#METABOLOMICS WORKBENCH emashin_20250314_081717 DATATRACK_ID:5722 STUDY_ID:ST003805 ANALYSIS_ID:AN006256 PROJECT_ID:PR002379 VERSION 1 CREATED_ON March 14, 2025, 10:22 am #PROJECT PR:PROJECT_TITLE Epigenetic changes, neuronal dysregulation and behavioral abnormalities in PR:PROJECT_TITLE Zmym2+/- mutant mice, a genetic animal model of schizophrenia and PR:PROJECT_TITLE neurodevelopmental disorders PR:PROJECT_SUMMARY Loss-of-function mutations in ZMYM2 are associated with an increased risk for PR:PROJECT_SUMMARY schizophrenia (SCZ) and neurodevelopmental disorders (NDD). ZMYM2 interacts with PR:PROJECT_SUMMARY proteins that regulate histone modifications and gene expression, but its PR:PROJECT_SUMMARY functions in the brain are unclear. In this multi-omics study, we found that PR:PROJECT_SUMMARY Zmym2 heterozygous knockout in mice leads to widespread disturbance of gene PR:PROJECT_SUMMARY expression and alterations in diverse molecular pathways, including those PR:PROJECT_SUMMARY related to histone modifications and neuronal activity, particularly in neurons. PR:PROJECT_SUMMARY Proteomic analysis of synapses uncovered dysregulation in lipid metabolism and PR:PROJECT_SUMMARY neurofilament pathways. In neurophysiologic and behavioral tests, Zmym2+/- PR:PROJECT_SUMMARY mutant mice exhibit abnormal EEG patterns and locomotor activity. Our findings PR:PROJECT_SUMMARY underscore the critical role of ZMYM2 in brain development and function and PR:PROJECT_SUMMARY establish Zmym2 mutant mice as a useful genetically valid animal model for SCZ PR:PROJECT_SUMMARY and NDD. PR:INSTITUTE Broad Institute PR:LAST_NAME Mashin PR:FIRST_NAME Eivgeni PR:ADDRESS 300 Binney St., Cambridge, Massachusetts, 02142, USA PR:EMAIL emashin@broadinstitute.org PR:PHONE 6177147061 PR:CONTRIBUTORS Wei-Chao Huang, Kira A. Perzel Mandell, Sameer Aryal, Bryan J. Song, Antia PR:CONTRIBUTORS Valle-Tojeiro, Nathaniel Goble, Chuhan Geng, Ahmet S. Asan, Xiao-Man Liu, PR:CONTRIBUTORS Courtney Dennis, Lucas Dailey, Amy Deik, Lucia Inunciaga, Eivgeni Mashin, Zohreh PR:CONTRIBUTORS Farsi, Yining Wang, Jen Q. Pan, Clary B. Clish, Hasmik Keshishian, Steven A. PR:CONTRIBUTORS Carr, Morgan Sheng #STUDY ST:STUDY_TITLE Epigenetic changes, neuronal dysregulation and behavioral abnormalities in ST:STUDY_TITLE Zmym2+/- mutant mice, a genetic animal model of schizophrenia and ST:STUDY_TITLE neurodevelopmental disorders ST:STUDY_SUMMARY Loss-of-function mutations in ZMYM2 are associated with an increased risk for ST:STUDY_SUMMARY schizophrenia (SCZ) and neurodevelopmental disorders (NDD). ZMYM2 interacts with ST:STUDY_SUMMARY proteins that regulate histone modifications and gene expression, but its ST:STUDY_SUMMARY functions in the brain are unclear. In this multi-omics study, we found that ST:STUDY_SUMMARY Zmym2 heterozygous knockout in mice leads to widespread disturbance of gene ST:STUDY_SUMMARY expression and alterations in diverse molecular pathways, including those ST:STUDY_SUMMARY related to histone modifications and neuronal activity, particularly in neurons. ST:STUDY_SUMMARY Proteomic analysis of synapses uncovered dysregulation in lipid metabolism and ST:STUDY_SUMMARY neurofilament pathways. In neurophysiologic and behavioral tests, Zmym2+/- ST:STUDY_SUMMARY mutant mice exhibit abnormal EEG patterns and locomotor activity. Our findings ST:STUDY_SUMMARY underscore the critical role of ZMYM2 in brain development and function and ST:STUDY_SUMMARY establish Zmym2 mutant mice as a useful genetically valid animal model for SCZ ST:STUDY_SUMMARY and NDD. ST:INSTITUTE Broad Institute ST:LAST_NAME Mashin ST:FIRST_NAME Eivgeni ST:ADDRESS 300 Binney St., Cambridge, Massachusetts, 02142, USA ST:EMAIL emashin@broadinstitute.org ST:PHONE 6177147061 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 SU:GENOTYPE_STRAIN Zmym2+/- mice (C57BL/6NJ-Zmym2em1(IMPC)J /Mmjax; #051239-JAX) SU:AGE_OR_AGE_RANGE 1-5 Months SU:GENDER Male and female SU:ANIMAL_ANIMAL_SUPPLIER Jackson Laboratory #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 - 101304_1 Sample source:mouse cortex | Sex:M | Genotype:WT | Age:1M | Brain_region:CTX | Mice_:Zmym2 Tissue_weight_(g)=0.063; RAW_FILE_NAME(HP)=B0121_SHE_AKAP11_3rd_Set_HP-101304_1; RAW_FILE_NAME(CN)=B0121_SHE_AKAP11_3rd_Set_CN-101304_1; RAW_FILE_NAME(CP)=B0121_SHE_AKAP11_3rd_Set_CP-101304_1; RAW_FILE_NAME(HN)=B0121_SHE_AKAP11_3rd_Set_Rerun_HN-101304_1 SUBJECT_SAMPLE_FACTORS - 101304_2 Sample source:mouse cortex | Sex:M | Genotype:WT | Age:1M | Brain_region:CTX | Mice_:Zmym2 Tissue_weight_(g)=0.096; RAW_FILE_NAME(HP)=B0109_SHE_AKAP11_3rd_Set_HP-101304_2; RAW_FILE_NAME(CN)=B0109_SHE_AKAP11_3rd_Set_CN-101304_2; RAW_FILE_NAME(CP)=B0109_SHE_AKAP11_3rd_Set_CP-101304_2; RAW_FILE_NAME(HN)=B0109_SHE_AKAP11_3rd_Set_Rerun_HN-101304_2 SUBJECT_SAMPLE_FACTORS - 109527_2 Sample source:mouse cortex | Sex:M | Genotype:WT | Age:1M | Brain_region:CTX | Mice_:Zmym2 Tissue_weight_(g)=0.077; RAW_FILE_NAME(HP)=B0127_SHE_AKAP11_3rd_Set_HP-109527_2; RAW_FILE_NAME(CN)=B0127_SHE_AKAP11_3rd_Set_CN-109527_2; RAW_FILE_NAME(CP)=B0127_SHE_AKAP11_3rd_Set_CP-109527_2; RAW_FILE_NAME(HN)=B0127_SHE_AKAP11_3rd_Set_Rerun_HN-109527_2 SUBJECT_SAMPLE_FACTORS - 109527_3 Sample source:mouse cortex | Sex:M | Genotype:WT | Age:1M | Brain_region:CTX | Mice_:Zmym2 Tissue_weight_(g)=0.067; RAW_FILE_NAME(HP)=B0094_SHE_AKAP11_3rd_Set_HP-109527_3; RAW_FILE_NAME(CN)=B0094_SHE_AKAP11_3rd_Set_CN-109527_3; RAW_FILE_NAME(CP)=B0094_SHE_AKAP11_3rd_Set_CP-109527_3; RAW_FILE_NAME(HN)=B0094_SHE_AKAP11_3rd_Set_Rerun_HN-109527_3 SUBJECT_SAMPLE_FACTORS - 109528_2 Sample source:mouse cortex | Sex:M | Genotype:WT | Age:1M | Brain_region:CTX | Mice_:Zmym2 Tissue_weight_(g)=0.079; RAW_FILE_NAME(HP)=B0107_SHE_AKAP11_3rd_Set_HP-109528_2; RAW_FILE_NAME(CN)=B0107_SHE_AKAP11_3rd_Set_CN-109528_2; RAW_FILE_NAME(CP)=B0107_SHE_AKAP11_3rd_Set_CP-109528_2; RAW_FILE_NAME(HN)=B0107_SHE_AKAP11_3rd_Set_Rerun_HN-109528_2 SUBJECT_SAMPLE_FACTORS - 109530_1 Sample source:mouse cortex | Sex:M | Genotype:HET | Age:1M | Brain_region:CTX | Mice_:Zmym2 Tissue_weight_(g)=0.075; RAW_FILE_NAME(HP)=B0120_SHE_AKAP11_3rd_Set_HP-109530_1; RAW_FILE_NAME(CN)=B0120_SHE_AKAP11_3rd_Set_CN-109530_1; RAW_FILE_NAME(CP)=B0120_SHE_AKAP11_3rd_Set_CP-109530_1; RAW_FILE_NAME(HN)=B0120_SHE_AKAP11_3rd_Set_Rerun_HN-109530_1 SUBJECT_SAMPLE_FACTORS - 109530_2 Sample source:mouse cortex | Sex:M | Genotype:HET | Age:1M | Brain_region:CTX | Mice_:Zmym2 Tissue_weight_(g)=0.079; RAW_FILE_NAME(HP)=B0093_SHE_AKAP11_3rd_Set_HP-109530_2; RAW_FILE_NAME(CN)=B0093_SHE_AKAP11_3rd_Set_CN-109530_2; RAW_FILE_NAME(CP)=B0093_SHE_AKAP11_3rd_Set_CP-109530_2; RAW_FILE_NAME(HN)=B0093_SHE_AKAP11_3rd_Set_Rerun_HN-109530_2 SUBJECT_SAMPLE_FACTORS - 109530_3 Sample source:mouse cortex | Sex:M | Genotype:HET | Age:1M | Brain_region:CTX | Mice_:Zmym2 Tissue_weight_(g)=0.076; RAW_FILE_NAME(HP)=B0097_SHE_AKAP11_3rd_Set_HP-109530_3; RAW_FILE_NAME(CN)=B0097_SHE_AKAP11_3rd_Set_CN-109530_3; RAW_FILE_NAME(CP)=B0097_SHE_AKAP11_3rd_Set_CP-109530_3; RAW_FILE_NAME(HN)=B0097_SHE_AKAP11_3rd_Set_Rerun_HN-109530_3 SUBJECT_SAMPLE_FACTORS - 109530_4 Sample source:mouse cortex | Sex:M | Genotype:HET | Age:1M | Brain_region:CTX | Mice_:Zmym2 Tissue_weight_(g)=0.063; RAW_FILE_NAME(HP)=B0096_SHE_AKAP11_3rd_Set_HP-109530_4; RAW_FILE_NAME(CN)=B0096_SHE_AKAP11_3rd_Set_CN-109530_4; RAW_FILE_NAME(CP)=B0096_SHE_AKAP11_3rd_Set_CP-109530_4; RAW_FILE_NAME(HN)=B0096_SHE_AKAP11_3rd_Set_Rerun_HN-109530_4 SUBJECT_SAMPLE_FACTORS - 109530_5 Sample source:mouse cortex | Sex:M | Genotype:HET | Age:1M | Brain_region:CTX | Mice_:Zmym2 Tissue_weight_(g)=0.089; RAW_FILE_NAME(HP)=B0106_SHE_AKAP11_3rd_Set_HP-109530_5; RAW_FILE_NAME(CN)=B0106_SHE_AKAP11_3rd_Set_CN-109530_5; RAW_FILE_NAME(CP)=B0106_SHE_AKAP11_3rd_Set_CP-109530_5; RAW_FILE_NAME(HN)=B0106_SHE_AKAP11_3rd_Set_Rerun_HN-109530_5 #COLLECTION CO:COLLECTION_SUMMARY The detailed procedure of brain perfusion and dissection was described CO:COLLECTION_SUMMARY previously31. In brief, mice were anesthetized with isoflurane, and transcardial CO:COLLECTION_SUMMARY perfusions were performed with ice-cold HBSS (Life Technologies) to remove blood CO:COLLECTION_SUMMARY from the brain, which was then immediately frozen in liquid nitrogen vapor and CO:COLLECTION_SUMMARY stored at –80°C. Brain dissection was carried out in a cryostat, with all CO:COLLECTION_SUMMARY tools precooled to –20°C. The cerebellum was removed first, and then the CO:COLLECTION_SUMMARY medial prefrontal cortex, dorsal hippocampus, thalamus, somatosensory cortex, CO:COLLECTION_SUMMARY and dorsal striatum, and substantia nigra, were meticulously dissected using CO:COLLECTION_SUMMARY biopsy punch and ophthalmic microscalpel in a cryostat (Leica). The brain CO:COLLECTION_SUMMARY regions were identified using the Allen Brain Atlas, with each excised tissue CO:COLLECTION_SUMMARY stored at –80°C in 1.5ml tubes. CO:SAMPLE_TYPE Brain cortex #TREATMENT TR:TREATMENT_SUMMARY NO TREATMENT ADMINISTRED TO THE ANIMALS PRIOR TO SAMPLE COLLECTION #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Brain tissues (n = 5 per genotype) were homogenized using a Qiagen TissueLyzer SP:SAMPLEPREP_SUMMARY II in water at 1:4 (w:v) (TissueLyser II; Qiagen) and the aqueous homogenate was SP:SAMPLEPREP_SUMMARY subjected to protein precipitation. Samples were prepared for each method using SP:SAMPLEPREP_SUMMARY extraction procedures that are matched for use with the chromatography SP:SAMPLEPREP_SUMMARY conditions: - HILIC-pos: Homogenates (10 μL) samples were extracted with the SP:SAMPLEPREP_SUMMARY addition of nine volumes of 74.9:24.9:0.2 v/v/v acetonitrile/methanol/formic SP:SAMPLEPREP_SUMMARY acid containing stable isotope-labeled internal standards (valine-d8, Isotec; SP:SAMPLEPREP_SUMMARY and phenylalanine-d8, Cambridge Isotope Laboratories). The samples were SP:SAMPLEPREP_SUMMARY centrifuged (10 min, 9,000g, 4°C), and the supernatants (10 μL)injected SP:SAMPLEPREP_SUMMARY directly onto column. - C8-pos: Homogenates (10 μL) were extracted using 190 SP:SAMPLEPREP_SUMMARY μL 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, 9,000g, SP:SAMPLEPREP_SUMMARY ambient temperature), supernatants (2 μl) were injected directly onto column. - SP:SAMPLEPREP_SUMMARY C18-neg: Homogenates (30 μL) were extracted using 90 μl methanol containing SP:SAMPLEPREP_SUMMARY 15R-15-methyl ProstaglandinA2,15R-15-methyl ProstaglandinF2α, 15S-15-methyl SP:SAMPLEPREP_SUMMARY ProstaglandinD2, 15S-15-methyl Prostaglandin E1, and 15S-15-methyl Prostaglandin SP:SAMPLEPREP_SUMMARY E2 as internal standards (Cayman Chemical Co.) and centrifuged (10 min, 9,000g, SP:SAMPLEPREP_SUMMARY 4°C). The supernatants (10 μL) were injected onto column. - HILIC-neg: SP:SAMPLEPREP_SUMMARY Homogenates (30 μL) were extracted with the addition of four volumes of 80% SP:SAMPLEPREP_SUMMARY methanol containing inosine-15N4, thymine-d4 and glycocholate-d4 internal SP:SAMPLEPREP_SUMMARY standards (Cambridge Isotope Laboratories). The samples were centrifuged (10 SP:SAMPLEPREP_SUMMARY min, 9,000g, 4°C) and the supernatants 10 μL) were injected directly onto SP:SAMPLEPREP_SUMMARY column. #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 30℃ #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive 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:MS_RESULTS_FILE ST003805_AN006256_Results.txt UNITS:abundances Has m/z:Yes Has RT:Yes RT units:Minutes #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS abundances MS_METABOLITE_DATA_START Samples 109530_2 109527_3 109530_4 109530_3 109530_5 109528_2 101304_2 109530_1 101304_1 109527_2 Factors Sample source:mouse cortex | Sex:M | Genotype:HET | Age:1M | Brain_region:CTX | Mice_:Zmym2 Sample source:mouse cortex | Sex:M | Genotype:WT | Age:1M | Brain_region:CTX | Mice_:Zmym2 Sample source:mouse cortex | Sex:M | Genotype:HET | Age:1M | Brain_region:CTX | Mice_:Zmym2 Sample source:mouse cortex | Sex:M | Genotype:HET | Age:1M | Brain_region:CTX | Mice_:Zmym2 Sample source:mouse cortex | Sex:M | Genotype:HET | Age:1M | Brain_region:CTX | Mice_:Zmym2 Sample source:mouse cortex | Sex:M | Genotype:WT | Age:1M | Brain_region:CTX | Mice_:Zmym2 Sample source:mouse cortex | Sex:M | Genotype:WT | Age:1M | Brain_region:CTX | Mice_:Zmym2 Sample source:mouse cortex | Sex:M | Genotype:HET | Age:1M | Brain_region:CTX | Mice_:Zmym2 Sample source:mouse cortex | Sex:M | Genotype:WT | Age:1M | Brain_region:CTX | Mice_:Zmym2 Sample source:mouse cortex | Sex:M | Genotype:WT | Age:1M | Brain_region:CTX | Mice_:Zmym2 Thymine-d4 [iSTD] 305445698 304804719 339474061 267807835 285769182 294416567 292825056 294156463 287946583 344385440 Inosine-15N4 [iSTD] 25749640 25192868 26926191 24700437 24350406 24293005 23876806 23388631 23399021 27015592 Glycocholate-d4 [iSTD] 189483662 185143347 204815158 203501544 189534742 188716626 192945132 171150232 180765671 214162294 Salicyluric acid 71528 81252 56829 46108 47057 90070 69917 49350 67040 68163 3,4-Dihydroxyphenylglycol 156979 159250 68151 187799 213991 173296 271586 226155 138683 120982 Homovanillic acid 2171145 5368300 5264632 1694658 1822296 2348241 2638213 2542402 2296620 2380419 Erythrose 4-phosphate 5147712 5444360 4019026 4574718 4318961 4194813 5392432 3719025 4353865 4384219 Pentose 5-phosphate 6927192 7350877 7188473 7834997 7748873 9420616 9698746 8983202 10200768 8002645 Hexose monophosphate 76482031 78733783 57717134 67548625 63236585 62341130 83495106 52741260 61661183 61523066 6-Phosphogluconic acid 307067 324443 208925 514329 217467 300970 499854 221241 452271 270300 Hexose diphosphate 15417012 18684683 17643447 14856261 12927711 15587631 26082066 15062657 24364200 17988639 Xylose 3458534 2964842 2449287 2982333 3555629 3235033 3949496 3055024 3651868 3062722 Glyceric acid 40239783 44110268 43837062 34660810 33913697 36253269 28095562 34419963 40111802 40823458 Erythronic and or Threonic acid 1062240415 987765827 1044325877 1123821512 1115977367 1052964403 1038728973 1046449515 1064367560 1165493358 Glucuronic acid 695708 811310 466377 636928 632847 550448 570250 427507 401526 546667 Ribitol 83206321 72029558 86148316 84534028 84664987 89862990 87965636 95434166 85217028 79507485 Sorbitol 226550920 184228833 160171706 218061386 220811000 326863775 250206567 245187447 258588777 268964315 2-Aminobutyric acid 1799240 2260863 1763808 1592731 1963924 2464734 1806315 2130947 1857032 2021212 2-Aminoheptanoic acid 365371 505020 337711 347684 170600 169624 115218 162970 180124 142313 Ketoisovaleric acid 1061104 1429373 891854 1081553 953742 943780 935399 901968 1086393 974456 Oxalic acid 7669876 7973187 8000506 7477452 7519487 7396464 7780781 6431853 7093458 7395221 Malonic acid 3008207 3324804 3121171 2838385 3276198 2982635 3213235 2739376 2933031 3348286 Adipic and or Methylglutaric acid 775212 1446783 998851 970420 1038824 1128022 949416 993345 1066389 778375 Aminoadipic acid 4408457 1562847 1050716 4166946 4641667 3843266 4275704 4332160 4548127 4602182 Suberic acid 604202 834191 826097 671495 952836 733668 558743 727943 951657 592275 Sebacic acid 433051 869922 515428 826416 439631 576339 569701 707477 770476 418041 Hydroxybutyric and or Hydroxyisobutyric acid 10456739 7896727 9428017 14375107 14824909 17751981 9452763 15325187 10099427 12783445 2-Hydroxyvaleric and or 2-Hydroxyisovaleric acid 12466419 10435854 10239090 11970623 12735198 17791168 20076897 16393307 18449688 17758989 2-Hydroxycaproic and or 2-Hydroxyisocaproic acid 3116043 4370833 3017254 3338321 3734012 4236963 2502807 4515548 3192320 3373165 2-Hydroxyglutaric acid 35183882 28828563 28769060 39058314 35377922 39843968 51150424 34688435 40850891 37344071 Propionic acid 1280475 1206927 964711 1650038 1497085 1556835 1368457 1628624 1195805 1547713 FMN 59919 57500 38101 65113 55890 56520 55377 66543 59263 51945 Adenine 52446049 43293364 32589880 211923453 49672015 54186676 102436883 25963844 90840153 58333483 Hypoxanthine 1537497574 1386479930 1202745382 1385198524 1406266205 1441597449 1427013806 1456258577 1286002067 1363029587 ADP 800058 881171 158032 850094 1399718 1012012 1540516 607336 526623 380612 GDP 697387 714447 334105 705662 1083501 734847 881427 576855 371092 462197 AMP 2873039 1903185 1965281 2540059 2292251 2259445 2638568 2229909 2930981 2407698 IMP 2143357 1647924 2144422 715364 1459291 1555410 1440929 2246304 1686052 1710213 GMP 759345 568047 651180 534180 573829 485079 538697 566224 707641 765608 Adenylsuccinic acid 107482 35279 67444 124567 68749 70783 119011 86848 170161 107008 ATP 1246567 1444259 1492598 1246668 1080969 1377546 1062590 1337224 1428744 1548993 Inosine 619613212 626393220 601733238 719041785 691889512 762915268 751730791 808342102 800410841 648569187 Guanosine 37366322 39711139 41934990 55395910 54145619 56356975 44648112 70613843 63322202 47389237 Succinyladenosine 731490 503471 489911 939449 659935 639728 629643 579029 657819 654053 Xanthine 984207759 941232239 835913217 945229073 874895915 898095322 900314657 690216613 734002325 811826587 Uric acid 6541064 6308346 5944507 6273060 4997001 6515978 8636662 5089124 5981390 5419361 1-Methyluric acid 944730 200118 494460 257193 590015 564072 587378 210099 450789 507653 dCMP 45929 50220 40654 47890 37576 37189 32491 52979 41069 46655 UDP-galactose or UDP-glucose 482594 544370 582640 968938 915662 1521866 621977 1262812 893767 643551 CMP 566346 520808 464833 595164 551370 527258 563472 625617 527635 517989 UMP 211994 154001 187101 176780 190632 211483 185352 233299 225127 221364 Cytidine 39145215 44405318 34089763 33973109 37977063 47096390 36872629 43150123 40300522 45244142 Uridine 1347187032 1314560118 1138670889 1397765801 1402217399 1314607196 1268948419 1449596295 1242164857 1193098406 Pseudouridine 16587916 14663175 15689306 16843556 15808266 16315470 12041597 16762201 11328303 13770312 Uracil 640743001 616115725 513697667 549349539 567223692 593777999 565227539 580320199 490381740 582174693 Thymine 5411917 6736318 5638906 4863491 5001444 5951555 4401587 5698828 3752659 5921336 Aspartic acid 828516264 673415999 669367056 720318140 724010690 666106372 945448537 764691230 751574734 764861959 Glutamic acid 955775636 886620660 850777756 997755379 982814902 947893443 1000983792 1046062181 1065297588 963648158 N-Acetylglutamic acid 20989757 24665926 19155371 20407467 21320757 20792974 23101682 19299666 19469823 21049702 Pantothenic acid 293383634 356698808 226489926 276136045 295767662 288059063 253939838 284265448 221720318 253319252 Cystathionine 776165 882505 679054 658225 765185 606337 712528 689118 484010 543591 N-Acetylcarnosine 63929 90494 105781 46729 60513 80417 66496 74533 48521 58114 Oxidized glutathione 3311569 2528685 2200655 5630965 4812814 5057950 4943866 5307167 6039514 4382365 sn-Glycero-3-phosphate 2017793 1498562 1388081 1738144 1640918 1616432 1967731 1915423 1997537 1486994 Pyruvic acid 36991399 38574314 29901665 30831876 50393690 40566194 53993492 65555036 45353155 49426257 Lactic acid 1404999503 1306574505 1236877081 1596878704 1408466703 1745062066 1589916915 1544752168 1667535694 1498136375 Fumaric and or Maleic acid 573551615 572732425 530756994 429388610 579761334 571381811 564841892 553253815 558829179 572802113 Succinic acid 23631142 25922668 22794797 21820814 22495019 22118683 21681883 20312210 20064852 21555283 Malic acid 757469344 758541579 708385099 784472837 785320047 758871835 750611845 733134654 753654393 761142639 cis-Aconitic acid 22138808 18487052 19899205 22165374 20707692 23049177 19630677 23413452 17994405 20525637 Citric and or Isocitric acid 480275123 427947103 418252738 475314862 448635304 507899439 435003579 491857313 387165896 432720257 Threitol 886804 816899 664050 871342 847544 869409 889767 940362 829382 874635 Myo-inositol/Theophylline 2162120872 1587352059 1303772565 2162130582 2216228942 2274121319 2588281886 2142812200 2337851765 1947411746 4-Hydroxybenzaldehyde 3204327 4824680 5915622 2802290 4028287 4484038 2998630 3115744 3663221 4970680 Glucosan 12574637 14750082 11949216 12692557 13156935 13535802 12428235 13128970 11745415 12617039 4-Pyridoxic acid 954139 622865 555918 651728 899225 795262 801129 557961 655355 654889 Glycocholic acid 1375892 1470223 1450298 1406857 1338175 1356243 1451295 1189887 1261639 1574392 Corticosterone 1030565 667741 808032 657853 925904 1325788 1207193 844261 1184859 935426 cys-gly oxidized 42968 18652 32467 77206 70888 57129 95524 63573 46930 60839 Dihexose 22276368 7212905 13744090 4572581 11036634 13014986 4519906 8768025 4801854 2895432 Glutathione 2765906 3281354 2568865 6130901 4140594 4210011 4386866 3139225 3940130 2381275 UDP-glucuronic acid 43861 40712 48295 66430 96989 79979 158076 123743 38405 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Study_Compound_ID MZ RT HMDB_ID Thymine-d4 [iSTD] TF75 129.0609 1.3 internal standard Inosine-15N4 [iSTD] TF53 271.06200000000001 3.37 internal standard Glycocholate-d4 [iSTD] TF44 468.32760000000002 3.86 internal standard Salicyluric acid TF66 194.04949999999999 6.04 HMDB0000840 3,4-Dihydroxyphenylglycol TF08 169.05080000000001 2.1 HMDB0000318 Homovanillic acid TF49 181.05109999999999 4.2699999999999996 HMDB0000118 Erythrose 4-phosphate TF34 199.0017 7.22 HMDB0001321 Pentose 5-phosphate TF62 229.01230000000001 7.15 HMDB0001548 Hexose monophosphate TF48 259.02269999999999 7.15 HMDB0000124 6-Phosphogluconic acid TF11 275.01780000000002 8.5399999999999991 HMDB0001316 Hexose diphosphate TF47 338.9896 9.77 HMDB0001058 Xylose TF83 149.04580000000001 1.67 HMDB0000098 Glyceric acid TF42 105.0194 4.16 HMDB0000139 Erythronic and or Threonic acid TF33 135.03 4.2699999999999996 HMDB0000613 Glucuronic acid TF38 193.03569999999999 4.9000000000000004 HMDB0000127 Ribitol TF16 151.06139999999999 1.79 HMDB0000508 Sorbitol TF68 181.07210000000001 2.0699999999999998 HMDB0000247 2-Aminobutyric acid TF03 102.0561 3.11 HMDB0000650 2-Aminoheptanoic acid TF04 144.10319999999999 2.58 HMDB0094649 Ketoisovaleric acid TF20 115.0403 3.56 HMDB0000019 Oxalic acid TF60 88.988100000000003 7.21 HMDB0002329 Malonic acid TF57 103.0038 6.92 HMDB0000691 Adipic and or Methylglutaric acid TF15 145.0505 6.59 HMDB0000448 Aminoadipic acid TF02 160.06180000000001 5.22 HMDB0000510 Suberic acid TF69 173.0823 6.54 HMDB0000893 Sebacic acid TF67 201.11349999999999 6.5 HMDB0000792 Hydroxybutyric and or Hydroxyisobutyric acid TF19 103.0401 3.61 HMDB0000008 2-Hydroxyvaleric and or 2-Hydroxyisovaleric acid TF05 117.05589999999999 3.55 HMDB0000407 2-Hydroxycaproic and or 2-Hydroxyisocaproic acid TF06 131.07149999999999 3.5 HMDB0000317 2-Hydroxyglutaric acid TF07 147.03020000000001 6.65 HMDB0059655 Propionic acid TF63 73.029600000000002 3.97 HMDB0000237 FMN TF35 455.09899999999999 7.27 HMDB0001520 Adenine TF13 134.04730000000001 2.27 HMDB0000034 Hypoxanthine TF50 135.03129999999999 3.21 HMDB0000157 ADP TF17 426.0231 9.51 HMDB0001341 GDP TF37 442.0179 10.28 HMDB0001201 AMP TF21 346.0566 7.47 HMDB0000045 IMP TF51 347.04070000000002 8.49 HMDB0000175 GMP TF45 362.05169999999998 8.25 HMDB0001397 Adenylsuccinic acid TF14 462.0675 9.9600000000000009 HMDB0000536 ATP TF24 505.98899999999998 11.14 HMDB0000538 Inosine TF52 267.07369999999997 3.4 HMDB0000195 Guanosine TF46 282.08479999999997 3.1 HMDB0000133 Succinyladenosine TF71 382.10149999999999 7.08 HMDB0000912 Xanthine TF82 151.02629999999999 4.79 HMDB0000292 Uric acid TF80 167.0213 5.05 HMDB0000289 1-Methyluric acid TF01 181.03710000000001 4.6500000000000004 HMDB0003099 dCMP TF32 306.05009999999999 7.25 HMDB0001202 UDP-galactose or UDP-glucose TF76 565.04909999999995 6.91 HMDB0000286 CMP TF27 322.04539999999997 7.29 HMDB0000095 UMP TF78 323.0292 7.39 HMDB0000288 Cytidine TF31 242.0787 2.1800000000000002 HMDB0000089 Uridine TF81 243.06229999999999 1.81 HMDB0000296 Pseudouridine TF64 243.0626 2.38 HMDB0000767 Uracil TF79 111.0201 1.59 HMDB0000300 Thymine TF74 125.03579999999999 1.3 HMDB0000262 Aspartic acid TF23 132.03030000000001 5.0999999999999996 HMDB0000191 Glutamic acid TF39 146.04599999999999 5.09 HMDB0000148 N-Acetylglutamic acid TF59 188.05680000000001 6.47 HMDB0001138 Pantothenic acid TF61 218.1037 3.89 HMDB0000210 Cystathionine TF30 221.06049999999999 5.33 HMDB0000099 N-Acetylcarnosine TF58 267.11 4.07 HMDB0012881 Oxidized glutathione TF40 611.14750000000004 7.64 HMDB0003337 sn-Glycero-3-phosphate TF18 171.0068 7.09 HMDB0000126 Pyruvic acid TF65 87.008799999999994 5.7 HMDB0000243 Lactic acid TF55 89.0244 3.84 HMDB0000190 Fumaric and or Maleic acid TF36 115.0038 6.75 HMDB0000134 Succinic acid TF70 117.01949999999999 6.69 HMDB0000254 Malic acid TF56 133.01429999999999 6.76 HMDB0000156 cis-Aconitic acid TF12 173.0094 8.74 HMDB0000072 Citric and or Isocitric acid TF26 191.01990000000001 8.75 HMDB0000094 Threitol TF73 121.0508 1.65 HMDB0004136 Myo-inositol/Theophylline TF54 179.05629999999999 2.72 HMDB0000211 4-Hydroxybenzaldehyde TF09 121.02970000000001 2.48 HMDB0011718 Glucosan TF22 161.04589999999999 6.59 HMDB0000640 4-Pyridoxic acid TF10 182.0461 3.62 HMDB0000017 Glycocholic acid TF43 464.30279999999999 3.86 HMDB0000138 Corticosterone TF28 345.20780000000002 1.22 HMDB0001547 cys-gly oxidized TF29 353.06 6.32 NA Dihexose TF72 341.10989999999998 2.72 HMDB0000258 Glutathione TF41 306.07709999999997 5.83 HMDB0000125 UDP-glucuronic acid TF77 579.02779999999996 8.7899999999999991 HMDB0000935 METABOLITES_END #END