#METABOLOMICS WORKBENCH RCulpHill_20220309_130542 DATATRACK_ID:3118 STUDY_ID:ST002109 ANALYSIS_ID:AN003450 PROJECT_ID:PR001336
VERSION             	1
CREATED_ON             	March 18, 2022, 8:32 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 1)
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           	-	BW45-41	Phenotype:NA | Treatment:Pre	RAW_FILE_NAME=BW45-41
SUBJECT_SAMPLE_FACTORS           	-	BW45-36	Phenotype:NA | Treatment:Pre	RAW_FILE_NAME=BW45-36
SUBJECT_SAMPLE_FACTORS           	-	BW45-37	Phenotype:NA | Treatment:Pre	RAW_FILE_NAME=BW45-37
SUBJECT_SAMPLE_FACTORS           	-	BW45-40	Phenotype:NA | Treatment:Post	RAW_FILE_NAME=BW45-40
SUBJECT_SAMPLE_FACTORS           	-	BW45-39	Phenotype:NA | Treatment:Post	RAW_FILE_NAME=BW45-39
SUBJECT_SAMPLE_FACTORS           	-	BW45-38	Phenotype:NA | Treatment:Post	RAW_FILE_NAME=BW45-38
SUBJECT_SAMPLE_FACTORS           	-	BW45-4	Phenotype:non-responder | Treatment:Pre	RAW_FILE_NAME=BW45-4
SUBJECT_SAMPLE_FACTORS           	-	BW45-6	Phenotype:non-responder | Treatment:Pre	RAW_FILE_NAME=BW45-6
SUBJECT_SAMPLE_FACTORS           	-	BW45-24	Phenotype:non-responder | Treatment:Pre	RAW_FILE_NAME=BW45-24
SUBJECT_SAMPLE_FACTORS           	-	BW45-28	Phenotype:non-responder | Treatment:Pre	RAW_FILE_NAME=BW45-28
SUBJECT_SAMPLE_FACTORS           	-	BW45-1	Phenotype:non-responder | Treatment:Post	RAW_FILE_NAME=BW45-1
SUBJECT_SAMPLE_FACTORS           	-	BW45-5	Phenotype:non-responder | Treatment:Post	RAW_FILE_NAME=BW45-5
SUBJECT_SAMPLE_FACTORS           	-	BW45-7	Phenotype:non-responder | Treatment:Post	RAW_FILE_NAME=BW45-7
SUBJECT_SAMPLE_FACTORS           	-	BW45-25	Phenotype:non-responder | Treatment:Post	RAW_FILE_NAME=BW45-25
SUBJECT_SAMPLE_FACTORS           	-	BW45-29	Phenotype:non-responder | Treatment:Post	RAW_FILE_NAME=BW45-29
SUBJECT_SAMPLE_FACTORS           	-	BW45-2	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-2
SUBJECT_SAMPLE_FACTORS           	-	BW45-8	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-8
SUBJECT_SAMPLE_FACTORS           	-	BW45-10	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-10
SUBJECT_SAMPLE_FACTORS           	-	BW45-12	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-12
SUBJECT_SAMPLE_FACTORS           	-	BW45-14	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-14
SUBJECT_SAMPLE_FACTORS           	-	BW45-16	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-16
SUBJECT_SAMPLE_FACTORS           	-	BW45-18	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-18
SUBJECT_SAMPLE_FACTORS           	-	BW45-20	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-20
SUBJECT_SAMPLE_FACTORS           	-	BW45-22	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-22
SUBJECT_SAMPLE_FACTORS           	-	BW45-26	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-26
SUBJECT_SAMPLE_FACTORS           	-	BW45-30	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-30
SUBJECT_SAMPLE_FACTORS           	-	BW45-32	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-32
SUBJECT_SAMPLE_FACTORS           	-	BW45-34	Phenotype:Responder | Treatment:Pre	RAW_FILE_NAME=BW45-34
SUBJECT_SAMPLE_FACTORS           	-	BW45-3	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-3
SUBJECT_SAMPLE_FACTORS           	-	BW45-9	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-9
SUBJECT_SAMPLE_FACTORS           	-	BW45-11	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-11
SUBJECT_SAMPLE_FACTORS           	-	BW45-13	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-13
SUBJECT_SAMPLE_FACTORS           	-	BW45-15	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-15
SUBJECT_SAMPLE_FACTORS           	-	BW45-17	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-17
SUBJECT_SAMPLE_FACTORS           	-	BW45-19	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-19
SUBJECT_SAMPLE_FACTORS           	-	BW45-21	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-21
SUBJECT_SAMPLE_FACTORS           	-	BW45-23	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-23
SUBJECT_SAMPLE_FACTORS           	-	BW45-27	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-27
SUBJECT_SAMPLE_FACTORS           	-	BW45-31	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-31
SUBJECT_SAMPLE_FACTORS           	-	BW45-33	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-33
SUBJECT_SAMPLE_FACTORS           	-	BW45-35	Phenotype:Responder | Treatment:Post	RAW_FILE_NAME=BW45-35
#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	BW45-41	BW45-36	BW45-37	BW45-40	BW45-39	BW45-38	BW45-4	BW45-6	BW45-24	BW45-28	BW45-1	BW45-5	BW45-7	BW45-25	BW45-29	BW45-2	BW45-8	BW45-10	BW45-12	BW45-14	BW45-16	BW45-18	BW45-20	BW45-22	BW45-26	BW45-30	BW45-32	BW45-34	BW45-3	BW45-9	BW45-11	BW45-13	BW45-15	BW45-17	BW45-19	BW45-21	BW45-23	BW45-27	BW45-31	BW45-33	BW45-35
Factors	Phenotype:NA | Treatment:Pre	Phenotype:NA | Treatment:Pre	Phenotype:NA | Treatment:Pre	Phenotype:NA | Treatment:Post	Phenotype:NA | Treatment:Post	Phenotype:NA | Treatment:Post	Phenotype:non-responder | Treatment:Pre	Phenotype:non-responder | Treatment:Pre	Phenotype:non-responder | Treatment:Pre	Phenotype:non-responder | Treatment:Pre	Phenotype:non-responder | Treatment:Post	Phenotype:non-responder | Treatment:Post	Phenotype:non-responder | Treatment:Post	Phenotype:non-responder | Treatment:Post	Phenotype:non-responder | Treatment:Post	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Pre	Phenotype:Responder | Treatment:Post	Phenotype:Responder | Treatment:Post	Phenotype:Responder | Treatment:Post	Phenotype:Responder | Treatment:Post	Phenotype:Responder | Treatment:Post	Phenotype:Responder | Treatment:Post	Phenotype:Responder | Treatment:Post	Phenotype:Responder | Treatment:Post	Phenotype:Responder | Treatment:Post	Phenotype:Responder | Treatment:Post	Phenotype:Responder | Treatment:Post	Phenotype:Responder | Treatment:Post	Phenotype:Responder | Treatment:Post
L-asparagine	2208314	2486152	2569303	461088.2	524191.3	3601663	3957224	2105982	547828	1798007	2815741	1799884	1183641	344983.2	2376216	1305286	2290383	2410898	371975.6	614794.5	2469214	2576778	383086.2	664373.2	2069170	680515.1	404598.1	1887425	1672685	2595896	2432126	529757.2	701934.8	820102.5	1760346	521551	978933	2119199	296614.7	595907.9	614319.2
L-aspartate	1962084	2520943	3392855	255799.9	346256.9	3468468	3154591	1502776	196289.8	2687404	2203614	6967290	1881486	302167.5	2471450	1964946	2873546	4143501	167316.8	241921	3937565	7632416	161205.2	286786.3	3125985	533367.4	518118.3	2545694	2300644	2879063	2809124	302828.1	398954.7	369666	3411298	235558.8	226745.3	2402194	299847.1	635537.6	367510.4
L-glutamine	50580760	30274330	49881730	10452880	11599510	42181700	47634500	38192120	10674090	43794770	53799920	35882910	28462530	6674978	41993660	25277690	49839950	40077430	6490910	13536700	64911980	35249230	7400142	13913540	31625540	13940420	6778674	37654810	36601700	59796000	41614180	13181130	16466700	18213140	36981490	11370670	17723510	43105460	4154017	14257480	13898340
glycine	1334704	1578291	1268845	957205.5	980106.8	1280230	1297043	1011632	990935.4	1915902	2094875	1128402	851952.6	803598.8	1786941	1854147	969242.2	1265032	756231.9	1975810	1546606	2280593	869497.2	1437412	1751185	1642508	972082.3	1447065	2172232	1647164	1282579	892321.7	1834631	1343042	1411384	942807.2	1520629	1415594	656149.1	1659298	925955.1
L-histidine	2214391	2253577	2440166	1187786	1122370	1748132	3403305	2238368	1869017	2381393	2371298	2193920	1065816	1348216	2227727	1234522	1584260	2869311	970187.2	1317922	1897664	3845280	1200664	806990.5	1888917	2685584	1243800	2615058	2227568	1802466	2900548	1468171	1628052	1090339	2519623	1441064	1295604	2572048	584778	1651707	1848151
L-threonine	2316663	3049906	3958902	1153600	1844469	3974651	4680782	2210619	1857583	2579262	6630236	2655970	1670021	1100041	2270456	3460633	2120913	2862362	1066361	1375746	4363470	3830689	834065.5	1577946	2885935	1284455	810684.2	1684100	4931989	2483138	3541888	1372966	2655782	1500063	4757188	1362228	2434927	5004215	586336.4	951895	772274.6
ADP	50177.33	549796.1	264499.8	10247.33	64798.48	199464.5	188731.3	194756.2	0	1040588	195957.4	0	112939.6	102128	398057.3	149740.7	167372.8	410176.6	10382.76	0	209994.4	547344.7	0	7159.277	289414.8	0	10930.22	82390.77	237837.7	445802.6	153133.2	42343.8	0	0	58072	8760.247	0	206845.9	103115.2	0	20630.71
AMP	56113.67	483467.4	93331.48	0	0	52130.64	142240	68461.7	0	859307.8	77861.52	6367.802	89948.12	28834.83	821377.9	265298.2	43148.53	141194.3	0	0	59701.71	1281124	0	0	713874.6	0	0	250821.8	156970.4	333712.4	88968.09	26774.23	0	0	49353.98	0	0	84910.75	166742.7	0	0
Thymidine	11302.24	18231.99	36231.83	461942.2	356508.1	65696.62	11942.54	36900.23	439172.5	22922.89	56673.19	28285.15	33016.76	23466.64	25843.85	15175.22	9249.101	45437.79	238868	352119.1	38497.5	9923.721	558168.1	269423.4	6683.769	207544.2	409777.7	15350.66	17506.43	27200.37	20178.63	567813.1	298202.6	286550.5	34680.1	591882.5	614379.2	47982.31	324445.6	294140.1	264956.8
IDP	2159480	4837778	2551928	113692.7	94674.43	938341.8	2654404	2100384	70984.09	3154932	2357537	603010	2154686	69965.55	3056115	1783197	1772491	2623825	88453.74	72781.11	2225868	2887037	81072.1	55288.33	5828634	53000.64	32849.73	3080330	2462918	2191223	1422343	82177.66	55340.96	95206.79	1887035	67627.76	77342.7	733455.4	70889.29	60372.42	68822.28
Inosine	33396.38	38086.47	128508.4	591338.1	206684.2	221829.2	54686.18	119643.7	91676.82	56493.43	138561.7	75036.54	155301.8	125028	52741.22	43713.28	66872.66	86035.04	10280.44	316251.6	81279.18	3187.771	59565.94	47889.18	9441.708	107666.8	125078.3	67518.29	64725.41	54547.12	80379.08	211058.3	2374234	122905	77679.59	75717.37	140549	131061.5	87983.88	855862.9	15216.77
Hypoxanthine	1952536	1744685	2607328	1507518	2104297	1900278	3590718	2455776	589499	1430020	1872045	1560279	1432332	530058.8	2710262	791050.2	977569.3	1585317	921977.5	781722.8	1579599	2783887	659087.1	561199.8	5582942	563437.6	1268188	2596735	1120559	2809835	1160961	568381.6	14300570	1950795	1798521	1532203	705867.8	1986007	747165.8	1233168	778269.4
Xanthine	164737.9	106294.1	325461.7	83009.78	106373.7	252748	228183.3	125402.5	41730.37	156034.2	216213.6	232935.2	96343.59	17619.42	132083.9	108837.8	204509	232209.7	9223.062	78424.63	221397.6	222898	24613.54	138743.9	86693.62	135316.5	9740501	40125.55	283334.7	319529.4	146184.4	40083.21	226854.5	242893.2	135855.6	124969.7	147421.3	174108.6	6375.863	24633740	89540.41
Adenylyl sulfate	50177.33	549796.1	264499.8	0	64798.48	199464.5	188731.3	194756.2	0	1040588	195957.4	0	112939.6	102128	398057.3	149740.7	167372.8	410176.6	10382.76	14929.91	209994.4	547344.7	0	7159.277	289414.8	0	10930.22	82390.77	237837.7	445802.6	153133.2	42343.8	0	0	58072	8760.247	17679.22	206845.9	103115.2	27732.72	20630.71
5-6-Dihydrothymine	3855160	1814513	2358846	675900.7	894104.3	2233420	3179744	2380571	769458.6	2852463	2709467	2212180	1970552	559173.3	2782621	1377920	2814732	2852761	419171.6	807596.1	3483352	2620748	633000.2	841822.3	2644726	958827.5	595394.2	1979208	1920789	3570777	2795702	961078	1024544	1079138	2081701	804039.2	962152.8	2472686	290144.8	994319.2	1166110
4-Pyridoxate	466491	106628.2	230056.8	293336.2	352827.2	231968.6	117611.8	327910.5	109204	68287.71	74616.22	111872.2	78334.09	4610.574	72265.99	34886.84	152895.4	76170.33	36568.93	284364.1	28121.9	152258.6	294413	14029.43	210419.4	35363.76	15618	169687.2	39895.07	69870.86	36962.81	12311.58	76203.4	26774.31	90233.21	586520.6	41526.52	75245.25	23816.47	8204.787	77847.47
Pyridoxamine 5'-phosphate	0	10639.33	12644.7	1687.195	2006.852	0	4492.485	24546.29	108856.3	87486.26	56823.54	13551.28	14727.01	48325.43	100411.5	1751.062	2002.94	7978.495	12148.6	42605	22971.2	64455.82	13931.73	4014.544	10339.51	1323.975	11672.55	8912.918	23417.3	5406.572	33196.8	4163.926	61746.97	0	70714.05	5661.814	12399.74	47589.29	34770.98	14757.26	31874.02
Nicotinate ribonucleotide	1859091	2789457	1540458	1256903	3651637	2314652	2909037	7260952	1880006	2480838	2091608	1788509	2055593	1999916	2352376	509630.1	2207931	2666006	771448.1	819869.9	618024.8	2249470	2106071	561648.6	1548847	930278.8	1182129	1220312	1133387	4863014	2608079	997004.7	1141338	845606.8	3844423	2014594	1364112	2274076	44189.78	893629.2	1608248
Phosphate	18362870	37575290	19100330	20310290	22432220	12524190	30243820	20662760	17528160	23633980	13723520	10410020	16655760	25023160	24278050	17991120	17577150	21972110	31203700	11875410	19333870	37279240	18505590	9159688	57970880	21267560	28031260	22561580	20627860	18579850	14956400	15209910	13350870	17751020	18402710	13316090	12348000	19198950	24145210	26262330	20348790
Diphosphate	266851.8	1339694	303381.3	991119.5	1421533	149380.9	528796.7	263247.6	618263.4	461928.6	182019	138561.7	201344.1	1536274	565649.2	253119.2	275803	457055.3	2013435	383420.9	325649.3	1550649	748499.5	253984.6	2669248	1383522	2065520	382403.2	311200.4	278387	234364.9	575116.4	606843.8	988965.5	350891.6	469127.6	522107.9	219009.5	1143345	1735846	1096267
D-Glucose	19657290	13119390	54511000	17634670	15248480	56500930	27404020	58220520	15608840	17745970	59448270	30295800	42769360	11082340	19429160	21360070	35682610	32154870	8135386	15812040	34853890	2948092	13825480	26409140	4340791	2522701	5125300	17822430	25839390	20831810	30528360	21079800	17294270	23345850	34414400	13619650	23882920	39449350	8667358	4571304	15310940
D-Glyceraldehyde 3-phosphate/Glycerone phosphate	527417.3	423475.2	527487.1	886552.5	545100.8	481132.1	502682	696720.7	165819.8	490815.4	570644.2	512891.4	428886.8	27127.32	810139	66924.57	188877.3	516130.7	14997.96	229379	324841	428378.1	326273.8	74605.13	604999.3	609383.2	85285.91	604923.7	393819.3	502813.8	312059.2	138409.3	567643.6	368652.7	865113.5	343185.5	490904.7	593295.9	16319.51	199581	573418.2
1-3-Bisphosphoglycerate	254405.8	23698.55	57686.77	55077.93	34103.97	320013.6	59818.57	62619.07	26783.57	61538.99	62517.17	171379.8	52597.69	387430.7	251703.9	84799.94	427172	389319.8	129644.5	26286.81	1206178	356995.9	13581.36	312714.9	0	53748.66	13622.58	13765.69	9974.558	193018.9	174940.5	73862.36	273056.9	1739161	120493.8	193421.9	29773.24	42635.34	830339.6	9891.888	46451.49
2/3-Phospho-D-glycerate	81290.05	453139.5	154418.9	1615.319	2377.407	225958.9	226937.5	86670.79	3340.356	744692.9	139408.3	148187.1	77038.8	105565.5	279897.2	530300.5	189309.9	265643.6	3201.156	1094.764	370629.3	894929.2	1046.013	2877.568	419002	9374.126	22594.34	94221.41	267041.7	492693.5	206971.4	2304.904	7149.737	268639.7	125296.2	3981.553	1577.11	105480.4	94065.13	34598.98	4850.843
Pyruvate	3620510	15683500	6956730	33294590	30273000	7832340	8370636	5885110	31744090	7720592	7054106	7438912	3411339	26906090	9202307	6195118	4681592	6089434	17635640	30433880	4996976	44587470	24404170	19665300	12901940	33125030	21955540	9432271	5790774	5661212	7899184	34060130	23115690	28044580	6195840	29029500	26430060	6974872	42106420	23562370	19976210
Lactate	59244250	190423600	97055340	65995820	83297540	103945200	121653200	104912400	82789190	143714000	107902500	76838430	62656220	92701820	148589400	72518080	85998750	94384830	38009530	77417610	94141690	361375900	50877500	36459990	236464400	245272200	320415800	139354300	69826950	121245800	93814180	36696640	117599000	96492610	88423850	96842860	70895260	112747100	77316220	360910700	114830500
Maltose	71745.88	586096.2	87756.75	43911.47	158935.2	184463	70752.76	185435.1	10039.93	194358.1	468569.7	972190.5	346234	13967.41	470951.7	61338.66	128703.6	265422.8	7504.939	24330.44	178350.5	426075.4	15145.13	63361.52	295343.3	43950.14	16245.65	1610128	376779.7	172466	441110.6	117865.3	261042.8	45343.64	86789.48	178490.9	140575.1	307794.8	17629.91	25530.85	12779.95
Mannitol	1489876	17554920	879403.3	460212.3	1438614	1005679	1890269	544526.1	479154.9	4931614	1099017	633594.6	780912.2	178248.8	3844785	477290.5	1044155	793917.1	696573.3	543604.4	1705230	1380624	472210.5	365870.9	2926634	465493.2	288626.7	680692.6	703637	2247989	559062.2	298777.2	494447.7	558763.8	925924.1	943621	519312.6	936152.3	59296.53	1061796	380769.2
D-Ribose	576243.9	759875	1692569	606324.8	537959.5	2122904	878530.1	1794715	605708	584235.3	1901033	917907.5	1267986	359889.9	1371364	668614.3	1039147	981903.1	306816.5	519487.8	1152916	1191425	484906	836210.5	1193285	111392	212258.6	933178.3	796674.5	996922.7	993735	748205	594002.7	808972.5	1111498	439731.6	790731.8	1279792	275791.8	268162.9	467915
D-Rhamnose	4066362	2049281	207769.9	1671882	1499572	432721.2	1938694	2209727	1221176	3295428	3354282	1905340	2266382	342268.6	4017251	1527263	1712631	4818786	29074.09	1000613	1402564	6455742	701371.2	1127835	3661565	1521970	86260.8	2196798	2816932	3655078	2701168	199073.6	1326018	724811	3825828	1531899	2081483	2058182	95598.21	249319.3	1393303
D-Arabitol	165968.5	249497.4	131337.7	145091.5	221474.5	160613.7	175639.2	159746.1	25076.9	237762	253110	154684	157253.5	96018.35	391523.2	80245.47	1292421	127708.5	5825.756	113880.6	355631.8	230875.5	71240.07	67563.15	395617.4	133261.7	49280.42	198290.2	139324.7	409551.6	136634.9	30880.14	141593.6	160938.2	200864.6	50818.86	161961.3	156140.5	11121.73	163769.5	434125.5
Citrate	18604910	24548300	32371510	1375329000	1352638000	19051310	30612520	22197510	1451032000	23031830	25180580	20621500	13496250	1318234000	25647730	15059560	15326450	22927140	1002757000	1382285000	25916580	16817290	1290032000	1099259000	19160450	1368950000	1158150000	15558740	25653490	28929550	21796660	0	1093239000	1234387000	17157700	1369848000	1424268000	25330630	1899854000	1126057000	1044194000
2-Oxoglutarate	382468.4	805100.2	511138.6	241022	352103.8	939255.8	428254.9	435143.2	221443.5	290013.2	391317.2	301041.7	239411.7	359543.7	531349.8	374023.7	388340.5	525838.7	140742.7	167732.6	436063.9	1427739	223328.4	166581.8	881404.8	613359.6	430747.2	390809.2	504173.9	408484	433500.4	245232.8	288737.1	478088.2	627338.9	243070.5	150936.9	326929.7	318214.8	523535.9	236302.9
2-Oxoglutaramate	110493.7	162515.8	97803.96	83680.98	77542.15	93160.44	174653.5	116991	88440.09	143405.4	117654.5	78433.88	96263.34	58555.86	122587.5	81437.51	78052.87	108799.1	31135.51	91101.88	91096.12	200817.2	91177.3	32432.23	180065.7	92341.01	113319.8	173960.1	79715.16	139906.7	116834.7	38233.97	75492.88	53543.04	125250	52268.55	63210.5	128060.9	14879.78	119436.4	79648.97
Succinate	398753.8	1079898	735214	365468	479237.2	1043585	501528.2	609186.7	202091.7	890987.1	582844.8	369431.6	579406.6	286883.7	767335	256615.3	355019.2	474484.6	189038.3	220568.4	611536.8	1101180	345853.7	396627	1802752	412104.5	438214.2	641875.5	377557.8	555988.2	402478.7	251510.7	283877.5	296706.8	498121.8	332184.4	340847.8	630738.4	296801.5	954530	695566.1
Fumarate	105011.8	241487.1	161679.1	571114.8	746766.1	180530.7	190701.5	149401.1	418271	131086.4	168230.6	81972.45	96144.41	391232.2	140670.7	86709.04	117568.4	89599.52	765797.4	722233	214730.5	446631.4	539729.8	653794.1	350081.5	567844.1	282303.7	116656	99025.09	156263.7	100919.6	459425.8	828989.7	756628.5	88651.06	460806.4	449095.1	123925.3	470648	638643.2	276957.8
Malate	897783.5	2368706	1166452	985683.2	954681.3	830096.3	1258837	914498.2	896949.6	775649.1	933806.2	580254.3	453645.4	637819.5	817895.8	640185.1	838954.7	797027.1	477448	840289.5	1590231	3948120	813196.2	686134.2	2429502	1805426	2184766	981206.3	764830.2	1069089	812981.8	933603.8	847068.4	983636.3	559399.8	1112599	763615.8	691892.2	993592.2	2321696	976829.2
Oxaloacetate	31067.69	31118.41	27814.67	1322014	1099367	16499.03	39179.11	37066.76	1231811	38142.57	34986.68	29384.41	31687.02	1208401	33904.72	29504.35	40494.24	19293.77	789326.8	1206132	47458.34	54020.98	982158.2	945091.5	31856.22	1182971	939418.1	53240.56	23229.53	22172.87	52373.11	1311893	965728.7	1146230	20159.08	1165085	1199219	26867.46	1212654	933495.7	817589
2-Hydroxyglutarate/Citramalate	554003.2	433112.4	1015139	3192505	3084591	560241.3	968615	434413.2	3323255	398537	249202	230282.4	265379.8	2784679	415792	199114.8	298510.8	409169.7	2380578	3098857	819974.7	410340.8	3260679	2331248	620152.7	2967555	2347497	349480.5	243214.9	279692.6	207917.2	3581186	2432352	2760070	216382.8	3169112	3311246	291694.4	4009590	2650793	2266718
6-Phospho-D-gluconate	49482.82	47093.33	109333.7	8764.181	109326.6	73462.56	91201.21	74817.25	5381.788	43480.4	82460.93	37035.91	84717.79	2320.614	59374.97	17815.44	77925.91	92659.19	0	13393.25	106868.5	11555.14	3402.533	26440.91	22341.16	7337.594	0	168802.9	57624.25	49391.5	69862.65	4543.259	70712.85	33091.96	49473.99	7194.202	12596.13	68187.26	24198.02	9141.965	24726.2
D-Erythrose 4-phosphate	43231.66	48831.11	44255.17	46117.89	124371.9	14323.96	662703.4	158876	85058.68	1278031	210864.4	147893.5	749795.8	99178.81	523625.6	6876.715	426896.6	26570	1075437	123280	302415.8	602683.9	24306.37	441348.3	84406.45	10994.82	20158.56	345946.7	167810.7	332811.4	261252.8	412357	117331.8	33135.17	1083263	19398.96	607493.8	222394.9	676312.8	25303.15	890252.8
Sedoheptulose 1-phosphate	36995.57	0	60674.28	1435201	1594369	36357.71	67661.51	24661.83	1714620	24517.18	15035.83	18475.68	7797.49	1976724	51678.88	10444.28	34044.8	37925.17	721244.8	1293260	30649.25	8491.773	1138363	590725.8	44432.56	1932058	1751145	40507.16	23704.1	11890.79	0	1438005	1255180	1778548	0	1634624	1773444	6536.674	1222606	1726672	1871196
Cys-Gly	116503.8	281100.8	127155.8	63303.36	52850.82	106561.6	201332.7	124072.6	83431.05	158023.5	129589.2	124677.9	104377.5	136193.3	159067.4	100201.4	211838.7	212188.9	48615.8	73697.18	124574.2	504550.3	77705.7	46754.16	177236.1	155538.4	65315.32	199298	111938.4	114454.9	173211.7	35459.59	52532.59	91487.44	157478.6	101248.5	87600.49	119440.8	42719.88	54906.2	99488.68
Ascorbate	381278	358619.8	865137.2	8661364	14264640	1010980	530887.5	968559.6	4923530	361439.6	859015.5	331573.5	529085.1	1935689	280012.8	212206.5	503225.9	468319.2	1219882	6627814	613038.4	123236.1	7617808	496368.5	69046.04	434086.5	53445.94	910692.6	375629	357948.3	468250.4	2160310	1676262	9588900	439540.8	7809218	1448061	721473.8	1835276	19793.22	1503854
Dehydroascorbate	962478.1	1384268	1220403	19432460	22765180	806161.3	1184874	1154968	20816260	879874.2	817502.4	582989.3	726973	22446860	1039883	642291.3	624615.9	924911.4	13590950	19316940	1023190	976006.7	19498270	16169640	765256.3	25642650	23817320	751955.2	1104717	1158880	927525.2	22796980	20039110	20624960	703082.4	20153130	19745820	948835.8	26504210	22977830	17037800
gamma-L-Glutamyl-D-alanine	137621.8	138353.3	245860.5	43549.72	24996.87	274529.7	227523.2	59846.14	50008.12	124898.1	113656.7	716089.8	72970.19	33278.78	90215.31	110614.6	243815.8	294221.8	20183.59	22498.37	360510.2	688005.4	13603.28	21319.18	123893.2	32890.72	70373.24	73346.8	146201.6	204887	226424.3	504.6792	61240.75	0	262166.3	20340.49	26141.51	174074.4	0	319684.6	10794.52
5-L-Glutamyl-taurine	16820.08	20533.21	22694.29	17042	20277.23	15973.54	29575.85	18557.71	17230.35	14252.25	14283.6	18978.71	16483.07	25095.61	6557.132	30189.69	12834.95	9943.356	23190.23	0	9001.198	38891.92	26991.5	30901.59	33805.68	17417.58	12313.68	11053.69	21060.58	14003.76	10594.72	14286.03	709650.8	24071.66	22428.77	18073.55	26844.15	16740.61	14167.92	8542.325	14731.03
Ornithine	2282735	1612536	564006.9	565055.8	725828.9	615406.3	2072158	1463912	324066.7	1530013	1753517	1387191	1634125	213280	1738576	1145897	1116439	1268532	116132.1	265668.1	1077497	1776374	442379.3	514179.2	1730222	369731.2	378924.8	1375828	1812609	1722072	2206469	283257.6	897368.2	296663	1256803	479633.1	894907.7	1451682	165785.2	491430.5	514538.1
L-Citrulline	3531619	2661738	1104125	717692.6	935445.2	1033095	3489234	2690830	419419.3	2759173	3111812	2368670	2835745	326484.4	2541668	1874269	1711424	2066636	136627.8	351347.7	1647426	2130387	486950.6	977147	2177409	492514.7	281809.2	1943998	3005978	2600036	3638149	329798.6	1236066	555800.8	2381059	606684.6	1385306	2354769	160157	524560.9	612528.8
Argininosuccinate	24594.44	14168.02	36323.14	23013.84	41851.4	105640.4	68392.52	33655.46	19987.94	48338.16	20301.16	23311.41	28046.32	8807.05	46422.28	12244.46	51172.79	11754.92	5027.147	40130.39	14516.11	69276.69	29666.53	5866.478	30315.72	39734.09	5014.473	11477.14	16922.43	18886.84	1907.808	10278.57	24578.18	15587.18	63852.21	26839.8	17095.72	11750.77	3618.771	4138.169	0
N-Acetylneuraminate	102303.9	198196.2	79378.41	169973.3	144715.8	88412.03	54559.77	133558.1	2162.187	294564.9	81206.76	35850.33	99610.98	12679.7	174478.1	70250.55	71239.16	117879.2	11817.6	66894.3	43349.48	93364.74	12009.69	22186.22	231647	66423.15	41399.97	79367.53	51440.83	147808.7	59476.61	37897.16	17138.02	25566.53	51833.12	19346.83	33537.9	93013.12	21340.6	50181.18	52677.46
1-4-beta-D-Xylan	775049.2	611694.5	2232139	761827.6	741311.2	3247500	1204278	2168815	702719.6	819534.3	2644791	1154864	1853585	453017.4	850754.8	705987.6	1374569	1390888	352564.5	678175.2	1616986	173652.4	629653.8	1112855	281328.8	171537.6	248700.8	795890.4	1085909	910802.8	1393064	834952.2	797885.3	1027892	1468311	582159	986510.3	1537019	328102.1	163789.3	648544.2
Guanidinoacetate	39406.76	52267.07	63804.62	30962.76	40790.31	52542.75	82301.1	75161.85	53045.33	33850.79	57543.76	59931.41	27821.96	55309.79	42012.82	49536.98	46310.98	53169.58	45254.44	54045.2	65561.41	45140.72	36410.7	24722.79	42200.77	32493.35	12680.38	22625.77	46397.59	32757.98	50494.47	26093.3	40757.72	57292.84	75224.85	31965.13	37909.62	51839.44	26791.02	10461.87	20380.32
trans-4-Hydroxy-L-proline	369544	452830.1	389186.3	236273.5	305074.8	268574.7	455406.6	316627.2	278676.6	731871.5	537082.8	290170.9	291523.9	222101.3	647583.6	334998.5	318514.3	332742.7	134432.9	241328.9	583679.7	1291428	200568.5	194998.2	529347.6	375819.4	193101.1	612745.2	671436.6	776997.9	724445.2	185909.9	523998.6	206145	824587.3	185662	260079.1	427173.3	78353.6	420027.8	249617.2
Pantothenate	205388.8	78473.5	209879.5	197617.7	196875.6	114569	142484.1	125899.2	40979.85	45432.29	234192.3	109089.5	69811.7	32812.99	32442.49	22112.97	114436.3	61996.44	32633.97	127831.5	87383.49	36612.91	146003.4	16669.4	199839.8	41406.87	129317.6	55677.19	36375.26	119825.1	53363	26547.26	98711.24	36866.11	29836.69	111005.5	37232.93	217385.7	18544.45	119577.1	31670.35
Taurine	11858870	26433320	16134520	2382750	4627362	11477080	15029750	17661790	1781017	38460560	22748840	5602256	11747090	3443062	20747520	6762626	7000320	12942550	1199469	3444916	7154526	29108130	1441826	2641974	24865280	3875695	2719263	9395387	14172100	15657840	6808970	4870968	4753356	3394579	6118854	1527670	3408573	19184990	1653678	4457232	2108810
3-Sulfocatechol	2221324	2591213	3187847	964342	1027287	668322.1	3366827	2375542	3771707	2651538	4069295	2894570	1737806	601206.8	7370222	262318.7	1973020	367369.3	1036872	6107596	653100	6682066	1146280	232037.6	973732	233769.3	397606.9	4599862	836450.5	1304409	2356475	324256.3	4024112	141811.2	8259102	1518226	4308892	3291662	215168.4	167133	1610623
L-Methionine S-oxide	60841.57	31867.85	43443.16	754962.1	94916.2	74989.66	186280	45117.6	867569.6	45763.23	37830.2	14960.43	59896.95	133529	36452.8	24360.61	67329.18	28958.35	2704.754	119804.8	50904.07	46106.44	248970	570359.3	31472.68	102222.7	42157.94	84430.4	34700.79	53527.76	29690.17	429255.6	178315.7	161416.9	91879.3	690004.4	256308.5	21437.39	146453.5	135752.5	148452.2
quinolinic acid	285550.4	296384.4	272753.8	194103.7	239108	283785.6	306780.1	395576.6	264713.8	312156.3	350789.8	295460.2	290862.5	207965.1	388302.8	165363.8	296926	337405.5	156798.7	133392.6	196596.5	297774.1	253773.1	142774.5	297342	177722.6	139441.5	247153.8	227803.2	364153.3	326382.4	172822.8	146723.7	160438.9	395219.2	218896	174152.1	312923.3	49500.97	151965.1	230711.8
Ethanolamine phosphate	70374.46	584588.2	208070	112887.5	89067.95	148479.8	230656.9	191375.4	63177.54	723036.1	103158.8	42778.6	80761.65	153729.5	231009.2	110185.2	115066	199249.6	47552.89	159075.6	102620.6	214496.9	66495.7	19857.85	295606.8	48861.32	43642.85	89398.29	202971.5	253432.8	80588.35	231133.7	62943.16	53666.19	40519.5	89758.54	66352.12	155122.5	174123.1	20374.17	65307.91
Pentanoate (valerate)	78954.44	117161.2	128219.7	373268.5	348647.2	125010.7	144312.3	86213.04	296289.8	123762.1	109366.2	117126.6	97718.7	305043.5	148733.6	126600	103826.8	140517	253109.3	271571.4	131869.4	130152.8	331668.9	280023	158172	426400.8	293392.1	0	120661.4	117730.4	98993.38	394056.3	272116.7	236892.7	127276.1	484473.1	456577.4	104246.8	484713.4	271040.1	272885.7
Heptanoic acid	427074.1	539528.4	441132.6	784237	643717.7	492471.4	489258	408361.9	555085.9	419666	466340	462552.2	378200.1	631927.8	445187.2	448200.5	529365.7	563253.8	655738.4	585022.5	472375	529288.3	669581.6	583559.8	461477.6	712600	378144	550844.6	502112.9	420880.1	419045.9	699278.7	610300.8	609309.2	508003.6	566041.4	697264.8	433174.7	702179.8	588885.4	483893.8
Octanoic acid (caprylate)	3152696	801692.9	758270.2	1316629	2680195	2326647	1894208	545718.6	1319337	810733.3	877075.3	985084.7	1879995	908305.2	986483.5	453136.5	812808.7	819764.8	1157515	1235067	912357.8	1058345	1142107	846659.3	1256715	966562.5	796229.3	697577.3	906895.7	942015.7	686820.1	3323953	3230898	1085522	1309962	1302330	1218828	666659	985546.2	994931.3	537322.2
Decanoic acid (caprate)	4031862	5685962	3748717	6108444	13082100	10592520	13341250	2330645	4912138	4442050	2997673	2608377	2748436	3244073	6646120	3302119	2275626	4049117	4535856	3899481	6376716	4103053	4966854	5457512	9374589	2684978	2680100	3406338	4098109	3905791	5317026	4075326	4419814	3709642	7813652	4415428	5772384	2851709	3756919	4263358	2359512
Dodecanoic acid	720021.6	5721116	4213598	2143349	2548569	2764839	10001530	920752.3	1705566	3891789	5521834	107061.5	3568222	1811026	5770676	1996530	885390.6	3460755	1876633	1900482	5295313	2614850	7819042	3086116	2765061	4492740	1857196	1834022	3438291	2729620	6338130	1419946	4321336	2445776	3611673	1606899	3212317	4847886	1068230	2808730	1424004
Tetradecanoic acid	971117.5	19814330	14659360	6310246	5396194	5568648	16264610	1496310	3740434	4845060	10058240	0	6324174	4124836	4844016	3951956	1362742	5833238	2203926	2929221	6721286	4112045	13194560	5108268	11274600	10740890	4063152	2395437	14169680	9472732	6321618	3419712	8393645	8168276	3615233	2830419	8099108	10890100	2246356	10924590	3612820
Hexadecanoic acid	16521920	141420400	84375430	71451560	76210940	53313740	76163240	15888390	41012800	64428130	93107640	0	62196850	43469340	83459500	36609080	18937040	63501300	29863090	37891220	69428100	50046190	95160190	37099210	68437220	92923670	56560910	25316730	89257690	75907120	43818510	64775490	99557500	97332480	40996520	33734840	76880530	63453070	26041950	110557100	47497670
Octadecanoic acid	6836198	26518730	38500780	21508600	22617390	22145750	39057240	8333576	15965960	22791200	24576960	0	30360560	21802870	26033570	13793960	11330580	25555690	14413750	19831780	23640300	19314250	24738470	17910220	18063140	36129600	19293540	13955910	30052350	25686920	20338590	33145660	42494160	26941800	21276880	15514310	19841730	27019820	13852310	39582280	15576700
Tetradecenoic acid	309323.5	5065840	3372711	2408699	1173419	1072434	2166100	194618.7	415612.6	1400932	3743162	0	664721.4	477300	730806.5	1156455	332015.7	1131456	367291.7	408709.5	3184555	681811.9	4528370	1296718	1944094	2614953	1277014	517155.6	2522877	2481553	757519.2	405388.6	2594546	3150317	694611.4	324297.8	905258.8	4210388	191615.4	3476132	668227.3
Octadecenoic acid	12177560	134740500	178576000	118167100	104559000	85097360	88346730	11858180	31712260	87049380	109783800	0	101491000	59646080	91812580	52830980	15085250	89440620	28527740	40994020	75509920	52539240	142096300	83674950	104078900	185443400	85174470	24044980	132081600	115404500	46426600	90148600	151623500	144304800	34307080	19162750	106539600	104425800	15686110	220316100	59921300
Linoleate	5319104	161155500	111363300	49966710	55681520	35070970	50760030	8621303	15688830	52001380	128020100	0	113224300	36691650	43721930	39704160	4640300	49359300	13871550	14673780	56118940	34943330	73416740	49373420	47642760	83454620	61743770	19473380	146575200	39670880	46601980	117420700	86087400	41889760	24382060	8656725	79809820	95992010	9053043	167988300	43957950
Octadecatrienoic acid	1941552	20946740	20583660	9455927	12267780	8341694	7270262	703614.5	2128600	3888726	11261120	0	23921150	6055388	4260198	5576702	454932	5887480	1413341	1948270	7408466	5916128	7707428	6918334	16599650	6206310	6442878	3927697	14102920	3510963	5420522	16739210	14073060	2920566	1768988	685235.6	10273840	9907825	686602.8	22129340	6216836
Eicosatetraenoic acid	1106400	4588944	7265042	4416754	1015869	4347596	2835304	1033178	1824313	1767393	3059602	0	3179543	2756405	744364.3	1073110	729479.2	2817240	1235669	1103816	3208351	1576410	4366840	1808417	938626.9	4541684	1489332	853475.3	4580324	1540621	2006489	3595148	1570546	1514382	1870257	1152415	2281197	3729381	925786.2	2519592	1121145
Eicosapentaenoic acid	393973	363032.5	938838.1	868362.5	157311.7	176300.1	951666.3	75980.33	650170.3	80330.23	455107.5	0	238215.8	1326706	191182.3	118763.2	175686.1	447539.9	110096.2	86024.91	414961.6	136878.1	1159391	279071.4	342377	671081.9	158011.7	142404.9	455932	222961.9	790039.9	404399.5	169500.1	211145.8	205643.3	237376.2	399962.8	490560.3	128991.3	283480.7	135094.4
(8Z-11Z-14Z)-Icosatrienoic acid	329786.1	994514.1	1851595	960795.8	358285.8	686564.2	551426.6	157455.2	247839.5	320782.4	1211145	0	422001	536803.1	386394.2	335768	195981.6	609869.4	227134.5	306955.2	828678.5	251359	996850.1	365946.6	316883.5	1157205	356625.8	175893.4	1522866	586666.7	495310.9	742598.9	662931.4	461248.2	384496.8	136942.4	444904.3	1114930	129724.6	658062.4	296884.2
(7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid	265410.3	907025.1	1445528	1021568	350516.4	440834.8	652384.7	120166.2	343735.8	171529.1	1108658	0	644004.1	678961.7	103652.3	195440.2	181529.4	765118.7	199094.2	173449.1	648202.6	159619.6	1517562	313035.8	208782	1577884	447548.3	80574.96	1062768	581971.3	525167.7	995694.5	421685.9	515548.9	245810.3	209189.6	459378.9	868275.8	94599.09	1007497	225833
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	KEGG	MW	RT
L-asparagine	C00152	131.0445	0.6208834
L-aspartate	C00049	132.0285	0.5370833
L-glutamine	C00064	145.0603	0.63015
glycine	C00037	74.02296	0.6224321
L-histidine	C00135	154.0606	0.7109685
L-threonine	C00188	118.0493	0.6389574
ADP	C00008	426.0211	0.5416489
AMP	C00020	346.0548	0.5623513
Thymidine	C00214	241.0821	0.6466886
IDP	C00104	427.0063	0.5175062
Inosine	C00294	267.0721	0.6513907
Hypoxanthine	C00262	135.0293	0.6045538
Xanthine	C00385	151.0245	0.636663
Adenylyl sulfate	C00224	426.0192	0.5374171
5-6-Dihydrothymine	C00906	127.0497	0.6359408
4-Pyridoxate	C00847	182.0447	0.6943446
Pyridoxamine 5'-phosphate	C00647	247.0448	1.726458
Nicotinate ribonucleotide	C01185	335.0443	0.5840333
Phosphate	C00009	96.96785	0.5574352
Diphosphate	C00013	176.9346	0.5533823
D-Glucose	C00031	179.0547	0.6406314
D-Glyceraldehyde 3-phosphate/Glycerone phosphate	C00118	168.9879	0.6609406
1-3-Bisphosphoglycerate	C00236	264.951	0.5403962
2/3-Phospho-D-glycerate	C00631	184.9846	0.5818924
Pyruvate	C00022	87.00701	0.5668754
Lactate	C01432	89.02262	0.5925222
Maltose	C00208	341.1082	0.6413074
Mannitol	C00392	181.07	0.6533093
D-Ribose	C00121	149.0448	0.6181245
D-Rhamnose	C01684	163.0598	0.6445629
D-Arabitol	C01904	151.06	0.6380444
Citrate	C00158	191.0184	0.5501434
2-Oxoglutarate	C00026	145.0127	0.5266868
2-Oxoglutaramate	C00940	144.0287	0.5709814
Succinate	C00042	117.0176	0.5604396
Fumarate	C00122	115.002	0.5608721
Malate	C00149	133.0126	0.5535666
Oxaloacetate	C00036	130.9985	0.554837
2-Hydroxyglutarate/Citramalate	C02630	147.0284	0.5500703
6-Phospho-D-gluconate	C00345	275.0181	0.6285892
D-Erythrose 4-phosphate	C00279	199.0058	1.714781
Sedoheptulose 1-phosphate	C06222	289.0362	0.5679088
Cys-Gly	C01419	177.0326	0.5956921
Ascorbate	C00072	175.0235	0.5919425
Dehydroascorbate	C05422	173.0076	0.5345629
gamma-L-Glutamyl-D-alanine	C03738	217.0821	0.5440667
5-L-Glutamyl-taurine	C05844	253.0547	1.755728
Ornithine	C01602	131.081	0.6413722
L-Citrulline	C00327	174.087	0.6302099
Argininosuccinate	C03406	289.1202	1.727408
N-Acetylneuraminate	C00270	308.0978	0.5695796
1-4-beta-D-Xylan	C02352	131.0332	0.6344703
Guanidinoacetate	C00581	116.0484	1.702247
trans-4-Hydroxy-L-proline	C01157	130.0493	0.6368641
Pantothenate	C00864	218.1024	0.5993623
Taurine	C00245	124.0062	0.620949
3-Sulfocatechol	C06336	188.9851	0.6499605
L-Methionine S-oxide	C02989	164.0378	0.6319254
quinolinic acid	C03722	166.0123	0.5825296
Ethanolamine phosphate	C00346	140.0098	0.603898
Pentanoate (valerate)	C00803	101.0591	1.696419
Heptanoic acid	C17714	129.0904	1.787757
Octanoic acid (caprylate)	C06423	143.1063	1.913535
Decanoic acid (caprate)	C01571	171.1377	2.207331
Dodecanoic acid	C02679	199.1692	2.38255
Tetradecanoic acid	C06424	227.2008	2.630146
Hexadecanoic acid	C00249	255.2323	3.005383
Octadecanoic acid	C01530	283.2636	3.535101
Tetradecenoic acid	C08322	225.1851	2.426242
Octadecenoic acid	C00712	281.248	3.036508
Linoleate	C01595	279.2323	2.722992
Octadecatrienoic acid	C06427	277.2167	2.52315
Eicosatetraenoic acid	C00219	303.2323	2.624
Eicosapentaenoic acid	C06428	301.2167	2.463679
(8Z-11Z-14Z)-Icosatrienoic acid	C03242	305.248	2.80074
(7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid	C16513	329.2488	2.630531
METABOLITES_END
#END