#METABOLOMICS WORKBENCH kevin.cho@wustl.edu_20240409_091613 DATATRACK_ID:4766 STUDY_ID:ST003162 ANALYSIS_ID:AN005190 PROJECT_ID:PR001967 VERSION 1 CREATED_ON April 10, 2024, 6:57 pm #PROJECT PR:PROJECT_TITLE Loss of dihydroceramide desaturase drives neurodegeneration by disrupting PR:PROJECT_TITLE endoplasmic reticulum and lipid droplet homeostasis in glial cells PR:PROJECT_TYPE Untargeted Metabolomics and Lipidomics PR:PROJECT_SUMMARY Dihydroceramide desaturases convert dihydroceramides to ceramides, the PR:PROJECT_SUMMARY precursors of all complex sphingolipids. Reduction of DEGS1 dihydroceramide PR:PROJECT_SUMMARY desaturase function causes pediatric neurodegenerative disorder hypomyelinating PR:PROJECT_SUMMARY leukodystrophy-18 (HLD-18). We discovered that infertile crescent (ifc), the PR:PROJECT_SUMMARY Drosophila DEGS1 homolog, is expressed primarily in glial cells to promote CNS PR:PROJECT_SUMMARY development by guarding against neurodegeneration. Loss of ifc causes massive PR:PROJECT_SUMMARY dihydroceramide accumulation and severe morphological defects in cortex glia, PR:PROJECT_SUMMARY including endoplasmic reticulum (ER) expansion, failure of neuronal PR:PROJECT_SUMMARY ensheathment, and lipid droplet depletion. RNAi knockdown of the upstream PR:PROJECT_SUMMARY ceramide synthase schlank in glia of ifc mutants rescues ER expansion, PR:PROJECT_SUMMARY suggesting dihydroceramide accumulation in the ER drives this phenotype. RNAi PR:PROJECT_SUMMARY knockdown of ifc in glia but not neurons drives neuronal cell death, suggesting PR:PROJECT_SUMMARY that ifc function in glia promotes neuronal survival. Our work identifies glia PR:PROJECT_SUMMARY as the primary site of disease progression in HLD-18 and may inform on juvenile PR:PROJECT_SUMMARY forms of ALS, which also feature elevated dihydroceramide levels. PR:INSTITUTE Washington University in St. Louis PR:DEPARTMENT Genetics, Medicine, Chemistry PR:LABORATORY Skeath and Patti Laboratories PR:LAST_NAME Cho PR:FIRST_NAME Kevin PR:ADDRESS 1 Brookings Drive, Campus Box 1134, St. Louis, MO, 63130, USA PR:EMAIL kevin.cho@wustl.edu PR:PHONE 314-935-8813 #STUDY ST:STUDY_TITLE Loss of dihydroceramide desaturase drives neurodegeneration by disrupting ST:STUDY_TITLE endoplasmic reticulum and lipid droplet homeostasis in glial cells ST:STUDY_TYPE Untargeted Metabolomics & Lipidomics ST:STUDY_SUMMARY Dihydroceramide desaturases convert dihydroceramides to ceramides, the ST:STUDY_SUMMARY precursors of all complex sphingolipids. Reduction of DEGS1 dihydroceramide ST:STUDY_SUMMARY desaturase function causes pediatric neurodegenerative disorder hypomyelinating ST:STUDY_SUMMARY leukodystrophy-18 (HLD-18). We discovered that infertile crescent (ifc), the ST:STUDY_SUMMARY Drosophila DEGS1 homolog, is expressed primarily in glial cells to promote CNS ST:STUDY_SUMMARY development by guarding against neurodegeneration. Loss of ifc causes massive ST:STUDY_SUMMARY dihydroceramide accumulation and severe morphological defects in cortex glia, ST:STUDY_SUMMARY including endoplasmic reticulum (ER) expansion, failure of neuronal ST:STUDY_SUMMARY ensheathment, and lipid droplet depletion. RNAi knockdown of the upstream ST:STUDY_SUMMARY ceramide synthase schlank in glia of ifc mutants rescues ER expansion, ST:STUDY_SUMMARY suggesting dihydroceramide accumulation in the ER drives this phenotype. RNAi ST:STUDY_SUMMARY knockdown of ifc in glia but not neurons drives neuronal cell death, suggesting ST:STUDY_SUMMARY that ifc function in glia promotes neuronal survival. Our work identifies glia ST:STUDY_SUMMARY as the primary site of disease progression in HLD-18 and may inform on juvenile ST:STUDY_SUMMARY forms of ALS, which also feature elevated dihydroceramide levels. ST:INSTITUTE Washington University in St. Louis ST:DEPARTMENT Genetics, Medicine, Chemistry ST:LABORATORY Skeath and Patti Laboratories ST:LAST_NAME Cho ST:FIRST_NAME Kevin ST:ADDRESS 1 Brookings Drive, Campus Box 1134, St. Louis, MO, 63130, USA ST:EMAIL kevin.cho@wustl.edu ST:PHONE 314-935-8813 #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 - WL_RPLC_POS_ifc_1 Genotype:Knockout | Sample source:Whole Larvae Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=WL_RPLC_POS_ifc_1.mzML SUBJECT_SAMPLE_FACTORS - WL_RPLC_POS_ifc_2 Genotype:Knockout | Sample source:Whole Larvae Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=WL_RPLC_POS_ifc_2.mzML SUBJECT_SAMPLE_FACTORS - WL_RPLC_POS_ifc_3 Genotype:Knockout | Sample source:Whole Larvae Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=WL_RPLC_POS_ifc_3.mzML SUBJECT_SAMPLE_FACTORS - WL_RPLC_POS_ifc_4 Genotype:Knockout | Sample source:Whole Larvae Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=WL_RPLC_POS_ifc_4.mzML SUBJECT_SAMPLE_FACTORS - WL_RPLC_POS_ifc_5 Genotype:Knockout | Sample source:Whole Larvae Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=WL_RPLC_POS_ifc_5.mzML SUBJECT_SAMPLE_FACTORS - WL_RPLC_POS_WT_1 Genotype:Wild-type | Sample source:Whole Larvae Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=WL_RPLC_POS_WT_1.mzML SUBJECT_SAMPLE_FACTORS - WL_RPLC_POS_WT_2 Genotype:Wild-type | Sample source:Whole Larvae Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=WL_RPLC_POS_WT_2.mzML SUBJECT_SAMPLE_FACTORS - WL_RPLC_POS_WT_3 Genotype:Wild-type | Sample source:Whole Larvae Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=WL_RPLC_POS_WT_3.mzML SUBJECT_SAMPLE_FACTORS - WL_RPLC_POS_WT_4 Genotype:Wild-type | Sample source:Whole Larvae Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=WL_RPLC_POS_WT_4.mzML SUBJECT_SAMPLE_FACTORS - WL_RPLC_POS_WT_5 Genotype:Wild-type | Sample source:Whole Larvae Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=WL_RPLC_POS_WT_5.mzML SUBJECT_SAMPLE_FACTORS - CNS_RPLC_POS_ifc_1 Genotype:Knockout | Sample source:CNS Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=CNS_RPLC_POS_ifc_1.mzML SUBJECT_SAMPLE_FACTORS - CNS_RPLC_POS_ifc_2 Genotype:Knockout | Sample source:CNS Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=CNS_RPLC_POS_ifc_2.mzML SUBJECT_SAMPLE_FACTORS - CNS_RPLC_POS_ifc_3 Genotype:Knockout | Sample source:CNS Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=CNS_RPLC_POS_ifc_3.mzML SUBJECT_SAMPLE_FACTORS - CNS_RPLC_POS_ifc_4 Genotype:Knockout | Sample source:CNS Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=CNS_RPLC_POS_ifc_4.mzML SUBJECT_SAMPLE_FACTORS - CNS_RPLC_POS_ifc_5 Genotype:Knockout | Sample source:CNS Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=CNS_RPLC_POS_ifc_5.mzML SUBJECT_SAMPLE_FACTORS - CNS_RPLC_POS_WT_1 Genotype:Wild-type | Sample source:CNS Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=CNS_RPLC_POS_WT_1.mzML SUBJECT_SAMPLE_FACTORS - CNS_RPLC_POS_WT_2 Genotype:Wild-type | Sample source:CNS Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=CNS_RPLC_POS_WT_2.mzML SUBJECT_SAMPLE_FACTORS - CNS_RPLC_POS_WT_3 Genotype:Wild-type | Sample source:CNS Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=CNS_RPLC_POS_WT_3.mzML SUBJECT_SAMPLE_FACTORS - CNS_RPLC_POS_WT_4 Genotype:Wild-type | Sample source:CNS Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=CNS_RPLC_POS_WT_4.mzML SUBJECT_SAMPLE_FACTORS - CNS_RPLC_POS_WT_5 Genotype:Wild-type | Sample source:CNS Chromatography=RPLC; Polarity=Positive; RAW_FILE_NAME(Raw file name)=CNS_RPLC_POS_WT_5.mzML SUBJECT_SAMPLE_FACTORS - WL_HILIC_NEG_ifc_1 Genotype:Knockout | Sample source:Whole Larvae Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=WL_HILIC_NEG_ifc_1.mzML SUBJECT_SAMPLE_FACTORS - WL_HILIC_NEG_ifc_2 Genotype:Knockout | Sample source:Whole Larvae Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=WL_HILIC_NEG_ifc_2.mzML SUBJECT_SAMPLE_FACTORS - WL_HILIC_NEG_ifc_3 Genotype:Knockout | Sample source:Whole Larvae Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=WL_HILIC_NEG_ifc_3.mzML SUBJECT_SAMPLE_FACTORS - WL_HILIC_NEG_ifc_4 Genotype:Knockout | Sample source:Whole Larvae Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=WL_HILIC_NEG_ifc_4.mzML SUBJECT_SAMPLE_FACTORS - WL_HILIC_NEG_ifc_5 Genotype:Knockout | Sample source:Whole Larvae Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=WL_HILIC_NEG_ifc_5.mzML SUBJECT_SAMPLE_FACTORS - WL_HILIC_NEG_WT_1 Genotype:Wild-type | Sample source:Whole Larvae Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=WL_HILIC_NEG_WT_1.mzML SUBJECT_SAMPLE_FACTORS - WL_HILIC_NEG_WT_2 Genotype:Wild-type | Sample source:Whole Larvae Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=WL_HILIC_NEG_WT_2.mzML SUBJECT_SAMPLE_FACTORS - WL_HILIC_NEG_WT_3 Genotype:Wild-type | Sample source:Whole Larvae Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=WL_HILIC_NEG_WT_3.mzML SUBJECT_SAMPLE_FACTORS - WL_HILIC_NEG_WT_4 Genotype:Wild-type | Sample source:Whole Larvae Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=WL_HILIC_NEG_WT_4.mzML SUBJECT_SAMPLE_FACTORS - WL_HILIC_NEG_WT_5 Genotype:Wild-type | Sample source:Whole Larvae Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=WL_HILIC_NEG_WT_5.mzML SUBJECT_SAMPLE_FACTORS - CNS_HILIC_NEG_ifc_1 Genotype:Knockout | Sample source:CNS Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=CNS_HILIC_NEG_ifc_1.mzML SUBJECT_SAMPLE_FACTORS - CNS_HILIC_NEG_ifc_2 Genotype:Knockout | Sample source:CNS Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=CNS_HILIC_NEG_ifc_2.mzML SUBJECT_SAMPLE_FACTORS - CNS_HILIC_NEG_ifc_3 Genotype:Knockout | Sample source:CNS Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=CNS_HILIC_NEG_ifc_3.mzML SUBJECT_SAMPLE_FACTORS - CNS_HILIC_NEG_ifc_4 Genotype:Knockout | Sample source:CNS Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=CNS_HILIC_NEG_ifc_4.mzML SUBJECT_SAMPLE_FACTORS - CNS_HILIC_NEG_ifc_5 Genotype:Knockout | Sample source:CNS Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=CNS_HILIC_NEG_ifc_5.mzML SUBJECT_SAMPLE_FACTORS - CNS_HILIC_NEG_WT_1 Genotype:Wild-type | Sample source:CNS Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=CNS_HILIC_NEG_WT_1.mzML SUBJECT_SAMPLE_FACTORS - CNS_HILIC_NEG_WT_2 Genotype:Wild-type | Sample source:CNS Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=CNS_HILIC_NEG_WT_2.mzML SUBJECT_SAMPLE_FACTORS - CNS_HILIC_NEG_WT_3 Genotype:Wild-type | Sample source:CNS Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=CNS_HILIC_NEG_WT_3.mzML SUBJECT_SAMPLE_FACTORS - CNS_HILIC_NEG_WT_4 Genotype:Wild-type | Sample source:CNS Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=CNS_HILIC_NEG_WT_4.mzML SUBJECT_SAMPLE_FACTORS - CNS_HILIC_NEG_WT_5 Genotype:Wild-type | Sample source:CNS Chromatography=HILIC; Polarity=Negative; RAW_FILE_NAME(Raw file name)=CNS_HILIC_NEG_WT_5.mzML #COLLECTION CO:COLLECTION_SUMMARY Whole larvae and dissected CNS CO:SAMPLE_TYPE Larvae #TREATMENT TR:TREATMENT_SUMMARY Untargeted lipidomics analysis was conducted on whole larva and dissected CNS of TR:TREATMENT_SUMMARY wild type and ifc-/- mutants at the late-third instar stage. Five replicates TR:TREATMENT_SUMMARY were prepared for each set of experiments. For whole larvae, at least 15 larvae TR:TREATMENT_SUMMARY of each genotype were used for each replicate. For the dissected CNS, at least TR:TREATMENT_SUMMARY 50 wild type and 60 ifc-/- CNS were used per replicate. Immediately following TR:TREATMENT_SUMMARY collection or dissection, larvae and the dissected CNS were flash frozen in TR:TREATMENT_SUMMARY liquid nitrogen and placed at -80°C. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Whole larvae and CNS samples were extracted utilizing a tissue homogenizer, SP:SAMPLEPREP_SUMMARY employing a solvent mixture of acetonitrile, methanol, and water in a 2:2:1 SP:SAMPLEPREP_SUMMARY ratio, using 40 µL per mg of wet weight. The samples were then stored at -20°C SP:SAMPLEPREP_SUMMARY overnight. Following centrifugation at 14,000 x g for 10 minutes at 4°C, the SP:SAMPLEPREP_SUMMARY supernatant was transferred into an LC/MS vial and subsequently stored at -80°C SP:SAMPLEPREP_SUMMARY until LC/MS analysis. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Agilent 1290 Infinity II CH:COLUMN_NAME Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.7um) CH:SOLVENT_A acetronitrile/water (60/40); 10mM ammonium formate; 2.5 uM medronic acid; 0.1% CH:SOLVENT_A formic acid CH:SOLVENT_B 2-propanol/acetonitrile (90/10); 10mM ammonium formate; 0.1% formic acid CH:FLOW_GRADIENT 0-2min: 30% B, 2-17 min: 30%-75% B, 17-20 min: 75%-85% B, 20-23 min: 85%-100% B, CH:FLOW_GRADIENT 23-26 min: 100% B CH:FLOW_RATE 250 uL/min CH:COLUMN_TEMPERATURE 60 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Orbitrap ID-X tribrid MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS Data were collected with the following MS source settings: spray voltage, -3 kV; MS:MS_COMMENTS sheath gas, 50; auxiliary gas, 10; sweep gas, 1; ion transfer tube temperature, MS:MS_COMMENTS 300°C; vaporizer temperature, 350°C; mass range, 100 – 1500 Da; resolution, MS:MS_COMMENTS 120,000; maximum injection time, 150 ms; isolation window, 1.6 Da. XCMS and MS:MS_COMMENTS Skyline software were used for data processing #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS peak area MS_METABOLITE_DATA_START Samples CNS_RPLC_POS_WT_1 CNS_RPLC_POS_WT_2 CNS_RPLC_POS_WT_3 CNS_RPLC_POS_WT_4 CNS_RPLC_POS_WT_5 CNS_RPLC_POS_ifc_1 CNS_RPLC_POS_ifc_2 CNS_RPLC_POS_ifc_3 CNS_RPLC_POS_ifc_4 CNS_RPLC_POS_ifc_5 Factors Genotype:Wild-type | Sample source:CNS Genotype:Wild-type | Sample source:CNS Genotype:Wild-type | Sample source:CNS Genotype:Wild-type | Sample source:CNS Genotype:Wild-type | Sample source:CNS Genotype:Knockout | Sample source:CNS Genotype:Knockout | Sample source:CNS Genotype:Knockout | Sample source:CNS Genotype:Knockout | Sample source:CNS Genotype:Knockout | Sample source:CNS Cer 14:1;2O/18:0 24961778 22264762 20099538 26634718 10113100 109215 32232 57683 17482 746 Cer 14:1;2O/20:0 95577312 81455824 70237128 89163424 46294076 1385163 650979 847050 454788 1036730 Cer 14:1;2O/24:0 3507467 3585756 3078294 3725060 2539771 157048 99307 144266 138460 159508 CL 32:2_34:2 1390492 1299993 1197654 916521 522651 8268124 6434310 5715181 4174793 7141712 CL 34:4_34:3 7191944 6681546 6630805 5728539 2642039 3025753 2120529 1705747 1649054 3415406 DG 16:1_18:3 14504058 9339145 8256343 9981108 5746445 1117480 721511 1367870 256968 1084648 DG 18:1_18:1 19500664 11704712 10179884 8763921 5958867 3161007 2068291 3275120 1564215 4278374 HexCer 14:0;2O/18:0 262276 93730 68979 63431 46407 24945880 14849616 16488217 7483087 19430346 HexCer 14:0;2O/20:0 290496 208162 149370 125908 91155 29979996 21928816 23088088 13459318 27223896 HexCer 14:0;2O/22:0 47972 9568 44741 20640 16923 9505316 7369927 7028458 4793756 8190399 LPE 34:1 224984912 195217712 164023504 196288848 133653512 460703360 362689984 361396096 233958000 415612480 LPE 36:1 263642368 213843600 202473904 169610368 131180800 393637696 314722848 285291232 285310496 458336192 LPE 36:3 941448512 729748928 633662528 620086080 437375840 397822944 309804064 308668864 179270576 327730112 PC 13:0_22:3 26915272 18066482 16917704 16597833 6554290 11714586 4402840 5301877 2593425 6253461 PC 14:1_20:2 2227642880 1589403520 1464473856 1480458624 597380992 891349312 555422464 661892928 346711872 798877056 PC 14:1_22:4 117927920 83846808 82763064 86007400 31668456 11151544 7406962 7711017 4475909 9858514 PC 17:0_17:0 11250409 8682896 7265422 8735168 6927580 7653545 6091573 6039775 4725710 7807113 PC 17:2_17:2 209913728 169918016 149845760 191743264 73382448 83244088 58258880 63243016 31114792 65981884 PC 18:1_18:1 1280264960 936485952 887335488 852073344 466332864 2178817024 1591254400 1614164480 807873728 1784738432 PC 18:2_18:2 840624896 601348800 567335040 582456640 221342784 187358864 126587472 145481760 74738760 180329872 PC 18:3_18:3 5309056 4463928 4136531 5450462 2140879 749278 570883 598123 263761 607448 PE 10:0_26:3 546808000 434120128 384012672 381152800 222357088 145078080 109956072 107979952 61838088 121701152 PE 14:1_20:2 824234624 740219200 659655360 607983936 295626784 215346752 149715440 160493520 95013488 177024928 PE 17:0_17:0 13414251 12111647 12691474 12286905 13519301 7556023 7093265 7145690 6454695 4705532 PE 17:2_17:2 115946760 91535448 87727040 97042288 38457608 50239404 31243328 34641324 19464278 39432616 PE 18:0_18:5 80102792 57000336 57214556 58800280 24727150 8302941 5461118 6266497 3332366 8269851 PE 18:1_18:1 1835307648 1473154432 1358884864 1356121728 920184960 2773572608 2049967360 2064938496 1114939648 2151108352 PE 18:2_18:2 480655904 384173952 361648448 348499264 171611360 163224816 109440928 114919392 62661508 132966480 PI 36:6 2266871 1701464 1840787 2021609 755548 353037 238807 200186 56903 185276 PS 18:0_18:3 69952752 56070224 46252324 43337524 21259232 17900776 10925116 10474394 6533055 12165430 PS 18:1_18:1 473990816 400343392 363622816 362367904 171675760 985099776 713266880 719044416 413033792 685519232 TG 12:0_16:1_18:3 10249836 10104936 9892115 5929701 5119448 1341343 1727988 996177 910650 728455 TG 14:1_16:1_18:2 36201136 38114052 37877048 20866760 20596908 6239923 6614201 4857289 5137004 3231657 TG 16:0_16:0_16:1 20299974 21833782 23572898 12323340 18454154 10658586 7428594 10244197 9604090 5772566 TG 16:0_16:1_18:2 132299160 148711968 147492288 74317384 103882160 39893908 46236032 36166104 41816920 19899334 TG 16:0_18:1_18:1 27736178 32332698 33350478 18015186 29226694 7031325 7384266 5979707 8418885 4851919 TG 16:1_16:1_18:2 119394632 129099240 125709432 69122224 80363192 16514755 17543312 13179558 15628201 8493711 TG 16:1_16:1_18:3 42505728 46739048 47282724 27331250 27237070 4718008 5247617 3421449 4283830 2442234 TG 16:1_18:2_18:2 90933208 98672272 99003096 55264708 63549544 6832706 7335347 5246633 6634174 3847249 TG 16:1_18:2_18:3 25030866 25455600 26928252 15744801 15673993 544204 623255 431153 504091 311613 C14 Sphinganine 1466338 1465397 2205794 1828763 621399 17630356 14581423 8981284 5364293 11122315 C14 Sphinganine-1 phosphate 348235 237633 504741 439411 126506 3328299 2607574 1139330 732673 1148243 C14 Sphingosine 640865 533406 557643 875937 320721 121745 132769 51636 64939 74734 C14 Sphingosine-1 phosphate 47092 24049 46224 59765 5541 0 0 0 0 0 Cer 14:0;2O/18:0 1704153 617843 601457 468380 292825 21023282 15848353 16454473 7587824 18031366 Cer 14:0;2O/20:0 1071632 1592028 706457 869861 812558 64050888 54661800 53529500 35173484 57902292 Cer 14:0;2O/24:0 657592 520867 346751 509038 262348 3188005 2633580 2729064 3352458 3437246 GlcCer d14:0/18:0 262276 93730 58530 63431 46400 24825222 14705885 16427885 7427772 19331816 GlcCer d14:0/20:0 195740 98976 112504 79379 76047 29850132 21848210 23036316 13403286 27048892 GlcCer d14:0/22:0 50616 9570 47578 25816 16923 9467129 7369927 7016507 4794701 8179180 GlcCer d14:0/24:0 0 0 0 0 0 574035 488525 486891 474015 567907 GlcCer d14:1/18:0 3290360 2427552 2107632 1679911 694820 51833 37906 29033 14457 29204 GlcCer d14:1/20:0 9694627 7817972 6556749 6170444 2642558 312551 54008 98393 108024 198896 GlcCer d14:1/22:0 4651878 3392321 2982011 2994599 2017847 1707346 1240594 1211354 651706 1471621 CerPE d14:1;2O/16:0 4292943 3444656 3462347 3561627 1496728 5289 0 0 0 2052 CerPE d14:1;2O/18:0 226934064 179614816 173546512 167630448 69835152 2217573 1132816 1454786 662633 1425631 CerPE d14:1;2O/20:0 467547968 388062240 333045888 345875488 191800976 11809190 6358537 8071314 4754493 8145543 CerPE d14:1;2O/22:0 249922432 239043888 212047264 228615072 179628704 11272880 7799289 8386142 5460843 7987569 CerPE d14:1;2O/24:0 17680170 19301912 18398132 17850046 15423148 870810 503529 594588 353423 418210 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Cer 14:1;2O/18:0 Cer 14:1;2O/20:0 Cer 14:1;2O/24:0 CL 32:2_34:2 CL 34:4_34:3 DG 16:1_18:3 DG 18:1_18:1 HexCer 14:0;2O/18:0 HexCer 14:0;2O/20:0 HexCer 14:0;2O/22:0 LPE 34:1 LPE 36:1 LPE 36:3 PC 13:0_22:3 PC 14:1_20:2 PC 14:1_22:4 PC 17:0_17:0 PC 17:2_17:2 PC 18:1_18:1 PC 18:2_18:2 PC 18:3_18:3 PE 10:0_26:3 PE 14:1_20:2 PE 17:0_17:0 PE 17:2_17:2 PE 18:0_18:5 PE 18:1_18:1 PE 18:2_18:2 PI 36:6 PS 18:0_18:3 PS 18:1_18:1 TG 12:0_16:1_18:3 TG 14:1_16:1_18:2 TG 16:0_16:0_16:1 TG 16:0_16:1_18:2 TG 16:0_18:1_18:1 TG 16:1_16:1_18:2 TG 16:1_16:1_18:3 TG 16:1_18:2_18:2 TG 16:1_18:2_18:3 C14 Sphinganine C14 Sphinganine-1 phosphate C14 Sphingosine C14 Sphingosine-1 phosphate Cer 14:0;2O/18:0 Cer 14:0;2O/20:0 Cer 14:0;2O/24:0 GlcCer d14:0/18:0 GlcCer d14:0/20:0 GlcCer d14:0/22:0 GlcCer d14:0/24:0 GlcCer d14:1/18:0 GlcCer d14:1/20:0 GlcCer d14:1/22:0 CerPE d14:1;2O/16:0 CerPE d14:1;2O/18:0 CerPE d14:1;2O/20:0 CerPE d14:1;2O/22:0 CerPE d14:1;2O/24:0 METABOLITES_END #END