#METABOLOMICS WORKBENCH jravilap_20240827_092849 DATATRACK_ID:5151 STUDY_ID:ST003438 ANALYSIS_ID:AN005651 PROJECT_ID:PR002121
VERSION             	1
CREATED_ON             	August 27, 2024, 10:30 am
#PROJECT
PR:PROJECT_TITLE                 	Genetic screening and metabolomics identify glial adenosine metabolism as a
PR:PROJECT_TITLE                 	therapeutic target in Parkinson’s disease
PR:PROJECT_TYPE                  	Metabolomic profiling of Parkinson's Disease Drosophila model
PR:PROJECT_SUMMARY               	Parkinson’s disease (PD) is the second most common neurodegenerative disorder
PR:PROJECT_SUMMARY               	and lacks disease-modifying therapies. We developed a Drosophila model for
PR:PROJECT_SUMMARY               	identifying novel glial- based therapeutic targets for PD. Human α-synuclein is
PR:PROJECT_SUMMARY               	expressed in neurons and individual genes are independently knocked down in
PR:PROJECT_SUMMARY               	glia. We performed a forward genetic screen, knocking down the entire Drosophila
PR:PROJECT_SUMMARY               	kinome in glia in α-synuclein expressing flies. Among the top hits were five
PR:PROJECT_SUMMARY               	genes (Ak1, Ak6, Adk1, Adk2, and awd) involved in adenosine metabolism.
PR:PROJECT_SUMMARY               	Knockdown of each gene improved locomotor dysfunction, rescued
PR:PROJECT_SUMMARY               	neurodegeneration, and increased brain adenosine levels. We determined that the
PR:PROJECT_SUMMARY               	mechanism of neuroprotection involves adenosine itself, as opposed to a
PR:PROJECT_SUMMARY               	downstream metabolite. We dove deeper into the mechanism for one gene, Ak1,
PR:PROJECT_SUMMARY               	finding rescue of dopaminergic neuron loss, α-synuclein aggregation, and
PR:PROJECT_SUMMARY               	bioenergetic dysfunction after glial Ak1 knockdown. We performed metabolomics in
PR:PROJECT_SUMMARY               	Drosophila and in human PD patients, allowing us to comprehensively characterize
PR:PROJECT_SUMMARY               	changes in purine metabolism and identify potential biomarkers of dysfunctional
PR:PROJECT_SUMMARY               	adenosine metabolism in people. These experiments support glial adenosine as a
PR:PROJECT_SUMMARY               	novel therapeutic target in PD.
PR:INSTITUTE                     	Broad Institute of MIT and Harvard
PR:LAST_NAME                     	Avila-Pacheco
PR:FIRST_NAME                    	Julian
PR:ADDRESS                       	415 Main Street
PR:EMAIL                         	jravilap@broadinstitute.org
PR:PHONE                         	(617) 714-1729
PR:CONTRIBUTORS                  	Sodders M, Kumari N, Okorie E, Shen M, Lakhani M, Marathi A, Sarkar S, Scherzer
PR:CONTRIBUTORS                  	CR, Clish C, Feany MB, Olsen AL, Bullock K, Pierce K, Dennis C, Jeanfavre D,
PR:CONTRIBUTORS                  	Avila-Pacheco, J
#STUDY
ST:STUDY_TITLE                   	Unbiased genetic screening and metabolomics identifies glial adenosine
ST:STUDY_TITLE                   	metabolism as a therapeutic target in Parkinson’s disease
ST:STUDY_SUMMARY                 	Parkinson’s disease (PD) is the second most common neurodegenerative disorder
ST:STUDY_SUMMARY                 	and lacks disease-modifying therapies. We developed a Drosophila model for
ST:STUDY_SUMMARY                 	identifying novel glial- based therapeutic targets for PD. Human α-synuclein is
ST:STUDY_SUMMARY                 	expressed in neurons and individual genes are independently knocked down in
ST:STUDY_SUMMARY                 	glia. We performed a large forward genetic screen, knocking down the entire
ST:STUDY_SUMMARY                 	Drosophila kinome in glia in α-synuclein expressing flies. Among the top hits
ST:STUDY_SUMMARY                 	were five genes (Ak1, Ak6, Adk1, Adk2, and awd) involved in adenosine
ST:STUDY_SUMMARY                 	metabolism. Knockdown of each gene improved locomotor dysfunction, rescued
ST:STUDY_SUMMARY                 	neurodegeneration, and increased brain adenosine levels. We determined that the
ST:STUDY_SUMMARY                 	mechanism of neuroprotection involves adenosine itself, as opposed to a
ST:STUDY_SUMMARY                 	downstream metabolite. We dove deeper into the mechanism for one gene, Ak1,
ST:STUDY_SUMMARY                 	finding rescue of dopaminergic neuron loss, α-synuclein aggregation, and
ST:STUDY_SUMMARY                 	bioenergetic dysfunction after glial Ak1 knockdown. We performed metabolomics in
ST:STUDY_SUMMARY                 	Drosophila and in human PD patients, allowing us to comprehensively characterize
ST:STUDY_SUMMARY                 	changes in purine metabolism and identify potential biomarkers of dysfunctional
ST:STUDY_SUMMARY                 	adenosine metabolism in people. These experiments support glial adenosine as a
ST:STUDY_SUMMARY                 	novel therapeutic target in PD.
ST:INSTITUTE                     	Broad Institute of MIT and Harvard
ST:LAST_NAME                     	Avila-Pacheco
ST:FIRST_NAME                    	Julian
ST:ADDRESS                       	415 Main Street
ST:EMAIL                         	jravilap@broadinstitute.org
ST:PHONE                         	(617) 714-1729
#SUBJECT
SU:SUBJECT_TYPE                  	Insect
SU:SUBJECT_SPECIES               	Drosophila melanogaster
SU:TAXONOMY_ID                   	7227
#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           	-	9Q	Sample source:Fly heads | Sample_ID:Synuclein	RAW_FILE_NAME_HP=22_0131_HP_21_1207_OLS_FlyPilot/B0001_OLS_FlyPilot_HP-9Q.raw; RAW_FILE_NAME_CP=22_0131_CP_21_1207_OLS_FlyPilot/B0001_OLS_FlyPilot_CP-9Q_2.raw; RAW_FILE_NAME_CN=22_0307_CN_21_1207_OLS_FlyPilot/B0001_OLS_FlyPilot_CN-9Q.raw; RAW_FILE_NAME_HN=22_0126_HN_21_1207_OLS_FlyPilot/B0001_OLS_FlyPilot_HN_9Q.raw
SUBJECT_SAMPLE_FACTORS           	-	3S	Sample source:Fly heads | Sample_ID:Control	RAW_FILE_NAME_HP=22_0131_HP_21_1207_OLS_FlyPilot/B0002_OLS_FlyPilot_HP-3S.raw; RAW_FILE_NAME_CP=22_0131_CP_21_1207_OLS_FlyPilot/B0002_OLS_FlyPilot_CP-3S_2.raw; RAW_FILE_NAME_CN=22_0307_CN_21_1207_OLS_FlyPilot/B0002_OLS_FlyPilot_CN-3S.raw; RAW_FILE_NAME_HN=22_0126_HN_21_1207_OLS_FlyPilot/B0002_OLS_FlyPilot_HN_3S.raw
SUBJECT_SAMPLE_FACTORS           	-	2S	Sample source:Fly heads | Sample_ID:Control	RAW_FILE_NAME_HP=22_0131_HP_21_1207_OLS_FlyPilot/B0003_OLS_FlyPilot_HP-2S.raw; RAW_FILE_NAME_CP=22_0131_CP_21_1207_OLS_FlyPilot/B0003_OLS_FlyPilot_CP-2S_2.raw; RAW_FILE_NAME_CN=22_0307_CN_21_1207_OLS_FlyPilot/B0003_OLS_FlyPilot_CN-2S.raw; RAW_FILE_NAME_HN=22_0126_HN_21_1207_OLS_FlyPilot/B0003_OLS_FlyPilot_HN_2S.raw
SUBJECT_SAMPLE_FACTORS           	-	6SA	Sample source:Fly heads | Sample_ID:Control + AKI-KD	RAW_FILE_NAME_HP=22_0131_HP_21_1207_OLS_FlyPilot/B0004_OLS_FlyPilot_HP-6SA.raw; RAW_FILE_NAME_CP=22_0131_CP_21_1207_OLS_FlyPilot/B0004_OLS_FlyPilot_CP-6SA_2.raw; RAW_FILE_NAME_CN=22_0307_CN_21_1207_OLS_FlyPilot/B0004_OLS_FlyPilot_CN-6SA.raw; RAW_FILE_NAME_HN=22_0126_HN_21_1207_OLS_FlyPilot/B0004_OLS_FlyPilot_HN_6SA.raw
SUBJECT_SAMPLE_FACTORS           	-	8Q	Sample source:Fly heads | Sample_ID:Synuclein	RAW_FILE_NAME_HP=22_0131_HP_21_1207_OLS_FlyPilot/B0005_OLS_FlyPilot_HP-8Q.raw; RAW_FILE_NAME_CP=22_0131_CP_21_1207_OLS_FlyPilot/B0005_OLS_FlyPilot_CP-8Q_2.raw; RAW_FILE_NAME_CN=22_0307_CN_21_1207_OLS_FlyPilot/B0005_OLS_FlyPilot_CN-8Q.raw; RAW_FILE_NAME_HN=22_0126_HN_21_1207_OLS_FlyPilot/B0005_OLS_FlyPilot_HN_8Q.raw
SUBJECT_SAMPLE_FACTORS           	-	5SA	Sample source:Fly heads | Sample_ID:Control + AKI-KD	RAW_FILE_NAME_HP=22_0131_HP_21_1207_OLS_FlyPilot/B0006_OLS_FlyPilot_HP-5SA.raw; RAW_FILE_NAME_CP=22_0131_CP_21_1207_OLS_FlyPilot/B0006_OLS_FlyPilot_CP-5SA_2.raw; RAW_FILE_NAME_CN=22_0307_CN_21_1207_OLS_FlyPilot/B0006_OLS_FlyPilot_CN-5SA.raw; RAW_FILE_NAME_HN=22_0126_HN_21_1207_OLS_FlyPilot/B0006_OLS_FlyPilot_HN_5SA.raw
SUBJECT_SAMPLE_FACTORS           	-	10QA	Sample source:Fly heads | Sample_ID:Synuclein + AKI-KD	RAW_FILE_NAME_HP=22_0131_HP_21_1207_OLS_FlyPilot/B0007_OLS_FlyPilot_HP-10QA.raw; RAW_FILE_NAME_CP=22_0131_CP_21_1207_OLS_FlyPilot/B0007_OLS_FlyPilot_CP-10QA_2.raw; RAW_FILE_NAME_CN=22_0307_CN_21_1207_OLS_FlyPilot/B0007_OLS_FlyPilot_CN-10QA.raw; RAW_FILE_NAME_HN=22_0126_HN_21_1207_OLS_FlyPilot/B0007_OLS_FlyPilot_HN_10QA.raw
SUBJECT_SAMPLE_FACTORS           	-	12QA	Sample source:Fly heads | Sample_ID:Synuclein + AKI-KD	RAW_FILE_NAME_HP=22_0131_HP_21_1207_OLS_FlyPilot/B0008_OLS_FlyPilot_HP-12QA.raw; RAW_FILE_NAME_CP=22_0131_CP_21_1207_OLS_FlyPilot/B0008_OLS_FlyPilot_CP-12QA_2.raw; RAW_FILE_NAME_CN=22_0307_CN_21_1207_OLS_FlyPilot/B0008_OLS_FlyPilot_CN-12QA.raw; RAW_FILE_NAME_HN=22_0126_HN_21_1207_OLS_FlyPilot/B0008_OLS_FlyPilot_HN_12QA.raw
SUBJECT_SAMPLE_FACTORS           	-	1S	Sample source:Fly heads | Sample_ID:Control	RAW_FILE_NAME_HP=22_0131_HP_21_1207_OLS_FlyPilot/B0009_OLS_FlyPilot_HP-1S.raw; RAW_FILE_NAME_CP=22_0131_CP_21_1207_OLS_FlyPilot/B0009_OLS_FlyPilot_CP-1S_2.raw; RAW_FILE_NAME_CN=22_0307_CN_21_1207_OLS_FlyPilot/B0009_OLS_FlyPilot_CN-1S.raw; RAW_FILE_NAME_HN=22_0126_HN_21_1207_OLS_FlyPilot/B0009_OLS_FlyPilot_HN_1S.raw
SUBJECT_SAMPLE_FACTORS           	-	4SA	Sample source:Fly heads | Sample_ID:Control + AKI-KD	RAW_FILE_NAME_HP=22_0131_HP_21_1207_OLS_FlyPilot/B0010_OLS_FlyPilot_HP-4SA.raw; RAW_FILE_NAME_CP=22_0131_CP_21_1207_OLS_FlyPilot/B0010_OLS_FlyPilot_CP-4SA_2.raw; RAW_FILE_NAME_CN=22_0307_CN_21_1207_OLS_FlyPilot/B0010_OLS_FlyPilot_CN-4SA.raw; RAW_FILE_NAME_HN=22_0126_HN_21_1207_OLS_FlyPilot/B0010_OLS_FlyPilot_HN_4SA.raw
SUBJECT_SAMPLE_FACTORS           	-	11QA	Sample source:Fly heads | Sample_ID:Synuclein + AKI-KD	RAW_FILE_NAME_HP=22_0131_HP_21_1207_OLS_FlyPilot/B0011_OLS_FlyPilot_HP-11QA.raw; RAW_FILE_NAME_CP=22_0131_CP_21_1207_OLS_FlyPilot/B0011_OLS_FlyPilot_CP-11QA_2.raw; RAW_FILE_NAME_CN=22_0307_CN_21_1207_OLS_FlyPilot/B0011_OLS_FlyPilot_CN-11QA.raw; RAW_FILE_NAME_HN=22_0126_HN_21_1207_OLS_FlyPilot/B0011_OLS_FlyPilot_HN_11QA.raw
SUBJECT_SAMPLE_FACTORS           	-	7Q	Sample source:Fly heads | Sample_ID:Synuclein	RAW_FILE_NAME_HP=22_0131_HP_21_1207_OLS_FlyPilot/B0012_OLS_FlyPilot_HP-7Q.raw; RAW_FILE_NAME_CP=22_0131_CP_21_1207_OLS_FlyPilot/B0012_OLS_FlyPilot_CP-7Q_2.raw; RAW_FILE_NAME_CN=22_0307_CN_21_1207_OLS_FlyPilot/B0012_OLS_FlyPilot_CN-7Q.raw; RAW_FILE_NAME_HN=22_0126_HN_21_1207_OLS_FlyPilot/B0012_OLS_FlyPilot_HN_7Q.raw
#COLLECTION
CO:COLLECTION_SUMMARY            	Metabolomics on fly heads was performed using a platform that relies on a
CO:COLLECTION_SUMMARY            	combination of four non-targeted liquid chromatography mass spectrometry (LC-MS)
CO:COLLECTION_SUMMARY            	methods which measure both polar and non-polar metabolites23. n = 3 replicates
CO:COLLECTION_SUMMARY            	per genotype of 25 fly heads each.
CO:SAMPLE_TYPE                   	Heads
#TREATMENT
TR:TREATMENT_SUMMARY             	NA
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Sample homogenates were generated by homogenizing the fly heads in 100 µL water
SP:SAMPLEPREP_SUMMARY            	using a TissueLyser II (QIAGEN) bead mill set to two 2 min intervals at 20.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Shimadzu Nexera X2
CH:COLUMN_NAME                   	Phenomenex Luna NH2 (150 x 2.1mm, 3um)
CH:SOLVENT_A                     	100% water; 20 mM ammonium acetate; 20 mM ammonium hydroxide
CH:SOLVENT_B                     	75% acetonitrile/25% methanol; 10 mM ammonium hydroxide
CH:FLOW_GRADIENT                 	The column was eluted with initial conditions of 10% mobile phase A and 90%
CH:FLOW_GRADIENT                 	mobile phase B followed by a 10 min linear gradient to 100% mobile phase A.
CH:FLOW_RATE                     	400 µL/min
CH:COLUMN_TEMPERATURE            	30C
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Plus Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	NEGATIVE
MS:MS_COMMENTS                   	Raw data were processed using TraceFinder 3.3 software (Thermo Fisher
MS:MS_COMMENTS                   	Scientific; Waltham, MA) and Progenesis QI (Nonlinear Dynamics; Newcastle upon
MS:MS_COMMENTS                   	Tyne, UK). Metabolite identities were confirmed using authentic reference
MS:MS_COMMENTS                   	standards or reference samples.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Abundances
MS_METABOLITE_DATA_START
Samples	1S	2S	3S	4SA	5SA	6SA	7Q	8Q	9Q	10QA	11QA	12QA
Factors	Sample source:Fly heads | Sample_ID:Control	Sample source:Fly heads | Sample_ID:Control	Sample source:Fly heads | Sample_ID:Control	Sample source:Fly heads | Sample_ID:Control + AKI-KD	Sample source:Fly heads | Sample_ID:Control + AKI-KD	Sample source:Fly heads | Sample_ID:Control + AKI-KD	Sample source:Fly heads | Sample_ID:Synuclein	Sample source:Fly heads | Sample_ID:Synuclein	Sample source:Fly heads | Sample_ID:Synuclein	Sample source:Fly heads | Sample_ID:Synuclein + AKI-KD	Sample source:Fly heads | Sample_ID:Synuclein + AKI-KD	Sample source:Fly heads | Sample_ID:Synuclein + AKI-KD
Thymine-d4 [iSTD]	229361860	231289575	231273992	231996982	250012415	249150437	240123510	252747906	231624478	224400702	234234518	230246788
Inosine-15N4 [iSTD]	38614413	39111453	41368203	37335176	39156917	38732381	41692619	42426810	39482680	34401891	38426333	36002298
Glycocholate-d4 [iSTD]	96054921	94765270	93122230	91149777	104348515	102905129	92329613	104487560	97725723	95165013	94869811	97491874
1-Methylhistidine		212347		271194	397948	474191	280459	394867	267610	823868	591625	541506
1-Methylxanthine	842352	1137250	948291	1409282	2452019	2056295	1146840	1957015	1901509	3014029	2382446	3721509
2-Hydroxybutyric acid or 3-Hydroxybutyric acid	500460	369986	533357	399793	520645	441213	461873	355645	402107	555958	523080	512082
2-Hydroxyglutaric acid	150564132	124965567	117565017	189492401	174540865	189834603	249174648	250870158	280415238	260492382	269526837	317170401
3-Methyl-2-oxovaleric acid or Ketoleucine	6914807	6066898	8162793	4950901	7211176	6671145	5554374	6320598	6005251	7226425	7617664	6720737
3-Methyladipic acid or Pimelic acid	2085725	1941588	2671000	1481271	2892676	2257301	1205124	2136306	1904163	3469760	2451108	1959485
3-Phosphoglyceric acid	4130319	2640584	2775263	4659312	3724643	3128839	3554020	3120658	3063701	5509889	3333486	6259628
4-Pyridoxic acid	183774	92430		259787	233526	187457	146821	377796	251747	261458	222148	282048
6-Phosphogluconic acid	85760		148952					87136	91322			
Adenine	13554341	16589514	14988045	19437685	20276891	22279605	13233503	14109013	12778593	22480761	14741580	13046441
Adenylsuccinic acid	8208667	7068581	5629240	7624708	5673259	7917161	4917112	6010949	6323877	8485395	7204340	6967636
Adipic acid or Methylglutaric acid	2163227	2129357	1692940	3769307	3864862	4266222	2097666	4776729	2167210	7993486	4139331	5803861
Adonitol or Arabitol	66408549	43915200	39120418	97624580	103898306	98146867	45457950	70114862	54694905	74491205	68807784	105043022
ADP	2192225	1928835	2253699	1980469	2067582	2191467	1932924	2187650	2261210	3487154	2216228	2106230
Aminoadipic acid	227178	509891	201369	2187654			225430		216282	1391790	640356	
AMP	179488077	146712154	135004982	185468232	153623464	173986323	158186119	151141738	157961623	256726533	183355214	181016765
Aspartic acid	36944435	51592048	52043396	18939431	14822994	25824297	33855312	8134565	23400977	7371019	17778659	11820024
ATP	78217	172582	141361	105734	224134	240728	89951	154080	67922	224367	94112	146880
Citric acid or Isocitric acid	372295784	238872230	291514061	219817444	213776362	246493708	287846794	293691663	334118764	322534415	254283043	239508549
CMP	490033	525733	364111	428025	412808	422131	381563	418398	717694	565418	413238	467450
Cystathionine	824452	457260	577568	908043	498439	490697	435556	284124	379788	805826	725425	653164
Cytidine	445285	647577	533805	706372	856710	905526	585513	531432	568009	696390	725755	859456
Erythronic acid or Threonic acid	50286856	58229106	58849484	41713630	69105441	67710132	51807326	87494777	59474643	41856452	39391330	43447698
GDP	92274	122046	93701	65730	96142	120467	87500	95125	123740	36525	76063	43344
Glucosan or 3-Hydroxymethylglutaric acid	7126144	7432129	7499000	6298558	9013162	8860053	4567787	6974946	6406712	8769058	7683397	7423995
Glucuronic acid	9723052	9408824	9394114	7186856	7528498	8268365	7449608	8182685	8108635	7122016	5867368	7186244
Glutamic acid	189519215	168471987	167643500	214553752	237664912	237093653	157511690	164513289	181010181	169209880	194353286	207011660
Glutathione	12892505	10361158	2598644	33391564	7969737	8388074	26543303	7689410	5754785	32244700	28165815	17866210
Glyceric acid	7075967	6516995	6559614	8622308	8268233	9763859	7091873	12476149	6454200	15107630	7389254	10916451
Glycocholic acid	683654	548127	491976	617726	655532	564361	685043	680042	610922	688538	644249	674725
GMP	29941174	22936864	21504280	28250736	23000591	25482758	26306667	22297255	27380932	30564146	28111514	28958703
Guanosine	80699170	72877119	64108209	70400720	69018763	67861551	74158345	76869386	87081715	79874185	86656255	102215745
Hexose	19000348	18072595	15930476	19757564	24297977	27449295	16929205	25683143	20041670	21912415	18588947	21818038
Hexose diphosphate	619807	597040	445345	493168	529027	594399	528910	758760	686199	659807	599032	670169
Hexose monophosphate	52961510	38774520	32950944	48095071	31203526	33859108	37029017	46863874	37028164	54148492	27952057	53381915
Homovanillic acid	468918	326027	476302	285427	325493	376236	401519	188899	368083	173298	379670	234756
Hydroxykynurenine	1615682	1319023	1418895	4221167	3121177	3631085	3185571	2358294	3225559	4133104	4809121	4402948
Hypoxanthine	16261310	15793099	15337842	18278910	22763622	23266463	15202064	24074265	17376699	27669962	14934572	18531328
IMP	12040803	9270262	7595849	14773495	12250893	13395900	11448424	13578809	12588075	20377252	14440366	15314838
Indolelactic acid	1403193	1219571	1218826	1184247	1099848	1486468	861533	933567	1256826	1227936	1289335	1376493
Inosine	100611427	92496365	83897912	98449868	109502235	107637944	93037390	129045226	101647996	176474140	91078896	118087061
Lactic acid	48996379	46412511	48894055	65969909	55871434	68669494	107766490	102854434	122323500	116873869	93228900	106023286
Malic acid	1024826917	982437304	902235804	982736934	982921037	1051988789	881147641	894684503	886091093	1047229085	910148182	888683787
Malondialdehyde	5148703	4571030	3491233	5437770	4205844	4546308	4599883	5172716	8250558	6530963	5260865	4866232
Malonic acid	714187	871291	884224	565954	908101	811935	576267	781113	651723	787234	775063	743942
Myo-inositol	55715708	52187964	48269478	66711023	76942314	75443488	55261934	62978900	60455813	74279288	55675387	63823072
N-Acetylglutamic acid	59721305	51466875	48279186	68722967	57058227	64921580	84017243	80606885	74057397	109319384	101795310	107957346
NAD+	312557	661996	314823	399583	765328	622131	189508	451397	337634	597814	276551	372111
Nicotinic acid	1409812	1051387	1102628	1889990	1826716	1965467	1267935	1415218	1338477	1872162	1490010	1862672
Orotic acid	1325826	991036	866256	1145314	1152068	1063636	847607	875808	1001790	1054323	1149843	1047606
Oxalic acid	6036762	4767117	5216804	5701167	4712142	4778957	6232334	4575016	4913227	4540354	4780375	4610007
Oxidized glutathione	722041	1073652	1223659	714795	464837	581784	826239	273581	1348268	59410	602619	132416
Oxoglutaric acid	14443450	7118117	15320202	18534551	18146360	10916533	12208509	21124947	18816424	27649570	21083222	40051240
Pantothenic acid	102109646	133869134	99166604	101618874	120621412	121753299	111945973	124613526	96803328	124312594	107588850	63053972
Pentose 5-phosphate	1508209	1118031	1334983	1788519	1016148	1018462	1243894	1288452	1200750	1244335	937006	1336568
Pseudouridine	12378921	9308109	9740397	21593428	21891302	26414441	10930335	11709924	10981864	13685282	12351927	16474670
Ranitidine	1746171	1760278	2292506	1317603	2411581	2024113	1261983	1910107	1926029	2635006	1966146	1801152
Sebacic acid	748881	818828	956478	779766	1190898	1026624	850948	1013786	1002613	1179787	1553690	1612847
sn-Glycero-3-phosphate	143752131	117329219	106189610	178829691	141680671	135996048	131175838	106974299	128572834	170102064	114033892	131338191
Sorbitol	26915100	31489555	30099340	39748717	38664349	47260134	32117374	40033420	29301876	41885822	25514445	30475319
Suberic acid	1069492	1340876	1505951	1168118	1845622	1544762	1151485	1402998	1422740	1322124	1496093	1714229
Succinic acid	179565919	204446041	145370578	188061030	181055068	167590403	173194735	171583676	186430243	143109387	179987087	177216370
Succinyladenosine	1112131	742248	866080	1773284	876376	1626657	864653	894846	1235004	18925698	801339	2948114
Sucrose or Lactose or Trehalose	96713647	69345773	103537204	70603793	73879202	86779814	125375281	291361256	244970397	46373066	70957259	77245310
Thymine	1763642	1428679	1946692	3163026	3193761	3881598	1199481	1861695	1501226	3075632	2494343	2936656
UMP	6354306	5137027	3789468	6556773	4949012	5668450	4027852	4503148	5820990	6383859	4364013	3501201
Uracil	62028558	60548873	52692604	71817119	83093935	83900119	56903316	71111821	65747906	78290671	62738491	73454658
Uric acid	4388671494	3870934668	3864806080	4400756130	3696981490	4021526030	4028467517	3541472533	3854565656	4514005475	4411703775	4439716809
Uridine	59667583	58692859	45627747	68156536	72111547	73372289	44629780	56184872	52470384	69537995	51397341	60359154
Xanthine	145047271	147719639	197690663	215735647	246022363	275340539	132024254	157497644	155673463	153525396	150739179	169872912
Xanthurenic acid	1065584239	935612799	921653015	1482236550	1336978034	1394192513	1051701104	1027907319	1083493502	1307743925	1310214026	1534088961
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	MZ	RT	HMDB_ID	HMDB_ID_specificity (1=match,2=representative)
Thymine-d4 [iSTD]	129.0608	1.29	internal standard	NA
Inosine-15N4 [iSTD]	271.0616	3.16	internal standard	NA
Glycocholate-d4 [iSTD]	468.3269	3.63	internal standard	NA
1-Methylhistidine	168.0779	3.22	HMDB0000001	1
1-Methylxanthine	165.0418	3.58	HMDB0010738	1
2-Hydroxybutyric acid or 3-Hydroxybutyric acid	103.0401	3.37	HMDB0000008	2
2-Hydroxyglutaric acid	147.0299	6.43	HMDB0000694	1
3-Methyl-2-oxovaleric acid or Ketoleucine	129.0557	3.34	HMDB0000491	1
3-Methyladipic acid or Pimelic acid	159.0663	6.33	HMDB0000555	2
3-Phosphoglyceric acid	184.9857	8.62	HMDB0000807	1
4-Pyridoxic acid	182.0459	3.32	HMDB0000017	1
6-Phosphogluconic acid	275.0174	8.26	HMDB0001316	1
Adenine	134.0472	2.17	HMDB0000034	1
Adenylsuccinic acid	462.0668	9.64	HMDB0000536	1
Adipic acid or Methylglutaric acid	145.0506	6.35	HMDB0000448	2
Adonitol or Arabitol	151.0612	1.71	HMDB0000508	1
ADP	426.0221	9.14	HMDB0001341	1
Aminoadipic acid	160.0615	5.03	HMDB0000510	1
AMP	346.0558	7.23	HMDB0000045	1
Aspartic acid	132.0302	4.93	HMDB0000191	1
ATP	505.9885	10.57	HMDB0000538	1
Citric acid or Isocitric acid	191.0197	8.37	HMDB0000094	2
CMP	322.0446	7.09	HMDB0000095	1
Cystathionine	221.0601	5.17	HMDB0000099	1
Cytidine	242.0782	2.07	HMDB0000089	1
Erythronic acid or Threonic acid	135.0299	4.06	HMDB0000613	2
GDP	442.017	9.87	HMDB0001201	1
Glucosan or 3-Hydroxymethylglutaric acid	161.0455	6.35	HMDB0000640	2
Glucuronic acid	193.0354	4.81	HMDB0000127	1
Glutamic acid	146.0459	4.9	HMDB0000148	1
Glutathione	306.0765	5.59	HMDB0000125	1
Glyceric acid	105.0193	3.95	HMDB0000139	1
Glycocholic acid	464.3018	3.63	HMDB0000138	1
GMP	362.0507	8	HMDB0001397	1
Guanosine	282.0844	2.91	HMDB0000133	1
Hexose	179.0561	2.07	HMDB0000122	2
Hexose diphosphate	338.9888	9.44	HMDB0001058	2
Hexose monophosphate	259.0224	7.04	HMDB0000124	2
Homovanillic acid	181.0506	3.99	HMDB0000118	1
Hydroxykynurenine	223.0724	3.79	HMDB0000732	1
Hypoxanthine	135.0312	3.14	HMDB0000157	1
IMP	347.0398	8.2	HMDB0000175	1
Indolelactic acid	204.0666	3.97	HMDB0000671	1
Inosine	267.0735	3.18	HMDB0000195	1
Lactic acid	89.0244	3.59	HMDB0000190	1
Malic acid	133.0143	6.55	HMDB0000156	1
Malondialdehyde	71.0139	4.31	HMDB0006112	1
Malonic acid	103.0037	6.72	HMDB0000691	1
Myo-inositol	179.0561	2.58	HMDB0000211	1
N-Acetylglutamic acid	188.0565	6.27	HMDB0001138	1
NAD+	662.1024	4.87	HMDB0000902	1
Nicotinic acid	122.0247	3.7	HMDB0001488	1
Orotic acid	155.0098	4.09	HMDB0000226	1
Oxalic acid	88.988	6.98	HMDB0002329	1
Oxidized glutathione	611.1447	7.39	HMDB0003337	1
Oxoglutaric acid	145.0143	6.88	HMDB0000208	1
Pantothenic acid	218.1034	3.67	HMDB0000210	1
Pentose 5-phosphate	229.0119	6.89	HMDB0001548	1
Pseudouridine	243.0623	2.26	HMDB0000767	1
Ranitidine	313.134	1.07	HMDB0001930	1
Sebacic acid	201.1132	6.26	HMDB0000792	1
sn-Glycero-3-phosphate	171.0064	6.88	HMDB0000126	1
Sorbitol	181.0718	1.93	HMDB0000247	1
Suberic acid	173.0819	6.32	HMDB0000893	1
Succinic acid	117.0193	6.49	HMDB0000254	1
Succinyladenosine	382.1004	6.88	HMDB0000912	1
Sucrose or Lactose or Trehalose	341.1089	2.58	HMDB0000258	2
Thymine	125.0357	1.28	HMDB0000262	1
UMP	323.0286	7.15	HMDB0000288	1
Uracil	111.02	1.51	HMDB0000300	1
Uric acid	167.0211	4.84	HMDB0000289	1
Uridine	243.0623	1.7	HMDB0000296	1
Xanthine	151.0262	4.61	HMDB0000292	1
Xanthurenic acid	204.0302	7.59	HMDB0000881	1
METABOLITES_END
#END