#METABOLOMICS WORKBENCH jravilap_20240827_092849 DATATRACK_ID:5151 STUDY_ID:ST003438 ANALYSIS_ID:AN005650 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 Reversed phase CH:INSTRUMENT_NAME Shimadzu Nexera X2 CH:COLUMN_NAME Waters Acquity BEH C8 (100 x 2.1mm, 1.7um) CH:SOLVENT_A 95% water/5% methanol; 10 mM ammonium acetate; 0.1% acetic acid CH:SOLVENT_B 100% methanol; 0.1% acetic acid CH:FLOW_GRADIENT The column was eluted at a flow rate of 450 µL/min isocratically for 1 minute CH:FLOW_GRADIENT at 80% mobile phase A, followed by a linear gradient to 80% mobile-phase B over CH:FLOW_GRADIENT 2 minutes, a linear gradient to 100% mobile phase B over 7 minutes, and then 3 CH:FLOW_GRADIENT minutes at 100% mobile-phase B. CH:FLOW_RATE 450 µL/min CH:COLUMN_TEMPERATURE 40C #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 POSITIVE 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 PC 12:0/12:0 [iSTD] 5131450 5096770 4952462 5121546 5136903 5045093 4971429 4868502 5157655 5034037 5278487 4888169 LPC 14:0 503084 531535 490722 600765 553816 596465 493388 635096 557877 434649 407019 591631 LPC 16:1 9018172 12250610 8713079 11994506 14343556 14403666 9431818 12270957 10454212 9411782 9754374 11055475 LPC 16:0 3226122 3853718 3019650 3871340 3836503 4276856 3294632 4184972 3989094 3945324 3318930 4426824 LPC 18:3 996591 1229144 1120532 1215152 1192321 1388321 772874 1001752 1131999 714021 836977 1390297 LPC 18:2 10710460 13861692 10606557 14331977 14782855 17160127 10631685 13841265 14132795 9836419 11099961 15894096 LPC 18:1 6621591 8801146 6464375 9889279 10209347 10976331 8542477 11870798 9388453 9290098 7731104 10970076 LPC 18:0 243659 288134 176153 392390 315201 456235 178201 189751 183246 347485 269897 252069 LPC 20:2 7952 13880 11596 18274 17224 21968 12300 16728 17520 17398 16787 24006 LPE 16:1 2916898 3776624 2780923 3664050 4414484 4509038 2891207 3865734 2921944 3277055 2765472 3074978 LPE 16:0 139664 168515 136201 202517 197615 237603 152611 207617 187129 237892 185667 249664 LPE 18:3 1520866 1871957 1577941 1847007 1810824 2058476 1254300 1556380 1701488 1248041 1382693 2031141 LPE 18:2 6628806 8428423 6388445 8300385 8625446 9615025 7492844 8780629 8170717 7056836 7404481 8727805 LPE 18:1 4005059 4988644 3733851 5808778 5943171 6706480 4651627 6525289 5220231 6808808 5017243 6164284 LPE 18:0 207714 246809 156898 328841 277786 351520 225065 233185 207688 404785 351702 322071 LPE 20:1 124266 173247 124238 169957 172959 190648 175741 223172 148099 156347 160351 165412 LPE 20:0 2499255 2523741 2501901 2608896 2575552 2639317 2557733 2587687 2568605 2529025 2552596 2583260 PC 30:1 3141226 3835210 3256698 4602890 4287834 4829365 2548563 3220178 3321157 5433537 3684452 3817003 PC 30:0 1304590 1414645 1358297 1594342 1401267 1691940 1546079 1827415 1780050 2467225 1864476 1974634 PC 32:2 10515232 14012452 11079158 13773908 14908886 16847436 9489189 13187951 13676492 27639296 16247405 14958683 PC 32:1 16925360 22599171 18253669 25258771 25945923 28920690 19662235 24658458 22019788 43039432 27230079 24610546 PC 32:0 6528374 8636344 7858573 9156192 7936884 9725907 7397414 7987150 8314741 12457688 10547113 9737264 PC 34:4 678767 871015 746290 934528 874572 1124818 585198 782864 836696 1411054 1004255 1012061 PC 34:3 11177023 13938685 12607032 15338566 13861534 18157751 10058035 14586631 15048901 27575949 17312718 17351451 PC 34:2 40997447 53637267 47489317 57134227 52980972 65465037 41747605 56504849 55621314 91202079 62199705 60002773 PC 34:1 21480303 29145392 25326132 32583816 31122337 36458185 28635593 33699676 32290850 49347813 39407587 34298302 PC 34:0 1888560 2263220 2102146 2775184 2413423 2988397 1681796 1839791 2001778 2782099 2544129 2619594 PC 36:3 15967048 22462950 21123050 26596585 24085169 30898432 18007139 24322479 24932086 45611958 30689175 30862817 PC 36:2 15891343 21351296 19686357 27119696 24472913 33934618 17403237 21232744 20817296 37065544 26487878 24968529 PC 36:1 4105733 5432471 5224961 6739039 6161834 8118859 4658136 5528647 5242868 7337533 6741594 5640938 PC 36:0 38666 51773 45172 65184 60110 75968 31743 37664 40639 66167 57568 65646 PC 38:6 1805761 2710010 2488439 3292769 2967817 3887413 2070344 3027279 3046638 5139051 3840124 3792892 PC 38:3 33511 49770 41909 65283 50979 77737 37854 50980 51568 94792 75165 68363 PC 38:2 123560 171047 167904 229610 196033 251334 104232 134939 147228 211787 177766 170391 PC P-34:1 or PC O-34:2 136020 190229 170087 172400 157449 206763 115225 172821 180008 200469 149208 152928 PC P-34:0 or PC O-34:1 97392 138620 122382 141468 127876 160725 109607 129820 114786 167625 129188 136038 PC P-36:2 or PC O-36:3 106642 152483 136627 134488 108739 160260 48616 68579 88189 92315 74136 105613 PC P-36:1 or PC O-36:2 608651 809582 759999 861729 757901 1066558 472647 582215 642900 703163 620312 630909 PC P-36:0 or PC O-36:1 37969 56364 48376 54091 55222 64857 48473 52116 46332 67810 53920 58426 PE 32:1 6312405 8148956 5756037 7856200 8982056 8956637 5626654 6682767 6220981 9651244 6175807 6104738 PE 32:0 45077 62051 55533 40286 28327 38278 48353 65153 52264 57650 44070 43139 PE 34:2 12602031 16123045 13566359 16378827 16997432 19353959 13778987 17972202 15803242 31429563 18900858 17106607 PE 34:0 356816 487914 456131 380956 286737 362040 430904 496651 379136 531042 398388 435696 PE 36:4 7656038 9169005 8960662 9638187 8813098 11565533 6460108 8937380 9858449 14722510 10829581 10735482 PE 36:3 10533878 14045713 13243121 15537538 14466228 17958835 11150444 14306780 13985242 26928889 17489235 16849337 PE 36:2 512996 718303 670892 647112 569396 715123 594926 804222 641086 1285858 865813 716975 PE 36:1 1294321 1963337 1645713 1734226 1467917 1792509 1874631 2146771 1644220 2877766 2073744 1980701 PE 36:0 731456 982752 946320 890342 728346 917590 863790 950853 837634 1266697 1023862 1127877 PE 38:6 1250535 1639016 1550248 1787853 1681837 2055161 1319228 1652204 1603244 2888238 1996068 1898109 PE 38:5 20758 31312 26602 27636 24041 33632 26239 31290 25459 57933 35537 31521 PE 38:2 1170791 1703528 1605860 1599473 1261821 1688304 1292516 1640693 1475405 2365218 1790319 1913160 PE P-34:2 or PE O-34:3 142550 178970 155476 151606 142755 170531 159767 202101 200316 185616 159776 186976 PE P-34:1 or PE O-34:2 16330 28322 29052 24890 27715 32208 20989 31272 34956 50080 23716 27864 PE P-36:2 or PE O-36:3 8151631 10180554 9280783 10387252 8901904 11372429 7268503 8722513 10018147 10758834 9730704 11138482 PE P-36:1 or PE O-36:2 9002627 11068328 10374161 12472486 11990815 14807962 11291097 13000147 12668009 14263019 14067488 11937539 PI 32:2 22267 33097 24269 26474 33208 30976 21164 26633 33348 44673 36753 27704 PI 32:1 49240 65777 50623 74596 67844 70704 52310 61788 61854 107699 65497 60697 PI 34:2 77573 114719 85192 114925 113592 138117 94886 128114 140580 203748 143248 143158 PI 34:1 36086 46746 38193 63245 52700 59187 47243 57585 56010 86140 60283 55804 PI 36:4 89834 113314 115655 118799 114553 139262 94959 129789 141567 195802 147849 156534 PI 36:3 117649 153708 143929 163950 164218 209430 147991 209078 207912 303698 256598 232729 PI 36:2 39492 53962 51611 69750 59393 81777 54469 64965 68406 96355 73262 75820 PS 34:1 37094 52575 51142 49505 46836 52641 61774 75893 72039 83840 72863 63129 PS 34:0 104607 127853 112420 152793 157585 188032 97803 142869 120504 371781 149363 156285 PS 36:4 392869 507908 489776 588675 517830 636884 556018 648804 712809 1042117 843687 777198 PS 36:3 427029 530673 525536 584616 515451 642793 516547 622415 700947 952970 772934 756410 PS 36:2 56200 71331 68040 68979 66005 77749 50562 76374 74716 143427 71285 79042 PS 36:1 77347 97653 91244 111771 115368 138164 75924 110303 98822 237876 122660 126940 Sphingosine 456742 471098 465932 454141 476320 569884 493898 465378 471377 462764 450774 447908 Palmitoyl-EA 48460 47763 49400 50470 52642 50101 51789 49334 50112 49835 49765 51045 Coenzyme Q9 456213 555770 537893 506944 531766 566201 394311 589741 474118 959220 580698 533296 Cer 18:1;O2/16:0 110985 148080 121613 156442 170291 176291 143619 163158 163914 226317 177088 201914 CE 18:1 154947 186642 167400 195143 230812 265887 88851 101560 140947 165521 187470 187648 CE 18:2 355944 411299 381405 320216 399032 362878 194863 247231 284733 270304 347660 206763 DG 30:0 528750 633192 620823 819520 694927 845388 591032 670298 599371 755637 601098 681062 DG 32:0 126815 141772 157858 167354 147805 175981 203060 164979 212675 181993 135229 165529 DG 32:1 5747669 6494225 6777582 8453114 7315243 8702595 7429373 7587603 7269727 8308282 7576271 9463616 DG 32:2 3620804 4304571 4302057 5364771 4897188 5909665 4862884 5156455 4943546 5383682 5353627 6291665 DG 34:0 82924 81997 126959 100545 94013 102826 232261 87570 192998 93982 83805 93394 DG 34:1 2023619 2603915 2579856 3768627 2895918 3489191 3451055 3400344 3189446 3838778 2995384 4745055 DG 34:2 2204050 2580843 2574312 3365929 2841711 3485444 3223171 3604819 3307920 3396744 3164761 4239593 DG 34:3 644389 766388 743527 980131 837828 1075123 859924 970299 1021407 1019188 980235 1310310 DG 36:0 61728 57984 92695 62139 61224 62309 140546 60373 86846 61243 66585 52843 DG 36:1 108445 158078 136554 173991 144619 172077 167030 175763 171813 217330 157901 213589 DG 36:2 388905 477358 446203 623135 530488 623195 673472 705844 650685 715588 567402 890504 DG 36:3 266676 321406 294729 393223 334481 421335 446456 458342 418083 475747 453074 548965 DG 36:4 253084 266416 249873 281804 255726 273012 330998 309243 350543 352743 367992 369967 MG 14:1 38642 40977 37260 56961 48371 61769 35593 45226 41020 39649 46713 58462 MG 16:1 316500 349173 326436 428716 372802 481806 374747 476983 438544 443575 447249 527091 MG 18:0 101618 114523 197715 160349 121628 152250 255112 115765 281545 99178 147321 130251 TG 41:0 1915921 2646729 2291594 1220295 1007666 1136942 2168691 2165834 1895556 1492799 1309166 1552597 TG 42:0 10466898 10645836 10887199 10407950 10329584 10363169 9706342 9905887 9993862 10442533 9670679 9093945 TG 43:0 863947 1352243 1043856 522284 369935 461486 1040559 1020597 903772 649911 514567 594760 TG 43:1 3842633 4869888 4368670 2876739 2544611 2873344 4395412 4479485 3860545 3352115 3122210 3637299 TG 43:2 318656 431509 362115 264713 223509 278345 467869 483058 444976 311708 319507 434063 TG 44:0 4928289 5142113 5146602 5330167 5461748 5487887 4261375 5050669 4675747 5385950 4758577 3893623 TG 44:1 17780412 17548581 17087324 17931261 17536788 17943110 16571305 16581764 16727260 17225034 17215322 16737152 TG 44:2 17886173 17488994 17947327 19332510 19856944 20022937 17765147 18152328 18642657 18816420 18651616 19469074 TG 45:1 4377210 5478272 4792083 3563352 3072257 3548701 4511094 4550407 3996956 3934387 3707014 4065244 TG 45:2 1037933 1311321 1155629 779999 701965 870852 1525484 1409329 1321358 1003893 1033001 1378830 TG 46:0 1448974 1651911 1591947 1643147 1677092 1685549 1380738 1679644 1564574 1817824 1442748 1234833 TG 46:1 16944656 16625756 17270742 17622492 17410927 17831195 16396035 16900463 16938304 17025851 17341905 16766433 TG 46:2 18166803 17030692 18164265 19731185 19670365 19812326 17842863 18158393 18453344 19231377 18669412 18597160 TG 46:3 5438003 5293478 5486005 6051128 6280818 6521890 6277491 6134338 7045867 6017234 6398233 7831764 TG 46:4 148867 164625 147604 148853 164961 173093 169139 193244 256320 170664 166278 271324 TG 47:1 5610037 7272320 6300210 4643896 3933407 4849344 5978887 5969965 5376877 5291696 4818934 5468886 TG 47:2 3211900 4034451 3577507 2540366 2373690 2830439 4254447 4147812 3790290 3238862 3350963 4195352 TG 48:0 516208 638862 605191 594544 548314 541377 622801 727833 710136 804788 522344 578449 TG 48:1 16444008 17804783 17265124 17675849 17722460 17684428 17642077 17564491 17789182 18072586 17186766 17782438 TG 48:2 17445276 17110851 18003229 18575507 19367858 19594790 18015268 17667791 18830623 18513286 18852854 18478958 TG 48:3 10842726 10653605 10809920 11804074 12315068 12500270 12115732 11826130 12493213 11656403 12281164 13013927 TG 48:4 458571 459230 442599 466603 486001 524868 542331 553971 688223 482031 527148 727603 TG 49:1 4279611 6830984 4875626 3990690 3223834 3904805 6433390 6497324 5745045 4967405 4057934 6388815 TG 49:2 3464818 5056178 4131358 3079710 2821668 3265073 5680881 5660340 5232465 4003425 3575177 5826663 TG 49:3 225351 282777 264484 251613 211426 246632 235039 237554 274096 308399 344183 323909 TG 50:0 139515 178775 205246 154053 151232 155942 195494 208725 221120 249348 183859 172187 TG 50:1 8598119 11064141 9326161 10624006 11076410 10371451 12967044 13559043 12577164 13447074 10126699 13637447 TG 50:2 13840235 14644691 14360177 15582843 15848165 15482384 16244205 17025510 17019529 16502173 15803319 17118089 TG 50:3 8415471 8762187 8883399 9205104 10002940 10037409 10626011 10856265 11420884 9894601 9622701 11527259 TG 50:4 1237041 1230096 1289339 1340703 1510585 1617717 1584616 1658790 2118157 1368236 1661116 2059711 TG 51:1 1484492 3005258 1796739 1550963 1176390 1454472 3121703 3230468 2635766 2231786 1498123 3467748 TG 51:2 250573 411398 297605 275909 218293 276887 417717 457897 425670 319432 290589 506061 TG 51:3 268260 358741 295594 340494 301622 326182 352108 383051 462374 410281 429247 606495 TG 52:1 1678396 2781128 1884650 2070116 2240750 1958528 3185125 3396610 3049704 4074146 2440446 3591482 TG 52:2 4465660 6027899 4922985 5970149 5863475 5548166 8450205 9507088 8472662 8212667 5782734 9907111 TG 52:3 2727403 3211663 3074018 3599662 3651715 3580113 4932397 5656558 5558450 4337800 3688453 5942377 TG 52:4 1100678 1249304 1148598 1357711 1356618 1433753 1495421 1621368 1999546 1347806 1428105 1898619 TG 53:2 22092 53448 33163 36022 24675 31278 50970 65197 54404 44510 34500 74375 TG 53:3 94765 139483 120395 147845 131914 138844 172948 170029 210525 173199 168931 364512 TG 54:1 532184 891169 624195 661307 714829 669818 1056267 1137567 1101756 1636151 994339 1297985 TG 54:2 933825 1408167 1079021 1152450 1126346 1225449 1451417 1679550 1542353 3472241 2347494 1664521 TG 54:3 537262 716935 631987 729654 662679 824618 1085319 1132695 1086525 1318233 1033427 1392077 TG 54:4 181123 211608 206127 298021 248342 334612 312436 343928 389119 333895 328839 452468 TG 55:2 176737 264125 175449 189529 171674 206305 201692 333432 278725 589479 452432 204567 TG 55:3 44242 62270 39736 40836 38047 43381 52473 89687 85809 99736 81472 52565 TG 56:1 182653 269083 215984 250341 213331 292371 295122 354793 371963 490598 436490 396695 TG 56:2 685082 973099 876511 888961 755371 1036108 909997 1211097 1056221 2693867 1926585 1020753 TG 56:3 305715 372049 373303 334007 263635 415336 474614 700386 546632 2041518 1623825 581627 TG 56:4 7762 16081 12501 13090 17234 20924 20104 27641 31875 44681 51845 66029 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name MZ RT HMDB_ID HMDB_ID_specificity (1=match,2=representative) PC 12:0/12:0 [iSTD] 622.4436 6.75 internal standard NA LPC 14:0 468.3087 4.36 HMDB0010379 1 LPC 16:1 494.3240 4.52 HMDB0010383 2 LPC 16:0 496.3400 4.87 HMDB0010382 1 LPC 18:3 518.3242 4.43 HMDB0010387 2 LPC 18:2 520.3397 4.71 HMDB0010386 2 LPC 18:1 522.3555 5.06 HMDB0002815 2 LPC 18:0 524.3718 5.60 HMDB0010384 1 LPC 20:2 548.3715 5.22 HMDB0010392 1 LPE 16:1 452.2770 4.53 HMDB0011504 2 LPE 16:0 454.2929 4.88 HMDB0011503 1 LPE 18:3 476.2771 4.45 HMDB0011478 2 LPE 18:2 478.2929 4.72 HMDB0011507 2 LPE 18:1 480.3085 5.08 HMDB0011475 2 LPE 18:0 482.3246 5.62 HMDB0011130 1 LPE 20:1 508.3403 4.78 HMDB0011512 2 LPE 20:0 510.3560 5.29 HMDB0011481 1 PC 30:1 704.5221 8.06 HMDB0007870 2 PC 30:0 706.5375 8.41 HMDB0007869 2 PC 32:2 730.5376 8.23 HMDB0007874 2 PC 32:1 732.5533 8.56 HMDB0007873 2 PC 32:0 734.5689 8.87 HMDB0007871 2 PC 34:4 754.5375 8.07 HMDB0007883 2 PC 34:3 756.5531 8.38 HMDB0008006 2 PC 34:2 758.5687 8.71 HMDB0007973 2 PC 34:1 760.5845 9.02 HMDB0007972 2 PC 34:0 762.6000 9.31 HMDB0007970 2 PC 36:3 784.5842 8.85 HMDB0008105 2 PC 36:2 786.5999 9.16 HMDB0008039 2 PC 36:1 788.6155 9.44 HMDB0008038 2 PC 36:0 790.6316 9.70 HMDB0008036 2 PC 38:6 806.5658 8.85 HMDB0007991 2 PC 38:3 812.6157 9.26 HMDB0008047 2 PC 38:2 814.6319 9.58 HMDB0008270 2 PC P-34:1 or PC O-34:2 744.5893 9.02 HMDB0011210 2 PC P-34:0 or PC O-34:1 746.6050 9.33 HMDB0011208 2 PC P-36:2 or PC O-36:3 770.6048 9.20 HMDB0011244 2 PC P-36:1 or PC O-36:2 772.6206 9.45 HMDB0011243 2 PC P-36:0 or PC O-36:1 774.6366 9.72 HMDB0011241 2 PE 32:1 690.5060 8.57 HMDB0008924 2 PE 32:0 692.5221 8.15 HMDB0008923 2 PE 34:2 716.5218 8.71 HMDB0008928 2 PE 34:0 720.5534 8.64 HMDB0008925 2 PE 36:4 740.5215 8.53 HMDB0008937 2 PE 36:3 742.5373 8.85 HMDB0009060 2 PE 36:2 744.5533 8.47 HMDB0008994 2 PE 36:1 746.5688 8.79 HMDB0008993 2 PE 36:0 748.5844 9.09 HMDB0008991 2 PE 38:6 764.5192 8.85 HMDB0009102 2 PE 38:5 766.5338 8.47 HMDB0009069 2 PE 38:2 772.5844 8.93 HMDB0008942 2 PE P-34:2 or PE O-34:3 700.5271 8.75 HMDB0011343 2 PE P-34:1 or PE O-34:2 702.5425 9.31 HMDB0008952 2 PE P-36:2 or PE O-36:3 728.5583 9.21 HMDB0011441 2 PE P-36:1 or PE O-36:2 730.5740 9.45 HMDB0009017 2 PI 32:2 807.5013 7.64 HMDB0009798 2 PI 32:1 809.5173 7.99 HMDB0009779 2 PI 34:2 835.5329 8.15 HMDB0009784 2 PI 34:1 837.5475 8.46 HMDB0009783 2 PI 36:4 859.5330 8.00 HMDB0009789 2 PI 36:3 861.5480 8.29 HMDB0009838 2 PI 36:2 863.5634 8.62 HMDB0009809 2 PS 34:1 762.5288 8.64 HMDB0012357 2 PS 34:0 764.5430 8.21 HMDB0012356 2 PS 36:4 784.5117 8.10 HMDB0012361 2 PS 36:3 786.5268 8.41 HMDB0012391 2 PS 36:2 788.5432 8.03 HMDB0012380 2 PS 36:1 790.5587 8.35 HMDB0010163 2 Sphingosine 300.2892 3.98 HMDB0000252 1 Palmitoyl-EA 300.2894 5.17 HMDB0002100 1 Coenzyme Q9 817.6094 10.57 HMDB0006707 1 Cer 18:1;O2/16:0 538.5193 8.69 HMDB0004949 1 CE 18:1 673.5890 12.18 HMDB0000918 2 CE 18:2 671.5732 11.84 HMDB0000610 2 DG 30:0 563.4646 8.95 HMDB0007011 2 DG 32:0 591.4958 9.40 HMDB0007098 2 DG 32:1 589.4797 9.09 HMDB0007099 2 DG 32:2 587.4641 8.77 HMDB0007128 2 DG 34:0 619.5272 9.76 HMDB0007100 2 DG 34:1 617.5112 9.51 HMDB0007102 2 DG 34:2 615.4953 9.22 HMDB0007103 2 DG 34:3 613.4798 8.91 HMDB0007132 2 DG 36:0 647.5579 10.13 HMDB0007158 2 DG 36:1 645.5428 9.92 HMDB0007216 2 DG 36:2 643.5271 9.63 HMDB0007218 2 DG 36:3 641.5113 9.35 HMDB0007219 2 DG 36:4 639.4954 9.06 HMDB0007248 2 MG 14:1 323.2189 4.39 HMDB0011562 2 MG 16:1 351.2501 4.89 HMDB0011565 2 MG 18:0 381.2973 6.05 HMDB0011131 1 TG 41:0 731.6152 10.81 HMDB0072022 2 TG 42:0 745.6302 10.98 HMDB0072780 2 TG 43:0 759.6472 11.12 HMDB0042062 2 TG 43:1 757.6307 10.90 HMDB0042098 2 TG 43:2 755.6147 10.71 HMDB0043169 2 TG 44:0 773.6618 11.30 HMDB0042063 2 TG 44:1 771.6455 11.09 HMDB0042301 2 TG 44:2 769.6297 10.85 HMDB0042279 2 TG 45:1 785.6621 11.21 HMDB0042099 2 TG 45:2 783.6458 11.02 HMDB0043170 2 TG 46:0 801.6933 11.62 HMDB0010411 2 TG 46:1 799.6767 11.41 HMDB0010412 2 TG 46:2 797.6610 11.16 HMDB0010419 2 TG 46:3 795.6454 10.94 HMDB0042751 2 TG 46:4 793.6302 10.72 HMDB0042548 2 TG 47:1 813.6933 11.52 HMDB0042100 2 TG 47:2 811.6774 11.31 HMDB0042076 2 TG 48:0 829.7240 11.97 HMDB0005356 2 TG 48:1 827.7083 11.73 HMDB0005359 2 TG 48:2 825.6924 11.48 HMDB0005376 2 TG 48:3 823.6769 11.25 HMDB0005432 2 TG 48:4 821.6618 11.02 HMDB0042811 2 TG 49:1 841.7246 11.85 HMDB0011705 2 TG 49:2 839.7086 11.62 HMDB0011706 2 TG 49:3 837.6934 11.54 HMDB0042103 2 TG 50:0 857.7566 12.32 HMDB0005357 2 TG 50:1 855.7399 12.04 HMDB0005360 2 TG 50:2 853.7238 11.79 HMDB0005377 2 TG 50:3 851.7082 11.57 HMDB0005433 2 TG 50:4 849.6927 11.33 HMDB0005435 2 TG 51:1 869.7560 12.19 HMDB0042104 2 TG 51:2 867.7407 12.12 HMDB0005362 2 TG 51:3 865.7246 11.87 HMDB0011701 2 TG 52:1 883.7719 12.41 HMDB0005367 2 TG 52:2 881.7558 12.14 HMDB0005369 2 TG 52:3 879.7401 11.90 HMDB0005384 2 TG 52:4 877.7245 11.65 HMDB0005363 2 TG 53:2 895.7721 12.49 HMDB0042196 2 TG 53:3 893.7565 12.22 HMDB0043058 2 TG 54:1 911.8035 12.80 HMDB0005395 2 TG 54:2 909.7877 12.52 HMDB0005403 2 TG 54:3 907.7720 12.24 HMDB0005405 2 TG 54:4 905.7564 11.98 HMDB0005370 2 TG 55:2 923.8035 12.72 HMDB0042226 2 TG 55:3 921.7883 12.44 HMDB0042466 2 TG 56:1 939.8348 13.25 HMDB0005396 2 TG 56:2 937.8192 12.89 HMDB0005404 2 TG 56:3 935.8034 12.62 HMDB0005410 2 TG 56:4 933.7882 12.33 HMDB0005398 2 METABOLITES_END #END