#METABOLOMICS WORKBENCH RCulpHill_20220309_150107_mwtab.txt DATATRACK_ID:3119 STUDY_ID:ST002110 ANALYSIS_ID:AN003453 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        	Positive 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 0.1% formic acid for positive 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                      	POSITIVE
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-alanine	8466603	10580650	9778162	8213416	11185150	9641360	9990393	6462932	11141930	6937938	8037176	8189692	3041346	8136880	11326120	9111733	7447514	10656430	8886589	7405322	8036150	10711920	6411642	5263364	8548934	7057792	14411660	10986090	8775410	5850200	8638075	6077082	9406222	6254634	8003722	8582791	7923170	10567020	10611160	11795660	5533030
L-arginine	3115256	370524.4	1430919	4968818	2695308	3124857	3458241	2855622	3224545	1119950	1605280	1919119	1819006	1127332	966703.8	683932.9	1922571	1763321	9771325	4004547	1153559	83895.16	6820428	9007889	189192.3	998251.2	827527.7	1075954	1120604	1595009	2163558	9541221	1934134	982257.8	1658866	7389642	4325663	1443057	6900842	505003.2	2987545
L-histidine	2453638	2597607	2567795	1377803	1364666	1818053	3440667	2695136	2291003	2564417	2887923	1726294	1486060	2110079	3140249	2251140	2086553	2663804	1747022	1444354	2123193	2581249	1489700	1457606	1951708	11561570	1940490	3174750	2782243	1844844	2608686	1974782	1917889	1560990	2310887	1824159	1743519	2350274	926305.8	4802746	2454169
L-leucine/isoleucine	85829670	58693920	86575510	60566000	54290890	58836610	121373400	50334220	57935950	57120500	38788800	52955720	60426860	65851370	54544060	71073110	51108180	90746620	57363920	28724500	92328540	72031920	38686980	68813320	50108800	55390740	129195400	77029010	44855280	50112800	91893540	59004390	49477990	48533320	66033740	74394920	59947960	45674560	26482660	78633560	53287760
L-lysine	6396636	4312242	5811074	3529997	3014004	6074292	11509280	5794668	4904258	3221752	4095096	5415991	3581125	3894760	3924193	6453988	2917896	5647162	4139526	2786795	5307454	9570940	2689148	3016006	3978712	3469320	5118812	2950467	5421498	3200481	5338135	2914251	3523685	2758166	5079622	4949698	2828919	3817930	1786465	4826352	2193088
L-methionine	5134428	4028231	4898022	5172984	3606051	5390480	7299968	3334575	5472968	3460304	4510402	4953172	3067188	3430975	3545000	5326788	3352109	5275296	5463608	4431512	4999832	2307977	3050440	6235180	2171936	2130661	3523888	2586520	2982813	3389472	3928522	5460188	5159752	5259058	3843799	7711618	5062052	5997392	2309143	2010160	3332421
L-phenylalanine	4646138	3912414	3445964	2840971	2697459	3595482	6604918	4597954	2573563	2974040	2770944	3122322	2874126	2361781	2566680	4334758	2534852	3815885	2101954	1886049	3077135	4406964	2647209	3240414	3128579	2763677	3370495	3630580	4028279	1612805	2995975	1904219	2815552	2417267	2692800	3423383	2835089	2960878	1684731	2788869	2097368
L-proline	87283900	61690920	38968540	61294690	41039900	37427120	86449440	50271090	64466350	63061820	53125660	49992220	39334630	39117240	74093290	106743300	72303370	64118960	56143280	56950500	88764040	90457250	55558590	37579140	37526820	41187500	81705580	60837090	62253300	62888610	78374710	38495270	60814660	39494660	69015640	84171140	43913990	79179780	88823260	69209600	52922440
L-serine	346282.3	697011.6	518234	335631.7	422918.6	562109.7	562828.1	352253.1	387150.2	819196.8	355995.6	321882.6	396249.8	423953.4	544747.1	680529.8	333371.4	389691.9	554048.7	454355.8	331717.3	568461.9	371743.8	528626.7	434624.4	609610.4	858893.8	489429.4	715747.7	309834.7	362959.2	367812.4	650412.2	595332.6	527864.2	537519.1	681755.2	473173.6	238571.3	879324.2	337463.2
L-tryptophan	32097770	22154110	31049590	15277710	25931580	30006800	55240800	48413120	28804430	22520520	33353560	37987000	21914500	36242090	30868390	39021710	35866880	38136800	29631350	29292030	41736900	29750380	20821540	24023670	32499540	16877300	17587940	18877420	29720060	24571320	25895670	14839520	20273230	26834470	39957370	33245500	23624180	33789320	16706850	6626824	15003420
L-tyrosine	21631470	13853410	13043410	13723960	25023490	14716740	20650940	10017410	19716960	9205407	13404610	7923860	8944685	17338560	9334320	18174200	12713460	10154100	13748060	18375120	14136200	13297030	17715860	19612260	13781580	15381130	27304930	11924360	12610730	12475580	9706201	12728320	19840540	23487140	11192300	32339840	21196210	17041730	10234610	17608050	17360120
L-valine	107421100	77410960	111199700	63152930	65491490	90382110	139429200	100495500	82309820	63804780	66070290	67099730	128833000	85538490	59230480	90830520	235886400	117553700	58855150	54516980	85117540	85042900	63294290	74125450	73501980	62005980	121117300	76648120	65620720	131398900	108762400	61245630	56390270	59300060	90007510	68871300	68758670	81908900	60774270	78500340	112737500
Thymidine	0	0	0	168271.8	189158.4	0	0	0	212551.5	0	0	0	4152.912	3951.285	0	0	0	0	129675.5	170629.4	0	0	170097.9	173923.9	3932.329	89195.93	166765.1	0	0	0	0	224073.1	108993.7	140344.8	0	189036.6	196889.4	5471.693	206685.4	101959.2	147134.6
Uracil	186194.2	198662.2	222481.1	232683	165908.4	185679.8	287790.5	249578.2	261953.9	287953.8	206110.7	138705.2	199804.7	173674.9	193987.4	198539.5	222243.2	193677.9	216509.4	147275.5	189721.6	194505.3	169598.5	169990.8	273357.2	185338.8	199481.9	266588.4	172884	246494.8	234916.8	196654.5	203318.9	171180.6	155515.5	166152.6	143593.6	195350.9	133103.4	231970.2	135039.3
Allantoate	653001.9	1326749	610819.9	694707	1165604	427956.2	1430900	671134.9	1287101	960463.2	679384.4	317346.3	670162.6	1051392	1168821	1133092	313533.6	423104.6	453872.7	709651.2	654061.2	1159431	566040.2	1163667	783875.9	1474648	1473569	1220471	1123129	486929.9	726672.8	344867.2	1180632	804804.1	936735.8	993270.8	1259725	758744.3	588229.5	1236419	1546568
5-Hydroxyisourate	1309694	655172	615442.2	68886.52	93662.22	631263.7	778086.1	576396.9	90760.56	1044359	472177.1	1510023	546361.9	56020.41	831658.4	654682.1	1280639	789591.8	46577.11	68663.1	1945063	1480131	79240.32	54266.23	682684.9	219012.2	61906.03	894124	721298.2	1006996	1065241	74825.52	202118.8	125248.2	768740.1	76112.5	79915.72	508040.2	80359.87	93942.46	132499.5
3',5'-Cyclic IMP	582219.8	505723.2	592419.4	0	2356.826	469161.6	545362.9	533771.9	0	590971.2	518459.5	430030.8	484267	1610.743	547382.3	524812.8	234941.4	697133.8	0	0	470623.8	271268.7	0	0	507593.9	0	0	281478.3	555248.4	585800.6	697578.6	1249.74	0	0	457375.4	0	0	506769.3	0	0	0
Nicotinate ribonucleotide	12125600	9743735	9655169	0	0	7872074	12344010	12744600	0	14432450	9080133	8313532	14207240	0	11099280	11619490	8685708	11562780	0	2038.049	10227500	10094960	0	1717.585	12054560	2885.678	5962.061	13857850	13214710	14118840	8319138	6572.131	0	0	11517210	0	3494.456	14752010	0	6289.373	0
5-Oxoproline	9165884	5862264	5909918	5178058	5938884	4988360	5739608	5980334	6052458	6786672	4883708	4936468	5639908	5596882	6732070	5929748	8107556	5594010	5835616	5199994	9232816	6283168	5850846	4563236	6827532	9701823	9609472	7586316	5255394	8302494	6125216	6050152	6481406	6571910	5973912	6584500	5196724	5561728	3136439	13334850	8009852
Cys-Gly	179241.2	383920.6	147224.6	178043.9	171225.9	117963.9	283130.1	167175.5	350366.5	227837.9	122054.2	107915.8	215385.8	377524	261077.2	212449.2	258577.5	290600.1	130157.4	264322.4	154426.3	581516.2	176248.4	181948.5	297018.5	390669.9	292045.8	368040.4	152470.9	265137.4	272685.3	187677.3	232863.8	363815.8	274330.8	308385.3	244974	213667.8	94900.63	262467	309679
gamma-Glutamyl-Se-methylselenocysteine	231000.3	475398.1	231916.2	289026	413480.4	163258.9	475170.3	309663.1	423976.9	373190.1	289359.4	85476.17	291576.4	412925.8	485692.3	456102	98396.02	165994.2	198686.5	269353.5	264411.6	398858.2	273159.3	361768.5	253458.8	562152.2	548231.4	484965.8	439072.8	167857.8	233066.6	155882.3	433970.7	330113.4	327698.7	356579	531438.6	237973.1	227640.5	511087.1	638789.4
gamma-L-Glutamyl-D-alanine	0	6017.256	1586.798	7742.498	0	0	179949.8	0	4323.402	7529.879	3196.844	1742.906	1800.667	86547.77	0	0	0	3047.894	8474.875	4865.618	1784.077	616232.7	4074.169	10963.3	0	463320.7	0	1977885	1856.221	0	0	6920.419	5490.064	0	2339.546	5080.203	1102943	0	9921.517	1961.433	3000852
gamma-Glutamyl-gamma-aminobutyrate	251538.8	123890.8	235668.5	0	58236.94	259612.5	451998.2	185508.5	47925.8	151068.3	207725.8	817709	330209.5	0	122360.2	212403.2	341743.6	379036.1	3026.487	6447.41	514005	616771.2	0	85759.91	266346	4491.18	118934.6	152390.8	133122.2	177818.9	443313.6	0	3114.74	0	316708.7	5973.256	1952.137	141054.2	0	46730.91	172714
L-gamma-Glutamyl-L-hypoglycin	0	0	7144.069	22642.41	29741.87	0	0	7825.144	77961.6	0	0	0	3634.386	12366.28	4375.548	0	3950.692	0	54936.29	37524.41	0	0	58250.91	48110.68	0	41336.41	51528.82	27312.85	2779.333	0	0	46243.69	18209.29	23342.76	0	96950.63	62996.25	0	82868.15	42800.46	42151.85
L-Homocysteine	72933.97	119769	97386.59	150580.1	142110.6	86223.8	288923.9	143761.3	435446.2	273465.5	194524.2	286327.6	179518.8	175598.2	296901.6	349406.4	167185	171123.7	95411	306694.3	184060.6	172261.9	238390.7	197711	77889.01	544751.2	545101.7	167386.4	123027.8	258002.4	143956.4	158345.6	180118.7	177357.8	114941.6	223878.7	539735.8	221709.7	127406.3	600760.9	529695.8
Dimethylglycine	1185265	1647599	2681348	1420458	2220765	1989498	1514210	1771341	1618222	1402468	1142989	1675787	2154870	1605567	779155.8	2330638	1924028	1557873	1376394	1117392	1491726	2128261	1138494	1856694	659372.3	1382025	3008253	6995410	1901669	1725381	1206966	1174954	1242206	839181.9	1211630	1889200	1698732	1165193	1472784	2547697	3718695
Phosphoserine	207185.7	201711.8	261199.9	265928.8	138869.3	149934.6	211862.6	238138.3	213236.8	183899	230936	215455.2	170725.4	201052.8	171047.7	221947.9	168017.5	189941.9	206976.1	215462.8	184197.7	238998.2	230088.6	250327.2	243726.9	195860	201197.6	140739.4	161459.1	176468.3	210884.7	198045.3	239832.4	249028.1	137693.9	203509	150492.4	157720.7	144316.5	218896.4	274838.8
Ornithine	1525677	2535724	1375180	829444	1288878	1008590	2998909	1383236	1722850	2344732	1342990	1005711	1127424	1377071	2423127	2706978	863840.2	927681	527741.2	854480.2	1621637	4440846	754060.7	1344280	1640782	1549211	1665838	2039924	2198116	983475.3	1551856	436305.2	1542970	1209435	1830743	1386961	1434854	1384226	604856.4	1823010	1797675
L-Citrulline	1706880	1097432	219060.2	1117476	1168186	390376.4	955534	1082039	582859.8	765832.9	624547.9	805980.4	998358.8	745806.7	1049342	793484.6	684394.8	529539.7	449530.7	635274.9	593232	902160.3	793304.2	467494	750490.2	570597.7	990122.1	933785.7	823278.5	749390.3	906348.3	540868.2	1143306	475463.7	738965.8	817356	939811.5	704424.5	529760.1	915171.5	1067569
Spermidine	27434.81	113421.3	21987.9	333065	93062.34	56317.93	5644.383	22489.43	77583.22	32648.12	0	66911.56	15763.7	126248.2	0	27485.31	53562.55	41704.56	36846.12	263858.7	78278.52	781123.8	94722.75	128659.1	67136.13	115748.4	93113.47	17752.12	18651.41	23458.65	35254.61	296830	57164.38	275258.2	11516.76	145415.1	91223.63	25956.13	503285.8	63900.79	29696.93
Spermine	10017.75	15524.3	0	353239.7	26874.8	0	0	0	27498.92	0	0	10362.7	0	125008.7	0	0	0	0	26393.03	281963.8	0	398434.9	58541.58	26977.69	19027.79	163613.5	55288.76	0	0	0	18994.14	449230.7	21662.76	26045.03	0	19576.38	22056.67	0	803558.3	78565.73	0
Creatine	9003621	9424171	5013058	2779440	3666052	14119540	17548870	16406130	10701780	7422906	6021656	12768660	11243780	17074110	12338580	34400780	6081944	12167340	9344631	8458873	10212930	35374910	16641800	34605840	4910822	17195650	10341140	4118129	32675920	5506472	7868072	6384906	17069960	7983494	16905130	27825620	29706310	6434016	28897750	11148130	5616478
Creatinine	20208620	13940880	13994650	27847940	23599410	19464480	14589400	21090260	29505810	14687010	29678660	15721120	16031590	29805420	14233180	14030320	10990480	17346920	18364530	20219410	13959200	18304890	12353420	10283770	11191600	12776130	23985500	25461200	15736100	7664222	18352880	16640980	17102260	11089720	20163520	15837380	21740060	32358970	14719360	20695790	20125450
4-Acetamidobutanoate	79314.12	168223.2	70396.85	65588.84	96238.13	26559.76	780132.2	87784.95	29563.71	4710110	106997.5	283182.1	318622.9	49241.74	331573.5	121767.4	97698.54	111078.8	1300059	187264.7	121182.7	129080.2	91357.4	3856835	139246.8	27907.7	52137.38	166414	387131.2	109582.9	193532.4	15177.8	88697.1	46381.02	1827669	33548.82	538646.7	115519.1	1782083	108873.5	1163827
N-Acetylornithine	383591.7	421678.6	232989	306189.6	378379.8	261460.2	638985.2	242224.2	385697.6	841890.1	165571.1	707145.2	357857.2	271143.7	900958.2	327633.2	533112.7	262113.3	211783.5	362207.1	612542.8	1236564	179079	387082.9	395083.7	235293.8	664690.9	517463.3	331126.5	1610715	340731	230850.6	509034.7	191119.9	1029324	179154.8	676047.6	211064.4	111853.5	675781	625264.1
Guanidinoacetate	297559.4	224188.4	87255.66	191380.8	144352.2	188862.9	229192.8	230440.4	445270.7	229705.9	199706.8	410739.8	133418	213557.2	230759.6	179585.5	196214	231813.9	372972.1	222850.3	197723.2	436367.1	272690.3	121753.2	136759.3	186329.6	192900.5	194339.1	163925.1	155953.3	246976.7	334221.8	222166.4	198535.7	304552.4	286366.2	341817.7	262044.6	188981.2	200268.3	175439.2
trans-4-Hydroxy-L-proline	4283378	2854935	3218624	476722.7	530723.7	3069545	2832781	2447218	396691.4	2480814	2531481	10147730	3804025	658558.4	2220662	3193801	5460984	4575082	406724.8	438256.6	7039516	10458250	324093	200788.4	3879000	563945.2	472901	2161072	2253751	3597741	6372890	256796.1	775881.8	303012.1	3947607	393968.8	387493.4	2253288	211364.8	769075.9	479501.5
Pantothenate	533479.2	111677.1	310650.3	359048.1	264292.8	163029	262416.2	289375.8	89677.79	74079.95	360524.3	190526.9	177313.2	55946.91	54219.12	51095.72	174287.7	86441.59	43807.59	238969	124021	115176.7	158905.7	64015.07	349848.5	111079.6	210289.6	66490.71	76292.27	186932.1	106895.7	70094.38	145239	72259.39	43802.06	173436.1	44592.37	205612.3	38444.96	142171.5	62480.89
Indole	178418.8	233165	145460.2	172088.1	349893.2	164063.1	340995.7	149865.1	246987.9	185493.9	194949	151619.4	162509.2	235325.4	127053.5	217322.4	38961.93	124066.4	160811.5	233823.8	239522.3	211039.7	244022.5	210092.9	222838.8	222339.8	293908.4	163649	203491.8	167106.5	133356.7	307795.6	625203.8	341866.4	168008.8	436627.3	268534.6	193325.6	50858.71	167302.2	222267.1
Indole-3-acetaldehyde	85570.35	49153.81	89897.88	39299.75	81207.62	66982.56	150740.4	120328.1	100255.9	70998.81	100107.5	91552.18	51406.18	103399.9	88632.68	91375.9	84793.66	102767.8	93031.97	65843.69	103186.2	84141.88	57258.43	62916.76	99031.8	39439.64	41920.02	24124.9	62639.28	73628.66	83578.71	55086.75	28886.64	69118.84	101811.1	106724.9	67924.86	83594.5	52136.3	17166.28	38112.71
Indole-3-acetate	140451.6	86893.76	94488.52	36827.75	80184.84	72932.61	144212.6	127728.1	101047	69297.07	201067	78196	83892.56	86703.73	75273.13	52637.29	179617.7	100051.5	49199.74	23247.63	76202.16	174344	91116.32	13696.51	89996.29	94492.34	19897.01	167929.1	89535.31	100601.4	62866.61	46485.42	86655.38	38152.71	107166.3	71055.52	35179.36	170464.4	42675.04	47090.33	182238.1
Indoxyl	1260033	216848	207654.8	250146.9	236850.3	106171.7	483138.7	1323653	355041.4	292118.8	449976.2	530823.5	106858.5	385740.2	619361.5	175429.5	174217.2	1281517	257299.8	599845.2	174617.9	308981.2	170361.1	200464.7	189985.2	101891.2	448116.1	910057.3	341769	342627.8	485546.8	141184.8	541450.3	128260.9	781355.4	177097.5	408038.8	424227.5	125505.1	320842.5	188310.8
kynurenine	136264.6	65606.54	69402.21	63027.75	74107.02	61145.92	99295.79	167835.8	43280.74	38152.85	106837.4	80500.73	91677.03	43263.75	78950.7	78658.75	61871.78	150014.9	29568.18	82846.1	56144.65	89901.4	55398.41	46104.58	116122.9	54549.25	52732.76	64185.89	80057.02	147965.8	127555.4	35848.96	66679.7	51351.29	129291.7	112342.8	71347.07	103721.7	36040.88	50000.23	69163.16
Anthranilate	282625.8	4978096	1409316	311636.2	199152.7	1337485	560907.8	3952663	10578100	6872548	4134383	518300.8	1527878	1489784	7558846	355637.2	287155.2	222808.2	8937898	6092742	1024230	8150278	2299508	630824.2	115278.8	547803.3	1165886	3267873	310639.1	358150.6	774553.8	1615142	7293346	207095.5	5360860	1348742	3304197	4373736	2800214	1611940	2883286
Picolinic acid	3769211	3447460	3057503	4928754	2763791	3515295	4790206	3747841	5509295	4078735	4949034	2694203	3271413	3390930	2437319	3809837	2479460	3821037	3057760	1659099	3165905	5301026	4060701	4237870	5937192	3657443	1774288	2408020	3049540	3204183	3744217	4426526	3295101	4064359	2501824	3569362	2075691	2468444	2201107	2777126	3086454
g-Oxalo-crotonate	0	0	136340.2	572913	753574.8	96011.49	21012.15	138568.3	467782.9	9850.295	70652.7	0	297059	736807.4	0	63006.72	11383.36	9876.814	304457.2	436989.4	41490.26	0	209750.6	451281.5	0	243708.1	34479.7	8788.166	233859.4	298893.8	0	567509.6	9311602	1509254	69554.04	730932.2	510712.3	102501.9	1439114	30282.34	11959.48
L-Adrenaline	1236369	1465772	1610516	4643331	2663132	1149739	963040.7	2718775	4083972	998157.9	2097699	3459428	844381.9	4276654	2385571	2533371	1803149	2379483	6783608	4601241	793397.8	3291419	4139028	4469541	1187061	2013098	5263336	454589.7	631015.7	1731451	1425564	5962898	3687450	2305215	3894322	8951494	3605650	2858676	10646060	3091891	1608984
Dopamine	10383.54	142380.5	19960.18	8398.882	7087.023	18331.02	29187.51	27391.65	8749.139	53345.81	31003.76	30676.71	55764.15	43394.73	26011.53	15890.48	7197.576	23701.3	7746.084	16414.87	12753.71	27001.06	22262.86	21136.96	147165.3	64062.04	21554.83	37706.22	55335.03	31071.67	8192.839	15130.04	59031.31	35457.68	16854.85	30244.85	27778.2	51289.45	14674.45	39355.06	101122.1
Serotonin	39214.69	2345192	9349.28	7982.3	1951.649	11291.9	1122.456	62683.18	2064.396	719810.1	1041.969	0	0	7413.786	819013.8	0	2123202	20353.16	3469.678	33348.98	2967161	2624340	1921.738	0	44891.64	254729.1	6817.846	831284.8	12597.68	3296270	15382.02	20024.66	4027.22	143365	1690404	3434.828	17351.21	13947.78	6622.946	11638.9	1057292
Ectoine	530835.3	396471.5	410002	111805.6	209049.7	459309.7	531079.4	407201.4	42049.89	376769	477817.4	1006077	361615	29359.6	344810	480684.3	497624.7	555209	52936.37	9017.933	664418.2	810143.2	23059.06	118004.8	434311	17821.57	53101.04	339140.6	316810	373089	625317.4	21232.62	27330.12	13193.89	457216.2	41968.31	165888.9	282689.7	26907.82	197235	90544.01
Sphingosine	38575.55	293173.9	38494.96	27723.17	44866.81	21697.48	62222.74	56639.02	26908.48	228807.8	48039.55	17159.11	67548.5	71803.84	83453.85	44211.43	16350.67	52115.86	14079.03	33697.26	14948.53	68931.45	15848.83	26971.86	178962.4	109449.2	67634.15	60537.29	49354.25	82760.8	36409.89	27494.69	33023.87	32031.68	31262.16	21447.87	39425.12	35955.28	30696.03	77465.87	20134.86
Acetylcholine	2612619	3306172	1415214	2220751	1586702	2281487	3261721	3368263	2885371	4219928	3745853	1868995	2685824	2709890	3277804	3679165	2513923	4108970	2585111	2594158	2071820	3674264	2104945	2258632	1767192	2367677	3524212	2923501	4022984	3148502	3422415	2361292	3644537	1519989	3770881	1841655	2797625	3628412	1734956	4746866	2087568
Choline	40518550	32164490	27208440	33717740	33376880	33219230	29280810	41841810	29966460	25835000	15439380	21155150	41323570	27941100	28944090	21011850	24657630	30516680	23388310	22491040	17215550	28413420	24763150	17628580	34778770	22207500	50501750	34493630	23443130	26141130	25753190	18560940	31829570	27918630	22180800	29767790	29839830	19255150	17392110	44861680	53542800
L-Carnitine	67987860	110815900	90975840	87185270	67291480	121759700	132537900	135767700	126609600	156225900	98654590	101686100	74610250	124329700	139382000	137505300	121977000	115707800	96780570	85090700	114009900	117733300	109785800	89112970	51624390	83408700	79799030	106452700	144019600	101185400	105085000	97468300	123956900	89339800	146406000	126392000	77780870	118886200	58825040	91503910	55733750
acyl-C2 (acetyl-carnitine)	39021360	97771490	101830300	42986200	44929680	76343210	40999880	74448550	25753660	97571940	49814480	28687330	111874000	27961190	75435220	87474620	96019580	49815960	18453630	25382860	74995420	42649010	30708740	32724590	41371420	53819380	68677500	45040640	89221700	118471900	44296860	20122660	43821400	43855550	67970380	31009660	37578230	65047620	13860910	97033120	65554140
acyl-C3 (propionyl-carnitine)	2723681	2288554	3282673	769771.7	1412256	4514462	5881802	2958550	1176864	2777774	2300106	1766331	1594806	1157790	2351889	4250708	2171809	1931771	1731916	1097582	979903.3	2750027	1037044	1182340	1614472	681244.4	1692484	1476323	3350635	1636354	1948371	707093.7	2315857	1092539	4289386	1575231	714851.2	3129039	704803.8	1954167	446395.6
acyl-C4 (butanoyl-l-carnitine)	1065591	619826.7	1007304	639420.9	657868.6	1319886	1718768	1130152	416512.6	1122873	1550931	1024295	802867.8	535363.6	964339	1833440	611753.1	751116.2	356658.1	592892.7	334157.5	1180172	741282.8	857598.8	596431.1	547163	638363.1	548019.7	3161439	696737.7	557566.6	265546.2	608132.1	325791.5	2063822	802943	890258.2	2046527	461732.7	807936.2	478263.8
acyl-C4-OH (Hydroxybutyrylcarnitine)	384640.9	325856.9	1339502	377781.6	435017.9	728195.8	204360.8	762746.3	73454.01	475219.9	203390.4	61860.6	621786.1	59111.16	159916.3	515343.8	465915.5	171560.8	7692.701	272467.4	448152.4	172123.9	132809.5	298605	215801.6	404008.5	1164262	156050.2	430403	423212.6	147093.4	55600.06	280997.7	255829.2	228073.7	58324.86	304478.4	309344.5	93570.73	1211464	596963.4
acyl-C4-DC	161229.8	132396.7	107694.7	5550.482	178409.6	93748.95	120926.4	114686.6	0	22811.2	74610.16	59224.73	102408.9	77981.63	156206.3	187056.3	46112.92	98152.87	20051.23	17303.8	0	108906.6	27346.38	0	114222.6	0	35081.27	108134.3	155383.3	111108.1	140490.1	0	35027.58	4596.117	183911.6	5193.063	0	149451.1	0	62979.11	52208.99
acyl-C5 (isovalerylcarnitine)	1067052	778205.7	1117471	430632.3	497119.6	2200115	3675912	1360611	889527.3	1918649	719867.6	1840368	4946166	1757215	766202.6	1643986	641488.8	1400162	1030717	344031.9	487257.8	1979840	918072.1	998896.9	262405.9	455315.2	788725.7	14040950	1429994	638704.4	1081404	522067.5	591417	470252.3	2209598	1204199	678921.3	931374.4	671763.7	714091.8	2704831
acyl-C5:1 (Tiglylcarnitine)	90674.59	101975.9	93623.62	68964.46	106206.8	105812.7	347261.9	87649.22	81034.84	47400.7	92543.07	107057.5	63941.19	54903.56	53921.03	55015.05	105508.2	66714.66	41365.66	68720.43	52209.36	54676.18	57534.12	65526.31	49809.29	19306.92	61301.09	34419.67	65379.91	81077.47	85461.09	34974.74	14549.56	36422.84	108640.7	74206.34	65568.59	82336.98	42233.05	61195.27	143352.4
acyl-C5-OH	150238.9	115305.1	197336.1	16593.94	51284.47	81768.54	265077.1	39158.3	0	72408.16	71366.8	61649.81	35616.78	32655.22	112588.5	113925	42025	96049.15	39351.67	0	44597.39	191939	0	50234.02	0	0	0	81625.09	197112.8	79591.95	195218.9	59642.68	36348.98	0	185716.8	6475.504	0	105906.1	0	0	0
acyl-C6 (hexanoyl-l-carnitine)	273409.1	399873	508116.7	200937.9	221337.6	528042.2	170153.8	284100.6	194552.1	506359.6	441525	242192.9	348195.4	233231.6	199130.5	498848.7	200278.9	316482.5	178342.5	112654.7	109430.2	365331.4	467588.5	210874	70346.87	275110.8	963598.7	164511.2	758013.7	266557.5	141684.4	198703.1	161385.5	104582.8	440780.6	324267.6	158689.5	498116.9	148557.5	1103048	135370.1
acyl-C6-DC	38139.67	18302.23	21984.35	55902.91	13071.14	21716.55	25056.21	67078.59	9853.501	56956.95	19925.14	11999.7	148467	10516.78	691848.9	61459.92	485996.1	12255.31	7779.116	23359.24	239087.1	31122.91	19090.54	4791.005	21939.14	7985.717	69058.38	25506.89	98115.35	427549.2	13880.43	8575.95	57815.66	8716.045	26476.25	15348.35	8263.856	16181.74	4693.676	112315.1	88701.38
acyl-C8 (L-octanoylcarnitine	3946468	1642388	1837216	1645701	1115514	3994081	802233.9	1712636	692589.4	3442396	3406048	1041317	1455765	1041914	825522.5	3209347	1246321	2842096	923087.9	999514.8	585903.6	2009743	2390144	1081175	443028.3	1306706	5710120	554682.6	4366784	1684814	1085009	522006.9	500099.7	704173.9	1981906	1221766	1013492	3820101	738427	5861462	886726.2
acyl-C8:1 (octenoyl-l-carnitine)	2624488	2732280	4618470	3761257	3522558	2826509	487358.2	2993690	1616581	930978.9	1263922	1669377	2920264	2991115	748476.1	2299284	367511.1	1193759	1030960	1615274	163113.4	2701607	1186812	1674672	1086126	945895.4	6054914	725471.8	4148195	498067	1436020	1622989	1883282	256034.2	2021338	1656560	3163216	1269326	2247954	8805948	1869912
acyl-C10 (O-Decanoyl-L-carnitine)	5682742	2660096	3044673	3506093	1707072	5717618	1757424	2748944	1127598	5725098	3922669	1645621	1751980	1056261	1718102	4570100	2351427	5496254	984354.7	1639975	965456.5	3411464	3663474	1296346	709845	1326753	5859672	831347.5	7075694	3158141	1487300	684882.2	806476.2	821090.3	3584815	1487937	1491966	4988965	999389.3	5358858	1280183
acyl-C10:1 (O-Decenoyl-L-carnitine)	1781128	1967326	2427422	1451210	899521.7	3933739	839539.9	1771677	599681.8	2961501	1827497	1285375	1807606	1108792	811394.1	3169510	989059.2	2441686	792949.7	1005822	691755.1	2431102	1324606	876118.5	536235.2	891331.2	3820187	809682	4274910	1312568	1424136	1057112	973006.8	419955.7	2537412	700546.1	1249071	1526719	690749.5	3964844	888198.4
acyl-C12 (O-dodecanoyl-carnitine)	563123.9	528369.1	900390	517198.5	303082.6	576993.1	296485.8	675310.3	255113.9	1158584	534807.2	333811.8	611042.5	319386.7	325019.6	833310.2	359071.8	974232.8	294686.8	385665.3	169954.4	440171.2	336481.9	277996.5	94328.52	340850.1	415663.7	147538.8	1008104	488628.4	371643.5	145201.2	196667.4	167872.4	525829.9	313245.3	367486	516929.5	131798.1	516520.2	336349.5
acyl-C12:1 (O-dodecenoyl-carnitine)	774260.3	953355	1277251	1891477	657175.1	1339657	498399.9	1352958	249949.7	1669032	451084.6	493515.2	1073276	390481.2	333780.2	933785.5	1060889	1287215	237111.8	629265.9	399868.4	629414.7	982112.1	343449.7	158170.7	597964	1288924	256214.6	1862712	1091222	277651.7	231623.1	300313.7	438632.5	619234.1	327375.7	366949.2	695180.6	203800.1	1115301	485451.4
acyl-C14 (O-tetradecanoyl-L-carnitine)	110303.1	198160.3	76583.48	59273.54	58915.79	88951.3	142943	169015.5	99433.29	280973.2	99007.12	70151.68	158440.9	54947.52	107125.3	128074	75207.3	94981.47	33451.12	39608.87	27245.72	323709.6	107869.9	31858.41	127140.2	125371.4	92182.34	46994.49	120877.3	113745.2	134784.4	41196.69	70227.63	47226.22	106562	54776.28	93166.05	91029.47	22462.87	134346.5	43928.27
acyl-C14:1 (Tetradecenoyl Carnitine)	647828.6	313638.2	604235.3	555787.4	415869	771215.8	194500.7	873797.2	143658.1	2212712	507147.8	195474.2	933205.4	311931.2	231846.5	720289.2	306135.5	512651.9	131292.8	324863.2	225697.7	717654.2	374731.5	293297.1	139692.5	300873.4	910915.7	147250.8	808040.2	813943.2	242796.8	182929.8	194779.2	224452.7	241259.6	208921.5	256088.7	334790.7	89669.23	1377004	225073
acyl-C16 (L-Palmitoylcarnitine)	86988.34	265884.8	157821.6	94929.54	89778.34	144449.5	200496.6	139299.2	115932.6	326840.4	164443.2	119361.1	142652.8	88630.23	275205.3	161892.5	56240.84	126094	45880.44	134521.3	92007.94	521869.2	72810.94	54797.33	146550.1	164668.2	180095.7	114780.4	112436.1	234159.8	167475	80122.19	106251.6	113503.9	60674.73	89889.99	81461.45	83122.52	62304.07	330370.7	109941.1
acyl-C16:1 (Hexadecenoyl-carnitine)	83293.63	143428.1	141000.2	801683.5	74467.01	54696.46	45787.58	137360.4	764483.8	407969.8	84419.2	43580.03	127868.8	177494.2	52347.34	165010	130610.5	83524.16	145418.6	185967.3	89938.09	436299.1	313829.8	411316.7	145430.2	109216	228121.7	39129.53	160568.8	147853.3	36841.86	417889.1	84161.54	169818.6	32726.68	935028.2	289890.8	70845.53	382708.1	343481.8	138397.1
acyl-C18 (Octadecanoyl-L-carnitine)	7201.133	19375.64	8007.021	3773.549	9331.421	7732.797	14398.76	16161.77	5371.141	28649.27	20845.72	17467.4	11536.75	6846.792	17405.42	20756.71	3748.655	15182.32	5770.818	9585.415	3621.902	58775.89	8675.329	13049.17	7615.506	15671.17	14219.81	7734.605	11128.65	14256.32	13690.92	15307.9	16181	13241.63	4318.003	12892.54	6876.754	10318.26	5269.628	22366.37	10525.78
acyl-C18:1 (O-octadecenoyl-L-carnitine)	152352.4	575183.3	352211.2	314086.8	282692.9	159263.7	178648	115538.8	131834.5	466111.8	151981.2	96071.38	227590.8	135655.5	172893.8	237518.9	159992.5	152723.9	70255.45	156211.5	106351.9	1593713	115522.4	121748.4	497357.3	502114.8	721887.3	80834.8	271364.5	270496	152170.7	76390.45	83765.01	264807.6	85088.29	260483	131866	125836.3	65525.81	1160201	148139.1
acyl-C18:2 (Linoleoyl-CoA)	140975.9	582450.6	361384.8	124474.5	185694.6	246433.5	357627.5	218039.5	166344	399280.9	215772.8	272197.1	356744	233725.9	265969.9	485566.8	68503.32	313306.4	134475.1	83591.23	82233.59	3252353	108843.9	107183.2	492733.1	460974.6	761458.8	331062.4	460419.9	190033	205656.5	156062.9	157152	136673.5	199168.2	197195.4	231703.2	261928.4	72623.26	1120828	268190.7
acyl-C20:4	23181.16	41575.29	30015.85	31178.95	9835.695	19962.09	42729.97	19683.89	19355.05	39281.61	11384.11	36867.53	21217.22	20018.19	40663.84	39483.26	15234.91	16850.45	13633.11	4668.212	9957.313	511950.4	22389.32	7008.616	97556.12	59086.5	72331.3	33452.76	37923.11	36244.38	14578.6	19697.72	13702.58	27842.26	17292.25	37735.38	13256.43	19807.61	6175.651	75911.57	25404.17
Biliverdin	12738.55	28801.9	41269.66	4766.245	7481.482	40894.59	27663.3	8853.584	28885.59	6640.467	20425.01	20070.09	103173.8	15179.14	12688.03	34231.08	15973.11	32249.59	23763.34	14322.15	31383.08	29482.04	21015.73	9936.694	29472.63	31108.22	109426.8	8137.728	157321.1	23487.13	29890.61	16957.1	110076.9	17549.07	32199.06	9112.903	23281.05	23481.5	0	174081.3	58071.05
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	CmpdID	parent	medRt
L-alanine	C00041	90.05488	0.6628233
L-arginine	C00062	175.1189	0.6348671
L-histidine	C00135	156.0767	0.6204716
L-leucine/isoleucine	C00123	132.1019	0.6849702
L-lysine	C00047	147.1127	0.6054684
L-methionine	C00073	150.058	0.6891148
L-phenylalanine	C00079	166.0862	1.527021
L-proline	C00148	116.0705	0.6805165
L-serine	C00065	106.0498	0.6576641
L-tryptophan	C00078	205.097	1.731296
L-tyrosine	C00082	182.081	0.6923363
L-valine	C00183	118.086	0.6832713
Thymidine	C00214	243.0988	1.71995
Uracil	C00106	113.0352	0.6097838
Allantoate	C00499	177.061	0.6333625
5-Hydroxyisourate	C11821	185.0318	0.6584816
3',5'-Cyclic IMP	C00943	331.0445	0.8019322
Nicotinate ribonucleotide	C01185	337.0613	0.6999574
5-Oxoproline	C01879	130.0498	0.6634483
Cys-Gly	C01419	179.0482	0.6838466
gamma-Glutamyl-Se-methylselenocysteine	C05695	313.0352	0.6330246
gamma-L-Glutamyl-D-alanine	C03738	219.1009	1.825868
gamma-Glutamyl-gamma-aminobutyrate	C15767	233.1134	0.7203517
L-gamma-Glutamyl-L-hypoglycin	C08280	271.1295	1.761055
L-Homocysteine	C00155	136.0426	0.6868439
Dimethylglycine	C01026	104.0704	0.6885051
Phosphoserine	C02532	186.0185	0.5865352
Ornithine	C01602	133.0972	0.6032888
L-Citrulline	C00327	176.103	0.6615478
Spermidine	C00315	146.1651	0.6130877
Spermine	C00750	203.2228	0.6154382
Creatine	C00300	132.0767	0.6699767
Creatinine	C00791	114.0661	0.6656604
4-Acetamidobutanoate	C02946	146.0811	0.6792893
N-Acetylornithine	C00437	175.1077	0.6829504
Guanidinoacetate	C00581	118.061	0.6603413
trans-4-Hydroxy-L-proline	C01157	132.0655	0.6798524
Pantothenate	C00864	220.1178	1.710373
Indole	C00463	118.0649	0.6933733
Indole-3-acetaldehyde	C00637	160.0756	1.729106
Indole-3-acetate	C00954	176.0704	1.882498
Indoxyl	C05658	134.06	1.816048
kynurenine	C00328	209.0919	1.500433
Anthranilate	C00108	138.0545	0.6945625
Picolinic acid	C10164	124.0404	0.5942289
g-Oxalo-crotonate	C03453	159.0278	0.6887937
L-Adrenaline	C00788	184.0946	0.6590636
Dopamine	C03758	154.0861	1.806243
Serotonin	C00780	177.1023	0.7550641
Ectoine	C06231	143.0815	0.7687673
Sphingosine	C00319	300.289	1.97919
Acetylcholine	C01996	146.1175	0.6724626
Choline	C00114	104.1069	0.6542141
L-Carnitine	C00318	162.1123	0.6675597
acyl-C2 (acetyl-carnitine)	C02571	204.123	0.6904247
acyl-C3 (propionyl-carnitine)	C03017	218.1385	0.6925316
acyl-C4 (butanoyl-l-carnitine)	C02862	232.1541	1.726858
acyl-C4-OH (Hydroxybutyrylcarnitine)	HMDB13127	248.1484	0.6897268
acyl-C4-DC	HMDB13133	262.1283	0.6912488
acyl-C5 (isovalerylcarnitine)	C20826	246.1696	1.745298
acyl-C5:1 (Tiglylcarnitine)	HMDB02366	244.154	1.735939
acyl-C5-OH	ac107	262.1641	0.6904229
acyl-C6 (hexanoyl-l-carnitine)	HMDB00756	260.1853	1.777153
acyl-C6-DC	ac109	290.1593	1.718334
acyl-C8 (L-octanoylcarnitine	HMDB00791	288.2164	1.813833
acyl-C8:1 (octenoyl-l-carnitine)	ac111	286.2008	1.800784
acyl-C10 (O-Decanoyl-L-carnitine)	HMDB00651	316.2479	1.873557
acyl-C10:1 (O-Decenoyl-L-carnitine)	CID57357170	314.232	1.853424
acyl-C12 (O-dodecanoyl-carnitine)	HMDB02250	344.2792	1.931244
acyl-C12:1 (O-dodecenoyl-carnitine)	HMDB13326	342.2635	1.90221
acyl-C14 (O-tetradecanoyl-L-carnitine)	HMDB05066	372.3101	1.986623
acyl-C14:1 (Tetradecenoyl Carnitine)	HMDB13329	370.2947	1.952785
acyl-C16 (L-Palmitoylcarnitine)	C02990	400.3415	2.04252
acyl-C16:1 (Hexadecenoyl-carnitine)	HMDB06317	398.3261	1.928922
acyl-C18 (Octadecanoyl-L-carnitine)	HMDB00848	428.3724	2.177638
acyl-C18:1 (O-octadecenoyl-L-carnitine)	HMDB06351	426.357	2.05496
acyl-C18:2 (Linoleoyl-CoA)	HMDB01064	424.3412	2.011861
acyl-C20:4	ac125	448.3411	2.005477
Biliverdin	C00500	583.2539	1.923434
METABOLITES_END
#END