#METABOLOMICS WORKBENCH jravilap_20171002_140622 DATATRACK_ID:1248 STUDY_ID:ST000879 ANALYSIS_ID:AN001429 PROJECT_ID:PR000610 VERSION 1 CREATED_ON October 25, 2017, 9:35 am #PROJECT PR:PROJECT_TITLE Diet, genetics and gut microbiome drive dynamic changes in plasma metabolites PR:PROJECT_TITLE [plasma] PR:PROJECT_TYPE Metabolite profiling of stool and cecal contents in mice of different genotypes, PR:PROJECT_TYPE vendors, diets, and antibiotic treatments. PR:PROJECT_SUMMARY Diet, genetics and the gut microbiome are determinants of metabolic status, in PR:PROJECT_SUMMARY part through production of metabolites by gut microbiota. To understand PR:PROJECT_SUMMARY mechanisms linking these factors, we performed LC-MS-based metabolomic analysis PR:PROJECT_SUMMARY of cecal contents and plasma from C57BL/6J, 129S1/SvImJ and 129S6/SvEvTac mice PR:PROJECT_SUMMARY on chow, high-fat diet (HFD), and HFD-treated with vancomycin or metronidazole. PR:PROJECT_SUMMARY Prediction of the functional metagenome of gut bacteria by PICRUSt analysis of PR:PROJECT_SUMMARY 16S sequences revealed dramatic differences in microbial metabolism. Cecal and PR:PROJECT_SUMMARY plasma metabolites showed multifold differences reflecting the combined and PR:PROJECT_SUMMARY integrated effects of diet, antibiotics, host background, and the gut PR:PROJECT_SUMMARY microbiome. Eighteen plasma metabolites correlated positively or negatively with PR:PROJECT_SUMMARY host insulin resistance across strains and diets. Over 1,000 PR:PROJECT_SUMMARY as-of-yet-unidentified metabolite peaks were also highly regulated by diet, PR:PROJECT_SUMMARY antibiotics and genetic background. Thus diet, host genetics and gut microbiota PR:PROJECT_SUMMARY interact to create unique responses in plasma metabolites, which can contribute PR:PROJECT_SUMMARY to regulation of metabolism and insulin resistance. PR:INSTITUTE Broad Institute of MIT and Harvard PR:DEPARTMENT Metabolomics Platform PR:LAST_NAME Avila PR:FIRST_NAME Julian PR:ADDRESS 415 Main Street, Rm 7175, Cambridge, MA, 02142, USA PR:EMAIL jravilap@broadinstitute.org PR:PHONE 6177148264 PR:CONTRIBUTORS Shiho Fujisaka, Julian Avila-Pacheco, Marion Soto, Aleksandar Kostic, Jonathan PR:CONTRIBUTORS M. Dreyfuss, Hui Pan, Siegfried Ussar, Emrah Altindis, Ning Li, Lynn Bry, Clary PR:CONTRIBUTORS B. Clish, and C. Ronald Kahn #STUDY ST:STUDY_TITLE Diet, genetics and gut microbiome drive dynamic changes in plasma metabolites ST:STUDY_TITLE [plasma] ST:STUDY_TYPE Plasma data ST:STUDY_SUMMARY C57BL/6J mice (B6) and 129S1 mice (129J) were purchased from Jackson Laboratory ST:STUDY_SUMMARY (Bar Harbor, ME) and 129S6 mice (129T) were purchased from Taconic Farms ST:STUDY_SUMMARY (Germantown, NY). Mice were maintained on normal chow containing 22% calories ST:STUDY_SUMMARY from fat, 23% from protein and 55% from carbohydrates (Mouse Diet 9F 5020, ST:STUDY_SUMMARY PharmaServ, Framingham, MA) or a high fat diet (Open Source Diet, D12492, ST:STUDY_SUMMARY Research Diets, New Brunswick, NJ) containing 60% calories from fat, 20% from ST:STUDY_SUMMARY protein and 20% from carbohydrates. For antibiotic treatment, 6-week old mice ST:STUDY_SUMMARY were treated with either placebo, vancomycin (1g/L) or metronidazole (1g/L) ST:STUDY_SUMMARY (Sigma-Aldrich, St. Louis, MO) in drinking water then started on HFD from age 7 ST:STUDY_SUMMARY to 11 weeks. The mice were fasted for 2 hours and anesthetized with isoflurane ST:STUDY_SUMMARY before collecting cecum and plasma. ST:INSTITUTE Broad Institute of MIT and Harvard ST:LAST_NAME Avila ST:FIRST_NAME Julian ST:ADDRESS 415 Main Street ST:EMAIL jravilap@broadinstitute.org ST:PHONE 617-714-8264 ST:NUM_GROUPS 12 ST:TOTAL_SUBJECTS 47 #SUBJECT SU:SUBJECT_TYPE Animal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS - 1_Chow_B6Jax Diet:Chow | Treatment:none | Strain:B6Jax Sample #=1; Run order=0005 SUBJECT_SAMPLE_FACTORS - 2_Chow_B6Jax Diet:Chow | Treatment:none | Strain:B6Jax Sample #=2; Run order=0007 SUBJECT_SAMPLE_FACTORS - 3_Chow_B6Jax Diet:Chow | Treatment:none | Strain:B6Jax Sample #=3; Run order=0004 SUBJECT_SAMPLE_FACTORS - 5_HFD Placebo_B6Jax Diet:HFD | Treatment:placebo | Strain:B6Jax Sample #=5; Run order=0006 SUBJECT_SAMPLE_FACTORS - 6_HFD Placebo_B6Jax Diet:HFD | Treatment:placebo | Strain:B6Jax Sample #=6; Run order=0009 SUBJECT_SAMPLE_FACTORS - 7_HFD Placebo_B6Jax Diet:HFD | Treatment:placebo | Strain:B6Jax Sample #=7; Run order=0013 SUBJECT_SAMPLE_FACTORS - 8_HFD Placebo_B6Jax Diet:HFD | Treatment:placebo | Strain:B6Jax Sample #=8; Run order=0011 SUBJECT_SAMPLE_FACTORS - 9_HFD Vancomycin_B6Jax Diet:HFD | Treatment:vancomycin | Strain:B6Jax Sample #=9; Run order=0008 SUBJECT_SAMPLE_FACTORS - 10_HFD Vancomycin_B6Jax Diet:HFD | Treatment:vancomycin | Strain:B6Jax Sample #=10; Run order=0010 SUBJECT_SAMPLE_FACTORS - 11_HFD Vancomycin_B6Jax Diet:HFD | Treatment:vancomycin | Strain:B6Jax Sample #=11; Run order=0003 SUBJECT_SAMPLE_FACTORS - 12_HFD Vancomycin_B6Jax Diet:HFD | Treatment:vancomycin | Strain:B6Jax Sample #=12; Run order=0001 SUBJECT_SAMPLE_FACTORS - 13_HFD Metronidazole_B6Jax Diet:HFD | Treatment:metronidazole | Strain:B6Jax Sample #=13; Run order=0002 SUBJECT_SAMPLE_FACTORS - 14_HFD Metronidazole_B6Jax Diet:HFD | Treatment:metronidazole | Strain:B6Jax Sample #=14; Run order=0015 SUBJECT_SAMPLE_FACTORS - 15_HFD Metronidazole_B6Jax Diet:HFD | Treatment:metronidazole | Strain:B6Jax Sample #=15; Run order=0014 SUBJECT_SAMPLE_FACTORS - 16_HFD Metronidazole_B6Jax Diet:HFD | Treatment:metronidazole | Strain:B6Jax Sample #=16; Run order=0012 SUBJECT_SAMPLE_FACTORS - 17_Chow_129Tac Diet:Chow | Treatment:none | Strain:129Tac Sample #=17; Run order=0017 SUBJECT_SAMPLE_FACTORS - 18_Chow_129Tac Diet:Chow | Treatment:none | Strain:129Tac Sample #=18; Run order=0027 SUBJECT_SAMPLE_FACTORS - 19_Chow_129Tac Diet:Chow | Treatment:none | Strain:129Tac Sample #=19; Run order=0016 SUBJECT_SAMPLE_FACTORS - 20_Chow_129Tac Diet:Chow | Treatment:none | Strain:129Tac Sample #=20; Run order=0020 SUBJECT_SAMPLE_FACTORS - 21_HFD Placebo_129Tac Diet:HFD | Treatment:placebo | Strain:129Tac Sample #=21; Run order=0019 SUBJECT_SAMPLE_FACTORS - 22_HFD Placebo_129Tac Diet:HFD | Treatment:placebo | Strain:129Tac Sample #=22; Run order=0028 SUBJECT_SAMPLE_FACTORS - 23_HFD Placebo_129Tac Diet:HFD | Treatment:placebo | Strain:129Tac Sample #=23; Run order=0018 SUBJECT_SAMPLE_FACTORS - 24_HFD Placebo_129Tac Diet:HFD | Treatment:placebo | Strain:129Tac Sample #=24; Run order=0023 SUBJECT_SAMPLE_FACTORS - 25_HFD Vancomycin_129Tac Diet:HFD | Treatment:vancomycin | Strain:129Tac Sample #=25; Run order=0024 SUBJECT_SAMPLE_FACTORS - 26_HFD Vancomycin_129Tac Diet:HFD | Treatment:vancomycin | Strain:129Tac Sample #=26; Run order=0030 SUBJECT_SAMPLE_FACTORS - 27_HFD Vancomycin_129Tac Diet:HFD | Treatment:vancomycin | Strain:129Tac Sample #=27; Run order=0025 SUBJECT_SAMPLE_FACTORS - 28_HFD Vancomycin_129Tac Diet:HFD | Treatment:vancomycin | Strain:129Tac Sample #=28; Run order=0029 SUBJECT_SAMPLE_FACTORS - 29_HFD Metronidazole_129Tac Diet:HFD | Treatment:metronidazole | Strain:129Tac Sample #=29; Run order=0022 SUBJECT_SAMPLE_FACTORS - 30_HFD Metronidazole_129Tac Diet:HFD | Treatment:metronidazole | Strain:129Tac Sample #=30; Run order=0021 SUBJECT_SAMPLE_FACTORS - 31_HFD Metronidazole_129Tac Diet:HFD | Treatment:metronidazole | Strain:129Tac Sample #=31; Run order=0031 SUBJECT_SAMPLE_FACTORS - 32_HFD Metronidazole_129Tac Diet:HFD | Treatment:metronidazole | Strain:129Tac Sample #=32; Run order=0026 SUBJECT_SAMPLE_FACTORS - 33_Chow_129Jax Diet:Chow | Treatment:none | Strain:129Jax Sample #=33; Run order=0036 SUBJECT_SAMPLE_FACTORS - 34_Chow_129Jax Diet:Chow | Treatment:none | Strain:129Jax Sample #=34; Run order=0033 SUBJECT_SAMPLE_FACTORS - 35_Chow_129Jax Diet:Chow | Treatment:none | Strain:129Jax Sample #=35; Run order=0040 SUBJECT_SAMPLE_FACTORS - 36_Chow_129Jax Diet:Chow | Treatment:none | Strain:129Jax Sample #=36; Run order=0042 SUBJECT_SAMPLE_FACTORS - 37_HFD Placebo_129Jax Diet:HFD | Treatment:placebo | Strain:129Jax Sample #=37; Run order=0038 SUBJECT_SAMPLE_FACTORS - 38_HFD Placebo_129Jax Diet:HFD | Treatment:placebo | Strain:129Jax Sample #=38; Run order=0034 SUBJECT_SAMPLE_FACTORS - 39_HFD Placebo_129Jax Diet:HFD | Treatment:placebo | Strain:129Jax Sample #=39; Run order=0041 SUBJECT_SAMPLE_FACTORS - 40_HFD Placebo_129Jax Diet:HFD | Treatment:placebo | Strain:129Jax Sample #=40; Run order=0035 SUBJECT_SAMPLE_FACTORS - 41_HFD Vancomycin_129Jax Diet:HFD | Treatment:vancomycin | Strain:129Jax Sample #=41; Run order=0047 SUBJECT_SAMPLE_FACTORS - 42_HFD Vancomycin_129Jax Diet:HFD | Treatment:vancomycin | Strain:129Jax Sample #=42; Run order=0039 SUBJECT_SAMPLE_FACTORS - 43_HFD Vancomycin_129Jax Diet:HFD | Treatment:vancomycin | Strain:129Jax Sample #=43; Run order=0037 SUBJECT_SAMPLE_FACTORS - 44_HFD Vancomycin_129Jax Diet:HFD | Treatment:vancomycin | Strain:129Jax Sample #=44; Run order=0043 SUBJECT_SAMPLE_FACTORS - 45_HFD Metronidazole_129Jax Diet:HFD | Treatment:metronidazole | Strain:129Jax Sample #=45; Run order=0032 SUBJECT_SAMPLE_FACTORS - 46_HFD Metronidazole_129Jax Diet:HFD | Treatment:metronidazole | Strain:129Jax Sample #=46; Run order=0046 SUBJECT_SAMPLE_FACTORS - 47_HFD Metronidazole_129Jax Diet:HFD | Treatment:metronidazole | Strain:129Jax Sample #=47; Run order=0044 SUBJECT_SAMPLE_FACTORS - 48_HFD Metronidazole_129Jax Diet:HFD | Treatment:metronidazole | Strain:129Jax Sample #=48; Run order=0045 #COLLECTION CO:COLLECTION_SUMMARY The mice were fasted for 2 hours and anesthetized with isoflurane before CO:COLLECTION_SUMMARY collecting cecum and plasma. CO:BLOOD_SERUM_OR_PLASMA Plasma #TREATMENT TR:TREATMENT_SUMMARY Mice were maintained on normal chow containing 22% calories from fat, 23% from TR:TREATMENT_SUMMARY protein and 55% from carbohydrates (Mouse Diet 9F 5020, PharmaServ, Framingham, TR:TREATMENT_SUMMARY MA) or a high fat diet (Open Source Diet, D12492, Research Diets, New Brunswick, TR:TREATMENT_SUMMARY NJ) containing 60% calories from fat, 20% from protein and 20% from TR:TREATMENT_SUMMARY carbohydrates. For antibiotic treatment, 6-week old mice were treated with TR:TREATMENT_SUMMARY either placebo, vancomycin (1g/L) or metronidazole (1g/L) (Sigma-Aldrich, St. TR:TREATMENT_SUMMARY Louis, MO) in drinking water then started on HFD from age 7 to 11 weeks. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY HILIC-pos: LC-MS samples were prepared from plasma (10 μL) via protein SP:SAMPLEPREP_SUMMARY precipitation with the addition of nine volumes of 74.9:24.9:0.2 v/v/v SP:SAMPLEPREP_SUMMARY acetonitrile/methanol/formic acid containing stable isotope-labeled internal SP:SAMPLEPREP_SUMMARY standards (valine-d8, Isotec; and phenylalanine-d8, Cambridge Isotope SP:SAMPLEPREP_SUMMARY Laboratories; Andover, MA). The samples are centrifuged (10 min, 9,000 x g, SP:SAMPLEPREP_SUMMARY 4°C), and the supernatants were injected directly. HILIC-neg:Plasma samples SP:SAMPLEPREP_SUMMARY (30μL) were extracted using 120 μL of 80% methanol (VWR) containing 0.05 SP:SAMPLEPREP_SUMMARY ng/μL inosine-15N4, 0.05 ng/μL thymine-d4, and 0.1 ng/μL glycocholate-d4 as SP:SAMPLEPREP_SUMMARY internal standards (Cambridge Isotope Laboratories). The samples were SP:SAMPLEPREP_SUMMARY centrifuged (10 min, 9,000 x g, 4ºC) and the supernatants (10 μL) were SP:SAMPLEPREP_SUMMARY injected directly. C18-neg: Plasma samples (20 μL) were extracted using 60 μL SP:SAMPLEPREP_SUMMARY of methanol containing PGE2-d4 as an internal standard (Cayman Chemical Co.; Ann SP:SAMPLEPREP_SUMMARY Arbor, MI) and centrifuged (10 min, 9,000 x g, 4°C). C8-pos: Lipids were SP:SAMPLEPREP_SUMMARY extracted from plasma (10 μL) using 190 μL of isopropanol containing SP:SAMPLEPREP_SUMMARY 1-dodecanoyl-2-tridecanoyl-sn-glycero-3-phosphocholine as an internal standard SP:SAMPLEPREP_SUMMARY (Avanti Polar Lipids; Alabaster, AL). After centrifugation (10 min, 9,000 x g, SP:SAMPLEPREP_SUMMARY ambient temperature), supernatants (10 μL) were injected directly #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Shimadzu Nexera X2 CH:COLUMN_NAME Waters Atlantis HILIC (150 x 2 mm) CH:SOLVENT_A 10 mM ammonium formate and 0.1% formic acid in water CH:SOLVENT_B acetonitrile with 0.1% formic acid #ANALYSIS AN:ANALYSIS_TYPE MS AN:OPERATOR_NAME Courtney Dennis #MS MS:MS_COMMENTS - MS:INSTRUMENT_NAME Thermo Q Exactive Plus Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_RESULTS_FILE ST000879_AN001429_Results.txt UNITS:Peak area #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak area MS_METABOLITE_DATA_START Samples 1_Chow_B6Jax 2_Chow_B6Jax 3_Chow_B6Jax 5_HFD Placebo_B6Jax 6_HFD Placebo_B6Jax 7_HFD Placebo_B6Jax 8_HFD Placebo_B6Jax 9_HFD Vancomycin_B6Jax 10_HFD Vancomycin_B6Jax 11_HFD Vancomycin_B6Jax 12_HFD Vancomycin_B6Jax 13_HFD Metronidazole_B6Jax 14_HFD Metronidazole_B6Jax 15_HFD Metronidazole_B6Jax 16_HFD Metronidazole_B6Jax 17_Chow_129Tac 18_Chow_129Tac 19_Chow_129Tac 20_Chow_129Tac 21_HFD Placebo_129Tac 22_HFD Placebo_129Tac 23_HFD Placebo_129Tac 24_HFD Placebo_129Tac 25_HFD Vancomycin_129Tac 26_HFD Vancomycin_129Tac 27_HFD Vancomycin_129Tac 28_HFD Vancomycin_129Tac 29_HFD Metronidazole_129Tac 30_HFD Metronidazole_129Tac 31_HFD Metronidazole_129Tac 32_HFD Metronidazole_129Tac 33_Chow_129Jax 34_Chow_129Jax 35_Chow_129Jax 36_Chow_129Jax 37_HFD Placebo_129Jax 38_HFD Placebo_129Jax 39_HFD Placebo_129Jax 40_HFD Placebo_129Jax 41_HFD Vancomycin_129Jax 42_HFD Vancomycin_129Jax 43_HFD Vancomycin_129Jax 44_HFD Vancomycin_129Jax 45_HFD Metronidazole_129Jax 46_HFD Metronidazole_129Jax 47_HFD Metronidazole_129Jax 48_HFD Metronidazole_129Jax Factors Diet:Chow | Treatment:none | Strain:B6Jax Diet:Chow | Treatment:none | Strain:B6Jax Diet:Chow | Treatment:none | Strain:B6Jax Diet:HFD | Treatment:placebo | Strain:B6Jax Diet:HFD | Treatment:placebo | Strain:B6Jax Diet:HFD | Treatment:placebo | Strain:B6Jax Diet:HFD | Treatment:placebo | Strain:B6Jax Diet:HFD | Treatment:vancomycin | Strain:B6Jax Diet:HFD | Treatment:vancomycin | Strain:B6Jax Diet:HFD | Treatment:vancomycin | Strain:B6Jax Diet:HFD | Treatment:vancomycin | Strain:B6Jax Diet:HFD | Treatment:metronidazole | Strain:B6Jax Diet:HFD | Treatment:metronidazole | Strain:B6Jax Diet:HFD | Treatment:metronidazole | Strain:B6Jax Diet:HFD | Treatment:metronidazole | Strain:B6Jax Diet:Chow | Treatment:none | Strain:129Tac Diet:Chow | Treatment:none | Strain:129Tac Diet:Chow | Treatment:none | Strain:129Tac Diet:Chow | Treatment:none | Strain:129Tac Diet:HFD | Treatment:placebo | Strain:129Tac Diet:HFD | Treatment:placebo | Strain:129Tac Diet:HFD | Treatment:placebo | Strain:129Tac Diet:HFD | Treatment:placebo | Strain:129Tac Diet:HFD | Treatment:vancomycin | Strain:129Tac Diet:HFD | Treatment:vancomycin | Strain:129Tac Diet:HFD | Treatment:vancomycin | Strain:129Tac Diet:HFD | Treatment:vancomycin | Strain:129Tac Diet:HFD | Treatment:metronidazole | Strain:129Tac Diet:HFD | Treatment:metronidazole | Strain:129Tac Diet:HFD | Treatment:metronidazole | Strain:129Tac Diet:HFD | Treatment:metronidazole | Strain:129Tac Diet:Chow | Treatment:none | Strain:129Jax Diet:Chow | Treatment:none | Strain:129Jax Diet:Chow | Treatment:none | Strain:129Jax Diet:Chow | Treatment:none | Strain:129Jax Diet:HFD | Treatment:placebo | Strain:129Jax Diet:HFD | Treatment:placebo | Strain:129Jax Diet:HFD | Treatment:placebo | Strain:129Jax Diet:HFD | Treatment:placebo | Strain:129Jax Diet:HFD | Treatment:vancomycin | Strain:129Jax Diet:HFD | Treatment:vancomycin | Strain:129Jax Diet:HFD | Treatment:vancomycin | Strain:129Jax Diet:HFD | Treatment:vancomycin | Strain:129Jax Diet:HFD | Treatment:metronidazole | Strain:129Jax Diet:HFD | Treatment:metronidazole | Strain:129Jax Diet:HFD | Treatment:metronidazole | Strain:129Jax Diet:HFD | Treatment:metronidazole | Strain:129Jax phenylalanine-d8 332179 357260 365682 364645 356414 370034 380561 351104 348761 349588 356471 359398 343917 366105 366870 384868 349827 340742 357552 373301 335957 346969 317971 284013 334142 371221 317737 358391 371656 343743 354958 368661 347636 350889 354737 358332 355179 373989 333498 318833 328130 339158 374583 328053 324028 337205 valine-d8 100861 100162 102878 97912 102188 105445 102219 92750 107306 103485 101894 100458 105873 106174 100783 111059 107059 104212 112041 105331 105208 112710 105534 109960 106715 103129 107475 116082 110806 108518 90972 103899 106992 102518 109308 113535 103741 104944 104687 100812 106028 107276 104809 103350 108630 114723 1-Methylhistamine 4346461 6769855 12079768 18299246 6809496 8380261 37272954 12663559 16909410 10832515 10586470 18578922 9861551 68886176 82045660 8461293 1995766 4522560 4895448 6247754 13826196 6692330 6330854 5555823 3077347 11912280 3097295 16404627 11773322 3663336 35260896 22896634 4009981 8177885 4448942 6804849 136550783 82689917 5252388 56388498 13175863 4698004 44938524 19561500 6630893 5180862 1-methyl nicotinamide 12350725 30494446 19096651 8781298 26983440 13137956 5782487 7036066 28753292 11353046 7846817 11313366 15064835 43224188 53912373 27522922 19126061 22165992 23097476 7449194 5264004 10873716 12828045 12188807 2392706 8630750 12997830 19756139 16659840 18766477 15577224 44224314 15162090 16377867 12956753 21658414 36298578 36500537 14222001 34972491 25779812 38528355 26064964 41268803 17708641 33083812 Deoxycytidine 2118752 1516026 2347897 1999761 2374455 2777259 2815630 2390578 2447885 2499393 3746713 1798554 1944353 2674476 2976970 2450366 1467391 1320386 1460253 2609474 3151528 3067379 2582963 3159818 2505892 2853514 2013565 5042291 3280305 2616025 2031641 4123041 1358651 2480253 2789269 3714058 7293102 6395680 2616443 3202010 1779303 2727279 4336800 5062464 2626515 2496352 3-Hydroxyanthranilic acid 55541 121291 70607 489534 220590 69362 43998 54577 47464 130901 229073 155910 529479 151069 193781 400622 508319 267575 574892 315809 323803 S-Adenosylhomocysteine 395396 2098408 754824 964820 208061 416681 402406 1077164 421314 42462 559994 809820 131230 2059791 1910826 3041525 2974371 256711 2733298 66940 2668656 2733665 667511 2085148 1463822 1448715 1494097 1048020 1555438 100225 619215 665547 77182 50768 551410 31401 783326 37235 2171212 1473700 2788068 5-amino-levulinic acid 32103122 29340756 23119456 14246284 30373377 16242718 25598194 19095440 21080510 31613934 64729089 19448497 24722222 14321483 18334252 23575227 21644330 27948208 32604934 10462240 12242785 11686777 9830010 12093725 21838292 11447541 14936922 23030023 21946897 14241567 13639964 18442106 19998923 19564232 9480750 14830538 7164994 8318024 7900574 9150785 7685167 8617280 8305178 11080686 7666110 10258837 5-Hydroxy-L-tryptophan 467777 1338580 10509235 10253919 915897 405429 31156975 5138574 17543993 724233 8337392 9307488 4277051 70616626 82077290 216593 787802 1353876 2052349 4006624 12479566 2539288 1235513 731668 50354 16772202 454824 176281 119875 1359173 38214815 32789342 1141699 7123695 1231459 766630 21127485 19188598 1817275 45293172 3224624 351857 33835402 12016988 2599634 119581 Acetylcholine 237029874 320205434 227295069 97373782 98307476 100704197 178513355 87664961 132544248 109490731 115932308 93885629 108960644 125049181 159283532 299024619 286533788 317558902 391194775 124765818 151079135 180069961 155508418 130961779 133895577 140063927 134750023 164008331 152944370 131982721 290778969 367321488 366110606 403459092 161636877 166625699 186775093 165569072 104904442 154938208 130576701 108237127 189857943 193915745 127723441 135644871 N-acetylglycine 269934 898655 153764 169364 763491 610862 713717 516057 1010986 849526 987029 237587 598527 282142 640322 129083 307831 166598 189774 77874 170205 202409 79894 70958 206101 143198 75424 162524 133357 96733 103953 286813 124109 238247 305503 47020 131530 103948 79991 140400 210266 38557 177134 301397 Adenosine 4115741 8483509 5332873 2084330 2295747 2677111 11235402 1651684 24940349 10508656 820497 2532596 4553039 26081422 39463577 3241310 1773944 2183380 2494028 693428 7578833 13195989 16907916 11564538 3791371 6054827 3029396 3464833 2212758 4218355 3567952 14913297 2307590 29033629 1449509 2041976 15568729 12654289 790151 8513451 5963088 4648755 16968835 18356504 2409774 2673018 Dimethylarginine 94324980 87819592 73414299 60377147 110417410 92082484 89166392 66813710 99208723 85732548 82798168 68723796 102118082 76592128 78330468 99914257 69377717 92650980 96316637 73821257 74882313 85185858 90512212 93297191 102106569 83645018 98712397 135237306 88637196 107242974 59649458 113767231 79834258 100795365 92406960 105959460 63376485 75825577 76818067 80604679 72107194 86801733 80288185 117937944 79926252 88201367 Alanine 73563321 74875196 46532397 52209582 196909938 60450151 77995965 49598295 70059697 54666908 86126616 69363555 88439229 89987438 84186191 80578446 71239186 101358299 109504428 67367784 109458947 102796854 94079055 164072119 129694061 112294145 104045070 225769498 102734489 90996064 57318413 107065550 78537372 87073517 62810145 124114510 107103977 88315913 68988215 106007512 76776754 76826657 105153631 144414051 71533812 83423602 Allantoin 1732329 1491264 1333245 1011974 2529110 1344041 1565195 1191339 1340407 1280054 1403625 888494 1213462 986178 1202681 1619542 1356768 1476896 1395627 984990 771853 1146649 1181828 872700 1128748 968090 1203722 2347872 2121526 1050717 1367244 1140950 1145062 1417601 1696843 1321185 818455 805416 1570023 919778 754562 1001598 1188532 684974 1006774 1010214 sn-glycero-3-phosphocholine 178006109 175077719 220620854 204755211 141298853 220428288 451304115 229394775 166252838 152424513 146485221 216920920 182552161 803467911 923766908 267602404 252297190 255973883 284629736 366738036 1216821605 377896430 507000057 469117930 269353241 448299616 241371271 318409595 215217429 253743521 674125542 495036515 231192727 442150220 398551596 257623002 2461557971 1822652892 364625435 1075856494 1160896862 434706333 1575610390 441995890 452866227 653805248 Aminoisobutyric acid 1444263 1772805 1332398 1347675 2066575 1265585 1935615 1315872 1336738 1069907 1748318 1784312 1907355 4090421 2297853 1540915 14038 11814 2354538 1859356 1901922 14779 1588046 71814 91553 11132 1732648 2565856 2731081 27777 11723 47440 25346 20226 13642 1903580 2114890 1883269 14241 104323 96532 2422701 52467 1853181 14682 2326235 Anserine 1869907 1887969 1992217 1809935 2408792 2087401 3090299 2063990 2309886 1827522 1621291 1738340 2202267 3789188 4388601 767864 807099 731647 723798 562863 659396 964271 748135 722339 1163858 1815055 802292 5043670 4150317 869783 1081773 3646008 598785 850903 883528 949611 3279348 4067872 732096 2752259 640144 793768 3656110 1826095 664965 1083071 2-Aminobenzoic acid 233375 230908 278117 334912 438461 314675 367933 68703 48263 149068 259330 371429 219745 441644 794690 367449 209825 182161 396019 361549 744448 595711 461424 477867 538902 348796 359046 547112 565310 455464 465782 560435 264712 410644 410065 628057 1046530 493994 328854 705412 909523 280557 1089643 744587 486658 485433 Arginine 7112371 4311176 3480123 2726960 5281788 4095887 225435 2712559 4828772 2863045 1960567 2900713 5754662 135647 67366 5452993 3122091 6010911 5997056 3720065 92268 3774606 1436440 6582399 6624783 3451324 5847924 7453810 4139659 5527288 67606 4620633 3181816 240787 4230137 5898619 72391 119358 3465995 204192 46496 3636009 113442 3859894 3974041 5381027 Asparagine 10691243 7043886 3856700 4332750 20216962 8404037 7715923 4895087 15916310 10795338 13644395 7965325 16578094 8181946 7184957 7462005 6758029 11105196 12371001 6548978 11541854 12486463 14420820 22718686 18754408 8362163 16534053 21555933 9462338 14573091 3343436 9747409 8642326 8037118 9905299 14617506 7354018 6305035 7715073 8549945 9384185 9285689 7362158 12879194 8450227 15040324 Betaine 31984693 39093009 29895469 16570908 34129243 20313453 17650083 19268592 24750884 19846746 25647459 19611672 24439800 18826956 28106563 35026600 32929738 37010660 40766068 13127723 17649367 20481103 26446407 17696317 13967001 17100353 22063593 28177984 22412051 18044771 19899377 30393496 27247378 32666998 17178144 27307727 19620430 21302756 17861501 24016914 18294411 18092762 19886495 35312472 18707212 21584883 Carnitine 47996447 35784913 34039215 21103253 19429265 20169784 28683316 18626385 24049403 21223140 18172652 20498923 26433876 28399807 26922762 51772325 53456392 50891302 59800920 28577837 39032919 34691393 31830936 36940726 32261802 29810502 32146027 32157334 27890988 27259035 36705286 46586043 45156494 47036941 22948588 22785334 38483565 31166797 22037283 32638282 28675116 13421316 36180319 33114178 21503245 22150528 CAR(2:0) 75432982 85784346 65482437 33479910 25491345 35482675 42146299 29400458 37501067 39407464 27495500 29473514 32548297 36414329 36166163 76699613 85789070 71074058 90123119 35800688 41396284 51467679 41320902 42045087 35188725 35802554 42762009 46359271 35578870 35291424 61749873 84565560 72052894 67898767 50135705 51418830 51012139 46450391 34259608 51207342 36318571 42239028 46552026 40722018 45270555 41505831 CAR(3:0) 4057200 2325079 2117540 1444507 445600 973791 1985856 754403 1315233 1103290 570035 1226162 1578818 2143223 2430637 5878941 4394825 5555941 6099175 2168925 3776654 4152419 2294106 4469887 4524363 1907142 2192787 5168998 2851729 1755599 3799889 2860284 4144605 3149730 1512085 1495813 3110096 1275410 1808280 2489183 3195979 1221117 3455570 2840359 2738573 1817995 CAR(DC3:0) 181841 214015 242906 131651 146483 124939 221969 100936 95736 142433 165150 127076 154548 337353 319434 213800 210057 154593 207843 100828 283997 232028 173799 144201 124909 399154 115835 415253 201840 172905 531693 1265985 179481 331904 153683 260308 1022362 894866 106599 728166 229346 141310 780515 454951 154471 169955 C3-DC-CH3 carnitine 36378 33832 55828 55674 26245 30445 94496 33549 39519 38617 29230 43427 37897 219381 127449 66748 32733 35157 55819 33029 103264 117268 57205 60148 40056 299274 28418 102705 52095 44594 215952 669645 39492 79004 30150 83832 728896 620676 25074 728763 57414 55766 495214 273649 59861 50143 CAR(4:0) 13097525 8431539 5295394 2568762 1135525 3395745 2728372 1845182 2778173 2429291 483257 2454848 3208664 3307403 2636894 8709207 7758290 10776349 24815811 2161517 3201097 2877551 1938569 5047811 2924869 2018239 2852357 2720441 2751034 3615148 8639398 4971831 7507808 6646950 3096205 1479780 3114102 1945322 1840354 2201714 2215964 1652518 3075474 2753487 3498444 2294013 CAR(4:0(OH)) 726215 1983202 895525 580640 326536 606746 805853 407600 593905 593835 353331 439215 488491 1159515 848144 795503 817843 545168 782514 398610 542575 715318 521180 525565 509590 912112 487958 716104 458008 506918 1005482 2563279 784377 855686 726657 1211464 1806811 1772643 410227 1724660 711628 1477253 1518014 1653025 917211 1076344 CAR(5:0) 418275 278597 288079 150899 83400 118233 206904 100888 121444 120515 65132 138317 178768 230741 232005 1159253 648736 1136348 1489188 507709 828954 469117 418772 985805 884616 528409 637585 1079340 716588 602137 722739 679744 690060 680622 316315 311671 644511 391253 325775 476261 483134 464430 614833 494981 428891 277359 CAR(5:1) 671654 554627 641012 588687 371304 467043 771777 354066 444892 318805 357645 300895 391362 540272 342257 1096752 802510 1138263 1213362 802684 1004397 822622 542213 1042680 1361516 984152 895734 1889691 1178638 730525 1600943 1633000 1065369 810196 637684 870083 1468313 1095092 668827 1313636 804520 905105 1248908 704575 851841 502807 CAR(6:0) 1226216 1068548 494685 276999 103845 342564 310920 195352 275643 285745 102842 230648 267052 353436 247385 540430 596421 699022 2636338 155991 174837 177596 123749 237656 163479 157605 151833 118718 170331 224226 853253 436082 518562 601373 244569 159055 211500 172322 131443 167813 143331 219061 224676 183365 234324 161228 CAR(7:0) 26542 30716 10063 4936 3507 5168 234 3897 3228 3558 4663 9695 6863 18861 17553 19542 65966 3540 4100 505 20816 2017 1011 1672 2753 393 7814 15236 13398 11100 16156 1766 4272 184 1388 768 382 8013 5577 2661 1760 CAR(9:0) 179567 225102 111550 59219 2311 56442 68559 8837 20699 24439 2464 20343 22593 128364 53205 147612 135560 125522 334373 17669 7881 35516 5804 33947 33499 12680 9191 10213 13817 23557 208351 182845 95064 97617 33321 11032 51524 23339 9018 28807 6870 23514 58352 42980 20873 38086 CAR(10:0) 27931 66225 51105 33779 12566 37325 43640 30330 27838 34245 15938 22751 18809 38282 23361 30710 32826 13011 28947 18928 16117 28806 14724 8647 22178 17953 12630 12229 22793 16513 42068 63054 30794 19372 26496 19734 20998 18678 12186 31935 16281 37128 31836 47444 33140 32028 CAR(10:2) 127815 238102 355884 187502 79031 172544 217510 167338 141119 201575 106667 128128 178058 129656 101567 276943 231095 129926 187678 243391 232874 203516 190545 137050 236072 140461 160713 130062 198085 228706 295314 334225 232393 153569 213996 97313 202115 192842 150699 225883 201405 188437 219442 139522 238037 352617 CAR(12:0) 43984 80743 131681 53730 30524 65454 70274 55648 60337 62671 42863 39961 39951 47654 32700 72527 71435 27329 37121 49187 36564 61558 40993 21934 48896 36078 38083 36216 50662 44151 74691 157673 67389 41888 73140 59800 40537 54210 45370 70255 37118 129264 63885 71690 93898 111925 CAR(12:1) 22839 47491 68574 27044 18177 36161 41553 32132 32919 35312 21338 20155 21807 26890 15115 33315 33542 10805 13068 22676 13112 26372 17672 6983 21395 13880 13854 14380 25365 15776 33737 99725 33001 13986 33276 26729 11581 18402 18978 26831 12150 56533 25468 36889 45756 64211 CAR(14:0) 106939 175481 229197 128213 93115 150131 157922 141729 145208 139218 142586 102520 107844 115870 84951 162763 148769 62505 71385 92364 71926 111128 84971 47084 91279 85031 81452 75368 99805 96604 163509 272627 145003 101937 148484 162658 95872 126577 100643 168337 84969 294487 143218 146758 188923 212643 CAR(14:1) 4035289 7434426 11303694 5102981 3259452 6452468 7531385 5765916 5678651 6716652 4442468 4087708 4080865 4737860 3137416 7183354 6734485 2152649 2555768 5163303 3633927 5683028 4125702 1752016 5009759 3430412 3528649 3390269 5875912 3993539 6280428 12409070 5702232 3071486 6530478 5902411 3290979 4409682 4628713 5385671 3087301 11643501 5597834 5698156 8907274 10023028 CAR(14:2) 1741133 3291817 5804931 2622490 1346838 3031628 4319123 3095552 2898222 3561421 2424850 1967836 2012856 2212664 1632980 2873753 2670578 1058514 1209322 2297333 1605949 2326672 1710983 1030770 2410333 1442744 1655332 1634207 2540704 1892630 2526912 5902266 2424013 1218556 2923611 2415542 1209522 1628026 2069234 2384740 1566561 4441000 2444792 2445147 3575662 5862958 CAR(16:0) 174729 351081 424564 302154 250373 327420 378445 357612 326568 337735 438415 306550 269652 252306 268168 229599 202580 116141 91267 174287 129121 178617 157373 60159 152567 203710 145658 111464 175198 180821 248144 377457 195063 178773 207605 298841 185721 251604 155203 249300 149044 453195 240439 280501 231072 309000 CAR(16:0(OH)) 3212 12055 7610 7021 8976 8698 10923 6696 7928 6079 8949 5523 8813 7699 6315 6690 5434 2601 1519 3724 5345 5884 3557 733 3494 5273 3821 3320 3481 3927 9982 20265 5861 4765 6925 12427 9681 11554 3599 15460 4996 16746 9114 11654 9744 12181 CAR(18:0) 53189 88966 126142 111236 95281 137333 198176 102208 109201 122491 165104 97788 115498 108856 140314 58003 69496 57723 56251 114864 108942 129343 145911 109178 132792 125063 149849 114254 117516 153070 72742 118958 67055 64031 128841 170080 124192 151454 106350 163278 134234 204513 145977 167315 146519 198277 CAR(18:1) 191771 455179 478289 377531 265484 422360 452737 436962 401750 421892 437610 308342 311966 322454 312114 228147 217048 82220 85579 207132 162191 294881 257920 119794 238033 215441 233259 175988 250126 280490 214337 427132 210373 134935 333021 436022 236263 305561 226781 341652 215394 613099 313186 462830 437410 463015 CAR(18:1(OH)) 269043 762192 688370 538182 588941 581791 950966 563507 559272 507575 659403 469209 455482 599617 415809 469585 377020 118561 75172 278729 338346 657403 312856 117250 312323 426423 286325 325367 387601 346700 514813 1052629 357652 204774 518110 1010909 705381 957580 333433 897465 350949 1262146 770997 899724 794497 821340 CAR(18:2) 43129 146321 160942 124065 76105 124450 143116 141972 97979 120596 147281 101882 76618 104073 85754 64456 80064 21086 21655 56000 42441 79911 52886 12987 75299 67628 50405 43435 92438 68133 87852 167620 56686 34755 91131 118681 45799 92307 63005 92395 41032 218870 99479 167922 118859 133269 CAR(20:4) 21009 26089 5923 7522 6534 10085 4894 7640 20225 535406 16850 5753 29239 17206 5942 27435 129253 5406 5409 113261 6046 4843 48968 366283 3927 354746 74234 499903 5366 6294 115208 105874 6004 Carnosine 388183 283884 323142 251704 363997 353432 460120 280175 473778 341939 245590 261564 516731 536296 654366 108595 121222 128761 96836 63440 73556 124037 130901 145644 198687 175034 103127 868120 719665 120523 78811 399704 59003 78594 126633 133016 322033 313701 68828 310487 71022 77617 330275 268517 106395 203631 Choline 8045391 22652844 12858590 9302635 14195219 11373226 13154293 10554074 16895033 11419793 8628452 10646124 15103102 15244977 20791048 10651710 14108857 10461870 14407165 8068525 13194768 21431635 22904725 8960208 12159563 12188294 17648305 12883752 11018413 12190121 9335299 19638596 12746193 16507055 12681610 18117611 20498375 18343485 10296777 20958050 13242726 15481227 26206247 28355677 13433451 20796141 Citrulline 908210 539852 271431 188721 995917 591457 415685 239815 1078565 467969 205181 266432 1079360 599071 382923 668550 288428 754418 836777 304250 458237 367846 704433 1105831 715755 253404 794644 1174289 430291 894537 201498 469307 322072 427035 438197 786337 342021 265815 293829 349965 449842 438095 376963 542487 388004 544941 Cotinine 42704 16286 41427 40782 32996 29875 69117 29904 22267 40672 25232 32841 37045 30137 26978 103363 89883 34603 52948 46043 43234 42227 24991 66543 53491 79230 65139 21904 32111 60287 60213 53616 211950 56685 23876 39181 48739 57362 39694 63778 43960 60473 42850 35732 44720 40856 Creatine 15819751 13555593 12180498 7929570 18673181 14230978 18986439 8133651 16286476 12652930 7813720 9739593 17260986 25101918 17855911 13957985 8428810 12051379 16074501 8194897 12267016 12334196 14598334 19501761 16169223 18970519 16134459 23756157 13208537 14451952 14703457 32079795 9566019 12847696 7481578 14215609 28881095 27169368 7002720 25543147 8089982 9779773 22333205 18924827 7590858 10603011 Creatinine 1179003 1028363 1119144 899783 1134364 881563 1162729 935855 826221 897128 867987 800357 888650 1044476 1087650 1170707 1004423 1134941 1204853 679324 623672 843382 653789 560979 932414 777216 702793 1177832 1246182 877015 1176128 1772144 1105129 1261928 888031 1203032 1519953 1103454 921565 1079154 658674 822856 1288445 1407031 853026 857087 Cytosine 27269126 20658231 29145830 24378348 29072052 29992065 32073026 30794846 28853988 28290660 46947901 21315848 24960936 31945172 35548309 28329305 20039278 17415100 19706363 27733805 40959098 34753646 29783171 33457135 31111848 36410041 26118522 51070657 36118877 32520998 27054318 49666544 17923169 32411425 35507791 43448592 77642679 70293051 30030810 38760074 23609762 32591347 48246201 53014791 29845117 27959189 Dimethylglycine 154892962 142250443 107708449 40677031 127946661 85835087 70307207 58797583 129738287 70748699 39606389 43071028 126494126 73821980 119226184 232135285 185982550 253556918 321148401 79919033 126327743 126191084 186339424 145839065 114853445 103286343 218175678 175384215 174819816 179754586 96706838 160562004 132988188 208080245 88427532 169641222 88081868 102814399 108053266 95377149 90331786 132055104 104015562 162815497 88718211 136614068 Gamma-Aminobutyric acid 408901 574607 463689 294776 206821 358001 544552 294063 350066 283376 334261 181163 342188 2861650 1084656 1026843 876756 1093637 1161232 1314620 1042631 829469 862782 1200924 1508881 863942 831682 1180140 1189778 871096 1179658 1190774 1103247 1037394 1128465 829794 1625636 1265649 973942 1189845 1305143 865576 1223130 892167 970120 1105486 Glucose 2939489 2983765 1377043 877703 3372722 2552400 3902326 903709 4407884 1970785 1000576 1464686 4101658 2709090 2276935 1752285 2169049 1960373 3553380 952381 1539613 4056820 3491541 4891543 2120314 628862 3888543 2643228 1344721 2430588 411771 531344 3070470 2552751 3225812 4247840 729729 703274 1936271 1425209 1588954 369454 1253735 1410293 2928781 812988 Glutamic acid 77576 32373 32164 26270 23947 21622 93843 20005 39634 40820 40013 27877 44329 141205 114889 36945 42698 74182 60811 23404 177812 57816 76921 93129 105673 93207 54800 87277 42739 46646 93734 189643 57416 81963 42492 110916 200982 184131 51212 215517 120911 50486 170172 109894 52598 60526 Glutamine 5523626 4576951 2531683 1560277 5306405 2531375 2298517 1734616 4560887 6185542 4022252 2770724 4465097 2931553 3289191 2222179 2766376 2828381 3389042 1247120 2553628 2572442 3559377 3589688 3025092 2027820 3166254 4057637 1919741 2425739 1246255 3911709 2693021 3112032 2342595 3285752 2314599 2221104 2016112 2928890 2523500 2571266 2723634 3485550 2204398 3125189 Glycine 27379 23648 14563 9053 29208 18848 17366 11993 35257 25170 23448 12126 26718 20429 26020 21384 24915 23278 32276 10694 14151 21906 23676 21858 20087 16659 21377 22672 15611 16774 9891 24101 22660 21540 17173 25095 19476 18317 13674 19202 14783 15332 16184 31810 11444 24814 Histamine 3832771 6473275 52352667 39471168 1614583 8417295 22228204 12524859 7094791 32847813 2006153 14202149 23398819 33705803 27887722 14945647 1787418 1617024 1778988 1249092 3647575 65444167 18633132 2638822 2938711 29625263 925036 4106041 1098766 1204661 41191654 150420852 1838160 15617090 1078891 36673002 70395208 122009727 2989133 62235207 2606917 20190277 33282859 150017250 5241305 5306934 Histidine 1304825 815044 478896 459558 1309899 664286 700537 442069 1320850 806709 508176 558127 1073862 770521 710529 669484 556556 1018644 1146557 505039 994540 664219 1451867 1485394 1106585 606359 1219514 1255588 602711 934234 385383 887254 453590 999835 652786 1236438 609645 638461 480034 861014 993971 905274 872063 1133159 741577 1150500 Isoleucine 1102008 1155754 1159337 1148159 1577694 1085637 1071720 1027605 1118515 965868 1099553 1371512 1246412 1370574 1368237 1236700 844464 1173746 1260696 1220053 1504589 1578922 1485322 2467257 1811706 1775407 1587910 2021370 1546617 2048124 875898 1176539 1033441 1072776 1022359 1891323 1346276 1221706 1227077 1770630 1742993 1877617 1667167 1676763 1306358 1638873 Kynurenic acid 84717 73934 98743 53522 185278 94145 69645 54896 104454 64577 72143 52095 86996 69481 138643 182309 82117 102520 111514 57426 90175 129421 100513 201529 142349 80467 141010 432695 162981 201847 83222 143290 139766 178021 70626 142569 66358 35400 110954 121447 70320 60646 116895 118117 93419 93480 Leucine 1654039 1907737 1476884 1557011 2477762 1593562 1441828 1371064 1668999 1329392 1506919 1923642 1889863 2210861 2142231 2152953 1542862 2303055 2564383 1966811 2635176 2846023 2546361 3986136 3085874 2762888 2934171 3445643 2811578 3481790 1617164 2141398 1958382 2032488 1718708 3210465 2241164 2191191 2017938 3056244 2980837 3213578 2782069 3171079 2260830 2850131 Lysine 1864060 957833 649464 744654 2306312 1624560 1630650 821392 2562349 1447671 550686 925114 3092701 1544861 1143026 1139149 615107 1708020 1840250 1346235 2324334 1898137 3040940 5200643 3761612 1206276 3469716 4144116 1484142 2925278 336935 1159343 827195 1308004 1491346 2462244 1079849 969422 1116458 1492630 1937963 1594129 1244989 2004133 1583116 1962156 Methionine 595212 412516 497243 457389 691400 486608 589039 424369 360416 389818 365005 621558 556906 494149 393997 723431 510895 1963546 1081192 773474 776067 680009 583540 925165 1023606 680932 722402 1179649 947901 727006 621427 536714 650785 606009 505283 610180 465383 426055 540248 529937 589790 487034 571757 546631 573701 502334 Methionine sulfoxide 13980595 9097230 5670469 4755267 13785141 9756772 13422593 6165676 12456608 6365369 2247375 5531373 15581414 14539280 9049425 20056310 4796920 32073553 39280172 8080932 8212818 7018698 17204053 37307354 23285818 4705023 16352729 32630534 5414760 17661069 4115541 29584410 8571263 34705524 7534113 28568766 13124429 12704588 3489161 14080200 21089398 19180712 12021334 27074156 18927358 16418776 Ureidopropionic acid 856572 1025519 1872964 1301940 2335161 1497564 1643800 1088981 1853719 1215178 1372728 1243055 1756253 1658718 2697224 576493 523027 597850 871008 334943 960128 1335436 1556036 1156994 1233932 569975 1281004 1724139 1310192 1016638 435992 655601 399992 712740 451441 1623043 872627 673875 490534 1220299 798676 932144 1568149 2134465 813447 1137507 Niacinamide 1054866 1894007 2197508 1433367 1647649 744711 3317403 953676 1666919 1104797 1631068 1524350 1039413 5568994 7366610 2479154 2001480 2303973 2705569 885328 6288747 2855496 3152147 1624706 773974 3355040 1370264 2748562 1537736 1930863 5296721 6111553 1558405 3537431 1082080 3570551 16640518 13017037 1291351 8620304 6171801 3998598 8613042 6871623 1998514 2599947 NMMA 230774 144870 117290 70407 131352 109033 106098 79868 131523 119639 112503 102504 135741 94388 91344 191585 156257 288590 307903 96386 115032 124442 125984 136258 146435 103501 139868 175011 140084 127752 88181 152575 150952 193141 117291 120526 71334 74610 87366 92492 90044 99226 85137 128025 87349 101174 Ornithine 31030459 8369311 4543592 2545912 13288867 9079237 20166076 2955925 29892797 13352864 2804657 4068666 21757793 23727569 17808919 12652980 6292865 24264417 31614431 5033601 33877103 11454168 48937357 45895854 19350075 6213729 25425365 22050009 5301165 16598649 8188159 18759879 7290599 35149414 10272263 24077521 19959629 17658110 6356349 26712494 34094811 14295157 20719968 30686957 8653107 15638108 Phenylalanine 2018506 2115581 1893580 1887772 2280892 1994503 1917224 1711971 1748081 1686129 1641711 2065775 1936190 2387812 2395174 2252717 1628423 2024620 2192925 1751954 1956741 2015670 1940510 1994419 2068822 2144778 1841164 2246177 2220782 2213357 1885799 2137655 1706663 1902366 1549194 1968920 1819172 1686625 1673554 1983755 1869615 2105030 2561600 2583662 1919500 1928344 Choline phosphate 16267961 20892245 21950871 23927832 27441833 21491578 25943427 25996968 30381435 16883611 17080201 27039450 23250331 73390523 90690088 11940568 8883377 11644650 15229439 6600777 116341300 33684929 23689747 49860539 18732596 24912604 16591176 41056972 11701199 16987972 68178629 64645136 10292170 30293214 16981599 34326875 166802729 89542875 16393224 98944142 38773740 25475559 92050525 40568774 24557545 19821384 Phosphoethanolamine 319136 304682 347898 178788 412282 218613 672589 294005 615173 465119 270546 246366 544101 1708656 1408640 244091 203576 233212 339552 48990 627511 820658 794057 557858 303636 567062 461435 745031 198387 352745 446659 1781968 249884 551941 211199 1161377 2063736 2095367 217766 1928680 594517 565920 1297061 2415663 325052 514026 Pipecolic acid 178919 179299 148259 82383 147740 105927 108335 88698 127427 172408 162915 98997 115802 74353 97933 164124 134586 143020 175139 138616 140761 169679 188055 171224 188323 159311 179878 216928 188330 194393 99455 188996 147815 175221 165610 233546 120660 116244 132374 124031 135843 153924 153818 156545 134712 162506 Proline 4640676 3462401 3227770 3309568 9158554 3377823 4864844 2714923 3427219 3455162 4898829 5901686 5267910 4110030 3636865 4126024 2149278 4961868 5070774 4292062 6133165 4023629 5071014 9385258 7988495 6965528 6716377 11369046 5244643 6161621 2341715 3748009 2894811 2985892 2461520 4497089 4844828 4632089 2790564 4213882 4169250 3503751 4146613 6098363 3320037 2939597 Putrescine 2577994 1656580 2232730 1662745 2368838 2897024 2300237 1868351 3049811 3009478 1929136 1537295 3383260 3601264 2454518 1988708 1183346 1555588 1437421 1502528 1925837 1925337 1690409 2821153 2692226 1369269 1723293 3776057 2728987 1490708 1482056 2776898 1930332 1605399 2349230 3261513 2309272 2183986 1640615 4007234 2131442 1944963 2199326 2725395 2200027 2602298 Pyroglutamic acid 4235652 3464243 1940976 1184007 3900148 1838487 1700232 1308243 3337397 4623167 3012819 2069593 3277790 2110358 2421084 1607236 2037797 2091770 2464429 899442 1876146 1839422 2558561 2560370 2264483 1445166 2342816 2908258 1366803 1790647 924258 2915551 1879066 2235460 1692761 2414933 1607565 1577432 1391036 2028189 1760805 1792931 2013255 2470133 1505806 2128229 Sarcosine 98238 85721 80646 53995 118791 84360 111865 53233 98672 80373 54820 66070 100902 142727 105746 83539 53690 73448 93576 50226 75744 73999 83249 117185 99485 117113 95366 143288 80039 83572 91182 183401 56760 74152 44962 89145 165280 155533 42441 139873 47116 55643 131978 110056 44155 60774 Symmetric dimethyl-L-arginine 24662727 31592157 20504758 14632698 31380493 24259231 24952337 17967136 29853033 24461097 22262308 19091643 30138700 21943375 28404102 28647783 24527140 21736068 24629030 20073538 20608742 28896585 29733534 23183679 28942136 24660817 26680470 34819594 32261168 33090465 18854438 37105839 25881437 31729291 32403344 35204959 25406928 24158684 24286294 26133265 25569589 26760173 33287103 39644118 24877682 33195348 Serine 31734 16113 10580 9287 44560 19009 15662 10611 32225 25607 19976 18120 39735 16446 14382 22609 22840 33718 33702 15211 23298 26024 36102 43527 36698 20088 35441 42928 24939 32896 6657 19869 22097 20080 20682 33478 13844 15754 17401 15851 19554 18689 12828 30009 16695 30138 Serotonin 839725 1526216 8653779 9134686 1163368 904064 21427678 5004279 14645477 1236798 6950916 9111205 3685580 46680884 48974005 784052 555610 1513325 2275581 3956171 9552251 2471066 1438392 1122014 584534 12905368 836710 764095 810423 1626148 26036818 23499178 1542508 5714900 1423760 1085720 13945725 12750493 2015314 30202893 2894037 1002402 23030399 8576049 2660459 658436 Taurine 6690053 6059460 4999629 3968259 8424853 3810586 6344421 3923498 6978442 4871492 9086121 4841928 6508729 10957438 12284564 5271315 4660795 5705733 8222805 3161145 10092813 9253457 10793891 8964766 6969667 9163164 7048779 14286592 7184530 8088414 7377209 15129891 5877236 7366366 6868855 15267261 20292897 16917314 6305009 18613391 9764272 7712117 15833670 13908464 5910710 9036922 Thiamine 57150645 85220950 59719659 39500894 49768964 51350778 39216721 38145647 60119336 41028455 21819190 39675688 47054427 73049958 79273232 67105872 54432297 55910189 64485912 27479221 34109112 51581857 37680309 49691981 32302050 23493758 41038033 68188794 45982388 39375452 38481832 60521856 52335072 59187181 33654330 25816412 40976582 26227581 24950214 34505338 35570698 28525185 53130557 60992997 39754242 47621423 Threonine 187744 109437 109776 134376 325936 203874 178500 149585 198962 141830 88381 171772 241700 177471 112630 209220 173242 257351 263600 249289 293521 276255 280495 483792 450293 240381 366053 495767 335631 362671 106165 159584 165264 158826 245927 290328 154528 152356 245424 201284 240678 217619 148594 196593 219164 224380 Thymidine 9448621 7113297 10656059 7331866 7605610 9355093 11221896 8899075 7412007 8936989 12017624 7480384 8664697 6214633 6386754 3685147 2168929 2935506 2339968 4183151 1258381 2708804 2149211 2859174 2666152 2145250 2676909 4787498 4306011 2173111 2450130 2835433 2280608 1793669 2823383 2988716 1767324 3122888 3028513 1522149 1049135 3387202 1312602 3379009 2825003 1850242 Thyroxine 170644 73854 163814 83239 112128 109571 187813 69911 113752 93385 105297 87469 122483 107008 67781 236088 163842 179317 158094 77972 103940 78412 92724 130479 140567 40241 112630 122482 116261 98462 106209 162924 250524 147577 163107 102171 38910 34070 83158 83449 6306 48852 83180 106601 90822 141726 cis-3-hydroxyproline 32103122 29313635 23119456 14246284 30373377 16242718 25598194 19095440 21080510 31613934 64729089 19448497 24722222 14321483 18334252 23575227 21644330 27948208 32604934 10462240 12242785 11686777 9830010 12093725 21838292 11447541 14936922 23030023 21946897 14241567 13639964 18442106 19998923 19564232 9480750 14830538 7164994 8308531 7900574 9150785 7685167 8617280 8305178 11080686 7666110 10258837 Trimethylamine N-oxide 459169 248029 485054 165429 49933 238721 200656 11248 10502 10563 10796 92674 65723 43728 92482 305332 182887 447258 350620 53026 49408 80114 23246 47798 34624 27469 27406 54463 193668 29235 113951 162297 209063 200366 54700 47709 36536 27824 11391 10993 11201 10539 45962 38092 33927 25915 Tryptophan 2077720 1491265 1640767 1747079 1530338 2063013 1722695 1637722 1631855 1565307 1278328 1616849 1939838 1974767 1758787 2431749 1785856 2071094 2174888 2169625 2609915 2305692 2278043 2620495 2780028 2237092 2018273 2584768 2706629 2147823 2276656 1312021 2012268 1731931 1816036 1875248 1459312 1366177 2630479 1793548 2069322 1452079 2356049 1416250 2433176 1547696 Tyrosine 522830 351529 573848 499168 599522 685098 595576 441614 418182 514680 493766 606708 567542 731355 447358 743940 365162 602068 524212 904442 689749 910772 525955 1249204 1216414 694191 614203 1679880 1204901 742803 460487 390568 472151 377210 662542 597962 534635 394196 743136 630759 625679 658922 647778 626880 799339 577687 Valine 243145524 221316000 213002071 242683784 342135005 253484318 220661202 198988044 238220401 214934740 207651477 288596182 276544935 295197021 249016889 276054851 188421923 280233200 304910144 301801772 393545418 371367365 330439288 657847312 507261353 359631870 431116549 563449777 406567733 486824076 184831401 231570749 225986055 230545429 237929516 427593156 289350826 245831983 281638207 377000260 401208576 407293795 326336845 322606816 304410376 343615855 Xanthosine 114876 5086086 462841 771030 462666 439932 375465 485463 1621657 869614 238381 518291 1024655 2306143 5724336 1859488 1974706 677539 1436693 207850 667541 3452885 1511878 1300086 585686 694123 591634 542283 371420 698585 1139439 2698493 1241874 2198429 682698 640038 1499764 600338 455533 2305170 621160 390588 4361898 5546892 1423677 1486079 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name retention time quantified m/z PubChem ID KEGG ID HMDB ID Study Metabolite Name Study ID phenylalanine-d8 6.64 174.1364 Internal Standard phenylalanine-d8 (internal standard) m280 valine-d8 7.36 126.1366 Internal Standard valine-d8 (internal standard) m281 1-Methylhistamine 9.87 126.1 103101425 C05127 HMDB00898 1-methylhistamine m282 1-methyl nicotinamide 8.22 137.07 103129273 C02918 HMDB00699 1-methylnicotinamide m283 Deoxycytidine 6.11 228.1 10317409 C00881 HMDB00014 2-deoxycytidine m284 3-Hydroxyanthranilic acid 1.8 154.05 103131612 C00632 HMDB01476 3-hydroxyanthranilic acid m285 S-Adenosylhomocysteine 8.06 385.13 10298220 C00021 HMDB00939 5-adenosylhomocysteine m286 5-amino-levulinic acid 7.82 132.07 103182993 C00430 HMDB01149 5-aminolevulinic acid m287 5-Hydroxy-L-tryptophan 6.12 221.09 103145428 C01017 HMDB00472 5-hydroxytryptophan m288 Acetylcholine 8.89 146.12 103061050 C01996 HMDB00895 acetylcholine m289 N-acetylglycine 4.63 118.05 103209017 HMDB00532 acetylglycine m290 Adenosine 4.93 268.1 103059163 C00212 HMDB00050 adenosine m291 Dimethylarginine 9.86 203.15 103067759 C03626 HMDB01539 ADMA m292 Alanine 7.72 90.05 103059020 C00041 HMDB00161 alanine m293 Allantoin 3.51 159.0512 10321113 C01551 HMDB00462 allantoin m295 sn-glycero-3-phosphocholine 10.65 258.11 103067557 HMDB00086 alpha-glycerophosphocholine m296 Aminoisobutyric acid 7.57 104.07 103120712 C03665 HMDB01906 aminoisobutyric acid m297 Anserine 10.58 241.13 103601754 C01262 HMDB00194 anserine m298 2-Aminobenzoic acid 1.78 138.05 103176227 C00108 HMDB01123 anthranilic acid m299 Arginine 9.18 175.119 103059136 C00062 HMDB00517 arginine m300 Asparagine 7.84 133.06 103059439 C00152 HMDB00168 asparagine m301 Betaine 8.89 118.0865 103345809 C00719 HMDB00043 betaine m302 Carnitine 8.79 162.1124 103585549 C15025 HMDB00062 carnitine m303 CAR(2:0) 8.63 204.123 104293557 HMDB00201 C2 carnitine m304 CAR(3:0) 8.26 218.1386 103124850 C03017 HMDB00824 C3 carnitine m305 CAR(DC3:0) 9.33 248.11 126524351 HMDB02095 C3-DC carnitine m306 C3-DC-CH3 carnitine 8.49 262.1284 126531166 HMDB13133 C3-DC-CH3 carnitine m307 CAR(4:0) 7.94 232.1542 10298479 C02862 HMDB02013 C4 carnitine m308 CAR(4:0(OH)) 8.82 248.1491 126531160 HMDB13127 C4-OH carnitine m309 CAR(5:0) 7.68 246.1698 114526391 HMDB00688 C5 carnitine m310 CAR(5:1) 7.82 244.15 119740109 HMDB02366 C5:1 carnitine m311 CAR(6:0) 7.44 260.1855 114526397 HMDB00705 C6 carnitine m312 CAR(7:0) 7.3 274.201 114526488 HMDB13238 C7 carnitine m313 CAR(9:0) 7.12 302.23 126531229 HMDB13288 C9 carnitine m314 CAR(10:0) 7.02 316.248 126523452 HMDB00651 C10 carnitine m315 CAR(10:2) 7.13 312.22 126531250 HMDB13325 C10:2 carnitine m316 CAR(12:0) 6.84 344.2793 10256772 HMDB02250 C12 carnitine m317 CAR(12:1) 6.86 342.2636 126531251 HMDB13326 C12:1 carnitine m318 CAR(14:0) 6.7 372.3106 126525344 HMDB05066 C14 carnitine m319 CAR(14:1) 6.91 370.3 119740108 HMDB02014 C14:1 carnitine m320 CAR(14:2) 7 368.28 126531256 HMDB13331 C14:2 carnitine m321 CAR(16:0) 6.59 400.3418 11533119 C02990 HMDB00222 C16 carnitine m322 CAR(16:0(OH)) 7 416.3368 126531262 HMDB13337 C16-OH carnitine m323 CAR(18:0) 6.48 428.3732 114526403 HMDB00848 C18 carnitine m324 CAR(18:1) 6.5 426.3574 126525343 HMDB05065 C18:1 carnitine m325 CAR(18:1(OH)) 6.92 442.35 126531264 HMDB13339 C18:1-OH carnitine m326 CAR(18:2) 6.56 424.3417 114524024 HMDB06469 C18:2 carnitine m327 CAR(20:4) 5.2 448.34 C20:4 carnitine m328 Carnosine 9.83 227.11 10298255 C00386 HMDB00033 carnosine m329 Choline 8.27 104.1073 103240245 C00114 HMDB00097 choline m330 Citrulline 8.26 176.1029 103590387 C00327 HMDB00904 citrulline m331 Cotinine 5.01 177.1022 103189391 HMDB01046 cotinine m332 Creatine 8.22 132.0768 102851574 C00300 HMDB00064 creatine m333 Creatinine 6.38 114.0665 103114987 C00791 HMDB00562 creatinine m334 Cytosine 5.92 112.05 103179050 C00380 HMDB00630 cytosine m335 Dimethylglycine 8.46 104.07 104222226 C01026 HMDB00092 dimethylglycine m336 Gamma-Aminobutyric acid 7.47 104.07 102735 C00334 HMDB00112 GABA m337 Glucose 4.43 163.06 103023828 C00267 HMDB03345 glucose m338 Glutamic acid 7.48 148.0604 103059048 C00025 HMDB00148 glutamate m339 Glutamine 7.93 147.0763 103059028 C00064 HMDB00641 glutamine m340 Glycine 7.83 76.04 103022976 C00037 HMDB00123 glycine m341 Histamine 9.37 112.09 103171935 C00388 HMDB00870 histamine m342 Histidine 9.14 156.0768 103182080 C00135 HMDB00177 histidine m343 Isoleucine 7.03 132.102 103059667 C00407 HMDB00172 isoleucine m344 Kynurenic acid 5.13 190.0498 103235692 C01717 HMDB00715 kynurenic acid m345 Leucine 6.9 132.102 103023962 C00123 HMDB00687 leucine m346 Lysine 9.42 147.1127 103059399 C00047 HMDB00182 lysine m347 Methionine 6.95 150.0583 103059281 C00073 HMDB00696 methionine m348 Methionine sulfoxide 8.58 166.05 103115155 HMDB02005 methionine sulfoxide m349 Ureidopropionic acid 4.04 133.0609 103187286 C02642 HMDB00026 N-carbamoyl-beta-alanine m350 Niacinamide 3.71 123.0556 103326781 C00153 HMDB01406 niacinamide m351 NMMA 9.41 189.1346 HMDB29416 NMMA m352 Ornithine 9.41 133.1 103241659 C00077 HMDB00214 ornithine m353 Phenylalanine 6.63 166.0862 103059644 C00079 HMDB00159 phenylalanine m354 Choline phosphate 13.88 184.07 103059512 C00588 HMDB01565 phosphocholine m355 Phosphoethanolamine 10.13 142.03 103061107 C00346 HMDB00224 phosphoethanolamine m356 Pipecolic acid 7.93 130.0863 10298256 C00408 HMDB00716 pipecolic acid m357 Proline 8.04 116.0709 10248984 C00148 HMDB00162 proline m358 Putrescine 9.38 89.11 102851508 C00134 HMDB01414 putrescine m359 Pyroglutamic acid 7.93 130.05 103524636 C01879 HMDB00267 pyroglutamic acid m360 Sarcosine 8.22 90.0555 102851555 C00213 HMDB00271 sarcosine m361 Symmetric dimethyl-L-arginine 9.75 203.15 103839531 HMDB03334 SDMA m362 Serine 7.57 106.0502 103059495 C00065 HMDB00187 serine m363 Serotonin 6.2 177.1 103165719 C00780 HMDB00259 serotonin m364 Taurine 6.01 126.0221 103545120 C00245 HMDB00251 taurine m365 Thiamine 9.64 265.11 103574063 C00378 HMDB00235 thiamine m366 Threonine 7.49 120.0658 103023885 C00188 HMDB00167 threonine m367 Thymidine 2.8 243.1 103240092 C00214 HMDB00273 thymidine m368 Thyroxine 5.58 777.69 10321528 C01829 HMDB00248 thyroxine m369 cis-3-hydroxyproline 7.8 132.07 100079 C01157 HMDB00725 trans-hydroxyproline m370 Trimethylamine N-oxide 8.05 76.0763 104296894 C01104 HMDB00925 trimethylamine-N-oxide m371 Tryptophan 6.4 205.097 103058907 C00078 HMDB00929 tryptophan m372 Tyrosine 6.72 182.0812 103059560 C00082 HMDB00158 tyrosine m373 Valine 7.33 118.09 103059097 C00183 HMDB00883 valine m374 Xanthosine 4.28 285.0828 103564523 C01762 HMDB00299 xanthosine m375 METABOLITES_END #END