#METABOLOMICS WORKBENCH RCulpHill_20220309_150107_mwtab.txt DATATRACK_ID:3119 STUDY_ID:ST002110 ANALYSIS_ID:AN003452 PROJECT_ID:PR001336
VERSION             	1
CREATED_ON             	March 18, 2022, 8:33 am
#PROJECT
PR:PROJECT_TITLE                 	Towards a mechanistic understanding of patient response to neoadjuvant SBRT with
PR:PROJECT_TITLE                 	anti-PDL1 in human HPV-unrelated locally advanced HNSCC: Phase I/Ib trial
PR:PROJECT_TITLE                 	results
PR:PROJECT_SUMMARY               	Five-year survival for HPV-unrelated head and neck squamous cell carcinomas
PR:PROJECT_SUMMARY               	(HNSCC) remains below 50%. We assessed the safety of administering combination
PR:PROJECT_SUMMARY               	hypofractionated stereotactic body radiation therapy (SBRT) with anti-PDL-1
PR:PROJECT_SUMMARY               	neoadjuvantly followed by adjuvant anti-PDL-1 with standard of care therapy
PR:PROJECT_SUMMARY               	(n=21). The primary endpoint of the study was safety, which was met. Secondary
PR:PROJECT_SUMMARY               	endpoints included radiographic, pathologic, and objective response,
PR:PROJECT_SUMMARY               	locoregional control (LRC), progression-free survival (PFS), and overall
PR:PROJECT_SUMMARY               	survival (OS). Among evaluable patients at early median follow-up of 16 months
PR:PROJECT_SUMMARY               	(448 days), OS was 83.3%, LRC and PFS were 83.3%, and major pathological
PR:PROJECT_SUMMARY               	response (MPR) or complete response (CR) was 75%. Circulating CD8/Treg ratio,
PR:PROJECT_SUMMARY               	CD4 effector memory T cells, and TCR repertoire emerged as biologic correlates
PR:PROJECT_SUMMARY               	of response to therapy. Using high-dimensional multi-omics and spatial data as
PR:PROJECT_SUMMARY               	well as biological correlatives pre- and post-treatment, three major changes
PR:PROJECT_SUMMARY               	were noted in responders within the tumor microenvironment (TME) (and within the
PR:PROJECT_SUMMARY               	blood) post-treatment: 1) an increase in effector T cells; 2) a decrease in
PR:PROJECT_SUMMARY               	immunosuppressive cells; and 3) an increase in antigen presentation.
PR:PROJECT_SUMMARY               	Non-responders appeared to fail due to a lack of one of these three identified
PR:PROJECT_SUMMARY               	steps needed for priming and maintaining activation of T cells. Multiple
PR:PROJECT_SUMMARY               	correlates for response, along with subsets of non-responders that may benefit
PR:PROJECT_SUMMARY               	from additional or alternative immunotherapies, were identified. This treatment
PR:PROJECT_SUMMARY               	is being tested in an ongoing phase II trial with a similar design, where we
PR:PROJECT_SUMMARY               	hope to confirm and expand on our understanding of the mechanisms underlying
PR:PROJECT_SUMMARY               	resistance to therapy.
PR:INSTITUTE                     	University of Colorado Denver
PR:LAST_NAME                     	Culp-Hill
PR:FIRST_NAME                    	Rachel
PR:ADDRESS                       	12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA
PR:EMAIL                         	rachel.hill@cuanschutz.edu
PR:PHONE                         	303-724-5798
#STUDY
ST:STUDY_TITLE                   	Towards a mechanistic understanding of patient response to neoadjuvant SBRT with
ST:STUDY_TITLE                   	anti-PDL1 in human HPV-unrelated locally advanced HNSCC: Phase I/Ib trial
ST:STUDY_TITLE                   	results (Part 2)
ST:STUDY_SUMMARY                 	Five-year survival for HPV-unrelated head and neck squamous cell carcinomas
ST:STUDY_SUMMARY                 	(HNSCC) remains below 50%. We assessed the safety of administering combination
ST:STUDY_SUMMARY                 	hypofractionated stereotactic body radiation therapy (SBRT) with anti-PDL-1
ST:STUDY_SUMMARY                 	neoadjuvantly followed by adjuvant anti-PDL-1 with standard of care therapy
ST:STUDY_SUMMARY                 	(n=21). The primary endpoint of the study was safety, which was met. Secondary
ST:STUDY_SUMMARY                 	endpoints included radiographic, pathologic, and objective response,
ST:STUDY_SUMMARY                 	locoregional control (LRC), progression-free survival (PFS), and overall
ST:STUDY_SUMMARY                 	survival (OS). Among evaluable patients at early median follow-up of 16 months
ST:STUDY_SUMMARY                 	(448 days), OS was 83.3%, LRC and PFS were 83.3%, and major pathological
ST:STUDY_SUMMARY                 	response (MPR) or complete response (CR) was 75%. Circulating CD8/Treg ratio,
ST:STUDY_SUMMARY                 	CD4 effector memory T cells, and TCR repertoire emerged as biologic correlates
ST:STUDY_SUMMARY                 	of response to therapy. Using high-dimensional multi-omics and spatial data as
ST:STUDY_SUMMARY                 	well as biological correlatives pre- and post-treatment, three major changes
ST:STUDY_SUMMARY                 	were noted in responders within the tumor microenvironment (TME) (and within the
ST:STUDY_SUMMARY                 	blood) post-treatment: 1) an increase in effector T cells; 2) a decrease in
ST:STUDY_SUMMARY                 	immunosuppressive cells; and 3) an increase in antigen presentation.
ST:STUDY_SUMMARY                 	Non-responders appeared to fail due to a lack of one of these three identified
ST:STUDY_SUMMARY                 	steps needed for priming and maintaining activation of T cells. Multiple
ST:STUDY_SUMMARY                 	correlates for response, along with subsets of non-responders that may benefit
ST:STUDY_SUMMARY                 	from additional or alternative immunotherapies, were identified. This treatment
ST:STUDY_SUMMARY                 	is being tested in an ongoing phase II trial with a similar design, where we
ST:STUDY_SUMMARY                 	hope to confirm and expand on our understanding of the mechanisms underlying
ST:STUDY_SUMMARY                 	resistance to therapy.
ST:INSTITUTE                     	University of Colorado Denver
ST:LAST_NAME                     	Culp-Hill
ST:FIRST_NAME                    	Rachel
ST:ADDRESS                       	12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA
ST:EMAIL                         	rachel.hill@cuanschutz.edu
ST:PHONE                         	303-724-5798
#SUBJECT
SU:SUBJECT_TYPE                  	Human
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
#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           	-	BW48-36	NA:NA | Pre:Pre	RAW_FILE_NAME=BW48-36
SUBJECT_SAMPLE_FACTORS           	-	BW48-37	NA:NA | Pre:Pre	RAW_FILE_NAME=BW48-37
SUBJECT_SAMPLE_FACTORS           	-	BW48-40	NA:NA | Pre:Post	RAW_FILE_NAME=BW48-40
SUBJECT_SAMPLE_FACTORS           	-	BW48-39	NA:NA | Pre:Post	RAW_FILE_NAME=BW48-39
SUBJECT_SAMPLE_FACTORS           	-	BW48-38	NA:NA | Pre:Post	RAW_FILE_NAME=BW48-38
SUBJECT_SAMPLE_FACTORS           	-	BW48-4	NA:non-responder | Pre:Pre	RAW_FILE_NAME=BW48-4
SUBJECT_SAMPLE_FACTORS           	-	BW48-6	NA:non-responder | Pre:Pre	RAW_FILE_NAME=BW48-6
SUBJECT_SAMPLE_FACTORS           	-	BW48-24	NA:non-responder | Pre:Pre	RAW_FILE_NAME=BW48-24
SUBJECT_SAMPLE_FACTORS           	-	BW48-28	NA:non-responder | Pre:Pre	RAW_FILE_NAME=BW48-28
SUBJECT_SAMPLE_FACTORS           	-	BW48-1	NA:non-responder | Pre:Post	RAW_FILE_NAME=BW48-1
SUBJECT_SAMPLE_FACTORS           	-	BW48-5	NA:non-responder | Pre:Post	RAW_FILE_NAME=BW48-5
SUBJECT_SAMPLE_FACTORS           	-	BW48-7	NA:non-responder | Pre:Post	RAW_FILE_NAME=BW48-7
SUBJECT_SAMPLE_FACTORS           	-	BW48-25	NA:non-responder | Pre:Post	RAW_FILE_NAME=BW48-25
SUBJECT_SAMPLE_FACTORS           	-	BW48-29	NA:non-responder | Pre:Post	RAW_FILE_NAME=BW48-29
SUBJECT_SAMPLE_FACTORS           	-	BW48-2	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-2
SUBJECT_SAMPLE_FACTORS           	-	BW48-8	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-8
SUBJECT_SAMPLE_FACTORS           	-	BW48-10	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-10
SUBJECT_SAMPLE_FACTORS           	-	BW48-12	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-12
SUBJECT_SAMPLE_FACTORS           	-	BW48-14	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-14
SUBJECT_SAMPLE_FACTORS           	-	BW48-16	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-16
SUBJECT_SAMPLE_FACTORS           	-	BW48-18	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-18
SUBJECT_SAMPLE_FACTORS           	-	BW48-20	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-20
SUBJECT_SAMPLE_FACTORS           	-	BW48-22	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-22
SUBJECT_SAMPLE_FACTORS           	-	BW48-26	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-26
SUBJECT_SAMPLE_FACTORS           	-	BW48-30	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-30
SUBJECT_SAMPLE_FACTORS           	-	BW48-32	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-32
SUBJECT_SAMPLE_FACTORS           	-	BW48-34	NA:Responder | Pre:Pre	RAW_FILE_NAME=BW48-34
SUBJECT_SAMPLE_FACTORS           	-	BW48-3	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-3
SUBJECT_SAMPLE_FACTORS           	-	BW48-9	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-9
SUBJECT_SAMPLE_FACTORS           	-	BW48-11	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-11
SUBJECT_SAMPLE_FACTORS           	-	BW48-13	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-13
SUBJECT_SAMPLE_FACTORS           	-	BW48-15	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-15
SUBJECT_SAMPLE_FACTORS           	-	BW48-17	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-17
SUBJECT_SAMPLE_FACTORS           	-	BW48-19	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-19
SUBJECT_SAMPLE_FACTORS           	-	BW48-21	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-21
SUBJECT_SAMPLE_FACTORS           	-	BW48-23	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-23
SUBJECT_SAMPLE_FACTORS           	-	BW48-27	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-27
SUBJECT_SAMPLE_FACTORS           	-	BW48-31	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-31
SUBJECT_SAMPLE_FACTORS           	-	BW48-33	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-33
SUBJECT_SAMPLE_FACTORS           	-	BW48-35	NA:Responder | Pre:Post	RAW_FILE_NAME=BW48-35
#COLLECTION
CO:COLLECTION_SUMMARY            	This was a multi-center, prospective, single-arm phase I/Ib safety trial.
CO:COLLECTION_SUMMARY            	Patients eligible for treatment had to be diagnosed with non-metastatic,
CO:COLLECTION_SUMMARY            	biopsy-proven p16-negative histology squamous cell carcinoma of the oral cavity,
CO:COLLECTION_SUMMARY            	oropharynx, larynx, or hypopharynx, and had to be eligible and amenable to
CO:COLLECTION_SUMMARY            	surgical resection. This study enrolled using a 3+3 model. Patients received one
CO:COLLECTION_SUMMARY            	dose of neoadjuvant Durvalumab 1500 mg approximately 3-6 weeks before
CO:COLLECTION_SUMMARY            	standard-of-care surgery given concurrently with the first dose of radiation
CO:COLLECTION_SUMMARY            	(RT). The starting RT dose level was 6 Gy for 2 fractions (12 Gy total) every
CO:COLLECTION_SUMMARY            	other day over approximately one week to sites of gross disease (Table 1) to
CO:COLLECTION_SUMMARY            	minimize exposure to normal tissue. If toxicity developed and surgery was
CO:COLLECTION_SUMMARY            	delayed by more than 6 weeks due to treatment toxicity (qualifying as a DLT),
CO:COLLECTION_SUMMARY            	the radiation dose was set to be dropped per protocol for the next set of
CO:COLLECTION_SUMMARY            	patients. If this dose was tolerated, the dose was increased to 6 Gy for 3
CO:COLLECTION_SUMMARY            	fractions (18 Gy total) for the next 3 patients. Patients proceeded to surgical
CO:COLLECTION_SUMMARY            	resection approximately 3-6 weeks after radiation as recommended by the ENT
CO:COLLECTION_SUMMARY            	surgeon. Post-operatively, pathology was reviewed at the multi-disciplinary head
CO:COLLECTION_SUMMARY            	and neck conference, and the need for adjuvant therapy was discussed. For the
CO:COLLECTION_SUMMARY            	first 8 patients, all patients were given adjuvant therapy based on presenting
CO:COLLECTION_SUMMARY            	features. However, after patient 8, adjuvant therapy was dictated based on
CO:COLLECTION_SUMMARY            	high-risk pathologic features as per the NCCN guidelines and treating physician
CO:COLLECTION_SUMMARY            	recommendations. Adjuvant radiation included intensity-modulated radiation
CO:COLLECTION_SUMMARY            	therapy of 60 Gy in 2 Gy once-daily fraction size once-daily fraction size
CO:COLLECTION_SUMMARY            	(total of 30 fractions). If indicated, adjuvant systemic therapy included
CO:COLLECTION_SUMMARY            	cisplatin or other cytotoxic chemotherapy or targeted biologics (Cetuximab) per
CO:COLLECTION_SUMMARY            	physician discretion. All patients received adjuvant durvalumab to be initiated
CO:COLLECTION_SUMMARY            	approximately 6-12 weeks post-surgery. It was given as 1500 mg intravenously
CO:COLLECTION_SUMMARY            	once every 4 weeks for a maximum of 6 doses, or until progression, toxicity, or
CO:COLLECTION_SUMMARY            	withdrawal from study. This was delivered either as monotherapy or concurrently
CO:COLLECTION_SUMMARY            	with adjuvant radiation +/- systemic therapy for high-risk patients. Safety and
CO:COLLECTION_SUMMARY            	toxicity evaluations were done throughout the study process. DLTs and adjustment
CO:COLLECTION_SUMMARY            	of radiation doses were done during the neoadjuvant period.
CO:SAMPLE_TYPE                   	Blood (plasma)
#TREATMENT
TR:TREATMENT_SUMMARY             	This was a multi-center, prospective, single-arm phase I/Ib safety trial.
TR:TREATMENT_SUMMARY             	Patients eligible for treatment had to be diagnosed with non-metastatic,
TR:TREATMENT_SUMMARY             	biopsy-proven p16-negative histology squamous cell carcinoma of the oral cavity,
TR:TREATMENT_SUMMARY             	oropharynx, larynx, or hypopharynx, and had to be eligible and amenable to
TR:TREATMENT_SUMMARY             	surgical resection. This study enrolled using a 3+3 model. Patients received one
TR:TREATMENT_SUMMARY             	dose of neoadjuvant Durvalumab 1500 mg approximately 3-6 weeks before
TR:TREATMENT_SUMMARY             	standard-of-care surgery given concurrently with the first dose of radiation
TR:TREATMENT_SUMMARY             	(RT). The starting RT dose level was 6 Gy for 2 fractions (12 Gy total) every
TR:TREATMENT_SUMMARY             	other day over approximately one week to sites of gross disease (Table 1) to
TR:TREATMENT_SUMMARY             	minimize exposure to normal tissue. If toxicity developed and surgery was
TR:TREATMENT_SUMMARY             	delayed by more than 6 weeks due to treatment toxicity (qualifying as a DLT),
TR:TREATMENT_SUMMARY             	the radiation dose was set to be dropped per protocol for the next set of
TR:TREATMENT_SUMMARY             	patients. If this dose was tolerated, the dose was increased to 6 Gy for 3
TR:TREATMENT_SUMMARY             	fractions (18 Gy total) for the next 3 patients. Patients proceeded to surgical
TR:TREATMENT_SUMMARY             	resection approximately 3-6 weeks after radiation as recommended by the ENT
TR:TREATMENT_SUMMARY             	surgeon. Post-operatively, pathology was reviewed at the multi-disciplinary head
TR:TREATMENT_SUMMARY             	and neck conference, and the need for adjuvant therapy was discussed. For the
TR:TREATMENT_SUMMARY             	first 8 patients, all patients were given adjuvant therapy based on presenting
TR:TREATMENT_SUMMARY             	features. However, after patient 8, adjuvant therapy was dictated based on
TR:TREATMENT_SUMMARY             	high-risk pathologic features as per the NCCN guidelines and treating physician
TR:TREATMENT_SUMMARY             	recommendations. Adjuvant radiation included intensity-modulated radiation
TR:TREATMENT_SUMMARY             	therapy of 60 Gy in 2 Gy once-daily fraction size once-daily fraction size
TR:TREATMENT_SUMMARY             	(total of 30 fractions). If indicated, adjuvant systemic therapy included
TR:TREATMENT_SUMMARY             	cisplatin or other cytotoxic chemotherapy or targeted biologics (Cetuximab) per
TR:TREATMENT_SUMMARY             	physician discretion. All patients received adjuvant durvalumab to be initiated
TR:TREATMENT_SUMMARY             	approximately 6-12 weeks post-surgery. It was given as 1500 mg intravenously
TR:TREATMENT_SUMMARY             	once every 4 weeks for a maximum of 6 doses, or until progression, toxicity, or
TR:TREATMENT_SUMMARY             	withdrawal from study. This was delivered either as monotherapy or concurrently
TR:TREATMENT_SUMMARY             	with adjuvant radiation +/- systemic therapy for high-risk patients. Safety and
TR:TREATMENT_SUMMARY             	toxicity evaluations were done throughout the study process. DLTs and adjustment
TR:TREATMENT_SUMMARY             	of radiation doses were done during the neoadjuvant period.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Metabolomics analyses were performed as extensively described in previous
SP:SAMPLEPREP_SUMMARY            	studies (Issaian et al., Hematologica 2021). A volume of 20μl of frozen plasma
SP:SAMPLEPREP_SUMMARY            	was extracted in either 480μl of methanol:acetonitrile:water (5:3:2, v/v/v)
SP:SAMPLEPREP_SUMMARY            	(D'Alessandro et al. JCI Insight 2021). After vortexing at 4°C for 30 min,
SP:SAMPLEPREP_SUMMARY            	extracts were separated from the protein pellet by centrifugation for 10 min at
SP:SAMPLEPREP_SUMMARY            	10,000g at 4°C and stored at −80°C until analysis. Ultra-High-Pressure
SP:SAMPLEPREP_SUMMARY            	Liquid Chromatography-Mass Spectrometry analyses were performed using a Vanquish
SP:SAMPLEPREP_SUMMARY            	UHPLC coupled online to a Q Exactive mass spectrometer (Thermo Fisher, Bremen,
SP:SAMPLEPREP_SUMMARY            	Germany) (Nemkov et al. Methods Mol Bio 2019). Samples were analyzed using a
SP:SAMPLEPREP_SUMMARY            	5-minute gradient as described ( Nemkov et al. Methods Mol Bio 2019, Nemkov et
SP:SAMPLEPREP_SUMMARY            	al. JCI Insight 2020). Solvents were supplemented with 0.1% formic acid for
SP:SAMPLEPREP_SUMMARY            	positive mode runs and 1 mM ammonium acetate for negative mode runs. MS
SP:SAMPLEPREP_SUMMARY            	acquisition, data analysis and elaboration were performed as described.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	Negative Mode: Samples were analyzed using a 5-minute gradient as described
CH:CHROMATOGRAPHY_SUMMARY        	(Nemkov et al. Methods Mol Bio 2019, Nemkov et al. JCI Insight 2020). Solvents
CH:CHROMATOGRAPHY_SUMMARY        	were supplemented with 1 mM ammonium acetate for negative mode runs.
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um)
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	NEGATIVE
MS:MS_COMMENTS                   	MS acquisition, data analysis and elaboration were performed as described.
MS:MS_COMMENTS                   	(Nemkov et al. Methods Mol Bio 2019).
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Relative Abundance
MS_METABOLITE_DATA_START
Samples	BW48-41	BW48-36	BW48-37	BW48-40	BW48-39	BW48-38	BW48-4	BW48-6	BW48-24	BW48-28	BW48-1	BW48-5	BW48-7	BW48-25	BW48-29	BW48-2	BW48-8	BW48-10	BW48-12	BW48-14	BW48-16	BW48-18	BW48-20	BW48-22	BW48-26	BW48-30	BW48-32	BW48-34	BW48-3	BW48-9	BW48-11	BW48-13	BW48-15	BW48-17	BW48-19	BW48-21	BW48-23	BW48-27	BW48-31	BW48-33	BW48-35
Factors	NA:NA | Pre:Pre	NA:NA | Pre:Pre	NA:NA | Pre:Post	NA:NA | Pre:Post	NA:NA | Pre:Post	NA:non-responder | Pre:Pre	NA:non-responder | Pre:Pre	NA:non-responder | Pre:Pre	NA:non-responder | Pre:Pre	NA:non-responder | Pre:Post	NA:non-responder | Pre:Post	NA:non-responder | Pre:Post	NA:non-responder | Pre:Post	NA:non-responder | Pre:Post	NA:Responder | Pre:Pre	NA:Responder | Pre:Pre	NA:Responder | Pre:Pre	NA:Responder | Pre:Pre	NA:Responder | Pre:Pre	NA:Responder | Pre:Pre	NA:Responder | Pre:Pre	NA:Responder | Pre:Pre	NA:Responder | Pre:Pre	NA:Responder | Pre:Pre	NA:Responder | Pre:Pre	NA:Responder | Pre:Pre	NA:Responder | Pre:Pre	NA:Responder | Pre:Post	NA:Responder | Pre:Post	NA:Responder | Pre:Post	NA:Responder | Pre:Post	NA:Responder | Pre:Post	NA:Responder | Pre:Post	NA:Responder | Pre:Post	NA:Responder | Pre:Post	NA:Responder | Pre:Post	NA:Responder | Pre:Post	NA:Responder | Pre:Post	NA:Responder | Pre:Post	NA:Responder | Pre:Post
L-asparagine	272893.4	314428.5	213124.8	152391	147108.7	230762.1	404093.1	231185.5	166337.1	252791.7	257012.5	223085.2	150452.5	153678.4	278966.4	232742.4	257744.7	271193.7	183767	152621.2	249887.2	195653.5	108536.3	125955.1	221449.8	129544	139956.7	259095.2	203654.7	262504.8	339656.4	157489.6	195643.7	150330.8	170474.4	185126.8	174453.1	203105.1	172603.9	125423.9	168735.9
L-aspartate	2882017	3334537	3250094	125054.8	178891.4	4435742	2862694	1776039	75523.62	2604932	2401050	3668438	2680436	208774.2	2919537	2328339	3827238	3437431	131101.1	107548.2	2722972	4171261	93105.1	152815.5	2650740	292649.6	351765.9	2734980	2189532	2909932	3765400	117204.3	179776	163111.3	3947349	63216.17	66051.37	2114507	172315	374636.4	111086.5
L-cysteine	118457.7	74124.32	121436.6	78489.41	67629.93	98249.66	88560.57	100809.4	113888.1	134311.4	100506.2	129727.8	80336.77	80424.65	93668.09	105260.5	80482.59	142260.1	61889.78	88746.31	68286.76	22545.59	73643.37	58381.51	56246	68613.09	20453.84	82893.37	128920.1	62487.74	96355.4	66125.18	75207.59	88507.22	62078.86	64005.32	103985.4	150870.1	51563.59	35862.03	65408.08
L-glutamate	2806248	11345880	11837280	1598391	2935074	10281480	5353240	2943828	1224911	6963946	5208592	1844233	7562336	4271176	7118822	8093454	6940274	5370454	2363601	1190069	4765420	12341720	1274094	1715719	7348526	6106458	6287920	7362314	5874244	8493564	4658304	2413500	2367871	4509234	11123910	1476009	1082239	5412930	881784.1	7685714	3494516
L-glutamine	8277500	4304742	5286612	4434540	3837815	4291142	6542146	5929238	4460636	6435192	6250204	6189008	5399716	4296778	5988568	6262514	8231382	5378858	3986465	5081836	10300470	4490853	4545604	4185565	4651342	4246926	3388289	5729084	6193868	7150796	6399724	5444914	5381836	4495158	5163939	4738290	4923720	5205662	3638002	3882009	6685810
L-threonine	902757.7	769541.6	816595.7	643042.4	667402.8	897629.7	1268864	643479.4	803294	523619.5	1364148	831112.2	532006.9	675753.4	710730.3	1129988	560131.7	661967	813132.2	646284.8	1308821	941071.6	500244.4	565740.4	759872.5	373942.5	477822.9	582712.8	1137858	519420.3	879095	683011.9	1119047	493247.7	1183394	629140.3	943257.5	1176021	490869.8	349544.4	363559.4
L-cystine	837846.9	695512.6	742270.1	418624.9	442809	680019.8	453278.6	703145.5	324658	558772.4	1106196	328926.4	553057.1	422325.8	725154.6	1185023	610128.8	650324.8	315272.8	311863	493033.9	601866.2	364009	361771.8	732476.3	714534.9	823809.2	319902.3	1104872	543334	431512.9	181080.3	458441.7	361985.6	808277.9	355385.7	281123	1272424	223072.4	724531.6	410182
IDP	1226966	3416996	1381376	798248.7	325557.6	834902	1489503	1002182	569327.3	1709890	905263.5	40119.41	1116911	443438.5	1937522	1904136	1489462	1707213	98897.95	1184223	1264231	2029729	232084.3	1087544	3538824	245180.1	679454.3	1896814	1956197	990507.1	1066340	2051922	132780.7	848052.7	1053976	2470754	1205460	832288.2	1588774	246055.9	285766
Inosine	69761.88	218931.2	279322	117286.3	128832.6	428357.5	240582.3	322278	177616.9	258231.2	415294.4	232621.5	136679.2	188177.2	260572.2	197667.6	153740.1	176888.9	54587.78	133177.9	289955.3	17713.65	80810.4	113789.3	100098.2	89199.9	268413.3	293438.5	223632.8	108834.8	285115.2	171373.3	636486.5	198590	165784.2	169620.2	186052.3	391549.1	48211.2	526773.2	279218.1
Hypoxanthine	2460541	2420556	2200661	846993.1	1026149	2151166	2751019	2539639	325784.3	1183857	1852247	704029.9	2217572	370479.5	2368342	1574953	1289687	1748334	924314.2	388161.5	1663820	1740664	511697.4	253352.4	4415328	456036	853250.2	2842937	1609799	2024118	1193528	426473.8	6209172	636201.8	1617870	380918.2	366964.1	1713255	538315.6	982795.4	575434.6
Xanthine	76750.03	58239.54	108221.1	58809.95	97986.65	82413.62	58542.92	36107.79	49816.36	59217.92	67891.38	60896.79	57867.81	14662.79	59288.23	85367.7	64035.73	65039.7	3846.565	28869.76	73126.77	66554.46	5210.963	100266.7	23205.4	106144	9894393	21572.68	80580.65	74176.95	38950.38	58140.96	148104	121773.4	35748.73	101509.3	55308.44	60317.21	2468.69	18415490	67877.48
Urate	22763430	24386420	16782850	14599740	24903610	19749070	22815930	35497030	19604400	21970350	20144080	21987080	21390920	23211690	20787780	11368090	17923080	26159850	13926840	13133170	13753560	23454590	19343230	14235650	16214720	11785220	15490040	18727700	17027480	30303140	22783210	15058620	17125480	12197560	22660610	22144270	16841950	20453400	6507682	12680260	19724380
5-6-Dihydrothymine	1112316	448350.5	443454.5	386477.4	376522.8	468876.1	680454.9	672678.5	405682.7	526683.7	570960.8	611119.9	583654	455840.6	781252.1	488253.1	765836.8	614018.5	440690.8	428544.8	877206.8	616570.1	356259.8	297722.9	539094.2	374463.9	396573.5	636390.3	485923.9	786694.3	679857.1	550928.5	468370.6	392851.2	459614.2	347626.8	418299.2	474254.9	288615.2	488203.6	633936.4
Phosphate	17246740	55117190	22324840	12544670	14063160	13578450	26372380	20358050	8228558	21835790	15177270	4855360	18587710	15433800	29997220	24708460	21447160	25147700	25213400	6380064	17262550	42854850	13547550	6843776	53214340	17254590	21343920	26881410	21315860	22146960	15249230	8441427	8840179	13875490	22364690	5978010	8396633	14332120	23895560	21747110	12785220
Diphosphate	208567.6	1632482	236865.2	95022.66	171507.1	101139.8	307237.2	151878.8	19876.41	373860.4	87451.05	0	163332	203764.7	476018.4	270298	248955	274172.5	551139.6	49287.31	206709.7	652755.9	150935.3	28240	2564475	249608	325888.9	366595.1	268309.4	186420	133412.8	51239.9	40349.21	120402.1	257271.6	0	60533.91	120278.2	180621.9	231401.8	146480
D-Glucose	10807600	5315136	23256870	15038760	9094500	34513680	10956570	28474610	15127160	4860762	25350050	15222480	21206540	12972450	9234467	10789870	15484430	13776570	13327700	15790050	18381660	2188047	14233630	13513450	1912342	1961542	4797890	9661015	11761460	9039307	12112100	16996270	13037510	10877180	14619280	8431905	15016440	20853010	11191210	3535355	12020270
D-Fructose 1-6-bisphosphate	71483.35	55030.06	52735.96	68364.25	105737.5	32098.92	47446.23	57196.58	90935.88	89682.31	50302.27	38675.5	41872.07	85269.36	51059.22	37138.33	52594.56	55589.48	61313.79	72006.91	59180.49	36478.72	86356.97	74521.32	55136.29	45448.41	42489.62	61380.98	53245.85	83100.66	31046.94	45667.2	63574.43	73417.42	32314.51	75234.49	43911.3	75314.12	46227.32	35241.54	100105.1
D-Glyceraldehyde 3-phosphate/Glycerone phosphate	620057.8	500678.9	494263	677038.7	547096.8	599284.1	598366.5	604145.4	617282.2	892895.7	458176	607129.4	739380.3	540198.8	409984.2	414135.1	946505.8	880082.4	782352.8	1050544	549068.6	524023.6	554708.3	737233.2	688351.1	1012091	791168.5	707838.8	510205.5	880549.4	660828	1440745	781256.8	451125.7	621043.4	1843454	908769.2	404523.4	1091339	732938.8	503140.5
2/3-Phospho-D-glycerate	144007.4	444771.5	155081.8	20201.29	0	211718.4	155656.9	124120.5	12000.45	532954.2	90409.02	20825.48	156669.8	124571.8	395369.1	738484.7	270250.2	432513.7	0	0	400560.7	975267.2	0	21600.92	491753.7	0	41557.18	68558.29	235669.9	360244	344410.2	46204.75	0	130600.9	190373.9	0	0	103886.7	131076	0	0
Pyruvate	3662224	17158530	7195846	16287110	11357520	10138240	8401193	6162096	13652220	9189409	9871263	7663592	5105022	13088050	10956230	9553361	5081656	6178892	11585770	18988640	6900666	37923890	11774570	12107300	14448820	14972120	17164950	12034560	7774048	5136642	10267650	21821960	11231030	10466280	6410994	19613660	24786380	8315600	15772880	15844110	10870260
Lactate	50155810	194352300	75135300	63732280	82444480	89907940	91391810	63748040	66401820	160343700	107034700	56063720	57296450	92873620	139429900	90410140	72619300	79111060	45001840	63778600	89293800	228094200	39244640	47202020	245378400	188322400	292556300	138850800	70945910	97608130	84349300	34559540	114437900	73928470	70366260	75897500	62468240	103952700	62467540	265059600	90496060
Maltose	15598.43	89283.23	0	0	50201.22	16394.4	15933.71	23712.12	4490.445	11794.91	19045.81	0	56145.66	28529.99	90739.56	12074.62	17480.47	69065.59	5775.239	5226.917	14707.24	119325.4	8680.284	3300.84	45236.54	9807.556	0	264747.2	6756.416	24919.38	0	33366.01	27816.02	4487.141	12591.24	4725.54	6564.461	15926.24	19644.43	0	4580.773
Mannitol	434824.8	11466700	273178.2	139672	1380867	575453.1	1319064	157036.8	634029.7	2169443	262230.4	159251.9	570126	167017.6	2928406	378041.7	694338	174750.1	1006214	129827.7	1211765	770499.7	125090.2	110016.9	1885365	152046.8	283260	465910.5	247003	1315657	196807.1	119614.2	277193.8	198711.8	197388.3	223901.6	281352.5	281385.5	92465.91	1775179	194866
D-Ribose	448017.5	661588.2	630922	413108.2	252420.3	957851.2	302330.2	908421.1	440418.1	264949.1	766218.8	425031.2	586998.9	337207.2	983280.5	288084.4	541293.6	365070.3	301543.7	471827	481879.2	691419.1	383729.5	357738.9	805811.2	45850.91	148117.5	890207.8	333373.8	1009866	347524.3	451567.8	351591.4	283952.6	818638.8	277060.4	464722.2	472497.7	300552.2	133573.2	349628.5
D-Arabitol	129872.8	115642.9	32618.45	122246.6	73637.99	93959.59	96683.21	111211.8	37440.79	64187.49	114778.4	67254.56	157235.6	76470.77	195908	64077.62	717331.1	46830.39	34627.05	76911.16	163599.1	111951.6	60335.38	26050.55	126759.5	69335.25	37642.68	185441.4	87072.85	220959.3	65710.37	61213.44	110194	24132.49	119008.9	43678.97	91501.79	67743.66	29064.43	119203.8	336500.2
Citrate	31793640	23048610	21301270	1297928000	1061293000	22981340	22409270	29523800	1300136000	15119880	19211550	29255400	20416930	1159851000	24704500	25534350	24762840	22112610	941453600	1388308000	31044600	26684660	944776200	1214312000	20320870	1140434000	1266051000	16895700	24572940	23193930	36950060	1515575000	986913900	1063357000	21015690	1779954000	1616306000	19991310	1498571000	1139381000	992961700
2-Oxoglutarate	378322	720784.8	479710.2	249637.2	324501	700275.3	375826.5	344351.8	164683.4	258577	390798.9	314260.8	246684.9	503868.3	480320.5	611015.5	444142	417392.8	106492.1	245234.1	687701.3	1941186	183074.2	182343.8	837519.8	652207.3	571935.2	491018.8	545640.2	397766.8	604289	124505.3	178049.9	360813.8	760598.3	280064.8	203475.8	376462.2	156310	692001.6	159704.7
Succinate	384377.8	1381999	323771.9	196500.9	221224.4	507498	438620.5	450869.2	182402.2	887290.3	337851.9	211869.5	425541.8	177656.8	737818.8	405809.3	414295.5	412319.7	89194.21	220259	329294.2	1150171	213964.4	178159	2302295	224909	293357.4	661293.1	296546.5	596355.7	305745.1	176006.7	173822.9	161793.2	293823.9	157431.2	201910.1	272880.1	227780.2	613229.1	562155.6
Malate	912257.8	1895013	974902	840812.7	875849.5	911952.2	880559	647547.8	595044.3	788938.2	734468.5	554642.1	323287.8	497072.5	658107.9	958694.3	1065786	732442	424914.3	893906	2248173	4140284	642637.4	565448.3	2536898	1244806	2415142	985830.7	756626.7	1068428	852204.5	829018.2	772694.3	750541.6	652501.3	947235.7	905525	740519.2	847196.8	2264865	942077.2
Oxaloacetate	48164.39	56645.09	53051.34	712976.8	536306.4	75231.48	53221.36	43305.14	615321.6	52310.39	71649.52	41202.35	68323.3	520244.1	37749.66	46827.32	66023.83	64737.62	547171.9	734234.8	50187.93	56057.58	515055.4	579726.7	47450.32	619978.8	536615.1	63665.34	52056.08	38420.8	41776.05	733209.1	463186.6	532870.9	62844.16	677801.8	877656.9	48482.52	622521.1	576383.9	559823.9
2-Hydroxyglutarate/Citramalate	828922.6	300562	1015324	4740214	4073363	573606	565263.2	475738.8	5012458	381025.8	256911.4	219613.6	332490.5	4636849	420860.2	270220.4	315718.7	360588.8	3370483	4950290	552318.5	326564.7	3470011	4507714	437486.9	4199692	4470402	386851	245476.5	258956.3	219208.3	5684392	3493605	3798006	153616.4	6268200	6256984	266985	5728636	4332298	3783126
alpha-D-Ribose 1-phosphate	56049.26	96520.46	53676.93	49115.52	22186.48	45318.82	46031.2	35548.82	0	101914.9	35661.99	0	88624.85	187153.2	66579.09	50627.71	28069.47	32282.55	17119.74	0	25618.3	25645.38	0	18365.54	112842.9	89684.54	48432.49	209416.6	37157.16	47995.88	19022.76	186435.1	9974.202	0	19504.4	0	18657.19	41884.89	158703.7	0	50227.84
S-Glutathionyl-L-cysteine	79990.33	134542.5	7698.25	38376.74	0	15032.35	134157.4	74158.95	98301.29	45555.73	110572.1	0	120843.6	47379.53	50753.07	167357.7	6338.267	104771	0	70324.96	0	430627.4	17670.15	0	14498.47	0	236824.1	22410.13	46717.15	27403.04	105039.9	0	26274.19	0	82761.93	0	139388.7	106118.8	0	143726.6	21671.77
Ascorbate	61557.16	90907.98	260872.2	3355931	6031228	396013.6	110542	335282.1	1616230	79252.1	293746.6	162265	221421	719457.2	98680.23	123482.6	140915.5	137958	328172	2224920	195312.9	50174.08	3042059	163123.6	14034.91	77693.74	44246.05	502497	119728.3	90453.88	151850.8	130212.6	496911.8	3736434	131878	2796418	202525.3	192987.9	222409	24506.82	477896.4
Dehydroascorbate	899323.7	845350.2	727972	16978500	15838610	729701.7	795414.2	792334	16484460	553514.6	696553.9	584650.8	625708	17758700	771308.5	828176.8	722181.1	696666.8	11160140	18963500	1041540	1063526	12607320	17093370	588779.7	19072590	25805750	660624.6	954270.3	732847.4	859353.2	19920850	15916310	16119610	823342.8	22273640	20736890	571603.8	20833610	21901160	13876530
(5-L-Glutamyl)-L-glutamine	750961.1	296734.5	316900.9	182589.3	51994.52	394831.5	903859.2	289442.8	286890.6	276871.2	464454	184717.2	508080.8	156374.5	245507.1	773809.8	507065.7	546607.8	159261	197360.4	396385	348999.8	257622.2	164344	146715.7	110219.8	271992.1	342274.8	578069.8	499647.4	620207.7	153874.1	259709.4	68522.3	410022.2	156735.7	214553.5	464123	58899.74	266168.8	136561.9
N-Acetylneuraminate	105984.2	197372.8	88216.38	75792.95	77740.3	80915.68	66366.81	130037.4	23413.5	190907.1	77039.05	24556.83	136512.1	24853.72	119469.3	90148.97	78811.18	118715.8	10980.29	24396.17	23596.7	42986.96	28340.7	23143.37	171090.9	19170.78	43396.91	105759.9	53975.59	160355.9	49764.91	22154.46	28970.8	22690.27	42028.19	14173.82	31251.42	79613.04	12134.73	15178.28	52985.08
N-Succinyl-L-glutamate 5-semialdehyde	65162.14	153750.3	68750.44	59554.02	77178.18	51606.65	149687.6	36917.75	72766.09	140651.9	118268.3	65727.88	41544.47	94939.02	124306.9	137377.6	66002.88	79409.66	51381.29	67482.98	153084.7	416528.7	28282.78	42934.21	295294.5	172077.9	146712.4	81995.99	147991.3	70677.03	94781.8	32962.66	140242	84415.98	99178.78	75445.35	96798.1	98988.38	38879.5	190224.8	58777.53
Taurine	1373039	3434553	1380037	974380	1620363	1055012	1410946	2362726	772100.3	4616545	2095329	683460.8	1618437	1798277	2270730	1576958	915634.1	1864383	873413.3	1331651	663976.1	3305623	740114.3	837715.7	3135423	1317204	1569731	1093494	1777994	1406925	800247.7	2074345	1486476	761682.4	538198.1	607442	1051973	1864107	1395834	1406382	887269.1
3-Sulfocatechol	181060.2	354090.8	274378.4	98119.01	201385.8	53970.22	201069.4	196014.2	875423.5	240293.7	321096.3	146023.1	245866.3	180355.5	918943.4	92762.13	275946.3	40231.59	384267.3	882145.2	59841.5	358388.8	221646.7	135533	136003.4	19050.88	112766.6	1025864	101085.3	149915.7	219124	77688.88	813606.3	43262.42	727407	277435.3	917523.8	333398.2	99041.15	42492.21	463555.2
Indolepyruvate	85087.53	66990.98	49292.36	29497.22	51987.67	92581.02	143137.4	63298.21	43992.42	29272.78	72484.19	22001.51	47407.82	49647.92	50632.31	90699.05	49080.78	56420.57	40619.57	52882.83	58681.25	34404.79	58359.42	31927.97	61061.21	46146.37	49223.93	49237.37	59198.91	49167.96	40491.84	29810.94	48042.2	28359.92	47938.1	64791.69	63009.48	54267.86	16055.13	41844.19	29446.04
3D-(3-5/4)-Trihydroxycyclohexane-1-2-dione	154780.4	104896.1	423539.3	197524.3	118043.6	660930.3	218107.4	518063	211725.2	85285.9	491150.7	240760.6	403622.5	210944.4	190343.1	215162.5	201583.1	203813.4	159509.2	212233.5	304317	0	207233.3	200523.4	30419.33	27589.4	87593.27	183106.6	151301.6	148970.6	221555.9	220234.6	232571.1	132700.3	251537.8	168138.3	185471.8	294342.4	120175.4	71478.37	150697.2
Sphingosine 1-phosphate	101962.3	180968	102723.9	125937.3	76474.92	107324.1	159911.1	99322.18	92626.62	205575.6	115455.8	105519.7	117493.7	96433.66	167914.1	143545.2	120594.9	151458.3	84807.52	94620.54	131460	172995.2	80817.43	70297.77	183278.9	152098.9	88294.69	121125.3	109166	128764.5	156475.9	89680.57	115501.6	121278.2	135256.4	76982.16	128635.4	119884.3	69045.12	135199.7	111883.7
Sphinganine 1-phosphate	14031.92	36625.88	29249.51	28149.41	18427.19	28628.68	40655.79	28474.51	14507.15	13194.74	30157.56	26664.31	35691.58	19441.23	37143.12	35344.45	14953.01	34990.1	29870.72	34437.88	27362.55	27335.08	37451.41	27019.3	22343.24	38634.4	35410.23	26427.13	41512.53	33686.86	24645.97	29763.7	34306.38	18747.36	34421.68	14409.07	25554.24	21899.99	12475.31	36230.77	25203.46
Heptanoic acid	94048.54	158208.3	82431.45	160881.8	72712.57	96424.01	154339.2	131101.5	105977.5	40015.72	148439.4	92721.66	133179	109832.3	146330.6	140750.4	186823.2	138927.1	119070.6	165672.1	89350.63	92399.47	148230	112218	180204.7	144344.2	81749.28	121412.2	86167.65	99629.31	112017.3	165081.9	101755.6	37386.3	124074.5	94194	206581.8	40554.54	48170.91	179978	76929.39
Octanoic acid (caprylate)	685622	151886.7	92685.09	151261.9	172447.4	559952.5	365207.3	195393	125835.2	39085.95	135763	82366.98	685067.8	101441.8	201016.8	118870.6	182558	164203.1	132890.5	122722.8	119649.3	113113.2	146271.5	69959.56	267079.6	98517.55	101826.9	131662.9	104384.3	165950.7	142554.7	546946.4	901486.9	30338.85	253824.4	107910.3	205533.3	37588.47	37407.92	155449.6	71112.65
Nonanoic acid (pelargonate)	509291.4	498489.7	278930.3	540537.8	231346.6	666052.7	608141.2	654987.8	411419.3	117530.6	539405.9	316764.6	694111.5	340965.3	655008.5	461056.7	680013.8	521713.5	347402.8	515803.7	588222.1	461932.2	521168.8	292854.5	741785	450895.9	285581.6	421517.2	434904.9	519399.2	444309.5	495002.2	531491	73962.96	847792.9	251817.4	573315.6	125221.1	159497.7	637890.6	289196.7
Decanoic acid (caprate)	600972.4	509083	189997.3	410865.3	434037.2	691915.7	1291586	276909.9	232255.5	59187.69	320111.5	129256.8	250729	127029.5	285396.7	291992.3	178475.5	294706.5	254901.1	154899.5	303626.2	196762	325398.7	171990.9	1257044	204890.4	164245.1	183430.1	195617.6	285170.3	357270.1	186346.4	291807.6	39784.54	511495.5	218398.6	338750.7	87797.65	52950.81	155655	168764.1
Dodecanoic acid	192442.9	769957.6	494787.9	386647.5	201791.4	429440.8	1481869	481183.9	298350	144634.7	1254185	277787.9	1112319	289139	897854.5	935434.5	347863.3	1029531	340499.5	387967	1035933	434550.2	1045645	334107.9	572744.6	732566.2	277429.2	386990.4	893394.6	504250.4	1688812	265811.2	701532.2	90291.37	808064.2	229688.9	558614.1	205290.3	83865.21	555929.2	261344.7
Tetradecanoic acid	742587.5	3393229	2085063	1301692	489629	1031074	3681522	1131115	1035047	274805.2	2795670	887459.4	3139265	980754.8	1635416	2731170	662472.1	2007874	894191	745305.8	2505031	1053530	3123344	1141180	2917336	2187002	1225706	1086522	2994682	1952624	1774781	1142468	2023355	357086	1125852	595244.8	1497762	739512	184601	2952431	1130416
Hexadecanoic acid	9286921	31738820	19060320	14840260	9030659	17751060	22728870	7260014	8794959	5063698	25635230	10788940	32645550	10715250	27120280	24294350	8847071	19288450	10920990	14802470	26863810	14162880	19723680	9730690	26839970	25847730	12427200	13962910	21406320	18314630	14746920	19053290	20881910	4801022	13965430	8074432	14922710	6192052	3972623	29736780	13327790
Octadecanoic acid	4687614	12185010	6771114	8834608	3276199	8982672	13003560	8634544	2870653	2423957	9641928	6232262	16489810	5527888	13398900	7491364	4218844	10138390	6984028	8532965	8778313	7983510	11542550	5118434	5854810	10725970	7692412	7646538	10169750	8431138	7906618	9539229	12198430	2086341	8704133	3524944	8769392	4847490	2102050	14342320	5908578
Tetradecenoic acid	16369.43	18695.06	21031.12	33594.37	7163.359	24294.84	11233.27	22221.89	4503.203	10441.29	15743.68	6512.582	23824.34	9308.664	11249.81	19282.93	13315.83	15754.92	7605.637	12310.47	8416.679	13258.86	16667.43	9979.768	8561.778	12107.75	15906.62	4934.225	19012.31	19721.07	8467.877	7605.495	11608.71	2793.705	9789.438	6279.779	15226.76	6277.902	2805.127	37924.1	9751.439
Hexadecenoic acid	755173.5	12263220	4409606	6578610	1071360	1504809	1682381	452853.2	501796.2	1190506	3008895	768184.8	3638505	968036.9	1899915	4937566	1801071	2864976	663860.1	546798.2	9926427	1388603	4770954	1929698	5914104	3663786	2846142	826224.8	6144354	6768266	1092480	749208.2	2707741	2278301	979106.3	334553.9	1806391	1695239	182922.4	7735226	2754514
Octadecenoic acid	6600708	33768950	23935780	19342230	10709570	16772800	16711300	6446818	7183652	6636278	21629990	10983880	32009560	11421460	19448060	23353140	7495418	20980940	10622440	8920941	19186370	12511980	24601460	15464300	25848830	24995170	12720560	10237990	28802040	25713790	12146660	17420170	20426270	8853915	9264613	5379054	18304420	15301840	1793988	35529080	19483070
Linoleate	2387645	21776420	11566540	8662997	5899106	8350726	9448003	2877555	3876571	5749068	19898300	7331924	31886520	8044936	9287427	16286150	1784171	14050870	4875550	4352028	10938650	8963327	10500450	8887941	10626420	14317540	12139930	5435100	27681540	5699300	8876629	21027120	15402430	3135863	4527513	2642448	11385640	8238024	1144503	23782040	10562550
Octadecatrienoic acid	430790.6	2916391	2076166	1999508	1433684	1509963	1078576	212865.3	365332.6	288518.7	2100451	886662	8216040	1000370	693208.5	2157884	92567.85	1197288	268463.2	277113.5	1010651	884683	1156915	1137340	2503540	1183855	1328285	809658.4	3309397	674825.3	862807.3	3471816	1692415	272797.7	273664.6	123165.3	1747548	1134499	68600.9	3364336	1444838
Eicosatetraenoic acid	479971.2	430670	737577.8	622391.3	133192.7	449190.6	451711.6	385789.2	342217.8	245569	638779.1	625001.8	924049.5	559214.6	179225.2	572465.4	210053.1	707381.1	361952.6	157717	680211.4	263233.7	710394.6	514128	211485.1	668706.4	438421.8	263211.5	780732.5	235387.7	374424.4	725177.2	333395.9	212028.2	340409.5	295976.8	271662.3	524588.6	143625.5	546967.2	258401.6
Eicosapentaenoic acid	113569.7	42938.59	102988.3	109286.6	26222.83	14519.81	87638.41	16589.7	119262.4	4271.531	47195.83	56255.44	43253.68	225616.2	26456.72	30452.17	31342.99	76875.84	19988.76	12260.7	56020.47	16660.13	149407.1	56183.78	46029.97	88168.93	28066.52	30377.63	97640.06	25996.92	106491.4	56770.41	29442.49	25636.91	15147.6	43994.6	42106.18	38744.18	18526.38	40072.6	19301.36
Docosahexaenoic acid	179189.2	322527.8	332416.4	124963.1	174094.1	158723.4	366217.3	86635.74	304948.4	100291.3	283645.8	491979.8	247213.4	841440.8	61612.95	197361.8	158535.4	399028.1	105713.8	140016.5	491436.3	131812.1	638805.6	391373.6	87730.85	701583.6	311728	73791.68	440664.6	213874.6	417707.1	217634.4	178004.3	207242.9	119516.8	229342.3	498760.2	256719	28259.26	408320.4	102088.9
(8Z-11Z-14Z)-Icosatrienoic acid	82510.91	116179	247625.2	184656.7	59765.34	65975.91	101689.6	47255.33	44621.49	31776.29	145279.7	108320.1	174970.3	83202.4	75173.27	180116.5	51079.18	124216.6	72313.07	56227.14	262412.7	49205	165505.6	75207.57	64536.83	195651.1	70267.27	36864.25	302309.5	82438.58	98479.73	167263.7	123506.3	32466.21	52495.62	32325.44	54055.5	113465.2	18304.41	129697.6	66718.61
(7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid	90667.03	110787.3	89319.51	147484	38055.31	56082.57	90084.77	28192.62	72108.5	18215.78	143303.5	121394.8	150183	137866	26457.7	87456.71	61727.47	155370.3	46929.55	28815.19	142292.9	23491	181270.1	65527.44	42504.51	247298.9	103694.4	13996.5	187452.7	113509	86093.32	116939	67377.54	59887.46	31117.54	45277.96	51736.14	110242.3	11614.65	151559.6	38287.44
Bilirubin	114049.9	25267.15	144125.1	44756.34	48411.17	83065.74	202805.4	149575.3	146877.9	35481.39	58685	149641.4	129492.2	132677.5	36952.79	119591.9	72039.18	197892.1	157752.7	77150.32	66850.75	83080.46	86959.22	45597.74	55101.97	125857.2	83970.92	25559.98	286094	81762.57	37206.07	113389.9	55398.32	94960.44	112569.9	140373.7	53495.61	86209.9	35972.12	32520.29	67869.38
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	CmpdID	parent	medRt
L-asparagine	C00152	131.0449	0.6527963
L-aspartate	C00049	132.0288	0.6251667
L-cysteine	C00097	120.0115	0.6691439
L-glutamate	C00025	146.0447	0.6262388
L-glutamine	C00064	145.0606	0.6574889
L-threonine	C00188	118.0496	0.6607223
L-cystine	C00491	239.0156	0.6391156
IDP	C00104	427.0076	0.6240832
Inosine	C00294	267.0726	0.6656222
Hypoxanthine	C00262	135.0289	0.6390426
Xanthine	C00385	151.0249	0.6899479
Urate	C00366	167.0201	0.6655482
5-6-Dihydrothymine	C00906	127.0499	0.6647686
Phosphate	C00009	96.96812	0.6348426
Diphosphate	C00013	176.9347	0.624542
D-Glucose	C00031	179.0553	0.6622741
D-Fructose 1-6-bisphosphate	C00354	338.9933	0.660002
D-Glyceraldehyde 3-phosphate/Glycerone phosphate	C00118	168.9883	1.756918
2/3-Phospho-D-glycerate	C00631	184.9849	0.5997024
Pyruvate	C00022	87.00729	0.6334038
Lactate	C01432	89.02293	0.6560704
Maltose	C00208	341.1087	0.669139
Mannitol	C00392	181.0703	0.6702167
D-Ribose	C00121	149.0446	0.6534518
D-Arabitol	C01904	151.0603	0.6681629
Citrate	C00158	191.0187	0.6111981
2-Oxoglutarate	C00026	145.0133	0.6200147
Succinate	C00042	117.0179	0.6394851
Malate	C00149	133.013	0.6095113
Oxaloacetate	C00036	130.9994	0.6212056
2-Hydroxyglutarate/Citramalate	C02630	147.0289	0.6164055
alpha-D-Ribose 1-phosphate	C00620	229.0117	0.6291977
S-Glutathionyl-L-cysteine	C05526	425.0805	0.6191225
Ascorbate	C00072	175.0241	0.6595463
Dehydroascorbate	C05422	173.0082	0.6135359
(5-L-Glutamyl)-L-glutamine	C05283	274.1045	0.6260245
N-Acetylneuraminate	C00270	308.0986	0.6388648
N-Succinyl-L-glutamate 5-semialdehyde	C05932	230.0646	0.6511307
Taurine	C00245	124.0061	0.6572334
3-Sulfocatechol	C06336	188.9855	0.685451
Indolepyruvate	C00331	202.048	0.8707243
3D-(3-5/4)-Trihydroxycyclohexane-1-2-dione	C04287	159.029	0.6624227
Sphingosine 1-phosphate	C06124	378.2411	3.860847
Sphinganine 1-phosphate	C01120	380.2553	3.720245
Heptanoic acid	C17714	129.0908	1.960606
Octanoic acid (caprylate)	C06423	143.1065	2.057464
Nonanoic acid (pelargonate)	C01601	157.1222	2.132802
Decanoic acid (caprate)	C01571	171.138	2.209159
Dodecanoic acid	C02679	199.1695	2.39302
Tetradecanoic acid	C06424	227.2011	2.6692
Hexadecanoic acid	C00249	255.2325	3.088991
Octadecanoic acid	C01530	283.2639	3.716565
Tetradecenoic acid	C08322	225.1855	3.778638
Hexadecenoic acid	C08362	253.2169	2.710695
Octadecenoic acid	C00712	281.2482	3.135594
Linoleate	C01595	279.2326	2.771214
Octadecatrienoic acid	C06427	277.2169	2.536908
Eicosatetraenoic acid	C00219	303.2326	2.661811
Eicosapentaenoic acid	C06428	301.217	2.473447
Docosahexaenoic acid	C06429	327.2326	2.554932
(8Z-11Z-14Z)-Icosatrienoic acid	C03242	305.2483	2.859316
(7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid	C16513	329.2483	2.684147
Bilirubin	C00486	583.2557	3.499512
METABOLITES_END
#END