#METABOLOMICS WORKBENCH RCulpHill_20190809_082957 DATATRACK_ID:1794 STUDY_ID:ST001240 ANALYSIS_ID:AN002059 PROJECT_ID:PR000830 VERSION 1 CREATED_ON August 19, 2019, 3:51 pm #PROJECT PR:PROJECT_TITLE Trisomy 21 activates the kynurenine pathway via increased dosage of interferon PR:PROJECT_TITLE receptors PR:PROJECT_SUMMARY Trisomy 21 (T21) causes Down syndrome (DS), affecting immune and neurological PR:PROJECT_SUMMARY function by unknown mechanisms. We report here a large metabolomics study of PR:PROJECT_SUMMARY plasma and cerebrospinal fluid showing that people with DS produce elevated PR:PROJECT_SUMMARY levels of kynurenine and quinolinic acid, two tryptophan catabolites with potent PR:PROJECT_SUMMARY immunosuppressive and neurotoxic properties, respectively. We demonstrate that PR:PROJECT_SUMMARY immune cells of people with DS overexpress IDO1, the rate-limiting enzyme in the PR:PROJECT_SUMMARY kynurenine pathway (KP) and a known interferon (IFN)-stimulated gene. PR:PROJECT_SUMMARY Furthermore, we show positive correlations among levels of IFN-inducible PR:PROJECT_SUMMARY cytokines and KP dysregulation. Using metabolic tracing assays, we determine PR:PROJECT_SUMMARY that IFN stimulation causes IDO1 overexpression and kynurenine overproduction in PR:PROJECT_SUMMARY cells with T21, dependent on overexpression of IFN receptors encoded on PR:PROJECT_SUMMARY chromosome 21. Finally, we show a mouse model of DS carrying triplication of the PR:PROJECT_SUMMARY IFN receptors exhibits KP dysregulation. Altogether, these results reveal a PR:PROJECT_SUMMARY mechanism by which T21 could drive immunosuppression and neurotoxicity in DS. PR:INSTITUTE University of Colorado Denver PR:LABORATORY Linda Crnic Institute, Costello Lab, D'Alessandro Lab PR:LAST_NAME Culp-Hill PR:FIRST_NAME Rachel PR:ADDRESS 12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA PR:EMAIL rachel.hill@cuanschutz.edu PR:PHONE 303-724-5798 #STUDY ST:STUDY_TITLE Global Metabolic Analysis Trisomy 21 - Cohort 2 ST:STUDY_SUMMARY A global metabolic analysis comparing the plasma of individuals with and without ST:STUDY_SUMMARY trisomy 21. Cohort 2. ST:INSTITUTE University of Colorado Denver ST:LAST_NAME Culp-Hill ST:FIRST_NAME Rachel ST:ADDRESS 12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA ST:EMAIL rachel.hill@cuanschutz.edu ST:PHONE 303-724-5798 #SUBJECT SU:SUBJECT_TYPE Human SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:AGE_OR_AGE_RANGE 0.5 - 76.5 SU:GENDER Male and female #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_1 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_3 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_6 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_7 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_9 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_10 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_13 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_16 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_17 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_19 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_20 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_22 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_25 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_28 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_29 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_31 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_33 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_34 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_35 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_37 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_38 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_39 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_40 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_41 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_42 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_43 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_44 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_46 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_47 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_48 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_49 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_51 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_55 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_56 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_57 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_58 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_59 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_60 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_61 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_62 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_63 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_64 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_67 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_68 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_70 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_71 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_72 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_74 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_75 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_78 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_79 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_80 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_81 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_82 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_83 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_84 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_86 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_87 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_88 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_89 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_91 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_93 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_95 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_96 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_97 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_D21_99 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_2 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_4 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_5 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_8 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_11 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_12 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_14 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_15 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_18 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_21 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_23 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_24 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_26 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_30 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_32 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_36 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_45 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_50 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_52 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_53 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_54 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_65 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_66 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_69 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_73 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_77 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_85 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_90 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_92 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_94 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4pos_T21_93 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_1 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_3 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_6 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_7 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_9 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_10 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_13 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_16 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_17 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_19 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_20 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_22 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_25 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_28 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_29 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_31 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_33 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_34 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_35 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_37 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_38 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_39 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_40 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_41 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_42 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_43 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_44 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_46 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_47 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_48 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_49 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_51 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_55 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_56 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_57 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_58 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_59 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_60 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_61 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_62 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_63 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_64 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_67 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_68 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_70 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_71 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_72 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_74 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_75 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_78 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_79 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_80 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_81 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_82 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_83 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_84 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_86 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_87 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_88 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_89 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_91 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_93 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_95 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_96 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_97 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_D21_99 Cohort:D21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_2 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_4 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_5 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_8 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_11 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_12 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_14 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_15 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_18 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_21 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_23 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_24 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_26 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_30 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_32 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_36 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_45 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_50 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_52 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_53 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_54 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_65 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_66 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_69 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_73 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_77 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_85 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_90 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_92 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_94 Cohort:T21 SUBJECT_SAMPLE_FACTORS - HTP_4neg_T21_93 Cohort:T21 #COLLECTION CO:COLLECTION_SUMMARY All human subjects in this study were consented according to Colorado Multiple CO:COLLECTION_SUMMARY Institutional Review Board (COMIRB)-approved protocols. Written informed consent CO:COLLECTION_SUMMARY was obtained from parents or guardians of participants under the age of 18, and CO:COLLECTION_SUMMARY assent was obtained from participants over the age of 7 who were cognitively CO:COLLECTION_SUMMARY able to assent. Deidentified plasma samples for Cohort 1 were obtained from the CO:COLLECTION_SUMMARY Translational Nexus Clinical Data Registry and Biobank (University of Colorado CO:COLLECTION_SUMMARY Anschutz Medical Campus, COMIRB 08-1276). Additional plasma and WBC samples were CO:COLLECTION_SUMMARY obtained through the Crnic’s Institute Human Trisome Project (University of CO:COLLECTION_SUMMARY Colorado Anschutz Medical Campus, COMIRB 15-2170, www.trisome.org). Plasma was CO:COLLECTION_SUMMARY collected in Vacutainer tubes (EDTA–purple capped or Lithium heparin–light CO:COLLECTION_SUMMARY green capped) and stored at -80°C. Participant medical history was collected by CO:COLLECTION_SUMMARY the respective biobanks. CO:SAMPLE_TYPE Blood (plasma) #TREATMENT TR:TREATMENT_SUMMARY N/A #SAMPLEPREP SP:SAMPLEPREP_SUMMARY For plasma analyses, a volume of 20μL of was extracted in 480μL of ice-cold SP:SAMPLEPREP_SUMMARY methanol:acetonitrile:water (5:3:2). Subsequently, these solutions were vortexed SP:SAMPLEPREP_SUMMARY for 30 minutes at 4°C. Insoluble proteins were pelleted by centrifugation (10 SP:SAMPLEPREP_SUMMARY minutes at 4°C and 12,000 g) and supernatants were collected and stored at SP:SAMPLEPREP_SUMMARY -80°C until analysis. SP:SAMPLEPREP_PROTOCOL_ID 3MMneg_method.pdf;3MMpos_method.pdf;4MMneg_method.pdf;4MMpos_method.pdf;5MMpos_method.pdf SP:PROCESSING_STORAGE_CONDITIONS -80℃ SP:EXTRACT_STORAGE -80℃ #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY UHPLC-MS metabolomics analyses were performed using a Vanquish UHPLC system CH:CHROMATOGRAPHY_SUMMARY coupled online to a Q Exactive mass spectrometer (Thermo Fisher, Bremen, CH:CHROMATOGRAPHY_SUMMARY Germany). Samples were resolved over a Kinetex C18 column (2.1x150 mm, 1.7μm; CH:CHROMATOGRAPHY_SUMMARY Phenomenex, Torrance, CA, USA) at 25°C using a 3-minute isocratic flow rate at CH:CHROMATOGRAPHY_SUMMARY 250μL/minute at 0% B (A: 95% water/5% acetonitrile, 5mM NH4OAc) for positive CH:CHROMATOGRAPHY_SUMMARY mode. To monitor possible technical variability, aliquots of each of the CH:CHROMATOGRAPHY_SUMMARY individual samples were combined to make technical replicates, which were run CH:CHROMATOGRAPHY_SUMMARY after every 15 samples. Additionally, in each experiment, several lysis solution CH:CHROMATOGRAPHY_SUMMARY aliquots were run as blanks for artifact identification. The Q Exactive mass CH:CHROMATOGRAPHY_SUMMARY spectrometer (Thermo Fisher Scientific, San Jose, CA, USA) was operated in CH:CHROMATOGRAPHY_SUMMARY negative ion mode using electrospray ionization, scanning in Full MS mode CH:CHROMATOGRAPHY_SUMMARY (2μscans) from 65 to 900 m/z at 70,000 resolution, with 4 kV spray voltage, 15 CH:CHROMATOGRAPHY_SUMMARY sheath gas, 5 auxiliary gas. MS analysis and data elaboration were performed as CH:CHROMATOGRAPHY_SUMMARY described74,75. Calibration was performed prior to analysis using the PierceTM CH:CHROMATOGRAPHY_SUMMARY Negative Ion Calibration Solution (Thermo Fisher Scientific). CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um) CH:FLOW_GRADIENT 0-100% B CH:FLOW_RATE 450uL/min CH:COLUMN_TEMPERATURE 45 CH:METHODS_FILENAME 4MMneg_method.pdf CH:SOLVENT_A 95% water/5% acetonitrile, 5mM NH4OAc CH:SOLVENT_B 95% acetonitrile/5% water, 5mM NH4OAc CH:INJECTION_TEMPERATURE 4 CH:ANALYTICAL_TIME 4min CH:CAPILLARY_VOLTAGE 4kV CH:WASHING_BUFFER 10% methanol #ANALYSIS AN:ANALYSIS_TYPE MS AN:LABORATORY_NAME D'Alessandro Laboratory AN:OPERATOR_NAME Rachel Culp-Hill #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_COMMENTS The Q Exactive mass spectrometer (Thermo Fisher Scientific, San Jose, CA, USA) MS:MS_COMMENTS was operated in negative ion mode using electrospray ionization, scanning in MS:MS_COMMENTS Full MS mode (1μscan) from 65 to 975 m/z at 70,000 resolution, with 4 kV spray MS:MS_COMMENTS voltage, 45 sheath gas, 15 auxiliary gas. MS analysis and data elaboration were MS:MS_COMMENTS performed as described74,75. Calibration was performed prior to analysis using MS:MS_COMMENTS the PierceTM Negative Ion Calibration Solution (Thermo Fisher Scientific). #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS relative abundance MS_METABOLITE_DATA_START Samples HTP_4neg_D21_1 HTP_4neg_T21_2 HTP_4neg_D21_3 HTP_4neg_T21_4 HTP_4neg_T21_5 HTP_4neg_D21_6 HTP_4neg_D21_7 HTP_4neg_T21_8 HTP_4neg_D21_9 HTP_4neg_D21_10 HTP_4neg_T21_11 HTP_4neg_T21_12 HTP_4neg_D21_13 HTP_4neg_T21_14 HTP_4neg_T21_15 HTP_4neg_D21_16 HTP_4neg_D21_17 HTP_4neg_T21_18 HTP_4neg_D21_19 HTP_4neg_D21_20 HTP_4neg_T21_21 HTP_4neg_D21_22 HTP_4neg_T21_23 HTP_4neg_T21_24 HTP_4neg_D21_25 HTP_4neg_T21_26 HTP_4neg_D21_28 HTP_4neg_D21_29 HTP_4neg_T21_30 HTP_4neg_D21_31 HTP_4neg_T21_32 HTP_4neg_D21_33 HTP_4neg_D21_34 HTP_4neg_D21_35 HTP_4neg_T21_36 HTP_4neg_D21_37 HTP_4neg_D21_38 HTP_4neg_D21_39 HTP_4neg_D21_40 HTP_4neg_D21_41 HTP_4neg_D21_42 HTP_4neg_D21_43 HTP_4neg_D21_44 HTP_4neg_T21_45 HTP_4neg_D21_46 HTP_4neg_D21_47 HTP_4neg_D21_48 HTP_4neg_D21_49 HTP_4neg_T21_50 HTP_4neg_D21_51 HTP_4neg_T21_52 HTP_4neg_T21_53 HTP_4neg_T21_54 HTP_4neg_D21_55 HTP_4neg_D21_56 HTP_4neg_D21_57 HTP_4neg_D21_58 HTP_4neg_D21_59 HTP_4neg_D21_60 HTP_4neg_D21_61 HTP_4neg_D21_62 HTP_4neg_D21_63 HTP_4neg_D21_64 HTP_4neg_T21_65 HTP_4neg_T21_66 HTP_4neg_D21_67 HTP_4neg_D21_68 HTP_4neg_T21_69 HTP_4neg_D21_70 HTP_4neg_D21_71 HTP_4neg_D21_72 HTP_4neg_T21_73 HTP_4neg_D21_74 HTP_4neg_D21_75 HTP_4neg_T21_77 HTP_4neg_D21_78 HTP_4neg_D21_79 HTP_4neg_D21_80 HTP_4neg_D21_81 HTP_4neg_D21_82 HTP_4neg_D21_83 HTP_4neg_D21_84 HTP_4neg_T21_85 HTP_4neg_D21_86 HTP_4neg_D21_87 HTP_4neg_D21_88 HTP_4neg_D21_89 HTP_4neg_T21_90 HTP_4neg_D21_91 HTP_4neg_T21_92 HTP_4neg_D21_93 HTP_4neg_T21_94 HTP_4neg_D21_95 HTP_4neg_D21_96 HTP_4neg_D21_97 HTP_4neg_D21_99 Factors Cohort:D21 Cohort:T21 Cohort:D21 Cohort:T21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:T21 Cohort:D21 Cohort:T21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:T21 Cohort:T21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:T21 Cohort:T21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:T21 Cohort:D21 Cohort:D21 Cohort:D21 Cohort:D21 dTMP 12154.68 3947.53 10602.66 13040.89 5987.859 3302.127 6126.136 769.7103 1688.062 787.5512 6179.314 1859.521 10054.22 8353.922 14888.02 2952.672 10442.84 3919.742 4126.59 28347.89 15444.8 2967.947 3950.161 15234.73 11284.16 4173.813 11305.15 14011.57 20436.34 20627.32 13722.45 16779.88 18608.81 8314.886 18354.44 10933.52 12076.46 9577.212 6578.533 9512.585 5771.857 3354.438 10571.14 11652.6 14060.69 13585.39 19480.23 14217.55 3608.807 11678.34 28150.57 24818.12 0 14723.61 15663.95 19746.93 16200.7 16674.91 25750.35 23541.85 22107.93 12846.69 26836.61 23184.96 12784.78 20393.52 36127.43 13518.9 18178.2 27637.7 80422.62 14594.95 5303.753 20673.69 4906.048 35539.84 27229.7 15483.02 24382.64 13297.17 5400.802 16190.02 30523.58 11015.17 3105.171 14285.81 21531.43 14499.91 35555.96 11763.36 31711.77 21374.99 17112.69 29569.77 20698.99 20732.05 Thymidine 30764.84 18956.37 17532.07 19382.38 16807.68 20430.54 85793.94 36027.15 42444.89 51890.71 25491.5 23472.23 28128.93 19762.89 27842.96 33927.34 32754.52 21440.63 30187.3 42159.08 29565.1 41164.37 38926.32 17039.52 40762.39 26889.5 32373.94 40591.3 19778.49 51207.36 36486.29 31415.53 29955.02 36782.38 25180.28 36438.16 32744.25 33765.32 35560.68 24570.8 22750.13 40756.96 26161.06 22565.91 34559.86 46829.43 29289.91 23574.72 41411.09 21026.07 36689.39 40262.14 626.6901 19834.87 26518.09 25853.44 12278.1 31854.17 18459.9 41255.04 41089.95 53077.22 32965.72 28235.73 24732.96 29354.8 21895.49 34301.58 21548.71 32435.71 49169.14 39649.89 30338.28 35906.23 25927.19 25399.58 30026.93 38428.71 43319.57 32420.83 20234.86 31602.92 31438.52 28237.61 43547.5 39070.1 28450.55 29568.28 26094.17 43447.96 35340.18 52300.25 28071.35 29760.38 35789.51 38497.12 UTP 77091.69 92125.84 58735.18 59069.61 55224.84 70171.95 70206.95 65733.53 89788.25 75266.02 38360.88 43044.1 46127.11 61173.61 46850.36 44561.56 29579.61 38122.16 36303.24 56517.14 58146.88 18807.6 63239.53 119997.7 59735.81 64211.81 46191.45 47729.36 85834.66 25488.72 59983.86 30437.21 49778.02 31987.5 81570.43 62794.68 73688.93 71402.84 63430.92 39319.24 48805.12 45477.49 54584.43 64598.82 55714.86 64995.3 57626.58 38759.47 21174.09 61322.46 57454.64 50951.8 0 51682.21 49356.38 42468.13 67403.6 62633.81 58844.8 31272.3 32252.21 33703.99 33669.39 16838.6 62453.91 51074.43 55179.61 40558.96 48699.03 61981.19 12163.19 38819.71 11474.1 41550.6 52019.41 54987.7 55619.98 32734.91 23723.29 23700.13 29592.81 39767.84 42105.86 19786.77 26845.13 28649.83 19782.01 28467.8 18474.18 39383.25 29039.4 35657.61 32269.53 41955.69 16172.03 13558.65 D-Fructose 1-6-bisphosphate 72374.98 81157.46 75883.7 66437.59 79630.22 47663.07 47507.44 47235.97 46763.21 32924.55 47563.57 54602.14 53824.8 58940.39 49257 61047.77 40769.28 37966.39 63240.88 53654.48 61517.82 41820.65 52857.64 72389.22 42830.65 52280.29 49764.91 51488.43 71123.95 38312.55 27383.75 44622.04 40679.21 44651.89 47321.71 34809.43 46991.55 48233.43 39862.37 47436.43 48343.51 38472.14 40675.98 58325.81 35642.77 37857.36 56460.89 32000.71 23373.6 36335.51 42579.34 29874.03 0 48058.88 31247.17 33851.05 34750.75 45503.86 54675.58 26008.91 33094.43 33057.2 33441.89 54903.21 42620.43 45451.79 26337.61 37818.18 33928 44678.14 30574.98 31190.15 36669.03 32911.43 56447.51 27670.87 20498.68 30622.29 28168.01 27118.01 21601.64 34541.32 17746 19729.72 16219.91 22821.51 22146.43 25175.06 16229.84 18200.84 31948.39 18094.16 26462.4 33183.54 15087.88 27607.19 Cystathionine 21310.73 29558.59 61922.09 29645.82 39701.47 23179.75 23422.88 47496.89 24569.02 28640.27 99590.38 77879.47 51978.88 57015.45 48165.02 85320.54 76470.27 76421.35 88988.46 66786.94 98634.46 101571.3 77782.6 75092.95 82254.29 79769.74 65734.46 73172.88 66765.99 62174.39 94257.26 68049.49 145373.1 70860.78 67366.68 59249.32 74673.54 88206.72 98863.31 80017.65 72792.32 74789.95 87204.69 82185.12 84064.13 111241.7 85158.12 73034.49 87266.85 129179.9 106281.3 121160 5565.252 89576.85 74170.33 55435.74 67718.16 75658.39 91837.27 83556.64 81208.14 109330.3 73806.65 118577.2 103424.8 460581.1 77043.27 87930.06 81332.63 94884.52 56325.8 82302.51 96389.5 128308.4 77598.71 73323.95 58072.78 84488.21 89560.16 103309.6 134604.3 67477.19 108845 86578.69 100507.2 113053.7 75686.03 88808.56 95495.2 82966.91 64514.41 71562.8 88259.65 71049.16 80686.77 113325.6 Tetrahydrofolate 26757.88 17440.8 72854.59 21234.06 27601.6 22518.99 24971.17 14894 8627.149 10250.91 34898.31 17765.89 12380.01 30701.68 28977.19 25378.77 24110.77 17329.83 14763.07 33401.93 128979.2 25292.87 33452.55 61462.2 36528.71 70874.61 46048.36 16991.05 52358.64 27482.7 35366.19 24468.44 10169.64 14006.73 23374.77 46463.53 34238.67 12079.45 29393.08 13813.86 36550.43 25245.12 12001.78 24232.19 31307.49 39105.81 28899.38 15074.71 17680.81 34779.85 36927.75 35770.86 0 54018.3 13508.02 28099.42 40999.2 36722.23 22347.63 66237.37 34798.99 53744.25 25033.3 15238.95 33436.65 8047.546 7535.495 20151.29 73153.34 20207.76 22124.87 15953.32 6990.629 46537.25 35806.32 15595.89 25612.24 49834.25 14737.52 24878.12 30407.02 20818.12 24303.28 14501.95 20737.11 13775.68 35612.4 21204.7 13405.9 32946.2 26986.97 7001.551 18839.71 16897.64 17241.68 27380.92 Heptanoic acid 8433.062 12574.57 12156.75 13158.93 14671.41 17564.57 8617.94 10651.43 9928.663 25642.1 14537.13 11672.31 11719.71 15282.07 13439.77 14399.34 30553.89 31559.11 16369.91 24752.17 22900.85 40579.04 20066.21 39170.57 20914.89 47777.81 52740.88 59328.38 42377.52 56898.62 32550.86 41220.26 44940.39 22237.74 47518.09 43620.43 52405.58 57981.57 58898.96 46428.39 51150.79 58348.3 58943.76 51027.55 54748.57 62325.18 53702.25 65757.43 60215.81 62448.19 64325.48 67292.8 64870.52 66082.84 64333.78 62992.02 36610.85 60519.3 39339.07 65265.28 62249.29 58794.11 69667.73 65430.11 69925.34 88905.16 68459.51 59108.45 35147.55 62543.67 79054.26 82832.88 53514.04 62678.87 40248.6 78284.83 65312.95 77023.66 77076.04 78932.06 60275.12 82273.46 56743.84 71760.96 68653.12 57874.34 74182.91 73718.75 66033.23 41196.63 71930.37 68346.24 69618.27 67340.96 52660.25 88028.23 Octanoic acid 45961.51 58051.2 26842.45 28875.8 138330.3 105642.9 110081.3 74785.84 73364.07 15509040 80037.74 135449.2 102082.2 150325.9 103609.9 178360.5 167178.5 46927.71 712869.9 208226 202923.3 523511 206517 297181.6 224793.7 463157.1 333101.4 479063.1 346842.8 315281.2 90272.44 242902.8 281862.5 116891.1 1530386 227762.7 363734.1 271310.7 312557.1 671198.2 347100.5 348697.7 374263.3 428369.6 354477.4 307318 362558 414970.8 314737.8 309988.2 381546.9 488912.4 155213.1 582536.1 423278.1 522683.3 140301.4 464278.1 95157.21 348344.7 375028.7 369093.7 626772 713272.2 556163.2 581535.6 6574322 511058.2 867545.2 431408.8 537981.6 630495.8 215656 580603.9 270132.5 571707.6 167397.8 637399.4 608663.6 636440.5 559218.9 506070.6 3897837 369926.2 330824.7 373204.2 358615.1 351209.4 483707 476829.6 487541.5 783153.1 671991 380142.4 370226 496532.4 Octadecanoic acid 58300.23 2853238 2445006 1111062 338729.5 472444.2 1223132 1215142 754612.1 1078873 339732 835838.8 1423920 1249083 768068.5 124092.7 928671.6 1087550 1177125 2111748 840916.1 4915082 2359668 2243739 1785322 2151071 3281391 1255381 2238235 269086.4 538983.8 2414148 2285309 2247434 1923204 2813903 4142079 2171782 1667837 2735750 2551186 4955296 2627702 3946946 274506.3 2684717 1700562 2216715 1079461 1423027 2207767 2405755 2374038 273397.8 4071856 2289956 1891468 2405680 7210958 277938.1 2603308 3613572 2031929 4615472 2436446 3395271 2167510 2142698 3179956 4606846 3512551 2395216 965736.7 2963653 5895086 2671568 5359712 3493815 3393379 3797377 1124471 2297934 2914300 3635838 2584516 2944648 4859678 3175465 318224.3 2905361 4877696 3431002 5597292 3575239 5368388 3547826 Tetradecenoic acid 724796.3 1442307 1010043 129716 158989.9 789933.1 459386.8 344483.6 226178.8 20839.73 301064.6 769983.5 223748.7 224675.7 595256.4 613889.5 716032 376500 1353553 1993659 4025205 1607996 5124864 4269021 3813039 991702.7 1259368 3842443 280072.7 3542559 1200439 687094.8 746200.5 562601.3 2135486 2895458 1716593 372840.7 1082073 1261866 1320929 1252210 657234.7 895125.7 1085882 214145.7 809510.2 433094.1 1182930 1020626 408622.7 395790.2 18849.68 3625610 349145.8 249259.7 1546474 3990455 376775 1134327 4064438 920710.4 1775822 2461732 1465019 182580.3 584737.2 335852.5 635499.1 913341.7 210754 1388266 316338.5 2039060 5794710 1701994 572158.7 1257932 1747635 288758.8 466829.9 320343.3 199562 223774.2 3125257 1741471 567450.7 3000211 589203.8 5116996 3747353 1144085 1028479 4033546 2319656 1032931 Hexadecenoic acid 20904820 10467040 10826190 1649276 936241.4 15835240 4610408 6379806 6213126 412557.1 6202088 19439700 6817600 2679998 8236154 6544108 15857880 7989638 21222120 39907060 45490640 14820630 45525860 35799270 55005830 11556460 19773950 55432780 3282676 71017800 18238390 4170480 15805820 6979094 14241840 60634290 27783110 4412414 5984108 7836366 9787927 14329450 17856630 28652540 19950760 3916071 11757740 3271879 12929240 22328010 6457966 6018258 125943.2 40915540 4183731 3232339 19345320 51662300 2383418 15071600 44248320 6749580 29879920 29864140 26735000 3262660 17204800 6745024 7614914 18772970 3799869 16449320 3060059 34416870 95973720 25409500 12563180 11104200 31455540 3042985 3143496 3102721 3161204 5998902 58826290 27209560 16689020 41631780 6239828 89091740 65083940 20432310 20424240 44401110 34697550 21079440 Octadecenoic acid 57107340 76416070 84465590 23744870 19145980 165660100 78572910 59114910 99775620 12499280 64101950 180915800 107295200 41865720 94729280 70495060 166408100 93956220 381016800 305243000 473069400 174869500 320700800 270862000 351783300 237809800 307401500 380570900 67366310 449835700 314965500 152664100 179967400 124579700 240830000 452895000 439504400 88680260 171066300 111563200 261406100 196891500 326011300 165314900 239537600 69911580 178089300 93635740 115122400 261714.2 262378.8 255429.9 254090.1 246730.2 250456.9 266382.6 598425.2 334130.8 493813.9 274699.9 257389.4 291413.8 263159.3 288129.8 304187.3 286967 267165.2 294602.1 736354.8 322839.8 315731.5 297481.1 418461.9 279984.3 316920.6 338276.5 430388.4 342833.8 312241.5 328750.8 355760.8 291936.9 289129 266579.6 293817 352154.1 281446.4 299595.7 278552.3 489606 338148 364319.1 360478.9 325969.9 319780.2 373358.5 Linoleate 230669200 75509140 63109020 15944370 11983600 81962500 55022060 33706100 55265250 8113824 34976410 100808200 51511150 25883110 52937390 53064000 71887100 56535730 128528800 165951700 146263700 73664640 160655200 146362900 157848400 149329400 137357100 151908900 38307030 235145800 145346500 56764890 94985130 57373340 64381780 236230900 265988700 34730540 89566880 37061990 151046000 112957100 114956400 76221260 117202000 52604140 107697300 48709090 39915750 74949460 43876690 41453510 324710.7 105848800 50873000 26048900 132884300 215066300 32983330 100055700 153175100 97276500 158768100 134611400 68463460 22715470 180621000 45937660 100433100 105789100 47776750 64490690 18024570 160320700 240110300 211636600 92737240 53337760 134286800 43612970 48279180 52974560 98833220 32431460 314139000 198865500 112983600 132094700 72708440 294755000 219979800 140623800 116656200 141978300 155812800 102477200 Octadecatrienoic acid 16436360 8939522 7936618 1247621 915054.4 7330606 5332088 2229386 4312390 538734.3 2913724 7815308 3800107 1962086 4501088 2885683 6184030 6164650 9899549 18780920 14070420 7461330 22433150 16271930 16396360 21683260 9710095 31127520 2753794 22925340 15543440 5767130 7314580 8317750 7806092 31157720 26002940 3017097 10382330 4379558 15720700 13681130 7682470 6415176 14905650 5922818 15255140 4154295 3917552 3412154 3742346 4379358 10775.85 10154680 3680255 1478400 9784591 30200330 2323144 13602300 17302200 7768606 17264930 9832747 3244273 1129950 12365050 3743659 13343210 7778456 2735523 4668714 1108822 17929290 20901290 12889040 6857590 3482536 10578000 4511958 6118832 5452418 9545748 1884428 24302210 22698320 10724600 16794130 3847802 29341750 24647410 15382660 12012210 14599810 19723690 11274210 Eicosapentaenoic acid 458283 708060.5 630701.7 185696.5 132722.3 422008.8 361360.6 176796.2 147940 96627.26 406828.4 463127.5 305671.5 88265.84 206031.6 275659.4 1017094 345366.4 1281155 1254628 3363544 345773.2 2344357 2108906 1883560 666530 2088529 2087766 688476.9 1495638 1168686 839669.4 236848 511722.2 498240.3 2917635 2116476 530495.1 612303.6 320578.2 2368175 838983.8 231945.8 714498.4 917596.3 651953.9 379326.8 275249.7 466559.5 915789.7 550497.8 951463.1 5764.458 2248689 562450.3 245276.6 1511601 1220768 345749.2 243304.9 1282511 578229.8 475922.8 287864.4 1010908 340291.2 290590.5 228857.1 876455.3 466086.8 259566 781371.2 199446.3 2182038 1254661 521715.5 459170.4 688148.6 480993.1 248034.7 291337.6 185358.6 278174.9 290782.5 926798.9 782758.7 1194522 1117480 273786.2 863894.1 995287.6 395021.8 350073.2 702718.2 710698.9 571226.2 Docosahexaenoic acid 12222790 3824792 2981369 1319257 1269817 4064943 5845506 1294281 1194081 375266.5 2579424 2669416 1474847 771388.8 1321058 1738888 5127180 3464186 8601634 10941640 25149400 3321100 15022140 17898110 10627750 5642876 11694430 8397535 3076009 11615740 9502316 8657431 2827453 6732742 7892726 17466280 17289990 5570320 9588886 5304764 27979190 6556858 2971590 9917355 9072566 4371472 5274900 2980294 3215673 6764158 3903961 5178195 15491.39 7538622 2730299 1460048 4803030 10542720 2726300 3197577 6563254 5599894 5704724 2804172 7853928 2285539 6073102 3525034 10576130 4009737 2769882 3906644 1780174 20169500 5492607 6108962 2424560 3476045 6471536 2003566 3897185 1472392 4728470 1967244 6996574 4333048 9812957 7889012 4722632 4759042 6192106 7565378 2743054 5997712 6277524 3417085 Dihomo-gamma-linolenate 994230.6 902870.1 598386.9 364646.5 316068.1 1021576 602409.9 340800.2 442977.8 97193.21 818433.3 1321690 644809.9 343234.5 589051 770845 1045925 1376740 2102859 3580802 2067351 883575.9 2521964 2840844 2356605 1842822 2259644 2505469 945180.2 3550289 1920378 842794.3 1789640 1228480 1587641 4420244 3714408 936760.2 2149371 1011760 3648984 1610664 1922184 1759534 1792695 1334305 1301456 1475803 550165.6 1333969 1018074 745497.8 9397.127 2928928 1483298 1073096 3292989 4949791 667417.2 1130622 1831733 2297748 3939506 1679079 1295209 515235.5 2143974 917448.7 1505578 1519610 515098.5 1145549 331018.1 2261630 3891790 2365802 1804840 1260819 2455044 888170.1 772206 556683.6 795388.1 623750.4 4786986 2238042 1259581 2249497 1370542 4200428 3949313 2583869 1387584 2211902 2011732 1670634 (7Z,10Z,13Z,16Z,19Z)-Docosapentaenoic acid 1910557 1179004 654148.1 197495.2 2144.803 1080246 824421.7 398760.2 379832.8 81581.8 746007.6 1277830 566846.8 5943.228 538296.6 704511.7 1634633 624034.4 1897685 2428939 4996076 1104473 3331264 3539272 2410012 1754004 3081281 3026066 636153.2 2938973 2062596 1541308 800268.5 881390.2 1741374 6755834 4191249 1293633 1382017 870319 5237140 1956858 1267599 1881011 1987070 1148111 1193537 553032.8 751522.2 1921648 863457.1 872337.2 3965.475 3744812 906202.2 545852.9 3094596 5108018 699225.8 792412.8 2591733 1198807 2099244 1623394 1717790 402546.7 992701.7 571324.7 1981083 2103254 499700.4 1148674 320574 3622709 5077348 3082757 1078796 1081029 1819097 655422.2 717742.8 457257.4 577576.9 751073.7 4881260 2526901 1695748 2660415 956078 3214486 3157520 1697673 1077598 2605453 2577656 1501650 Arachidonic Acid 21300010 4811228 2763510 1990656 2028571 3144270 3503961 1985032 1786007 671469.8 4119061 5002986 3009014 1842105 3546818 8537515 5843628 4471338 9734005 12394070 8299894 4585058 8301224 9438896 7986362 9560215 14764670 13042590 5661782 15829380 6800740 5241570 6209928 6811088 10882510 17731530 14790540 8407249 11437840 5153305 19490110 8784260 7266112 5798240 8649931 10322020 8922324 3571599 2926470 6873890 3566766 3849060 57504.07 17005540 6651434 3549265 11572350 26002880 4875510 4116826 6294836 9359985 6582994 7911238 6725190 3363248 8252540 4332388 7864384 11681780 3547612 3870136 1662551 16777400 19154660 15314780 7264172 4381664 8561515 3445129 3321292 3939406 4874318 3351366 16096850 13053280 5292146 8442799 4879028 16009820 13541250 7469118 5328660 13750390 8520384 5939256 Adrenic Acid 398926.7 698843.3 480040.4 216048.2 209149.2 487569.5 387926.2 255146.8 314560.6 45642.54 630846.1 1146606 571130.1 257830.8 504394.8 502977.1 730909.2 707850.3 1612523 1509960 1643233 686462.2 891328.7 1229108 913295.4 1348074 2037901 1551548 637696.9 2660673 1060160 569521.9 1203029 763293.7 1278739 2802984 1991204 944323.2 1527449 807501.7 2310916 999950.1 1513260 839640.1 1124552 1086042 1165802 1019339 391710.1 1066065 405489.5 323360.2 2775.737 2067016 851842.2 687227.2 2837708 3692216 519511.9 686766.6 967271.8 1391919 2099704 1958840 820538.9 368306.6 931810.1 529275.1 1062701 1743839 480953.6 547932.9 203832.9 2127778 4784877 3177130 1694515 868842.8 1845996 528623.2 471854.6 549780.5 590686.7 601491.1 3708619 2269834 640730.8 1204553 856207.1 3578377 2885886 1458126 864037 2063264 1246621 1109103 11(12)-DiHET 0 0 0 0 0 5121.77 0 0 0 0 0 11023.73 4748.336 0 15263.39 6882.437 13460.01 10612.09 36239.88 19374.99 30385.77 26275.94 41606.85 61843.9 53671.54 47343.8 67698.57 126336.6 66599.12 61186.8 67324.23 82507.37 188071.9 100236.8 108539.4 99575.38 89408.91 50795.44 63040.08 52683.22 76675.89 72533.48 78162.55 79675.57 79240.48 66412.73 65531.55 32845.18 69417.51 68955.91 60290.95 49889.26 6944.445 105133.7 69664.66 75142.23 96312.44 120003.6 57783.79 88700.63 81991.84 88062.37 112898.5 89999.55 85385.74 73876.3 72374.02 67996.14 100110.1 98067.34 45912.09 77911.53 53079.96 101838.5 109189.7 102136.8 110995 81914.98 98962.53 52522.39 89902.81 76480.3 93810.9 52996.36 104181.1 126129.8 96234.66 80933.47 86659.01 132068.6 109018.5 116565.3 129003.5 143714.1 122968 99786.96 Prostaglandin A2 38716.46 168453.3 150985.1 9265.254 15922.06 72592.77 27726.51 164109 78366.09 135074.7 65953.77 54360.5 252567.9 91904.19 211280 206727.2 60642.74 14754.09 1306639 406381.5 23903.3 262204.7 144054.2 998449.3 284495.2 421573.2 924098 214642.8 23589.34 248894 270933.6 232921.5 32085.05 27184.15 673865.1 1407034 1080180 312863.8 1259953 49205.22 33382.3 141771.3 122262.1 33884.1 719296.3 31991.92 22904.16 22565.96 266714 35147.87 18151.96 348105.3 4715.345 94981.71 18129.86 236403.8 66345.09 99372.71 37251.3 142510.5 50888.14 422194.4 44557.76 358156.3 27400.33 112817.8 31534.09 27534.21 382428.2 47888.37 315593.8 8939.465 6076.627 367500.2 131471.2 28641.91 30104.83 232645.8 28746.67 171465.6 758458.7 69218.12 22764.38 44401.29 117099.2 191502.5 261372 13767.47 154590.3 16195.23 125772.7 39824.75 174092 123196.3 1266734 304206.2 Prostaglandin D3 12798.55 4244.67 2958.848 22438.44 11680.9 6329.714 2304.022 1385.587 4624.751 4258.02 2864.322 26020.01 5419.002 1225.411 10709.57 20168.49 32305.9 16665.17 43735.89 95830.97 73540.59 52298.72 137835.5 131702 240619.7 48837.48 66172.42 189997.2 9451.546 270725.9 87459.38 22102.45 46533.16 38755.05 83301.68 417573.5 183013.2 28341.07 36052.63 51898.02 53594.88 113682 135103.9 220342 119161.9 29130 102355.2 12803.03 91591.65 187356.6 39349.3 41842.91 861.7415 353400.2 29605.3 25020.71 78581.59 281746.1 16549.4 153519.6 288971.4 65449.2 153870.7 183256.4 251598.1 45718.45 342013.5 98809.38 101318.4 183587.7 44937.5 166336.7 40465.2 323111.1 364668.2 209178.3 58381.97 122691.4 333337.5 38935.58 41984.21 40232.39 40463.88 64444.46 535831.6 243816.5 205897.1 279516.6 52474.22 462022.2 348112.7 108492.1 160618 381588.5 327841.3 147637.6 Prostaglandin E2 5084.955 5812.494 0 5961.916 12499.29 38517.83 37859.88 43442.53 117446.6 35255.83 128705.4 309663 196499.4 136865 271669.5 293032.8 467921.4 339826.2 699678.6 639712.6 806021.5 659139.9 879548.2 929262.7 1337532 946108.5 1003784 1534824 573458.9 1876671 1290690 806845.8 945619 892775.1 1108831 1804607 1720223 708548.1 1114658 965080.2 1344883 1119430 1507121 1391333 1151173 974752.3 1049065 823136.3 689403.5 1245486 877804.6 991766.4 161948.8 859344 1111247 780847.3 1395947 2175053 398054.2 1486803 1138623 1781732 2209415 1793850 1665544 1040474 1786984 1201322 1365849 1132138 593093.6 1145286 684686 2046110 1892185 1937192 1510362 1337196 1447550 830329.8 1056667 1211727 910918.8 966742.9 2660377 2573617 1200714 1703166 1304468 2317210 2131602 1617728 1401552 1951400 1463773 1474177 Protein glutamine 39312.38 37967.8 37836.96 34722.5 34325.34 34398.01 33980.22 27908.07 25559.34 20675.74 29616.62 39504.26 31584.99 40971.38 40440.68 36425.63 33605.62 40430.77 35807.73 39293.8 31342.46 35814.02 39833.61 25385.1 37739.92 28452.05 36016.47 43430.45 36581.17 35377.68 38668.38 41215.25 34415.26 38424.61 27344.84 43006.89 39941.12 34963.27 37175.99 30822.3 42483.14 34497.93 34785.08 38621.16 33147.41 37661.93 40271.51 33408.61 26883.06 36067.8 38200.17 36473.85 8121.602 40597.58 45112.42 34090.31 42605.14 35188.2 41801.72 34232.39 27537.69 38244.85 41908.79 44386.4 39440.21 38180.97 43232.5 32310.59 34757.23 34099.27 43311.07 46628.64 28345.53 37561.77 35611 37487.74 38502.56 38114.22 44281.71 38781.75 34059.41 41595.06 37651.77 22568.69 33675.82 33932.64 36859.76 32191.38 36313.64 37129.08 37989.47 39881.1 27216.45 34909.96 29329.12 28466.34 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG ID quantitated m/z Retention times dTMP C00364 321.0505 0.6048141 Thymidine C00214 241.0815 0.6789515 UTP C00075 482.95 0.7207673 D-Fructose 1-6-bisphosphate C00354 338.9941 0.6593103 Cystathionine C00542 221.0659 0.6778197 Tetrahydrofolate C00101 444.159 1.763451 Heptanoic acid C17714 129.0906 1.849142 Octanoic acid C06423 143.1064 1.951561 Octadecanoic acid C01530 283.2637 2.004428 Tetradecenoic acid C08322 225.1852 2.466067 Hexadecenoic acid C08362 253.2168 2.747467 Octadecenoic acid C00712 281.248 3.177753 Linoleate C01595 279.2324 2.814818 Octadecatrienoic acid C06427 277.2168 2.587579 Eicosapentaenoic acid C06428 301.2168 2.527558 Docosahexaenoic acid C06429 327.2325 2.606284 Dihomo-gamma-linolenate C03242 305.248 2.907028 (7Z,10Z,13Z,16Z,19Z)-Docosapentaenoic acid C16513 329.2479 2.740024 Arachidonic Acid C00219 303.2324 2.708493 Adrenic Acid C16527 331.2636 3.01482 11(12)-DiHET C14774 337.2356 3.124767 Prostaglandin A2 C05953 333.2072 1.94467 Prostaglandin D3 C13802 349.2043 2.745244 Prostaglandin E2 C00584 351.2197 3.127086 Protein glutamine C02583 170.0558 0.6343597 METABOLITES_END #FACTORS #END