           	-	serum_noDT_4	Sample source:Blood serum | Treatment:vehicle	RAW_FILE_NAME(Raw_data_file_name)=190723_QE2_AlexanderMuir_Job1623_50.raw
SUBJECT_SAMPLE_FACTORS           	-	serum_noDT_5	Sample source:Blood serum | Treatment:vehicle	RAW_FILE_NAME(Raw_data_file_name)=190723_QE2_AlexanderMuir_Job1623_51.raw
SUBJECT_SAMPLE_FACTORS           	-	serum_noDT_6	Sample source:Blood serum | Treatment:vehicle	RAW_FILE_NAME(Raw_data_file_name)=190723_QE2_AlexanderMuir_Job1623_52.raw
#COLLECTION
CO:COLLECTION_SUMMARY            	Mice were euthanised 24 hours after treatment by CO2 asphyxiation and blood
CO:COLLECTION_SUMMARY            	collected through cardiac puncture. Serum was isolated using BD microtainer
CO:COLLECTION_SUMMARY            	serum separator tubes as per manufactures’ instructions and stored at -80
CO:COLLECTION_SUMMARY            	until analysis.
CO:SAMPLE_TYPE                   	Blood (serum)
#TREATMENT
TR:TREATMENT_SUMMARY             	CD11b-DTR mice were produced as an F1 cross between
TR:TREATMENT_SUMMARY             	B6.FVB-Tg(ITGAM-DTR/EGFP)34Lan/J mice and C57BL/6J mice (Jackson Laboratory).
TR:TREATMENT_SUMMARY             	Male mice between 8-12 weeks of age were used experimentally. Orthotopic PDAC
TR:TREATMENT_SUMMARY             	tumours were established from 5x104 KPC-7940B PDAC cells injected into the
TR:TREATMENT_SUMMARY             	pancreas were established as tumors for 14 days. Mice were then treated with
TR:TREATMENT_SUMMARY             	diphtheria toxin (Enzo Life Science) at a concentration of 25 ng/kg or vehicle
TR:TREATMENT_SUMMARY             	by intraperitoneal injection. Mice were euthanised 24 hours after treatment by
TR:TREATMENT_SUMMARY             	CO2 asphyxiation and blood collected through cardiac puncture. Serum was
TR:TREATMENT_SUMMARY             	isolated using BD microtainer serum separator tubes as per manufactures’
TR:TREATMENT_SUMMARY             	instructions and stored at -80 until analysis.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Metabolites were quantified as described in Sullivan et al eLife 2019 (PMID:
SP:SAMPLEPREP_SUMMARY            	30990168). Briefly, in order to quantitate metabolites in serum samples, we
SP:SAMPLEPREP_SUMMARY            	first constructed a library of 149 chemical standards of plasma polar
SP:SAMPLEPREP_SUMMARY            	metabolites. These compounds were selected to encompass a number of metabolic
SP:SAMPLEPREP_SUMMARY            	processes and have previously been included in efforts to profile plasma polar
SP:SAMPLEPREP_SUMMARY            	metabolites by LC/MS (Cantor et al., 2017; Evans et al., 2009; Lawton et al.,
SP:SAMPLEPREP_SUMMARY            	2008; Mazzone et al., 2016). We pooled these metabolites into 7 separate
SP:SAMPLEPREP_SUMMARY            	chemical standard pools. To do this, each metabolite in a given pool was weighed
SP:SAMPLEPREP_SUMMARY            	and then mixed (6 cycles of 1 min. mixing at 25 Hz followed by 3 min. resting)
SP:SAMPLEPREP_SUMMARY            	using a Mixer Mill MM301 (Retsch, Düsseldorf, Germany), and mixed metabolite
SP:SAMPLEPREP_SUMMARY            	powder stocks were stored at -20°C prior to resuspension and analysis. Stock
SP:SAMPLEPREP_SUMMARY            	solutions of the mixed standards pools containing ~5mM, ~1mM, ~300µM, ~100µM,
SP:SAMPLEPREP_SUMMARY            	~30µM, ~10µM, ~3µM and ~1µM of each metabolite were made in HPLC grade water
SP:SAMPLEPREP_SUMMARY            	and were stored at -80°C. We refer to these stock solutions as “external
SP:SAMPLEPREP_SUMMARY            	standard pools” throughout. External standard pools were used to confirm the
SP:SAMPLEPREP_SUMMARY            	retention time and m/z for each analyte and provide standards to quantitate
SP:SAMPLEPREP_SUMMARY            	concentrations of stable isotope labeled internal standards used in downstream
SP:SAMPLEPREP_SUMMARY            	analysis, as well as to quantitate metabolite concentrations in TIF and plasma
SP:SAMPLEPREP_SUMMARY            	samples directly where internal standards were not available (see below for
SP:SAMPLEPREP_SUMMARY            	details). To extract polar metabolites from plasma, TIF or the external standard
SP:SAMPLEPREP_SUMMARY            	pools, 5µL of serum or external sample pools was mixed with 45uL of
SP:SAMPLEPREP_SUMMARY            	acetonitrile:methanol:formic acid (75:25:0.1) extraction buffer including the
SP:SAMPLEPREP_SUMMARY            	following isotopically labeled internal standards: 13C labeled yeast extract
SP:SAMPLEPREP_SUMMARY            	(Cambridge Isotope Laboratory, Andover, MA, ISO1), 13C3 lactate (Sigma Aldrich,
SP:SAMPLEPREP_SUMMARY            	Darmstadt, Germany, 485926), 13C3 glycerol (Cambridge Isotope Laboratory,
SP:SAMPLEPREP_SUMMARY            	Andover, MA, CLM-1510), 13C6 15N2 cystine (Cambridge Isotope Laboratory,
SP:SAMPLEPREP_SUMMARY            	Andover, MA, CNLM-4244), 2H9 choline (Cambridge Isotope Laboratory, Andover, MA,
SP:SAMPLEPREP_SUMMARY            	DLM-549), 13C4 3-hydroxybutyrate (Cambridge Isotope Laboratory, Andover, MA,
SP:SAMPLEPREP_SUMMARY            	CLM-3853), 13C6 glucose (Cambridge Isotope Laboratory, Andover, MA, CLM-1396),
SP:SAMPLEPREP_SUMMARY            	13C2 15N taurine (Cambridge Isotope Laboratory, Andover, MA, CNLM-10253), 2H3
SP:SAMPLEPREP_SUMMARY            	creatinine (Cambridge Isotope Laboratory, Andover, MA, DLM-3653), 8-13C adenine
SP:SAMPLEPREP_SUMMARY            	(Cambridge Isotope Laboratory, Andover, MA, CLM-1654), 13C5 hypoxanthine
SP:SAMPLEPREP_SUMMARY            	(Cambridge Isotope Laboratory, Andover, MA, CLM-8042), 8-13C guanine (Cambridge
SP:SAMPLEPREP_SUMMARY            	Isotope Laboratory, Andover, MA, CLM-1019), 13C3 serine (Cambridge Isotope
SP:SAMPLEPREP_SUMMARY            	Laboratory, Andover, MA, CLM-1574) and 13C2 glycine (Cambridge Isotope
SP:SAMPLEPREP_SUMMARY            	Laboratory, Andover, MA, CLM-1017). All solvents used in the extraction buffer
SP:SAMPLEPREP_SUMMARY            	were HPLC grade. Samples were then vortexed for 10 min. at 4°C and insoluble
SP:SAMPLEPREP_SUMMARY            	material was sedimented by centrifugation at 15kg for 10 min. at 4°C. 20µL of
SP:SAMPLEPREP_SUMMARY            	the soluble polar metabolite extract was taken for LC/MS analysis.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Thermo Dionex Ultimate 3000
CH:COLUMN_NAME                   	SeQuant ZIC-pHILIC (150 x 2.1mm,5um)
CH:SOLVENT_A                     	100% water; 20 mM ammonium carbonate, 0.1% ammonium hydroxide
CH:SOLVENT_B                     	100% acetonitrile
CH:FLOW_GRADIENT                 	linear gradient from 80% to 20% B; 20-20.5 min: linear gradient from 20% to 80%
CH:FLOW_GRADIENT                 	B; 20.5-28min: hold at 80% B.
CH:FLOW_RATE                     	0.150 mL/min
CH:COLUMN_TEMPERATURE            	25
#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                   	LC/MS analysis was performed using a QExactive orbitrap mass spectrometer using
MS:MS_COMMENTS                   	an Ion Max source and heated electrospray ionization (HESI) probe coupled to a
MS:MS_COMMENTS                   	Dionex Ultimate 3000 UPLC system (Thermo Fisher Scientific, Waltham, MA).
MS:MS_COMMENTS                   	External mass calibration was performed every 7 days. 2μL of each sample was
MS:MS_COMMENTS                   	injected onto a ZIC-pHILIC 2.1 × 150 mm analytical column equipped with a 2.1
MS:MS_COMMENTS                   	× 20 mm guard column (both 5 μm particle size, EMD Millipore). The autosampler
MS:MS_COMMENTS                   	and column oven were held at 4°C and 25°C, respectively. Buffer A was 20 mM
MS:MS_COMMENTS                   	ammonium carbonate, 0.1% ammonium hydroxide; buffer B was acetonitrile. The
MS:MS_COMMENTS                   	chromatographic gradient was run at a flow rate of 0.150 mL/min as follows: 0-20
MS:MS_COMMENTS                   	min: linear gradient from 80% to 20% B; 20-20.5 min: linear gradient from 20% to
MS:MS_COMMENTS                   	80% B; 20.5-28min: hold at 80% B. The mass spectrometer was operated in full
MS:MS_COMMENTS                   	scan, polarity-switching mode with the spray voltage set to 3.0 kV, the heated
MS:MS_COMMENTS                   	capillary held at 275°C, and the HESI probe held at 350°C. The sheath gas flow
MS:MS_COMMENTS                   	rate was set to 40 units, the auxiliary gas flow was set to 15 units, and the
MS:MS_COMMENTS                   	sweep gas flow was set to 1 unit. The MS data acquisition was performed in a
MS:MS_COMMENTS                   	range of 70-1000 m/z, with the resolution set to 70,000, the AGC target at 1e6,
MS:MS_COMMENTS                   	and the maximum injection time at 20 msec. Metabolite identification and
MS:MS_COMMENTS                   	quantification was performed with XCalibur 2.2 software (Thermo Fisher
MS:MS_COMMENTS                   	Scientific, Waltham, MA) using a 5ppm mass accuracy and a 0.5 min. retention
MS:MS_COMMENTS                   	time window. For metabolite identification, external standard pools were used
MS:MS_COMMENTS                   	for assignment of metabolites to peaks at given m/z and retention time, and to
MS:MS_COMMENTS                   	determine the limit of detection for each metabolite. Metabolite quantification
MS:MS_COMMENTS                   	was performed by two separate methods. Where internal standards were available,
MS:MS_COMMENTS                   	first, comparison of the peak areas of the stable isotope labeled internal
MS:MS_COMMENTS                   	standards with the external standard pools allowed for quantification of the
MS:MS_COMMENTS                   	concentration of labeled internal standards in the extraction buffer.
MS:MS_COMMENTS                   	Subsequently, we compared the peak area of a given metabolite in the TIF and
MS:MS_COMMENTS                   	plasma samples with the peak area of the internal standard to quantitate the
MS:MS_COMMENTS                   	concentration of that metabolite in the serum sample. For metabolites without
MS:MS_COMMENTS                   	internal standards, the peak area of each analyte was normalized to the peak
MS:MS_COMMENTS                   	area of a labeled amino acid internal standard that eluted at roughly the same
MS:MS_COMMENTS                   	retention time to account for differences in recovery between samples. From the
MS:MS_COMMENTS                   	normalized peak areas of metabolites in the external standard pools, we
MS:MS_COMMENTS                   	generated a standard curve describing the relationship between metabolite
MS:MS_COMMENTS                   	concentration and normalized peak area. The standard curves were linear with
MS:MS_COMMENTS                   	fits typically at or above r2=0.95. Metabolites which did not meet these
MS:MS_COMMENTS                   	criteria were excluded from further analysis. These equations were then used to
MS:MS_COMMENTS                   	convert normalized peak areas of analytes in the serum samples into analyte
MS:MS_COMMENTS                   	concentration in the samples. The relationship between metabolite concentration
MS:MS_COMMENTS                   	and normalized peak area is matrix dependent, and the external standards are
MS:MS_COMMENTS                   	prepared in water, which is a different matrix than serum. Therefore, we
MS:MS_COMMENTS                   	consider metabolite measurements using this external standard method
MS:MS_COMMENTS                   	semi-quantitative.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	micromole/L
MS_METABOLITE_DATA_START
Samples	serum_DT_1	serum_DT_2	serum_DT_3	serum_DT_4	serum_DT_5	serum_DT_6	serum_noDT_1	serum_noDT_2	serum_noDT_3	serum_noDT_4	serum_noDT_5	serum_noDT_6
Factors	Sample source:Blood serum | Treatment:Diptheria_toxin	Sample source:Blood serum | Treatment:Diptheria_toxin	Sample source:Blood serum | Treatment:Diptheria_toxin	Sample source:Blood serum | Treatment:Diptheria_toxin	Sample source:Blood serum | Treatment:Diptheria_toxin	Sample source:Blood serum | Treatment:Diptheria_toxin	Sample source:Blood serum | Treatment:vehicle	Sample source:Blood serum | Treatment:vehicle	Sample source:Blood serum | Treatment:vehicle	Sample source:Blood serum | Treatment:vehicle	Sample source:Blood serum | Treatment:vehicle	Sample source:Blood serum | Treatment:vehicle
2-aminobutyrate	16.58206841	10.40826316	8.797613955	11.18974295	7.000373744	10.46246429	22.80401203	21.81586947	33.89294099	24.19108908	28.005384	9.26986781
N6-acetyllysine	0.553791277	0.594841806	0.576745977	1.105778364	0.689065803	0.643398049	0.640196393	0.358792331	0.824000462	0.965811647	0.853440137	0.536461239
gamma-glutamyl-alanine	0.921868417	1.831219108	0.889718035		1.228854241	1.078860516	1.596024465	0.169631525	1.025482231		0	0.761911066
pantothenate	2.433377291	3.590881119	2.764160155	2.825014459	2.23656454	3.475354039	4.714815782	4.446637484	3.211570513	4.441922265	5.604054452	1.978618784
glycerophosphocholine	27.36178057	8.930696976	27.10518938	34.44467288	12.37919919	16.55067531	654.5172655	1024.280043	542.002414	745.8400036	1569.936761	154.6471897
aminoadipate	9.541266419	5.057720982	6.594377594	11.3957707	12.57823715	12.80687666	21.92524036	20.34622188	19.74723015	28.3593168	20.30044331	10.28526151
cystathionine	1.778018851	1.3277972	2.134931637	2.840104911	2.079586818	2.118562662	6.276123121	7.321769109	10.95049747	8.117833929	10.93936533	4.791443744
niacinamide	6.576988383	4.553413699	6.026329097	9.481170161	5.621145859	7.16778238	66.17522048	100.0437354	68.40451919	73.04007657	119.5749752	19.02425624
methylthioadenosine	0.010952009	0.013680545	0.013986713	0.02184472	0.010110219	0.018764162	0.214906831	0.534265703	0.371770746	0.421547422	0.446626501	0.080773581
SAH	0.063912433	0.151959743	0	0.16882824	0	0.707254059	0.070260335	0.35551796	0.032184404	0.14156361	0.099431255	0
methionine sulfoxide	2.006015087	2.645910612	2.678561032	4.333297843	3.577822417	1.810846295	4.632365534	2.898114402	5.417978786	5.462493236	3.467551248	1.476162568
acetylglutamate	0.363548652	0.352242223	0.157599773	0.468821242	0.178783924	0.555043221	0.638828606	0.54196071	0.727423224	0.86164877	0.971261012	0.248441695
asymmetric dimethylarginine	0.909507393	1.931551419	1.108846067	0.888622968	0.78274502	2.544688054	0.84228	0.578350491	1.634995289	0.905484833	0.875561497	1.4806692
trimethyllysine	0.816340745	0.802510252	1.20613032	1.310868489	1.415009616	1.264636302	1.704423408	0.906038238	1.410257952	2.593566706	2.0386802	1.299055851
creatinine	6.904493612	8.192232234	9.653837157	11.88348617	12.59013677	9.994774245	26.55051999	13.34401373	16.38811656	21.12444243	30.54032865	7.86556262
acetylalanine	0.327405877	1.516412352	0	2.574038865	0	0	7.216375906	0	6.674269723	0	1.976552781	4.786887817
3-hydroxybutyrate	155.3051279	161.409914	159.9282278	183.1314695	197.3921599	447.4164091	21.63571328	22.07958817	27.41639114	71.67442351	79.55329344	35.21790871
hypoxanthine	0.02386804	0.016306091	0.042243435	0.101605121	6.698904751	0.114315073	45.92013553	197.2033046	17.57073038	10.27122802	205.2447652	7.066315851
acetylglutamine	1.228685994	0.635126045	0.566382491	1.878659603	0.630897139	2.152175671	0.567654495	0.857547076	0.904260798	0.759544783	0.986038472	0.497761683
NAD	0	0	0	0	0	0	0	0	0	0	0	0
gaba	0	0.170729934	0	0	0	0.114684096	0.83689396	0	0	1.242254494	6.096206803	0.140836672
phosphocholine	3.24795529	2.99545579	2.789018026	3.530169947	2.758232729	6.030024923	381.4130896	884.9933323	397.2791976	480.9045921	791.8220878	69.21551607
gssg	13.61146912	14.72704248	5.245865523	42.78405993	7.317904748	17.53140884	171.6677236	384.7492953	129.7301866	156.7802848	334.7067768	41.55930891
choline	69.95580677	64.41025134	71.03574	88.89487317	43.41053457	140.101752	252.1209757	289.0483058	214.5479322	238.3381602	426.1847314	69.09686671
gsh	0.194121023	0.156030337	0.130188133	0.176090905	0.073176267	0.156456204	1.056979569	12.93405434	0.585151367	0.351093216	4.210889917	2.641063139
UMP	0	0	0	0	0	0	44.52067157	77.95674414	68.18578789	74.61440851	88.86688341	13.82647387
CMP	0	0	0	0	0	0	14.53422116	19.94607564	19.03830469	22.23093118	23.43119493	4.922055739
phenylalanine	117.7058749	160.4937958	127.8572526	173.83861	101.6037433	155.2187652	141.9252023	110.9786649	162.1474704	180.8273427	175.1320259	109.0978284
leucine	290.3664773	305.4109804	318.2549728	449.7186174	200.4109316	325.6982804	380.4528715	297.5540052	406.9534499	462.8105462	383.8202716	296.7924931
methionine	71.67479401	89.27718133	107.5872104	104.4983945	90.72091545	71.4190615	136.1323636	104.5356058	152.0016261	158.2260982	133.5228458	75.07103523
tryptophan	110.798161	102.3252978	107.1217146	129.2691453	81.23862266	106.0918156	110.0373878	51.27751757	75.97122499	117.0475326	105.3382284	53.91219867
valine	304.4737664	339.1615472	326.7038854	430.3817347	237.3426702	339.7924487	370.7764096	324.3272781	497.1842233	501.8346726	363.9440374	300.8244377
proline	86.84299935	138.9722274	115.0173409	122.5672023	102.9732806	88.48479683	286.6094858	304.3340273	347.9441478	323.8690954	392.0234986	157.5586823
tyrosine	93.22945255	134.0614888	85.42853819	123.7170421	82.17040103	101.1883383	164.9191054	110.6924331	177.1011622	171.8363383	237.0968764	84.56116029
threonine	171.9693614	182.8800807	216.2774844	185.6777109	182.8086426	151.570958	396.3117155	334.8560494	435.6112429	408.6750466	371.6286821	206.9322863
histidine	85.24093507	124.1763113	118.869703	140.6127544	94.81402899	96.49291106	147.5013642	148.235936	167.6848855	169.3015812	184.1496002	156.9406138
alanine	447.8084778	755.1773225	608.6514628	546.6275583	458.1140048	591.2069414	1410.933163	1495.63889	1261.653327	1407.546212	2369.731479	645.8904399
isoleucine	168.9898402	169.3224022	169.7572562	252.2496474	118.5231478	208.9515648	203.1564022	159.3161333	229.7469553	247.4684718	207.8138844	144.2249672
glutamine	1187.94565	1376.471018	1767.25918	1717.187257	1180.784692	1411.888659	1068.386103	944.036859	1001.389767	1057.246616	1202.90923	859.3459131
asparagine	43.06883637	106.6047347	56.33323331	50.92651089	42.96179117	48.02743125	148.4491069	134.8620582	134.2679817	140.7812958	259.6156289	81.78077521
glycine	304.1010581	434.8457489	412.1254199	367.4467913	330.3174614	365.0538523	1187.021805	1494.231468	1818.944297	1468.910138	1921.037769	633.388181
citrulline	68.26234406	82.75077816	82.02820536	101.4801354	80.39815966	57.55068203	103.3090189	84.52580949	92.15788694	90.77249796	94.72732235	63.12795945
cystine	2.681833799	2.197004783	3.327847825	4.610249062	9.275564219	6.157629541	16.14776252	10.53865802	28.35859955	23.08870064	12.44330138	33.7864684
ornithine	106.9807828	192.778119	161.2691093	181.3117584	145.0074077	111.4061745	414.9906027	242.2405921	372.7841733	352.763636	314.7542017	224.1817948
lysine	393.611208	455.9314728	594.5171758	609.5928814	403.1729341	406.8224185	569.9721103	425.4964091	613.7122878	649.999406	542.4498774	407.9282905
arginine	269.4821649	214.4408662	375.0749735	400.2240465	266.4652428	269.3347424	4.395211891	3.757559975	4.96165094	8.09232496	6.10607161	17.95285607
indolelactate	0	0	0	0	0	0	0	0	0	0	0	0
picolinate	0	0	0	0	0	0	0	0	0	0	0	0
homocysteine	0	0	0	0	0	0	0	0	0	0	0	0
cys-gly	0	0	0	0	0	0	0	0	0	0	0	0
sarcosine	0.44	0.61	1.21	0.02	0.24	0.32	1.41	1.81	3.2	1.47	1.5	0.28
homocitrulline	0	0	0	0	0	0	0	0	0	0	0	0
riboflavin	0	0	0	0	0	0	0	0	0	0	0	0
inosine	0	0	0	0	20.77	0	35.52	48.64	4.88	39.24	31.84	8.8
beta-alanine	0	0	0	0	0	0	26.45	34.48	22.6	35.02	47.68	0
kynurenine	0.71	2.16	1.58	2.56	2.08	1	6.82	6.95	17.28	10.11	17.28	7.64
guanidinoacetate	0	0	0	0	0	3.9	0	0	58.07	4239.87	0	0
glycerol-3-phosphate	0	0	0	0	0	0	0	0	0	0	0	0
NADP	0	0	0	0	0	0	0	0	0	0	0	0
fructose-1,6-bisphosphate	0	0	0	0	0	0	0	0	0	0	0	0
phenylacetylglutamine	0	0	0	0	0	0	0	0	0	0	0	0
pyridoxine	0	0	0	0	0	0	0	0	0	0	0	0
deoxycytidine	0.83	0.78	1.37	0.84	0.78	0.72	0.79	0.18	0.94	0.8	0.75	1
hypotaurine	0	0	0	0	0	0	0	0	0	0	0	0
phosphocreatine	0	0	0	0	0.53	0	151.33	56.48	111.32	156.59	86.06	38.97
dATP	0	0	0	0	0	0	0	0	0	0	0	0
folate	0	0	0	0	0	0	0	0	0	0	0	0
acetylcarnitine	29.8	33.01	40.31	39.53	18.82	34.64	39.51	28.15	34.21	45.17	55.4	18.46
CoA	0	0	0	0	0	0	0	0	0	0	0	0
acetylaspartate	0	0	0	0	0	0	0	0	0	0	0	0
ADP	0	0	0	0	0	0	0	0	0	0	0.61	0
CDP-choline	0	0	0	0	0	0	0	0	0	0	0	0
UDP	0	0	0	0	0	0	0	0	0	0	0	0
CDP	0	0	0	0	0	0	0	0	0	0	0	0
GDP	0	0	0	0	0	0	0	0	0	0	0	0
pyridoxal	0.11	0.17	0.06	0.2	0.04	0.28	0.1	0.04	0.28	0.22	0	0.14
biotin	0.01	0.03	0.02	0.01	0	0	0	0	0	0	0	0
betaine	107.82	81.6	129.44	75.38	41.95	81.45	124.13	70.62	133.12	116.18	146.06	69.03
cytidine	0	0	0	0	0	0	0	0	0	0	0	0
trans-urocanate	0	0.48	0.44	1.36	0.49	0.17	1.8	1.71	0.79	2.3	2.1	0.58
creatine	52.25	76.91	92.16	61.1	86.99	72.33	806.5	527.36	321.25	318.19	1158.15	114.79
carnosine	0	0	0	0	0	0	0	0	0	0	0	0
IMP	0	0	0	0	0	0	0	0	0	0	0	0
hydroxyproline	1.28	2.48	1.84	4.16	1.24	4.05	0	0	8.68	5.68	0	5.16
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name
2-aminobutyrate
N6-acetyllysine
gamma-glutamyl-alanine
pantothenate
glycerophosphocholine
aminoadipate
cystathionine
niacinamide
methylthioadenosine
SAH
methionine sulfoxide
acetylglutamate
asymmetric dimethylarginine
trimethyllysine
creatinine
acetylalanine
3-hydroxybutyrate
hypoxanthine
acetylglutamine
NAD
gaba
phosphocholine
gssg
choline
gsh
UMP
CMP
phenylalanine
leucine
methionine
tryptophan
valine
proline
tyrosine
threonine
histidine
alanine
isoleucine
glutamine
asparagine
glycine
citrulline
cystine
ornithine
lysine
arginine
indolelactate
picolinate
homocysteine
cys-gly
sarcosine
homocitrulline
riboflavin
inosine
beta-alanine
kynurenine
guanidinoacetate
glycerol-3-phosphate
NADP
fructose-1,6-bisphosphate
phenylacetylglutamine
pyridoxine
deoxycytidine
hypotaurine
phosphocreatine
dATP
folate
acetylcarnitine
CoA
acetylaspartate
ADP
CDP-choline
UDP
CDP
GDP
pyridoxal
biotin
betaine
cytidine
trans-urocanate
creatine
carnosine
IMP
hydroxyproline
METABOLITES_END
#END