#METABOLOMICS WORKBENCH RCulpHill_20220309_130542 DATATRACK_ID:3118 STUDY_ID:ST002109 ANALYSIS_ID:AN003451 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        	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	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-alanine	10856220	11939430	13832620	7794978	8407627	13037380	12178000	11108120	10258880	9062329	13457470	6207248	4983348	6126218	11784100	15642720	8662803	12363960	8084794	6585160	7031900	9053601	6629334	5975832	11122350	8692564	8348578	9612011	11113280	8155214	12576740	4820104	8406671	5996314	11087740	6354124	4131385	11411750	7228080	7998242	5376538
L-arginine	2365782	229425.7	939805.3	3198099	1422124	2107663	2264989	1817350	1980248	660914.4	752160.2	1121672	1343748	622189.5	618278.9	532478.7	1430957	955018.7	7680662	2793478	962774.4	80892.25	4936462	5309765	153098.2	707073.2	706529	680647.5	543930.8	1041289	1543253	6162342	1226764	693048.8	1036017	4049163	2380066	807124.4	3650923	302525.2	1519612
L-cysteine	794550.8	622581.4	892225.2	608276.6	393661	704282.6	648835.1	753771.8	704862.2	867603.1	838887.3	603596.2	764027.3	531675.5	720655	918314.5	715731.5	1100797	483234.8	549962.8	521306.7	206909.1	589177.2	502666.8	645307.7	686431.2	239486.3	454235.2	831227.7	571216	632667	423699.6	446532.8	539177.3	676339.6	459330.5	495987.8	688085.1	204775.6	238756	543717.2
L-glutamate	932856.2	4216756	5380414	1357354	2429389	3724740	1774972	1662024	1629546	3027749	1804624	946825	2904907	2463110	2775144	3236541	3674832	1534720	1663644	986272.4	2463755	4695362	1246644	1784784	4198402	5926542	4949110	2444051	1905599	2960596	1717600	1820014	1898907	3795362	4506386	1466002	666275.8	1707096	697722.8	3931017	3623275
L-leucine/isoleucine	85761540	54596900	96959490	44125400	35682290	85300300	168916800	43519190	40603440	71226460	51581570	38359440	66622420	47077770	46491780	89197700	16987000	73985860	66924450	19208210	80829290	55235720	22883050	52975800	48450350	58149820	99223210	63677610	42075350	40281090	84279310	34199520	40547110	36742340	76577300	49677280	33320040	41382120	24692490	53107860	30457870
L-lysine	4682668	3631344	4427386	3120721	1460772	4862066	7781500	4581164	3764895	2195839	2343758	2951970	3661752	1636276	2524932	6418226	1504406	3608183	3648305	2174115	3043492	4187208	2510973	3054602	3021543	3036893	3157000	1624840	2468058	2195337	3760608	2027410	1978046	2111757	4744166	2826164	1810551	2611623	1563337	2276148	1846780
L-methionine	5937616	5895874	9698923	4510482	2836470	9348307	17581080	5995136	4208000	5897942	8786879	5764528	4682970	3167564	4306339	10640280	2678477	6133444	7236098	3594704	6566760	2742743	3297204	5321760	3368473	2679526	2822397	3178893	6368500	5100362	5694994	3703030	4749091	4085208	5596552	5112474	3459718	8165458	3202476	1549495	2839421
L-phenylalanine	8634191	9031257	7187960	4723746	4828122	9934788	13742230	4174406	5718930	6470626	5779162	5316938	5861820	5235743	3397013	8950268	461184.2	7013704	5978068	9412315	5294240	8308338	1289176	7312284	6728956	6177282	7140628	5719772	5520780	3495904	6607174	3668339	6462276	5017322	7956886	5647804	3582958	6540762	4558956	4765026	4292834
L-proline	125892800	90359900	79206120	71432280	47490210	56041500	158003100	59155540	73494980	86298430	116902200	49776180	64929520	33844630	104629900	184210400	65114500	90681140	69346420	64669300	85373790	82134410	57351400	49296180	70206220	68689850	69489850	69181080	92428330	80586330	116250900	37506190	78628630	43959940	102487100	79303540	43062150	95976790	54308300	61714530	66326960
L-serine	414014.7	723372.3	878646.9	342830.2	364508.2	757883.8	717028.3	692374.4	477267.2	762121.2	466360.8	319348	587457.7	300473.3	828625.2	1004338	520161.6	513231.5	545548	442134.9	298403.2	528699.6	410524.5	598405.2	563464.5	867539.2	675968.7	485408.7	856727.8	530694	584819.3	379177.3	600202.8	527277.4	637230.4	419865	387962.5	443749.1	237384	595765.9	388895.5
L-tryptophan	20116580	20129460	33777290	7873214	10827090	31076930	56479020	43163630	18781330	17034980	24271770	30237750	20688380	8622226	22002360	38195460	24402290	29893610	11534910	12682400	25383180	19242780	10129840	13902220	21867250	10920240	5662378	11744150	17615910	23304350	26124670	7217978	14906790	22010340	41903830	14889060	9552710	25398850	5995176	2343529	11046680
L-tyrosine	21744810	17257880	24950890	8948393	13173080	29441550	43156910	16215220	12864800	14074160	22777310	10869650	15747200	13065390	10478230	34629530	12490990	13067100	16895170	11912910	18805220	17885390	14881490	12934640	18109870	14317930	17304000	14156210	18446780	18498780	14469560	7205560	12692040	14245540	15828680	17814810	10368800	22013260	12335020	10648840	10821720
L-valine	117009900	85970410	175395300	61637200	72836770	122924700	251197900	101036400	74043270	97435860	110439800	80638630	160315100	78246020	68700270	131658800	215187100	134197400	77744460	44330260	84894460	86496420	46760360	62844220	86626820	81992280	100363100	74999740	80275650	139682400	136073800	50438610	60226460	54481240	110561800	74948420	60371740	93030310	47455880	70114100	87061260
L-cystine	1010092	678464.1	1043118	1110913	697090.7	899501.8	447789.5	644798.9	823998.4	619296.8	1035453	504890.7	3654841	570315.2	714408.6	1467067	633501.2	642405.9	677602.5	444180.7	529072	226336.3	621587.1	945926.9	604650.4	718328.8	441980.1	354209	924759.6	472596.1	552321.3	497869.1	482372.8	838625.3	831318.2	692561.5	470885.6	1107577	442448.8	549912.9	850552.3
Guanine	264282.9	272241.3	442935.8	203325.7	93330.76	424426.6	734218.2	260793	192369.5	263402.3	370722.1	223777.5	215183.8	112964.8	204059.7	465555.8	82076.15	347490.8	374833.2	125332.4	278649.5	100213.4	176198.5	207657.2	153498.6	76766.88	130236.7	160557.3	271871.4	169405.4	250184.7	179979	205840.1	190620.7	241167.4	169810.8	136379.8	386690.2	123693.2	66319.47	122775.9
IMP	0	115372.6	35177.65	1357.805	0	14672.56	16702.56	25784.62	0	224505	14676.58	1746.958	18751.69	0	49441.22	17864.97	14584.49	36081.93	0	0	2383.848	40915.95	0	0	57412.93	0	2086.314	21826	13571.34	57908.08	4516.582	2902.601	0	0	20630.69	0	0	20110.43	19756.79	0	0
Allantoate	315155	679063.8	334727.4	439233.5	585930.8	244300.3	728666.6	401389.3	706106.4	525239.7	350379.6	141980.9	358201.9	526637.8	581874.4	622765.9	181931.1	183090.5	307153.7	427496.2	290471.2	551253.2	382347.3	576273.1	418068.8	886408	805478.2	620099.8	393135.1	279366.8	461362.8	215939.9	668514.6	555160.6	530462.1	596047.6	651053.4	378429.2	293347.8	737948.1	743907.5
5-Hydroxyisourate	502651	241415	519139	39204.7	25706.71	353996.8	474652.2	304375.5	21621.31	488173.2	381772.6	655583.4	481325.5	24461.01	427653.3	482331	705229	463739	42990	32550.49	916173.7	587092.1	90588.24	22877.61	339269.4	93427.45	20503.24	310396.5	389091.1	517470.8	514706.9	27259.29	52795.54	48337.64	468050.2	10446.57	16161	250451.7	14340.77	20581.98	47774.32
Urate	6644310	9301949	9079517	5255608	6533622	9733447	7772700	21804940	8153510	8301376	7842354	5356918	14332370	5880240	6295342	7141372	9011843	9796799	5735904	3922327	4361992	6357000	12223980	4792200	6792958	5792736	3853934	5894486	5759710	14690070	8690181	3818313	4897688	4018079	9366736	6042946	4354360	8347932	1989018	4508802	7508602
5-Oxoproline	10778310	8170462	12152780	6933370	5747848	9287275	10542530	11555430	7429520	11239510	9734334	6764706	12200720	5037836	11113240	12247410	17652210	7926356	6033308	5817116	13770280	10590530	9700993	6407346	9281998	11339190	6968182	10342120	9339612	13872590	9334733	6260382	8139864	8913427	9099987	5362223	5280632	8634635	4404658	9332004	10908850
S-Glutathionyl-L-cysteine	46400.32	29726.16	9869.212	14995.83	6149.809	22056.17	48623.56	50386.53	66540.96	30579.88	33567.07	33160.89	57467.64	23851.08	15901.39	84420.9	0	38504.84	15450.47	43265.22	6850.111	205194.3	35912.37	15502.22	11144.93	31491.44	125079.7	10207.71	16328.45	11586.6	58508.93	8260.911	35952.34	0	70295.37	26921.53	67998.52	35273.72	17855.86	58651.46	4887.602
gamma-Glutamyl-Se-methylselenocysteine	97277.84	268440	145651.8	200257.1	267143.2	84072.96	275074.2	192861.2	265526.4	199996.9	151950.5	44686.35	129871.6	236967.4	254704	206869.9	84839.26	70786.84	134873.3	161208.2	130415.7	184349.2	168860	309721.4	174622	349727.8	362889.5	246484	195348.7	84742.18	138082.5	85899.93	286715.5	217602.8	210093.5	213846.9	339984.3	156469.2	129815.1	293409.6	372368.4
(5-L-Glutamyl)-L-glutamine	357538.2	129787.2	245082.4	178035.2	94281.77	220560.3	396150.3	280359.5	337160.7	177987	308917.2	178273.5	324128.6	140206.5	97008.48	486517.1	628676.1	275142.2	221757.9	193095.9	380400.2	295108.1	447154.5	175663.4	68423.28	145300.6	314498	141756.1	302195.1	304010.1	337386.5	150558.4	250584	98392.31	270722.1	296149.4	255165.2	231421.5	66857.73	198786.8	172582.6
L-Homocysteine	85747.77	183118.4	203009.5	91274.59	57765.36	115164.5	623134.8	181020.5	136148.8	399240.5	277464	338254.8	196550.8	125561.9	285744.2	626789.6	119760.7	168874.9	122179.9	178050.5	246237	192972.8	205677.2	106468	147721.1	434595.3	293865.8	142389.6	231461.4	201316.7	205134	70814.17	176447.4	160496.1	162668.4	131319.4	281662.7	264078.2	108726	440666.2	309718.9
Dimethylglycine	2246329	2769133	5311598	1763762	3023056	3539243	2891986	2822083	1888367	2301750	1920326	2095026	4757548	1554101	1279483	3716003	1846619	2108092	1620930	1294666	1503764	1518432	1719106	2327448	1653660	2375515	2594299	9096679	3079965	2105101	1924103	1460088	1557836	967690.5	1619654	1967540	1404111	1906506	956263.4	2309243	6495254
Phosphoserine	168751.2	162433.2	212165.7	346139.3	120010	195550.2	133251.9	484707.8	260105.9	187474.5	110921.9	96777.12	156168	190744.4	131157.9	225387.9	269716.6	162998.2	251026.1	199303.9	138725.4	95458.23	309941.6	254481.8	163900.6	210390.2	172406	185293	129570.6	190067.6	130204.1	230981.2	373859.9	240256.8	127840.4	158659.7	152018.3	177655.9	219654.4	206365.3	236880.3
Spermidine	29267.2	83198.48	12851.68	176631.4	42838.54	22348.4	0	14446.81	34324.16	34222.5	17329.06	62431.83	18709.63	72195.07	10731.38	73252.63	15291.01	41102.16	9626.242	143872.4	57711.31	603757.1	25159.37	94712.82	56773.95	71927	52857.35	0	23266.43	27916.12	42000.5	168418.9	27282.03	175811.3	17258.18	78053.16	39544.99	5892.545	296103.4	36664.19	8755.364
Spermine	0	25232.92	0	194275.9	13245.67	0	13808.49	12817.86	13275.95	14003.19	7842.85	8979.542	0	68483.81	9114.519	0	0	25381.1	0	156353.8	14369.37	325981.3	9782.342	13489.82	50075.16	76533.49	35535.64	7640.217	30260.64	0	15178.55	311993	0	0	10550.44	9749.384	35226.9	7580.473	583271.7	93402.35	0
Phosphocreatine	114896.5	118149.6	86560.53	18600.52	24979.56	36936.88	122375	83862.46	18128.94	63350.83	32267.76	26281.68	19008.36	12735.14	86627.55	89956.9	78931.98	111980.2	24352.75	21386.04	32937.99	53330.08	20230.28	11369.42	32209.04	1506.395	0	55904.34	47282.75	45281.7	110039.7	14278.01	3078.282	0	49127.67	10715.93	25761.15	49845.41	18085.75	0	12814.31
Creatine	19222700	13816240	10290910	4062465	4428804	21662830	35961210	30578530	14248120	11717900	11387490	17699810	24341230	14506630	21099110	70477510	8200342	19094520	9282559	9475525	11090190	29927160	21324370	55703820	8766664	28517340	9590935	5733254	54075810	8519741	11251720	7156198	23054620	8464219	22531740	29951570	21429700	9777855	17066550	10954430	8823403
Creatinine	51052660	49144450	42821130	64317060	48957100	54119850	50218930	78450600	66401200	54850130	90934620	34291310	68426810	44540040	45294280	52195620	28882290	54667780	31579810	42525490	25226810	40724500	32677210	29464490	47033040	36427460	39098260	54946340	36104400	35351670	61460070	27074280	42040610	20979450	50930850	32422660	28546720	74276040	19354440	35993750	59919900
N-Acetylornithine	475861.7	371616.3	431677	132700.8	221916.3	341609.9	954229.8	379234.6	215390.4	1076361	300423.5	707905.8	492733.5	202538.6	854333.7	324766.3	309802.1	374362.2	184123.9	276251.3	476767.1	1075452	124485.9	212096	347241	213693.7	306781.7	534947.7	422332.8	1356000	512706.2	158626.3	346956	146085.8	1179184	87410.75	278938.4	253891.9	95501.81	456089.7	414944.9
2S-5S-Methionine sulfoximine	160715.5	43739.62	67703.62	33829.67	58414.44	56978.7	231419.9	77214.47	47287.77	16064	37966.18	32572.06	8094.686	44326.09	12153.09	81120.3	13501.77	22004.03	66592.78	44779.03	8519.692	76198.34	56450.39	34366.77	40780.98	8489.604	37282.9	23384.21	26358.81	19340.94	48237.15	11759.88	33925.08	16452.53	76867.4	60196.65	32346.54	30969.48	49518.18	7310.629	21154.04
Indole	231781.1	255600.6	395812.2	184690.7	348347.6	396175.8	590821.2	484724.9	398574.5	247650.1	323832.1	398827	311199.9	297749.3	248985.5	441995.3	288175.4	308040.1	245311.6	259632	301757.6	263471.2	234843.8	238722.2	242162.2	195382.1	154042.2	312566.8	246711.3	322372.7	295560.5	1574300	3735839	384337.4	474058.2	264140	208542.4	343249.3	148623.8	80989.07	234192.4
Indolepyruvate	1391827	852044.7	1199199	472827	781038.6	1072449	3017510	741226.3	750309.2	831888.3	1236796	370589.1	619133.2	804801.3	624287.2	1835718	345071.5	785957	781496.2	705863.3	825405.2	911154.2	667721.6	760720.9	986652.2	836568	1211280	779820.2	998556	915173.1	988986.8	316603.4	693100.4	810705	1092996	1062124	799531.2	984815.7	387639	744016.4	657895.4
kynurenine	351434	216859.8	317403.8	157687.4	178449.6	246637	246714	255784.8	143631.9	109424.5	288566.8	183356.4	311296.7	92856.73	174859.7	301184.7	65120.56	396980.4	164074.1	173117.7	128417.5	210068.3	53096.34	180803.9	308711.2	186811.7	179393.4	152775.2	151215.8	366340.6	343659.5	86744.31	201940.9	150902.1	428758.8	229858.1	162624.2	307909.9	121754.7	161614.8	234210.9
N-formyl kynurenine	5172.403	111088.2	4724.337	100281.2	155739.9	5360.473	6181.125	4710.79	226096.7	168662.3	7573.24	11933	7831.357	133104.6	11121.3	7354.488	4469.542	8758.954	370967.2	109073.8	8494.764	10443.48	139382.4	104703	5011.025	108429.6	156550.6	715131.3	14010.42	5402.909	9641.276	114148.8	38829.46	67171.64	9439.546	81031.1	48222.84	6048.929	291320.9	89917.65	133859.4
Anthranilate	2437772	3218275	1363390	1292872	919593.6	988658.7	2694994	2243049	4972518	3982742	3207353	632015	1540581	735277.3	4398612	2577751	705720	1468838	3271167	2446909	1171071	5506727	1052612	750149.7	1340584	1147899	1363509	1586882	1823261	1201099	1803419	665256.5	3922552	677862.2	3572925	1462132	1269643	2650057	1102268	1169711	1631458
L-Adrenaline	3112460	5857620	5397448	6183218	3678762	7268652	5880522	7455968	9993941	7342908	6438426	2950717	5165809	7464806	6332962	9708136	4343288	5097582	7010912	6198346	3935748	5559326	7596610	8727582	3951975	6944440	5059726	3432669	6012958	6223186	5518984	8453553	7193396	6591154	6717182	10493110	4023104	6248828	5780456	5395032	3289287
Ectoine	144907.8	83353.52	167014.4	103222.8	235354.3	133413	505819.4	90099.06	76091.12	105202.6	254355.9	176695.5	228683.2	42872.36	127133	110452.3	106086.4	166682	59766.44	45030.03	115973.3	115559.2	27598.11	116952.1	154592.8	39625.68	48707.11	244775.9	109611.5	168596.5	180575.7	31308.73	54428.25	21262.41	201416	57463.44	114257.9	215259.6	33598.98	188304.9	97385.65
N-Methylethanolamine phosphate	4722176	3836314	1935332	649329.8	649685	3187279	3296340	4725322	448549.7	2149214	1835674	8338328	6173018	531940.8	4259260	2134008	10900270	6101702	636258.3	657927.4	3094795	3572363	739699.7	688468.2	4370294	711573.8	709562.2	2563063	2368542	6052370	4851296	678776.5	869430.8	881816.6	2665420	685680	836119.7	2091077	982146.8	464044.3	993312.7
Acetylcholine	2151806	2080954	1318926	1051269	1056125	1186644	2043300	2077956	1586596	2399262	2954178	1671824	2129243	1025486	2104509	2799238	1769164	3172841	992252.4	878447.2	1279060	2421155	1158574	1214778	1871042	1641275	1513568	2054442	1882699	2377058	2322546	783428.1	1362561	750591.1	2110057	1146536	882241.6	1709689	813307.9	1740454	1418614
Choline	31403470	22068130	20905280	20883580	21594560	28640700	18507060	29917960	24038430	21959070	13865120	14782820	39876210	17923030	25737630	20368200	18671730	23767130	14463200	14733850	8785129	21991770	18529710	17182830	31804430	20366730	32735750	15853780	16032580	22954970	27462460	13356540	19816650	21412550	17799750	27370050	12965300	13467940	12696600	33603320	26966590
L-Carnitine	32851570	60768940	46010860	42605150	30211610	68421030	58280430	81183700	61328560	81939640	56876640	43097490	56124400	44900470	73932510	95403970	71109000	61905580	36683310	30363550	37930380	70947980	55897040	39755300	44000690	53676430	34413980	32704700	57228680	72835160	56935570	35575020	49458860	42718740	74333730	59351650	23222280	50533550	29638280	46243380	26683580
acyl-C2 (acetyl-carnitine)	21726150	61328010	76794410	35425160	23716440	53951690	38294610	51653240	16803040	80820920	49322900	24371790	87446230	15379060	40353280	71914700	37372970	40860880	12689590	17601000	51234740	37831490	22595240	28336840	28343150	39141290	37179470	28779850	55235320	75429800	35378600	12778200	25297500	20844010	43899990	21666720	20207260	40797150	9900727	57190800	36337120
acyl-C3 (propionyl-carnitine)	1868872	1568602	2881111	870448.3	957858.5	3821851	6732038	2154046	901518.8	2569310	2789353	1599020	1290137	793756.2	1538433	3951174	772545.7	2016370	1365766	779602.8	735223.1	3675820	949945	999324.1	1017980	625628.5	1061383	1086559	2358586	1177186	1742082	483241.5	1465463	534047.7	3083099	1278486	574070.8	2244237	692412.4	1273417	412531.8
acyl-C4 (butanoyl-l-carnitine)	507984.3	283891.1	492280.8	228922.1	298175.2	721175.9	838737.5	182851.4	207141.3	495919.5	703110.8	220695.4	278186.6	207803.6	417683.1	1024349	39306.33	337848.1	226549.4	212334.2	113104.4	737287.8	153763.9	485842.6	284762.3	202302.1	202775.2	263482.7	801980	263683	352097.2	89829.88	387285.2	110365	1132385	314915.4	241078.9	694477.9	138055.9	308232.7	220322.5
acyl-C4-OH (Hydroxybutyrylcarnitine)	239968.4	206996.6	1161884	271808.4	246667.6	494189.6	165675.1	484051.5	63744.22	356355.8	203623.6	58571.44	556810	55654.93	73845.29	341372.6	178496	137927.2	27526.6	188080.2	324609.4	194322.4	71689.57	142599.5	166180.1	365015.9	690593.1	92171.07	219562.3	181464.4	117817.8	42196.38	180386.2	96708.34	159570	111152.2	142946.1	165431.1	67614.24	705566.4	392533.1
acyl-C4-DC	62173.96	55861.15	61664.64	45910.98	42181.32	47210.28	115576.6	102101.6	15524.63	57224.38	101466.1	51762.86	105273.1	19903.3	56912.77	102729.8	7556.572	77204.95	24277.8	27519.27	21065.87	87658.76	8993.854	29366.32	88389.25	27423.44	35392.02	86352.63	58493.09	40994.06	75609.98	6922.184	14980.12	18181.62	102605.5	25068.08	20215.05	78239.77	3333.845	17837.2	16425.22
acyl-C5 (isovalerylcarnitine)	811276.8	831840.1	1134010	299862	349236	1854042	4159432	1105563	669418.1	1165765	715360.1	1509928	3519781	600549.9	562608	1826683	373599.6	1160684	881392	238575.9	416210	2118998	499557.2	962725.9	245738.8	352098	440509.7	9329374	627269.6	611675.7	1007215	308086.4	369137.2	367452.5	1568624	856044.2	451235.5	918330.5	405690.7	462334.8	1654767
acyl-C5:1 (Tiglylcarnitine)	9593.821	14589	3117.408	138487.2	78585.37	12780.04	27440.79	4824.542	381738.8	6285.809	12770.03	2776.953	0	73052.57	2214.945	8915.713	5852.795	2375.404	44452.06	96925.82	2835.763	8069.246	144147.6	375234.4	5908.467	84675.72	52478.18	4486.031	11729.43	2925.634	5795.922	152128.9	138589.5	157881.4	3022.513	306634.5	195610	4960.129	74312.52	121242.6	274683.8
acyl-C5-OH	126550.9	91911.23	138307.6	41529.7	56889.2	116692.9	255337.6	51451.67	19197.06	92207.84	105335.2	110471.7	21785.42	51548.06	63318.83	145891.7	20497.61	99285.63	43735.89	10978.12	116787.8	161545.1	25684.04	19340.67	53268.53	13891.91	27916.6	74345.43	44431.45	30492.51	166583.4	15316.33	49845.46	39294.52	145388.4	17281.22	45883.35	90397.79	19316.98	7154.178	35268.36
acyl-C6 (hexanoyl-l-carnitine)	138017.6	206097.9	250370.2	118956.1	116515.3	239230.5	95615.04	117530	93743.66	243545.4	182946.8	88503.34	132148.9	127444.6	74593.53	209961.6	54473.06	119402.6	132196.8	50770.95	39154.2	165258.4	148572.1	93363.46	19397.61	138946.5	413714.2	52429.82	160707.2	105848.1	80865.93	83921.18	92091.76	47805.92	198227.2	119049.1	62767.05	192474	101100	439843.9	65860.12
acyl-C6-DC	119769.4	41075.09	201427.5	173857.2	56638.61	111915	89222.21	254243.6	23071.46	83296.9	103560.2	32748.42	571948.6	72220.66	205770.1	290677.3	6043.275	116069.4	18513.96	79575.75	48334.85	115906.4	12898.62	18002.79	87024.77	43520.31	203790.5	187338.6	127566.3	126909.7	81558.91	13626.88	122526.4	13570.92	238025.9	14443.29	39787.88	93998.44	40351.47	261620.5	18210.89
acyl-C8 (L-octanoylcarnitine	2031690	1132441	1139531	1018477	654945.2	1464907	485213.4	691677.9	403448.7	1650008	1652854	497695.7	765533.5	371403.6	381986.2	1584217	388690.7	947566.2	595443.7	443236.7	212919.6	1156784	821139.2	633184.1	170346.9	556661.8	2015801	246467.8	1274232	835039.2	648728.2	311183.8	306516.4	311362	1339667	771449.1	560272.6	1391869	384662.6	2283181	409998.4
acyl-C8:1 (octenoyl-l-carnitine)	1381770	1476844	2848624	1590018	1456454	1134483	290434.6	1108246	931421.1	433543.2	578013.3	838184.3	1247521	944966.7	335647.1	1145233	104917.5	600054.4	463863.3	717190.3	83286.09	1319385	480565.9	761606.8	417758.2	449791.2	1994429	245234	1401985	320051.9	620237.2	695495.6	759814.8	136748.1	1087074	600529.7	808075.3	587515.8	1150006	3503145	1032454
acyl-C10 (O-Decanoyl-L-carnitine)	2607875	1031453	1964890	1105708	887518	1909680	754679.5	908922	541819.6	2760861	1794560	548579.7	758032.2	498691.8	434083.8	1936193	424412.4	1899722	575723.6	583294.1	498745.5	1430617	1084064	550231.2	280758.5	628372.8	2139730	351596	1735909	977104.7	685018.6	218930.6	286899.1	291093.2	1207696	843936	876235.2	1207414	316756.4	1748049	672656.3
acyl-C10:1 (O-Decenoyl-L-carnitine)	1103065	918853.2	1145540	956281.9	595402.5	1707713	417278.8	950330.7	413352.5	1735386	951688.1	761427.8	1289827	588196.6	390773.1	1652978	281219.4	1551200	489343.3	635516.8	321242.1	1233543	786771.5	436532.9	211595.9	421418.2	2813291	456950.2	1394558	571814.8	839138.9	592773.2	557525.4	221408.4	1024993	442503.7	637481.8	840021.2	385599.5	2009758	686127
acyl-C12:1 (O-dodecenoyl-carnitine)	251332	364809.2	626989.5	648428.7	241684.2	650072.8	193530	375891	139752.4	932871.7	219135.8	144747.8	511585.4	137224.4	120724.8	461536.2	192310.5	469213.4	128886.3	172265.2	203762	295084.8	363290.5	106484.4	52776.12	203527.7	588237.8	80385.05	494692.6	436859	118302.1	86290.51	118578.9	197178.6	180373.2	158293.9	253578.9	134197.4	92424.98	549898.3	236978.9
acyl-C14 (O-tetradecanoyl-L-carnitine)	21926.77	45411.95	33882.37	18401.03	15380.41	34893.18	49329.26	43289.82	29154.88	90934.73	29764.62	16765.73	44243.52	16036.48	31268.37	39625.54	13414.47	27309.27	13270.03	24523.07	13139.22	121059.2	22082.62	9675.694	25758.27	46067.89	43737.61	15476.69	26867.99	32677.99	31940.41	17380.21	17970.99	22218.84	29178.85	22434.31	20968.15	21305.02	6484.082	56928.51	36356.21
acyl-C14:1 (Tetradecenoyl Carnitine)	213906.7	133615.8	405558	310190.1	95178.59	190248.2	62005.53	148179.8	48092.19	582847.7	111325.1	61572.54	278058.2	86338.13	59170.43	269402.6	54238.36	204747.1	36773.7	90937.6	38843.47	193724.5	136395.3	108643.9	71275.55	131426	364508.8	52437.75	224543.3	181850.8	61258.98	55629.58	63202.02	91941.5	67062.8	67963.99	121214.8	83806.76	30740.36	468441.5	123772.3
acyl-C16 (L-Palmitoylcarnitine)	53130.95	261499.8	89500.85	44387.48	63557.4	93085.02	107052.7	94495.75	82511.76	175501.6	86743.03	73777.76	143828.5	68283.41	144218.7	86688.78	42514.3	79306.53	46205.31	83543.21	50319.95	374176.1	52025.33	43622.78	154369.1	114680.5	208901.3	75202.09	86436.51	119555.9	94222.34	57807.92	77999.27	83022.56	81298.95	56346.59	64589.36	88875.76	43635.36	224211.4	94355.77
acyl-C18 (Octadecanoyl-L-carnitine)	12436.51	91307.74	36360.41	8927.491	14987.38	24075.7	36649.56	22932.61	20278.36	76874.38	33359.96	37480	29315.94	27796.21	44886.53	30049.76	7455.279	45770.73	26192.56	32409.09	18199.68	123295	14730.95	21030.63	17206.63	36975.64	41805.8	22492.6	22678.25	42968.85	34342.41	17628.31	20652.74	34668.87	33026.62	27632.77	20152.52	27887.1	15064.05	39007.49	28827.97
acyl-C18:1 (O-octadecenoyl-L-carnitine)	125708.8	417969.5	301718.7	125520.8	212497.5	119947.4	187088.1	155661.2	122175.7	458061.7	142768.6	150733.1	116179.8	86019.89	164204.5	252625.3	59016.03	163830.5	70109.49	119931.4	101890.9	1232442	84000.46	95866.99	403505.1	369756.8	508168.2	104777.1	143164.2	305090.2	108992.1	61737.59	109604.3	195154.4	121219.6	120198.8	137580.6	143992.1	69560.03	669406	198664.2
acyl-C18:2 (Linoleoyl-CoA)	42860.36	303242.6	120157.8	35787.79	83727.88	84361.55	158565.2	92638.43	87750.91	170908.3	99156.38	114548.8	208756.7	126567.8	143315.6	189566.9	14671.08	109182.4	43048.46	69722.1	39311.25	1248866	50792.94	48846.42	291553.8	156439.6	448764.2	171421.4	108716.8	101997.7	192373	65567.41	82663.2	59160.53	96513.31	80433.38	86470.6	75703.93	40840.44	567034.2	173172.5
acyl-C20:4	7714.475	16365.58	11144.49	7592.594	4251.764	5292.897	19134.96	8177.65	8555.092	19319.13	7420.031	9811.079	4220.123	11694.09	12593.8	11490.27	2019.082	7126.249	6253.291	5011.066	3834.922	137938.2	6202.898	3256.581	38439.46	26527.34	26025.64	13993.77	6127.817	13953.45	10992.64	4750.054	4354.791	7600.215	8877.261	14085.5	5682.794	4425.208	4252.897	33156.8	15122.14
Bilirubin	125501.4	119554.9	168563.1	104634	154136.5	57228.04	214409.5	75672.5	147932.4	65065.89	141400.7	117493.7	411387.2	280819.9	9228.627	281432.1	39199.97	79788.34	185971.2	116331.6	124861.4	173597.9	366876.8	56300.97	182732.9	215751.5	387778.4	76319.3	846513.8	73886.3	183418.7	108802.2	123851	152179	127906.5	161735.2	182476.7	60190.32	59089.97	680570.8	392788.2
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	KEGG	MW	RT
L-alanine	C00041	90.05565	0.6376148
L-arginine	C00062	175.1189	0.6142555
L-cysteine	C00097	122.0273	0.6519808
L-glutamate	C00025	148.0604	0.6391723
L-leucine/isoleucine	C00123	132.1019	0.664311
L-lysine	C00047	147.1128	0.5783963
L-methionine	C00073	150.0582	0.6576511
L-phenylalanine	C00079	166.086	0.6688426
L-proline	C00148	116.0708	0.6492962
L-serine	C00065	106.0503	0.6366037
L-tryptophan	C00078	205.0969	1.721372
L-tyrosine	C00082	182.0809	0.6582835
L-valine	C00183	118.0865	0.6529556
L-cystine	C00491	241.0308	0.6598423
Guanine	C00242	152.0551	0.6631668
IMP	C00130	349.0541	0.8127363
Allantoate	C00499	177.0611	0.6083511
5-Hydroxyisourate	C11821	185.0312	0.6488884
Urate	C00366	169.0355	0.6798298
5-Oxoproline	C01879	130.0499	0.6479259
S-Glutathionyl-L-cysteine	C05526	427.0947	0.6592044
gamma-Glutamyl-Se-methylselenocysteine	C05695	313.0352	0.6067708
(5-L-Glutamyl)-L-glutamine	C05283	276.1189	0.6470959
L-Homocysteine	C00155	136.0426	0.6534844
Dimethylglycine	C01026	104.0711	0.6482037
Phosphoserine	C02532	186.0185	0.5560616
Spermidine	C00315	146.1651	0.5829804
Spermine	C00750	203.2231	0.5754949
Phosphocreatine	C02305	212.043	0.7014289
Creatine	C00300	132.0768	0.6411741
Creatinine	C00791	114.0665	0.6434112
N-Acetylornithine	C00437	175.1078	0.6531208
2S-5S-Methionine sulfoximine	C03829	181.0609	1.75927
Indole	C00463	118.0654	1.725413
Indolepyruvate	C00331	204.0633	0.6587605
kynurenine	C00328	209.0918	0.6646314
N-formyl kynurenine	C02700	237.087	1.723644
Anthranilate	C00108	138.0543	0.6536377
L-Adrenaline	C00788	184.0948	0.6375426
Ectoine	C06231	143.0815	0.6560593
N-Methylethanolamine phosphate	C01210	156.042	0.6439167
Acetylcholine	C01996	146.1176	0.6493148
Choline	C00114	104.1074	0.6264017
L-Carnitine	C00318	162.1123	0.63605
acyl-C2 (acetyl-carnitine)	C02571	204.123	0.6599446
acyl-C3 (propionyl-carnitine)	C03017	218.1386	0.6585501
acyl-C4 (butanoyl-l-carnitine)	C02862	232.1542	0.6742796
acyl-C4-OH (Hydroxybutyrylcarnitine)	HMDB13127	248.1491	0.6595371
acyl-C4-DC	HMDB13133	262.1285	0.6585981
acyl-C5 (isovalerylcarnitine)	C20826	246.1699	1.74682
acyl-C5:1 (Tiglylcarnitine)	HMDB02366	244.1542	0.6730329
acyl-C5-OH	ac107	262.1647	0.6617768
acyl-C6 (hexanoyl-l-carnitine)	HMDB00756	260.1855	1.783238
acyl-C6-DC	ac109	290.1593	0.6609576
acyl-C8 (L-octanoylcarnitine	HMDB00791	288.2167	1.860136
acyl-C8:1 (octenoyl-l-carnitine)	ac111	286.2011	1.827403
acyl-C10 (O-Decanoyl-L-carnitine)	HMDB00651	316.248	1.923221
acyl-C10:1 (O-Decenoyl-L-carnitine)	CID57357170	314.2323	1.898856
acyl-C12:1 (O-dodecenoyl-carnitine)	HMDB13326	342.2636	1.971708
acyl-C14 (O-tetradecanoyl-L-carnitine)	HMDB05066	372.3105	2.126387
acyl-C14:1 (Tetradecenoyl Carnitine)	HMDB13329	370.2949	2.052704
acyl-C16 (L-Palmitoylcarnitine)	C02990	400.3418	2.334837
acyl-C18 (Octadecanoyl-L-carnitine)	HMDB00848	428.373	2.61409
acyl-C18:1 (O-octadecenoyl-L-carnitine)	HMDB06351	426.3573	2.372742
acyl-C18:2 (Linoleoyl-CoA)	HMDB01064	424.3419	2.211481
acyl-C20:4	ac125	448.3418	2.183353
Bilirubin	C00486	585.2698	1.899407
METABOLITES_END
#END