#METABOLOMICS WORKBENCH Jung_DNLI_20240919_115027 DATATRACK_ID:5207 STUDY_ID:ST003501 ANALYSIS_ID:AN005748 PROJECT_ID:PR002147 VERSION 1 CREATED_ON September 26, 2024, 4:43 pm #PROJECT PR:PROJECT_TITLE TREM2 expression level is critical for microglial state, metabolic capacity and PR:PROJECT_TITLE efficacy of TREM2 agonism PR:PROJECT_TYPE Preclinical Mouse study PR:PROJECT_SUMMARY Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator PR:PROJECT_SUMMARY of microglial activity and sequence variants are major risk factors for late PR:PROJECT_SUMMARY onset Alzheimer’s disease (LOAD). To better understand the molecular and PR:PROJECT_SUMMARY functional changes associated with TREM2 signalling, we generated a TREM2 PR:PROJECT_SUMMARY reporter mouse model and observed a gradual upregulation of reporter expression PR:PROJECT_SUMMARY with increasing plaque proximity. Isolated microglia were sorted based on PR:PROJECT_SUMMARY reporter expression and their transcriptomic profiles acquired in both wildtype PR:PROJECT_SUMMARY and APP transgenic animals, allowing us to disentangle TREM2 versus PR:PROJECT_SUMMARY pathology-specific effects. Bulk RNA sequencing highlighted TREM2 PR:PROJECT_SUMMARY level-dependent changes in major immunometabolic pathways, with enrichment of PR:PROJECT_SUMMARY genes in oxidative phosphorylation and cholesterol metabolism in microglia with PR:PROJECT_SUMMARY increased TREM2 expression. To confirm these findings, we next analysed uptake PR:PROJECT_SUMMARY of fluorodeoxyglucose (FDG) and examined metabolomic and lipidomic profiles. PR:PROJECT_SUMMARY Again, independent of Aβ pathology, TREM2 expression correlated with uptake of PR:PROJECT_SUMMARY FDG as well as increased cellular redox, energetics, and cholesterol PR:PROJECT_SUMMARY homeostasis. Finally, we performed chronic treatment with a brain penetrant PR:PROJECT_SUMMARY TREM2 agonist and identified a window of TREM2 expression where microglia are PR:PROJECT_SUMMARY most responsive. Thus, our data provide novel insights into TREM2-mediated PR:PROJECT_SUMMARY regulation of microglial metabolic function and informs current efforts to bring PR:PROJECT_SUMMARY TREM2 agonists into clinical application. PR:INSTITUTE Denali Therapeutics PR:DEPARTMENT Development Sciences PR:LAST_NAME Suh PR:FIRST_NAME Jung PR:ADDRESS 161 Oyster Point Blvd, South San Francisco, California, 94080, USA PR:EMAIL suh@dnli.com PR:PHONE +1 6507973837 PR:FUNDING_SOURCE Denali Therapeutics PR:PUBLICATIONS https://www.biorxiv.org/content/10.1101/2024.07.18.604115v1 #STUDY ST:STUDY_TITLE TREM2 expression level is critical for microglial state, metabolic capacity and ST:STUDY_TITLE efficacy of TREM2 agonism ST:STUDY_SUMMARY Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator ST:STUDY_SUMMARY of microglial activity and sequence variants are major risk factors for late ST:STUDY_SUMMARY onset Alzheimer’s disease (LOAD). To better understand the molecular and ST:STUDY_SUMMARY functional changes associated with TREM2 signalling, we generated a TREM2 ST:STUDY_SUMMARY reporter mouse model and observed a gradual upregulation of reporter expression ST:STUDY_SUMMARY with increasing plaque proximity. Isolated microglia were sorted based on ST:STUDY_SUMMARY reporter expression and their transcriptomic profiles acquired in both wildtype ST:STUDY_SUMMARY and APP transgenic animals, allowing us to disentangle TREM2 versus ST:STUDY_SUMMARY pathology-specific effects. Bulk RNA sequencing highlighted TREM2 ST:STUDY_SUMMARY level-dependent changes in major immunometabolic pathways, with enrichment of ST:STUDY_SUMMARY genes in oxidative phosphorylation and cholesterol metabolism in microglia with ST:STUDY_SUMMARY increased TREM2 expression. To confirm these findings, we next analysed uptake ST:STUDY_SUMMARY of fluorodeoxyglucose (FDG) and examined metabolomic and lipidomic profiles. ST:STUDY_SUMMARY Again, independent of Aβ pathology, TREM2 expression correlated with uptake of ST:STUDY_SUMMARY FDG as well as increased cellular redox, energetics, and cholesterol ST:STUDY_SUMMARY homeostasis. Finally, we performed chronic treatment with a brain penetrant ST:STUDY_SUMMARY TREM2 agonist and identified a window of TREM2 expression where microglia are ST:STUDY_SUMMARY most responsive. Thus, our data provide novel insights into TREM2-mediated ST:STUDY_SUMMARY regulation of microglial metabolic function and informs current efforts to bring ST:STUDY_SUMMARY TREM2 agonists into clinical application. ST:INSTITUTE Denali Therapeutics ST:LAST_NAME Suh ST:FIRST_NAME Jung ST:ADDRESS 161 Oyster Point Blvd, South San Francisco, California, 94080, USA ST:EMAIL suh@dnli.com ST:PHONE +1 6507973837 ST:NUM_GROUPS 5 ST:TOTAL_SUBJECTS 26 ST:NUM_MALES 26 ST:STUDY_COMMENTS Release as soon as it is possible ST:PUBLICATIONS https://www.biorxiv.org/content/10.1101/2024.07.18.604115v1 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 SU:AGE_OR_AGE_RANGE 15 mo SU:GENDER Male #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 Pool_1 HSA-000019615 genotype:NA | condition:NA | group:NA | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_002; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_001; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_002; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_002 SUBJECT_SAMPLE_FACTORS 2_59_mid_WT HSA-000019571 genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_003; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_009; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_003; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_003 SUBJECT_SAMPLE_FACTORS 12_63_mid_WT HSA-000019581 genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_004; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_027; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_004; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_004 SUBJECT_SAMPLE_FACTORS 24_78_low_APP HSA-000019593 genotype:APP | condition:low | group:low_disease | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_005; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_017; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_005; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_005 SUBJECT_SAMPLE_FACTORS 10_62_mid_WT HSA-000019579 genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_006; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_016; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_006; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_006 SUBJECT_SAMPLE_FACTORS 15_69_low_WT HSA-000019584 genotype:WT | condition:low | group:low_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_007; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_022; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_007; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_007 SUBJECT_SAMPLE_FACTORS 25_78_mid_APP HSA-000019594 genotype:APP | condition:mid | group:mid_disease | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_008; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_012; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_008; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_008 SUBJECT_SAMPLE_FACTORS 18_74_mid_APP HSA-000019587 genotype:APP | condition:mid | group:mid_disease | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_009; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_003; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_009; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_009 SUBJECT_SAMPLE_FACTORS 17_74_low_APP HSA-000019586 genotype:APP | condition:low | group:low_disease | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_010; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_004; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_010; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_010 SUBJECT_SAMPLE_FACTORS 8_61_high_APP HSA-000019577 genotype:APP | condition:high | group:high_disease | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_011; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_011; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_011; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_011 SUBJECT_SAMPLE_FACTORS 21_76_mid_WT HSA-000019590 genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_012; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_020; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_012; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_012 SUBJECT_SAMPLE_FACTORS 14_65_mid_WT HSA-000019583 genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_013; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_028; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_013; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_013 SUBJECT_SAMPLE_FACTORS 7_61_mid_APP HSA-000019576 genotype:APP | condition:mid | group:mid_disease | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_014; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_023; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_014; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_014 SUBJECT_SAMPLE_FACTORS 1_59_low_WT HSA-000019570 genotype:WT | condition:low | group:low_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_015; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_026; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_015; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_015 SUBJECT_SAMPLE_FACTORS 5_60_high_APP HSA-000019574 genotype:APP | condition:high | group:high_disease | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_016; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_007; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_016; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_016 SUBJECT_SAMPLE_FACTORS 22_77_low_WT HSA-000019591 genotype:WT | condition:low | group:low_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_017; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_010; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_017; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_017 SUBJECT_SAMPLE_FACTORS Pool_2 HSA-000019616 genotype:NA | condition:NA | group:NA | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_018; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_014; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_018; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_018 SUBJECT_SAMPLE_FACTORS 23_77_mid_WT HSA-000019592 genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_019; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_015; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_019; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_019 SUBJECT_SAMPLE_FACTORS 11_63_low_WT HSA-000019580 genotype:WT | condition:low | group:low_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_020; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_019; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_020; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_020 SUBJECT_SAMPLE_FACTORS 3_60_low_APP HSA-000019572 genotype:APP | condition:low | group:low_disease | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_021; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_008; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_021; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_021 SUBJECT_SAMPLE_FACTORS 26_78_high_APP HSA-000019595 genotype:APP | condition:high | group:high_disease | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_022; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_025; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_022; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_022 SUBJECT_SAMPLE_FACTORS 19_74_high_APP HSA-000019588 genotype:APP | condition:high | group:high_disease | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_023; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_013; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_023; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_023 SUBJECT_SAMPLE_FACTORS 9_62_low_WT HSA-000019578 genotype:WT | condition:low | group:low_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_024; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_002; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_024; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_024 SUBJECT_SAMPLE_FACTORS 6_61_low_APP HSA-000019575 genotype:APP | condition:low | group:low_disease | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_025; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_021; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_025; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_025 SUBJECT_SAMPLE_FACTORS 20_76_low_WT HSA-000019589 genotype:WT | condition:low | group:low_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_026; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_024; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_026; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_026 SUBJECT_SAMPLE_FACTORS 4_60_mid_APP HSA-000019573 genotype:APP | condition:mid | group:mid_disease | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_027; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_006; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_027; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_027 SUBJECT_SAMPLE_FACTORS 13_65_low_WT HSA-000019582 genotype:WT | condition:low | group:low_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_028; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_018; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_028; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_028 SUBJECT_SAMPLE_FACTORS 16_69_mid_WT HSA-000019585 genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_029; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_005; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_029; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_029 SUBJECT_SAMPLE_FACTORS Pool_3 HSA-000019617 genotype:NA | condition:NA | group:NA | Sample source:microglia RAW_FILE_NAME(Raw Source Name.LP)=20220209_BL_HEX-000330_Lipid_Pos_030; RAW_FILE_NAME(Raw Source Name.TG)=20220324_BL_HEX-000330_TGs_Pos_029; RAW_FILE_NAME(Raw Source Name.MP)=20220209_BL_HEX-000330_Met_Pos_030; RAW_FILE_NAME(Raw Source Name.MN)=20220211_BL_HEX-000330_Met_Neg_030 #COLLECTION CO:COLLECTION_SUMMARY Microglia isolation was performed using the Magnetic-activated cell sorting CO:COLLECTION_SUMMARY (MACS) system (Miltenyi Biotec). No CD11b enrichment step was performed as the CO:COLLECTION_SUMMARY intrinsic mKate2 reporter is only expressed in TREM2 expressing (microglia) CO:COLLECTION_SUMMARY cells. Hence, fluorescence-activated cell sorting was performed based on the CO:COLLECTION_SUMMARY mKate2 fluorescence signal and sorted into low, mid and high expressing CO:COLLECTION_SUMMARY subpopulations, as a proxy for the TREM2 expression of individual cells. CO:SAMPLE_TYPE microglia CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY No treatment #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Pellets from the sorted subpopulations were reconstituted on ice in 9:1 SP:SAMPLEPREP_SUMMARY MeOH:water including internal standards, vortexed for 1 minute, and spun down SP:SAMPLEPREP_SUMMARY for 5 minutes at 10,000 g. Supernatant was transferred to glass vial for SP:SAMPLEPREP_SUMMARY analysis by LC-MS. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY For each analysis, 5 µL of sample was injected on a BEH amide 1.7 µm, 2.1×150 CH:CHROMATOGRAPHY_SUMMARY mm column (Waters Corporation, Milford, Massachusetts, USA) using a flow rate of CH:CHROMATOGRAPHY_SUMMARY 0.40 mL/min at 40°C. Mobile phase A consisted of water with 10 mM ammonium CH:CHROMATOGRAPHY_SUMMARY formate + 0.1% formic acid. Mobile phase B consisted of acetonitrile with 0.1% CH:CHROMATOGRAPHY_SUMMARY formic acid. The gradient was programmed as follows: 0.0–1.0 min at 95% B; CH:CHROMATOGRAPHY_SUMMARY 1.0–7.0 min to 50% B; 7.0–7.1 min to 95% B; and 7.1–10.0 min at 95% B. CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Agilent 1290 Infinity II CH:COLUMN_NAME Waters ACQUITY UPLC BEH Amide (150 x 2.1mm,1.7um) CH:SOLVENT_A 100% water; 10 mM ammonium formate; 0.1% formic acid CH:SOLVENT_B 100% acetonitrile; 0.1% formic acid CH:FLOW_GRADIENT 0.0–1.0 min at 95% B; 1.0–7.0 min to 50% B; 7.0–7.1 min to 95% B; and CH:FLOW_GRADIENT 7.1–10.0 min at 95% B CH:FLOW_RATE 0.40 mL/min CH:COLUMN_TEMPERATURE 40 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME ABI Sciex 6500+ Qtrap MS:INSTRUMENT_TYPE Triple quadrupole MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS curtain gas at 30 psi; collision gas was set at medium; ion spray voltage at MS:MS_COMMENTS 5500 V; temperature at 600°C; ion source Gas 1 at 50 psi; ion source Gas 2 at MS:MS_COMMENTS 60 psi; entrance potential at 10 V; and  collision cell exit potential at 12.5 MS:MS_COMMENTS V. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS log2(area) MS_METABOLITE_DATA_START Samples HSA-000019615 HSA-000019571 HSA-000019581 HSA-000019593 HSA-000019579 HSA-000019584 HSA-000019594 HSA-000019587 HSA-000019586 HSA-000019577 HSA-000019590 HSA-000019583 HSA-000019576 HSA-000019570 HSA-000019591 HSA-000019616 HSA-000019592 HSA-000019580 HSA-000019572 HSA-000019595 HSA-000019588 HSA-000019578 HSA-000019575 HSA-000019589 HSA-000019573 HSA-000019582 HSA-000019585 HSA-000019617 HSA-000019574 Factors genotype:NA | condition:NA | group:NA | Sample source:microglia genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia genotype:APP | condition:low | group:low_disease | Sample source:microglia genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia genotype:WT | condition:low | group:low_healthy | Sample source:microglia genotype:APP | condition:mid | group:mid_disease | Sample source:microglia genotype:APP | condition:mid | group:mid_disease | Sample source:microglia genotype:APP | condition:low | group:low_disease | Sample source:microglia genotype:APP | condition:high | group:high_disease | Sample source:microglia genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia genotype:APP | condition:mid | group:mid_disease | Sample source:microglia genotype:WT | condition:low | group:low_healthy | Sample source:microglia genotype:WT | condition:low | group:low_healthy | Sample source:microglia genotype:NA | condition:NA | group:NA | Sample source:microglia genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia genotype:WT | condition:low | group:low_healthy | Sample source:microglia genotype:APP | condition:low | group:low_disease | Sample source:microglia genotype:APP | condition:high | group:high_disease | Sample source:microglia genotype:APP | condition:high | group:high_disease | Sample source:microglia genotype:WT | condition:low | group:low_healthy | Sample source:microglia genotype:APP | condition:low | group:low_disease | Sample source:microglia genotype:WT | condition:low | group:low_healthy | Sample source:microglia genotype:APP | condition:mid | group:mid_disease | Sample source:microglia genotype:WT | condition:low | group:low_healthy | Sample source:microglia genotype:WT | condition:mid | group:mid_healthy | Sample source:microglia genotype:NA | condition:NA | group:NA | Sample source:microglia genotype:APP | condition:high | group:high_disease | Sample source:microglia 1-Methylhistidine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 1-Methylnicotinamide 17.118408370819942 17.31274655484715 18.01711947555489 17.686134128413396 18.189922250373186 16.961519760710697 16.78274552869033 19.165511951919218 17.313594991758105 17.40318442346489 15.601279001104334 18.892452019697956 18.92664430570262 16.659682653572922 15.844360348982725 17.15885434488249 19.90185050952142 16.29600082467393 16.648407399963492 16.091872384354506 16.76874166129185 16.990310479780515 17.174978101728332 16.736659507416174 16.011464254100215 17.224275457823655 17.071523541044833 17.319115073341237 15.619058470251268 1-Methylxanthine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 1-Methylxanthosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 1,3-15N2-Uric acid NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 13C10,15N5-Adenosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 13C3-Thiamine 25.577874667449514 25.362623122922024 25.415665211640658 25.330774787175628 25.389492127368896 24.93418996819922 25.012849434167222 25.39015382785082 25.61208856539153 25.44566199860753 25.39778889344053 25.35628441931235 25.254025504452883 24.79257939545175 25.312779214677782 25.51224338527625 25.252586612618426 25.21745558304828 25.463761750594774 25.10629975556374 25.61412793294246 25.47268706299516 24.978910130930803 24.975608867402503 25.469136011306993 25.219056764420195 25.01539078 25.52793849314567 25.054208147420823 13C5-Hypoxanthine 14.683005193274733 14.553114818179294 14.646664140244345 14.878575590629325 15.203488200854732 15.294624875782555 15.206829429559741 14.922995936915212 14.184900287033239 14.798774611196242 14.12586552151649 14.475755677353394 14.891317843978145 15.087855934261377 14.472474253590033 13.954475910887565 15.443012389734006 14.784532440414027 14.780965956439399 14.968684640428568 14.965944857863247 14.572970509792196 15.129131010018726 14.951482714666925 13.675615260167442 15.191462144905502 14.069355175035499 15.363251836151123 14.373427610755947 13C5-Xanthosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 15N4-Inosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 2-Aminobenzoic acid NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 3-Hydroxy-N6,N6,N6-Trimethyllysine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 3-Hydroxybutyric acid NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 3-Hydroxykynurenine 17.003947746937264 16.09963319555699 12.006154167544945 16.430852673351136 16.686642429354748 17.07368057810111 16.70619348410331 16.469501937525703 16.031081966303233 16.409600822421837 16.560756315391444 11.965403133460242 16.716811253954777 16.760448801002404 15.701861589181998 16.388133825951446 16.084082321131408 15.959477758401594 17.051555173645976 15.914626528863161 16.24411258279926 16.32290524094969 16.208438927892182 16.25109486832237 16.29106041492129 16.51190852 16.02156380234307 16.54111026724706 16.023733726154163 3-Hydroxytyrosol 16.65724730283869 17.35886120130693 17.248930619526348 16.909105750483793 16.996835530093158 13.942294250924512 17.247045472655167 16.924568926824254 15.979131312680122 16.673399693471374 13.141109590259187 17.83543674438836 17.389722711521053 15.905980519648594 16.952365576177236 16.480724095112265 17.652460336296535 15.751436897788661 16.300428854738225 15.446652757824701 15.44278869825715 16.446647148341064 15.402113457914844 14.176906646954635 15.707968627540021 16.612863428466415 NA 16.437257754229027 15.120652869692748 3-Methoxytyrosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 3-Methylxanthine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 3-Methylxanthosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 4-Hydroxyproline NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 4-Trimethylammoniobutanal NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 5-Glutamylalanine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 5-Hydroxyindoleacetic acid NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 5-Hydroxytryptophan NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 5'-Methylthioadenosine 18.354038683927566 18.803734464606904 18.50278328351489 17.80320232 18.00054746263811 15.160735877600114 18.571773179009547 18.718577678732835 16.80217922295671 19.464898053835118 15.72822690573377 19.331682353749706 18.829119747237936 17.132956849968533 17.77779344276955 18.393181621875552 17.846345987007254 16.78034710141305 17.336729964534236 20.40214518644453 18.65388546171587 17.23323354 17.77612185885989 15.846478986304584 18.301746065373912 17.34877788611036 14.685415798525822 18.592380999461724 18.900213939282754 6-Aminouracil NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 6C13-Phenylalanine 27.472838054367234 27.490184477987803 27.613672107042145 27.562802847105548 27.637753139559653 27.610068283119936 27.50014001 27.638191301075086 27.637065094003447 27.570009099143576 27.597708564530272 27.58808816753631 27.597874100264406 27.570809556423786 27.634425744033365 27.573164351366522 27.61579597572967 27.622828766218717 27.66880515293595 27.46398927458619 27.626672187061292 27.627004008289397 27.48823999471858 27.603310333264485 27.595528224616057 27.649536910444514 27.62018812109662 27.588724651501263 26.718548738201328 6C13-Tyrosine 20.384412942302323 20.323136877640838 20.51678016854169 20.510314141419723 20.440279380088366 20.93876234466297 20.36904466107429 20.75230362329213 20.580510853104244 20.313372348232562 21.560996453270917 20.90665154484772 20.47058787725018 20.41715615679044 20.638704138429457 20.487722512694518 20.48993937598882 20.43759954887383 20.46312298189139 20.450601566988446 20.59955360566843 20.533243629978468 20.757478404020407 20.483578596226803 20.373845528938485 20.646328633127755 20.698074053230798 20.458218101918707 20.015497442776997 7-alpha-Hydroxy-3-oxo-4-cholestenoate NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 7-Methylguanine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 7-Methylguanosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 7-Methylxanthine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 7-Methylxanthosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 8-Hydroxy-deoxyguanosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 8-Oxo-deoxyguanosine-13C,15N2 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 8-Hydroxyguanosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 9-Hexadecenoylcarnitine 13.973423617410168 12.64437407969967 NA 12.931000584352892 12.601577771814146 13.857756829080019 13.120301648400185 12.639626987600678 12.982079124772735 13.136522241910386 13.51784332864928 13.816148723709013 12.869597305674944 12.016862236815122 14.369078499355195 13.397288091312536 13.758076224678405 12.966866491537207 12.613935589398967 14.269837755365685 12.428003647540852 12.532561470201767 11.77748792605901 14.398940877798392 12.735403518886507 13.705743337591137 13.04659366975495 13.355393483988939 NA Acetylcarnitine 19.80792004 19.686059122514635 19.448299376570446 20.410212308937517 18.71923277838725 19.58704297945618 20.018620548424494 19.371577565976718 19.332773376587813 19.091728404395976 16.670761406430305 20.000952773721018 18.935820514096115 19.178571078456354 20.944088517201955 19.685453353548283 19.805187649216904 19.31309078219522 19.468442421160827 20.191758979619458 19.334005941102273 19.472446659083676 19.36486800320355 19.98980652974402 18.585203933862836 19.95771331490842 17.07486474088401 19.594951687169246 18.86608248213692 Acetylcarnitine-d3 28.89237133403795 28.873537000180335 28.93963881861603 28.88238725427018 28.922634570814832 28.995113568015448 28.822706973715583 28.94489111558559 28.92815512714889 28.81589134505859 29.05002983344718 28.97689674477418 28.82075701481232 28.794011445215666 28.87741315445613 28.837090774722856 28.847019300054182 28.82009152378574 28.824846904432217 29.05561388877217 28.827378946754024 28.807710980637506 29.09605920617971 28.78117949277725 28.720959735922595 28.86386331606282 28.844952670088837 28.73523705369352 28.613672321405684 Adenine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Adenosine 21.198604423091243 21.64807128961282 21.615785087410153 19.08478374123092 21.09456670982843 18.162314632850496 21.859577798517723 23.626072612549038 19.430732210973165 23.39291336939078 19.936695393497676 21.768057959072777 22.022221139735223 19.181263917777493 18.783526229923684 21.112211848675916 22.896803611859195 18.942292317409855 18.849179938367005 22.039555611920367 22.42016518299388 18.34841933871912 19.875619621546047 18.047102736204845 22.234451690075833 19.242635858497813 20.992673835535502 20.949713590911887 20.994748811261754 Adenosine diphosphate ribose NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Adenosylcobalamin NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA AICA-riboside NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Alanine 14.106931099424765 13.27741284280711 13.09298935353301 12.95890754856042 NA NA 13.979494250371783 13.590103020169373 12.88411448667209 13.238968471641966 13.119643332960566 13.469887299256827 13.899387663664971 12.913608644801492 14.082232866839215 13.112331204784693 13.911491649280812 13.16467306902687 11.938420048398898 14.276091458861965 13.988707260670408 NA NA NA 12.84139975565986 NA 13.379558346363726 13.951482264407577 12.638775967562943 Alanine-d4 22.26498122503556 22.203571993529227 22.288189994451773 22.23199716328404 22.28597505997208 22.28715274 22.25223782127885 22.292575185447443 22.226770864078585 22.210995336618602 22.323105652279637 22.290109609692703 22.29471868026405 22.26289883892225 22.290525769126805 22.20148619958405 22.25714964599716 22.207889323168086 22.24725738395803 22.248536312690828 22.287452833131027 22.24178679176621 22.28781804 22.283952517968977 22.269422632579964 22.268937283065306 22.269623123585724 22.39780686640341 22.175643889990013 alpha-Tocopherol 14.952311494433546 15.033480956140975 15.294895605956455 14.545741538498174 14.172130638171563 14.185283499408492 14.618437281277325 14.939363978516408 14.660728701441203 15.196540047561033 15.10012363398734 14.627386449110793 14.586095323691397 14.78839083308713 14.90152821572995 15.129485131533992 14.900879899160028 14.918703493389637 14.717278776287944 15.392344002678984 14.263504934414104 14.524015514327145 14.771659443846922 15.303629627859431 14.995164766929191 14.827507319318437 14.073171468144238 14.83152066244029 15.366738147064192 Arabitol 25.09729077356892 25.032282407245376 25.098631878613496 25.12347091159628 25.088207248451624 25.12951530552963 25.072470190203134 25.16567603690244 25.121023125303026 25.049312254238746 25.136850722393813 25.13305340989708 25.00338258800037 25.13279935 25.14786230427495 25.11911368075316 25.08567893933996 25.18267378 25.148362172921214 24.977081804101402 25.154181536985323 25.07309955736022 25.068510053206953 25.099201611260025 25.048863818688343 25.177611146471133 25.160418060909112 25.111392924251465 25.040271705098704 Arginine 20.61193459932719 20.060868764185194 19.59530796760613 19.629774734476754 19.25746617113221 18.63695017743476 20.103579056867694 19.731952448589244 19.108633627193907 19.878299012778797 18.98993520574481 19.80756074901581 19.534177743164477 18.862517619155962 20.343781001188436 19.70764331800858 19.97599316320981 19.023949068673144 19.194380648191686 20.677765133493754 19.784498464261496 18.916736786436754 18.96091658004129 19.16905279294859 19.329586386956024 19.72239384489524 19.25388413 19.777356646859328 20.38797485825977 Arginine-d4C13 28.11996208600588 28.133228154803064 28.19602168220512 28.26473037017669 28.283874099936586 28.263846618097887 28.307913099519013 28.298258827245018 28.30914067045756 28.34422569 28.32450802821162 28.271359346928644 28.38201178229538 28.471757299649177 28.483806184174682 28.570940969206827 28.542016129633076 28.53812396119281 28.541484844736964 28.565690242356098 28.535100219017142 28.452084910674458 28.47894341598992 28.552468059600038 28.71608978851727 28.551859225830082 28.501634569187708 28.68743242107724 29.53235293008801 Ascorbate NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Asparagine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Aspartic acid 16.18938487 15.782213705426901 15.687578024132831 15.777486646772196 14.829919021961276 14.777582215403658 16.605978007511858 16.236011906525444 15.459517955851718 16.32116896222294 14.58350784671112 16.373291281317243 15.642253690501596 15.494718862203436 16.709311810979102 16.007133787307758 15.997048271397533 14.856074540677564 15.316503980623285 17.207626281340083 16.058775687400466 15.427329501687069 15.385941414790016 15.062385340073481 15.469558642737121 15.358897511434925 14.511234387591553 16.25880777120405 15.555906861255691 Aspartic acid-d3 22.244810250688378 22.094239514481245 22.181458376229255 22.110190438636632 22.215113599707916 22.12986461964467 22.085274851915603 22.14997147236352 22.17423737304825 22.157295961950037 22.215993654544818 22.11684842934175 22.09511332714505 22.17196012682076 22.212629820934314 22.199865344628556 22.042480695370323 22.14065128774188 22.150484628162186 22.238265096376235 22.16219646025337 22.157853624195244 22.035709665588698 22.194543078380278 22.170183801915087 22.19847355 22.17853577450766 22.05893305819702 22.03713696820736 Asymmetric dimethylarginine 17.60829312798485 16.53425425327367 16.298435395446887 16.49758498 15.642767201382954 15.585544792103592 16.89528711683311 16.44890992910876 15.668048065193043 16.69273144 15.65331205140808 16.785130048860182 16.413578704222804 15.413635060827351 17.415902504972564 16.67201059906775 16.64145768752538 14.678886836883883 15.48508173571164 17.352557045806996 16.550080098062622 15.37131564395346 15.226914059479004 15.365495101596098 15.434912546512027 16.16925134654875 15.265218103012822 16.181037309783182 16.107781469970806 Betaine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Betaine-d11 23.87607188944563 23.806605807578794 23.92086931 23.848449218092185 23.883975064249245 23.936360647610815 23.801788322039414 23.93330414273275 23.87184100578095 23.74232997416758 23.984342329968054 23.91411174456994 23.738691377658782 23.663329250737096 23.733001871290618 23.67391467 23.63739013738067 23.674312599589605 23.746766074477556 23.100932084339114 23.73647805739974 23.68944246 23.335490333927474 23.647791287665743 23.564276113150715 23.737685562844344 23.766363463581687 23.605955940415328 23.2576449 Bilirubin NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Butyrobetaine 14.471822108767169 14.309626252385739 14.342839550720461 14.74530049301668 14.55038717150264 14.935712354857408 15.063742060766247 14.415786519093503 13.83172097218676 14.138807632799791 13.19834639448211 14.195746403991022 13.877221038971502 14.60298589433853 14.69449134076109 14.462661653802488 14.334120229989397 14.733659137824416 13.91561485092951 14.65946145168452 14.656777970321127 13.88132183187164 14.917872605442046 14.583588399644446 14.811152022184064 14.43442524151028 14.247700951388556 14.424669395410225 14.753003464212675 Butyrylcarnitine 16.812528805702726 16.53246668417705 16.181964798618615 17.294876083855772 15.72637281 16.89400743954997 17.11134807695286 16.64278956946042 16.86080402649158 15.687340355965182 15.082257535800743 17.13078238667388 16.192238928619403 16.50327983277774 17.96378153237943 16.876905017111596 16.825552228915992 16.36492087689599 16.51428794615172 16.851290280230643 16.581699852524974 16.62927134158292 16.016448790250642 16.953558133167792 15.829789740070874 17.433263844317384 15.411928618255958 16.921352151083667 16.37001849523472 Butyrylcarnitine-d3 27.882880951558537 27.908844460201788 28.000995801244223 27.903073807019812 27.936470116249836 27.896304428802814 27.911266375705726 27.87383130131599 27.915166174606405 27.815072206022904 27.93522277696823 27.989166992069364 27.885603601734772 27.906577626496947 27.984199644769404 27.871472786399643 27.963671964814033 27.88874398783021 27.97211951424321 27.82903058372278 27.877483932981423 27.86931015052388 27.830545104383212 27.931373580278375 27.890876314568253 27.908539731037465 27.909534755616193 27.861183935015436 27.764598598661237 Cadaverine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA cADPRibose NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Caffeine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Capsaicin NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Carnitine 17.248067468432033 16.28393844196501 15.962739963064381 17.15207941 16.14400659788161 15.781499526656999 18.05163960071371 17.97460464500121 16.513881470072235 16.92714886032315 17.32464980750349 17.244860216275246 16.79544362771422 15.373422595160985 18.082548989592574 16.906476955139333 17.038127189567145 15.126209630166416 15.375599919743872 17.66491419 16.729828581187856 15.65470031283082 14.738243371832432 17.331135769208622 15.136988999620906 16.480380230304522 16.58151974067468 16.825741567687437 15.94003634326616 Carnitine-d9 26.365016990678697 26.300935041961157 26.328518601645985 26.27535183174414 26.315337966894834 26.31512337028364 26.315137577623197 26.29578362038947 26.294505522623705 26.284851123056185 26.299492166957165 26.278367200110274 26.307202081604384 26.289676413640287 26.283724822201247 26.297058592915928 26.29253727282485 26.257733909376984 26.294097916209218 25.940354589001327 26.317968985751985 26.287003056552106 25.970998524787333 26.294835647938978 26.30687626284781 26.32028991051104 26.312207293578517 26.343981778190205 26.309420044432972 Choline 23.016539304465248 23.880383654915494 23.425610114776003 22.47770196962472 23.01594469571616 20.364424835902657 23.80216008906415 23.62670926033768 21.744709865248137 23.519727845729907 20.376873891540832 23.933323276488274 23.445480567828376 21.843557853898655 22.48853558914866 22.976009536083183 23.42100739 21.800910727606087 22.453649024022354 23.93019349511574 23.143323393303774 22.035859330489778 22.303872927582447 20.761565692960236 22.649810539942976 22.610554162468155 20.90429557959109 22.925216300119867 22.893191604226583 Citrulline NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Citrulline-d2 21.02521643402773 20.97248479278872 21.011680428587916 20.995936254352575 20.956015724981327 21.00043040159655 21.015344024379548 20.983085231875688 21.007147797683324 21.00601807801584 21.04801822634408 21.035121407563988 21.01922025426742 21.080903125226286 21.048431590740915 20.915522497646847 21.03584297 21.049976362991032 21.019530576184348 20.99670270305053 21.080227859372037 21.03600709652506 21.054077437192674 21.04068657155558 21.076994765372955 21.09136072658037 21.068027646985243 21.02132787331605 20.986064700233648 Cotinine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Creatine 20.95588314 20.882976186770687 20.35154935011922 20.286062300202218 20.28720617761238 17.95962466 21.85182454779407 21.58774149094661 19.22154032679121 21.94726896896956 17.534454167975557 21.095918740605423 21.39013677 18.345637790624245 20.19417538904663 20.977635439768243 20.611148393771185 18.646906374928538 19.636412891872386 22.699846967811787 21.80747155297413 19.237933852530702 18.999003625711143 18.323851774681103 19.601859246424343 20.501787761021802 17.609488110528133 20.870611386370083 21.227015119354384 Creatinine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Creatinine-d3 16.693876238833358 16.792617671592797 18.40989404008063 16.53287777431495 16.80184443839904 12.12227135242033 17.66946696 20.124476630105814 15.990649316376782 16.464215347719964 19.67979226965765 19.25297086975014 16.42832876988087 15.986497608885475 14.519387139982785 16.505330576747642 14.72073588473771 16.736746242061653 14.080543671810354 16.061722988193566 14.91613658228409 13.169361067847028 15.55201226882152 15.335024771238059 17.178215121298514 16.485746654001453 16.7212019 16.792661711668202 17.676166461704135 Curcumin 15.994775404945363 16.288906027692978 16.281137348736255 16.075101642530054 15.87377047014937 16.84289303282502 15.956680387314837 16.511577778913022 16.392466206434342 15.935724624046856 16.51394771712434 16.613409926702563 16.031136031700566 15.977545319957997 16.374388472566135 15.778614536555049 15.687237601772576 16.069615437621234 16.215934103834506 16.42049890733199 16.067503299791873 15.961115386224225 16.83942041731535 16.100704058651306 15.221113956297302 16.50844752371271 16.545063865736076 15.32124937364128 16.98326575148943 Cyanocobalamin NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Cystathionine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Cysteine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Cysteinylglycine 21.72458779307514 21.80950438826582 21.86385195145079 21.92152529639869 21.923672646052886 21.90995001767658 21.94976648862345 21.91851861962898 22.005043286496402 21.981276452593136 21.93326351274515 21.955904848150332 22.009484388523337 22.01629964378878 22.17282671147211 22.167799309773393 22.22064107122147 22.17778254969885 22.160598257421597 22.171724068836138 22.132851119621257 22.162472902934027 22.12801713473991 22.170106546423835 22.376761083474616 22.26274892922129 22.183608119122432 22.430617045458813 22.891336773498875 Cystine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Cytosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Decanoylcarnitine 14.404302991350585 14.506141787427962 15.059780351200992 14.405702183116192 14.435444546101683 14.504985403812416 14.898435347916871 14.826781833490399 13.915302741542057 14.026937196273728 14.576952366784926 14.280765628720506 14.304930941951259 14.56924280710484 14.274355712591664 14.494917666844913 14.649196477403189 13.975824856051814 14.882001042897867 14.830262732794788 14.313236322348915 14.373886355086794 14.07253771991291 14.419983652928734 15.052904398137526 14.416884952877602 15.15376317 14.636121132195335 14.444907308048638 Demethoxycurcumin NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Deoxyadenosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Deoxyguanosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Deoxyinosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Dimethylethanolamine 18.60622419778922 18.167866666400975 18.257125654859017 18.212234491060663 18.50059697341356 18.404210350225895 18.262911683495922 18.270500560293286 18.366743384895567 18.159965474413852 18.41071525072366 18.51402643388487 18.365278771995914 18.043750098026432 18.56615645674349 18.44028674437474 18.113202878588645 18.28790502811671 17.92910336544652 18.589253191879525 18.33911584271072 17.95158125509631 18.237361928330646 18.138859832082257 18.343828951838255 18.214311527915328 18.39762579030445 18.463835753780206 18.176987535107475 Dimethylglycine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA DNL201 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Dodecanoylcarnitine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Dopa NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Dopamine 17.817592572062118 17.77118360561703 18.038177225435703 18.012916069526813 18.01492989 17.991042758080734 17.82975289737473 17.972005596016295 18.076726726868497 18.136736088377646 18.02785617869292 17.924872176058535 18.00164965968978 17.845284919373846 18.07318803774783 17.915758874548875 17.80884844041545 18.042266448508332 18.24643933461958 17.94839792965566 18.001265317772962 18.09068868236904 17.809326821990933 18.134360508732772 18.008861793022394 18.05788490212085 17.85157561599467 18.115075537073146 16.75381341495799 Dopamine 3-o-sulfate NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Dopamine 4-o-sulfate NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Epinephrine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Ergothioneine 15.458497536507334 11.247236507801352 12.400818833195231 17.78676925187155 NA 16.627677319784553 12.597830898739574 13.680886901030993 16.944186825264882 11.531383010642893 11.409395327373113 11.44214233372015 NA 15.376201966030491 18.285149594819472 16.070387096360026 11.800156895284474 16.27619029348272 16.577718465605518 11.981016489779613 11.449182112808902 16.05654012834217 14.931679306740001 18.104865606032728 NA 17.41776976778714 12.961126836216016 16.29417986496964 12.39397866568123 Ethanolamine 12.805461480851093 12.251127988201656 13.954191084170876 13.518004175250043 13.908045920536528 14.192985580437886 NA 14.841764585542698 13.636611181241355 13.638517079562643 14.694669974908267 13.780173556695942 13.196820292988903 NA 13.874760768465666 12.596978402633379 12.987430359233752 14.079183473260095 NA NA 13.813554081277351 13.425182171020664 14.141439843442706 13.235910368555045 13.15177329656099 13.87911980140232 13.401576775914418 12.912114986837693 NA Formylanthranilic acid NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA gamma-Aminobutyric acid 12.378876982280453 11.605170051634817 12.627672513484248 12.476695248588054 NA NA 13.343356551731487 14.888158813406536 12.397891450687187 13.067520469035582 NA 13.43563340526424 13.165613061600444 11.81051577774924 13.244820033060467 12.868149705286028 12.703433518227811 11.858803631250051 NA 13.144709865542726 12.315125211746633 11.885400727665639 11.789320949480773 11.27190142021933 12.247632108512331 12.364494274032955 11.948138334469594 12.711769562666078 13.183601060374556 Gamma-Glutamylcysteine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Glucosamine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Glucose 20.649864517889622 20.716401857864287 20.801900976270282 20.816422627669333 20.865552386489583 20.535569909490118 20.829775241914234 20.60961785731558 20.737570790352795 20.893776048922597 20.322248587756036 20.474625814446135 20.938857687519484 21.09748894507676 20.80475260760576 21.071520361029023 20.913915847781368 21.012317824116924 20.88305661725152 20.357489756850722 20.887275163802503 20.936979606733896 20.182900956793855 20.82001944652585 21.134354611375244 20.864698249014925 20.91723826636114 21.055808712374457 21.58543798859367 Glutamic acid-d3 21.673321191442948 21.64598856640256 21.71053599926481 21.585379131449468 21.69214564461532 21.677716832631255 21.648513428921873 21.702761985569467 21.666544394426193 21.642307577594707 21.693171107542398 21.76172294506816 21.63662985979418 21.679813490371735 21.634470230441796 21.637044771756333 21.652349317138505 21.641415868446938 21.682598448459117 21.687470942383438 21.67213430483506 21.68145556249218 21.71681244664434 21.70861692 21.63735742971562 21.69626005724248 21.674890441339738 21.58794100148026 21.600005184870245 Glutamic acid 18.552846909512645 18.37561199048406 18.05828421847734 17.982354346516534 17.748115214450042 16.936380860221323 18.774434795709233 18.241600217640702 17.187749392366715 18.015843754475533 16.621447278444563 18.564275336277444 17.947542043066285 17.159989408139058 18.301630379629135 18.104536644580588 18.181867234834463 16.982277672619798 17.377154854123038 19.00861886010098 18.254695431507365 17.289278533396885 17.180082669245383 17.08351854 17.359059288035294 17.77063883071319 16.54632583965848 18.12215288659281 17.75882512392021 Glutamine 16.45415074425471 15.674367627202953 15.55799458037339 15.043740879796887 14.762655112178527 13.72138246768253 15.892674386449409 16.022355410104332 14.939343863103614 14.843194074525563 14.590308748329257 15.763428179607436 15.032511632254776 13.645908321628951 15.602812941510068 15.168903996772613 15.458926530855564 13.994896045398983 13.834685179671014 14.786708419530148 14.906148030462536 14.197491131141499 14.067422155689421 14.164577851429312 14.316126181440195 15.099259123939396 13.974918625783932 15.403402874749252 14.957558024290865 Glutathione 17.062630529124696 17.53534557 17.31379737647513 17.098238507204503 16.944650090577525 16.304281705039276 18.276769491913885 17.497503845549907 16.606586629076883 18.387025163665143 14.98538553 18.37665569973408 18.18273117856265 16.468275380890496 17.860869777980046 17.656380638162954 17.902972992287005 16.302144151011166 17.125871399563966 18.817902192669866 18.21488666354575 17.00476118 16.62607368867259 16.491145511381823 17.109051459919133 17.355562304523477 14.951591881086392 17.691475751342384 17.72868035032558 Glutathione disulfide NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Glutathione-(glycine-13C2,15N) NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Glycerophosphocholine 23.08227369 24.00987527192083 23.768210550931407 22.815768772704637 23.321291696003968 19.81432839896242 24.305796814646296 23.457978839782722 21.702989820596045 22.957843004417565 21.702850227254515 24.493328735496483 23.228810554945127 21.711496926908737 22.464980976505775 22.995272386399243 24.233291670850306 21.814437466137733 22.055835203526016 24.02078742942423 22.974604094433204 21.870619522673536 22.001631847684873 19.91027975024615 22.28820090269382 22.80035762476854 21.891456272277377 23.09849683403319 22.067353996768098 Glycine NA NA NA NA NA NA NA 13.570003899766307 NA NA NA NA NA NA 11.537582419913065 11.638020701961018 NA NA NA NA NA NA 11.077786545289943 NA 10.853510714178457 NA NA 10.66310465288334 11.804864029726485 Guanine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Guanosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Hexanoylcarnitine 17.380598309776424 18.476106159722256 18.12757606079445 17.431884429192387 16.994010230309527 15.72439004538549 18.404866286265605 17.781880290603358 16.675368455179104 17.656640457166276 14.551224612263985 18.745779829055227 16.943436327361603 16.88118664359058 17.512919520255814 17.562243205272754 18.48276662586969 16.65414680456953 17.32675846539493 17.84209050761294 18.027847590496073 16.83917765916871 16.86601482760265 15.934326615691958 17.48094370626635 17.764727941959308 14.707544828503805 17.42420295130001 17.527210905314217 Histamine 16.747296559943788 14.986164885892999 NA 12.79266664968627 NA NA 15.075191952517654 NA 13.448872906196446 NA 16.47610940058027 14.804586844044914 NA 15.314449551855606 18.993972891377137 16.942823055418906 15.410456331357477 NA NA 16.188490222457258 NA NA NA 15.974643213501967 NA 15.645833456736739 17.134241822198607 16.47614351685287 NA Histidine 20.709856133808923 19.818977047035453 19.12412128304146 19.008886969174757 18.476945221455715 18.082777376661895 19.178194029545008 18.226195029959364 18.036806556519917 18.694372468185076 19.02110981503545 19.141445032291703 18.69548222367223 18.116134358532644 21.083413163664556 19.897973631178115 19.369675949104714 18.074984812550117 18.11222597657764 20.234760964250068 18.678320380743244 18.180164180089662 17.765684119912702 19.23375856667653 18.972915353445185 18.736027862753726 19.653942850803183 20.03265968418958 20.38576992895243 Homocysteine 21.94954711 21.97500032376416 22.054660223910936 22.01368068995361 21.980280621488323 22.026313155010545 21.979052206721263 22.036685769268416 21.994984749628895 21.993919934090243 22.052334327099537 22.056561257919185 22.013570758712206 21.98196281 22.025356669110902 22.021778049036275 22.019349690823812 22.020763009402014 22.08123753887984 21.833619811735726 22.055539931557117 22.014188925475306 21.913203888414518 22.06570911574103 22.026687005374207 22.086312213384975 22.077133395893725 22.050819271369836 21.954805983358423 Homoserine 14.264520616786312 13.741252094470923 14.292484200904292 13.850801542690231 13.11267064359166 13.616490081592472 14.472806362911438 13.595578943228274 13.053647308769053 13.468255451918088 13.62454932640322 14.669630345578193 13.84305839300487 13.884158290649955 15.274355624777327 14.034988330560195 13.436465143733349 12.479652642728274 13.274176130659681 14.363474821114025 13.175293094342903 12.365629738869936 12.965082071333127 14.049237657971187 13.178804837248826 13.67864760454797 14.15067922330779 13.57814834 13.783023838334644 Hydroxybutyrylcarnitine 18.48005691995576 17.91747022640561 17.751129343880912 18.36841041 16.954357132229525 17.713622050456927 19.16879187636243 18.103717524491366 17.629617403648414 19.111042577363058 13.96098169069309 18.47693155275344 18.39851953474539 17.504444515403694 19.089560054229676 18.434398009792723 18.473579827178632 17.443977532806347 17.69202716394483 19.73725258125983 19.05432815775426 17.82485967 17.23916672080922 17.963913490800564 17.389063398716495 18.337190448222806 15.167221164943196 18.497899322641622 15.705975200454157 Hydroxyhexanoylcarnitine 14.641870518784659 14.968541719702257 15.023411335143791 14.312761587072684 14.432534260381997 12.514367797057512 14.343093739468456 14.157878217672474 13.135168413763237 14.062922127673113 10.556446187880576 14.464322333991422 13.234842634902177 13.936198187596224 14.820850769423156 13.956562815796334 15.371688680555211 12.766073026838319 13.178852301732224 14.544084725729752 13.713291445034114 13.459211208955153 10.991380210396656 12.43882451967766 12.604900952941719 14.065478293007555 NA 14.681632030994448 12.12461661961509 Hydroxyisovaleroyl carnitine 15.158031849628234 15.535301056709889 15.426707343216552 14.851250982147592 15.045075571405816 14.396788690616837 15.907660629001077 16.052359163295236 14.903617143972593 15.686248347771585 11.381555648785254 16.293599652241888 15.183722990606576 13.893358153642547 15.807521806579476 15.661776981448671 15.712724034915686 14.310251874567767 14.748059361674946 16.766919518947898 15.668294906460645 14.465978533876811 14.439850808579923 14.882537497506247 14.636496634861295 15.755965104151814 12.821576279184649 15.358087885726246 15.083012960521428 Hydroxypropionylcarnitine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Hypoxanthine 16.231534377385167 17.16596796640894 16.82506316232304 16.429212857015695 16.712555346688113 14.094492200317704 17.253678818020866 16.386653835547296 15.867046738524525 16.02938831 NA 17.570497675575645 17.170614545387018 15.310027124993912 16.56446926230415 16.36287260936517 17.379683466846636 15.368599521732866 15.573444314048714 15.364139929514025 15.56041977114842 16.385270600306413 14.793270637256912 13.595114843604557 15.370746769797012 15.98506324659195 NA 16.05976076287279 14.376592952428314 Imidazoleacetic acid 18.503588531069603 18.379930715467317 19.354491637426474 18.83771099112655 19.348510077559176 20.069819547650177 18.48052592248643 19.976456421563864 19.681207487991163 18.600058638549637 20.313232061752263 20.143760346957045 18.935640056955695 18.64069431 19.574738614792164 18.736944904925206 19.081076922282776 19.13991464519243 19.430835245723404 19.071366875062758 19.628741241961407 19.27046781879519 19.93959807891926 19.115334053499463 18.756772128511212 19.84897900663149 19.833417023627124 18.885848867230496 17.611023977275718 Indole NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Inosine 14.16732293680048 14.71597686156689 15.095428622780934 14.883662776404822 15.47525451392004 14.74360815727309 14.120360150454847 16.52558414838559 14.663566479147786 13.76361352515316 13.777732528313752 16.98213265436428 16.65576261419288 12.648881556605065 12.271200390318144 14.696509800592029 17.18134606437972 15.04357551154192 13.616718723857772 13.432901137912044 14.095058595630183 14.030162150365575 14.488015657695755 13.759238391197057 13.596839395238723 14.595053290179125 14.409158950884157 14.339912189715257 12.90250645 Isovalerylcarnitine 14.875380746333239 14.710786278352222 14.684710018333456 15.053539951082895 14.57263804904662 14.282825817998875 15.572110852898819 15.24479609441135 14.149462744593077 13.798298529518114 14.499138143692536 15.334058163009495 13.979152028681952 13.507157926147984 16.77974920896426 15.076566123287236 15.57831792915756 13.10624674923194 14.030075652855874 15.099286497565567 14.459028414789826 13.926621085507337 13.594810337743512 14.72547335 14.625115302981477 14.756669831014289 14.588876479792937 15.240549482171417 14.899917400513464 Isovalerylcarnitine-d9 28.19192718982505 28.157646601835186 28.20440094399901 28.192864688941455 28.217443630880258 28.25144610256222 28.194641410192695 28.166654772227808 28.19081137423039 28.186743518284846 28.203936238084754 28.220378373540672 28.18437637 28.244927726026674 28.216460220796634 28.15859126863189 28.178932826547037 28.204197441125654 28.230781856302777 28.056142490945923 28.158162139651573 28.15199696581307 28.110124002186645 28.18985529 28.155707875939903 28.190933179759373 28.206051186285826 28.200882015092578 28.10817078129545 Kynurenic acid NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Kynurenine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Leucine 17.720919402909065 17.094361326865258 16.80708526010287 17.546456581902135 17.216847969273324 16.727619514093266 18.06462958 18.25732709 17.25888583121548 17.474202872381255 17.45673594444586 17.78160123 17.57382998563851 16.753427780645733 18.915990690318733 17.85843969083688 18.06826879603301 16.846005923929763 17.13434326533527 18.14968422578748 17.825289859547585 17.16039218562278 16.98946212518837 17.564870972945602 17.19451224368717 17.353087022084754 17.28632264928963 18.06090114784824 16.54214901952685 Leucine-d3 27.29262323479989 27.243402535636697 27.464000829595552 27.35479649588383 27.427865609079014 27.516242444160962 27.29920494186443 27.53098596067071 27.483705599242775 27.333880981648505 27.537973220597863 27.511973063399633 27.368796277900074 27.36769913947281 27.485422962013764 27.389083113883515 27.445823883158766 27.425445251415688 27.47221229133769 27.257631225451853 27.502537835059847 27.466184002082958 27.384422965446323 27.444598177274017 27.37900664468479 27.496525472485793 27.510415237108905 27.393771060774437 26.60648864162695 Linoleyl carnitine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA LPC(18:1(d7)) 27.034291375025344 26.979772543005794 27.11640562636024 26.99294325253128 27.011566642512346 27.016936384030668 27.089745060437412 27.058090343210452 26.978145431584018 26.95407461661559 27.115688085046656 27.084088490346844 27.01061439941912 26.970714574009776 27.060855768155957 27.02946056948586 26.969892793006508 27.022830713333978 26.99077722133581 26.833471536581992 26.987310500989953 26.917697610515404 26.870682244670054 26.998571871557573 26.97926073590329 26.922131869330745 27.045795682300835 26.937462056668245 26.85619277991735 Lysine 17.70334987929512 16.645652969299444 16.287640919265485 16.41979816390562 16.084345461057357 15.801487339609459 16.389829298866726 15.86025749563935 15.26553163 16.04276217510664 15.145130936294978 15.981517501422912 16.14011082265718 15.148053558907504 16.484011027418024 15.986514381430577 15.81136551 14.258933594627042 14.839500371006297 16.60208265788786 15.756917138538276 15.031138069869119 15.373796637692406 14.756467194233924 15.624488243613765 15.640552675436366 15.482177144118515 16.226557511647965 16.20943859 Mannitol NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Mannose NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Melatonin NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Methionine 14.750498261382178 14.692978407851317 14.85062419271545 14.412677891447704 14.792506240830468 14.207598688055434 14.750802437059226 14.330263082888502 14.768498451329663 14.207597841297867 14.877955429400401 14.621361469775309 14.722054472297755 14.537671003128317 14.810075743000299 14.764263486949142 14.722122408496274 14.405127319311184 14.296006792842896 13.981238352176845 14.28776013195922 14.558238842927357 14.078150807728061 14.40015103430886 14.26805441622217 14.98518566563026 14.418142774307816 14.778414735343809 14.632862436744471 Methionine S-oxide 13.217221743244046 12.806352340945251 12.298398456136985 12.596129796381069 11.963792073050152 12.051969059353617 12.659822874768201 13.885964925406622 12.46163134499481 NA 12.486901290046134 13.514870802819692 12.868116967838098 12.938841908896153 12.60421916617348 13.446772425893503 11.917571164406445 12.001985500718158 NA 13.253311115439864 13.328996489420014 11.981495964163507 11.850294333580388 12.553847859003033 11.939146254430415 12.355727702004254 13.088682633766933 12.84595053274221 12.548861770928585 Methionine-d3 23.17961505929578 23.12481156538569 23.183423044152313 23.120434614077467 23.182428722340973 23.20454750002942 23.09096048388285 23.224599438556513 23.18338787565891 23.123479851838365 23.19871856767362 23.19929642765682 23.167875686753856 23.196656269154364 23.240629682138028 23.15085450727558 23.178294360784147 23.15955755477831 23.18983868 23.003964807960283 23.18653230008174 23.164880268467307 23.096372635705656 23.19331990518476 23.193282257232596 23.22678276062752 23.20798022131862 23.163982819152515 23.112601097272677 Methylcobalamin NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Myristoylcarnitine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Myristoylcarnitine-d9 26.10109637842314 26.02177744443934 26.02697648867966 25.96422479104348 26.119156930163996 26.142020787277005 25.936909665050425 26.13398575971256 26.118619922253675 25.986456990607056 26.005798354695642 26.044763269687593 26.04561852760299 26.027760518510515 25.912664811632805 25.945461514796264 25.977255931703027 26.036914598570892 26.010788114020723 26.013587972037516 25.9790653 26.039103834554005 26.06978423963095 26.007768926394427 26.006155703560793 26.07738708 25.987707392287437 26.03533004573836 26.008564922094855 N-Acetylalanine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N-Acetylaspartic acid 20.448901070502714 20.39967548218536 20.35833271364302 20.47498118586747 20.565524811563797 20.492869075901755 20.52352797885853 20.586739668655312 20.191465704157153 20.40202464888944 20.44702588572129 20.252535170870292 20.50854145695518 20.371970655241626 20.642891063904866 20.423772640240696 20.311862736787727 20.19376054396404 20.32533032108147 20.501648788211458 20.594969126153053 19.624953214911752 20.34869512873104 20.37839839630643 20.21341456823302 20.34398321917666 20.405389038181703 20.328538338964783 20.082278159618987 N-Acetylcysteine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N-Acetylglutamic acid NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N-Acetylneuraminic acid NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N-Acetylputrescine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N-Acetylserine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N-Alpha-acetyllysine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N,N'-Bis(gamma-glutamyl)cystine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N1-Acetylspermidine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N1-Acetylspermidine-d6 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N1-Acetylspermine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N1-N12-Diacetylspermine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N1-N8-Diacetylspermidine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N1-N8-Diacetylspermidine-d6 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA N15C13-Glycine 19.82384715487633 19.509445773862574 19.630127527395285 19.63684616698314 19.54824533234505 19.700384189942866 19.54751787 19.61131529 19.650021140636603 19.493328508350444 19.61998026320105 19.596806668782268 19.564036244227278 19.652473869209633 19.540608578390664 19.57229672007966 19.524121859005405 19.56093901219394 19.570822376263703 19.533506671438733 19.611898442385563 19.580727546747685 19.64093122644242 19.597249239154667 19.588796248102803 19.576074440575773 19.62081640970659 19.62298996704193 19.468036528965403 N6,N6,N6-Trimethyllysine 18.04267273469967 17.005581858567254 16.96681159819445 17.053845840130194 16.431072993111034 15.94987202589919 17.48034891403248 17.27682754476374 16.626169520319444 17.547869384287875 15.787103129196693 17.029228939218086 17.040563895376494 16.027704418386946 17.408600261985928 16.912014518909128 16.93781945777911 15.785542820777637 16.175680008614282 17.795533838499072 17.37551555036239 16.224485883891248 16.29463604719879 16.10404741807553 16.41673041476104 16.98263165002811 15.393823980891204 17.13581363 17.17106261042046 NAD NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Niacinamide 18.002267679059408 17.646778007022593 17.642899281123533 17.928061832313027 18.066448202833396 16.962992403705144 17.898035077673878 19.11609618396807 17.49243335016466 17.144995053745486 15.324650200354457 18.929623225032735 17.764970710486004 16.791474393457676 19.09343204428754 17.88873284666844 19.29145741588962 16.766810834896035 18.024615181909503 17.333938122952333 16.976075072430692 17.79580517583075 16.516720061819605 16.496277694229633 16.44230588346905 18.40920478108533 16.28062710765184 17.72982492375163 15.713189686998188 Niacinamide-d4 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Nicotinamide mononucleotide NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Nicotinamide riboside NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Nicotinic acid NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Nitrotyrosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Nonanoylcarnitine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Norepinephrine 13.840558122691126 13.415532819378733 14.201717191056973 14.097893780345444 13.807141175419877 14.141351353999019 13.436323255174589 14.38839203577153 13.587663738925782 13.461240587149792 14.772117773019865 14.11100012599909 14.025661068956838 13.68007793735634 12.85405152709919 13.274050924490792 13.806694010128904 14.565254231630782 14.193809768031663 14.794587545548506 13.507819896960235 13.761368851868601 14.979936168952213 13.829307128748201 14.087547875522398 13.805865802365778 13.900587561107036 14.785147232722396 13.805802780620382 Octanoylcarnitine 17.054534377175464 17.285542659971536 17.33036106192944 16.984716734466513 16.693572130580684 16.432402793820444 17.241020661701587 16.719119569761883 16.88183446568302 16.546489329436923 16.437894853082497 17.09401128063108 16.438110085795625 16.661041915452266 17.26626878367068 16.716849746732784 17.013542069036234 16.566317448207617 17.008618457694876 17.64413025656774 16.806553437355035 16.889190407694688 16.69579844000993 16.49904448384354 16.75342795468545 17.00385841081162 16.28469753481663 16.375086369204254 16.644765942048096 Octanoylcarnitine-d3 27.37666245653872 27.30506815057369 27.40864377051349 27.42557994694404 27.439233356839956 27.499783294145967 27.24923680929351 27.273427675911364 27.381498223540124 27.25405170190478 27.30475277021732 27.252619655036316 27.270852004388775 27.31056729829622 27.31284138912101 27.291203788908245 27.254263066891845 27.527778481990577 27.297092643657383 27.196794161949832 27.26258483936655 27.330718176855253 27.280413778192795 27.28928059204009 27.310056792685153 27.287944395756686 27.31517911144387 27.317761191851403 27.18419936429872 Ornithine 15.686908206626576 14.767890773058086 13.946421788878848 13.962727787223024 13.686330661565966 13.322303115515428 13.205331142313627 12.575092670200021 13.900243559825809 13.486228011282483 14.718308326431517 13.69563834647929 12.672681393832923 13.508689019516707 16.745766392582777 15.26286304563388 13.972540171440299 12.080243073946521 12.511756707032383 14.514689737723751 13.577110495925526 12.620296083320504 11.91971277986579 13.642032835666052 13.516740581740407 13.147741058245115 14.531158189807197 14.461754499907917 14.645224018301432 Ornithine-d2 22.384137865649276 22.56109953049755 22.55697644707262 22.868279845513708 22.719537660680167 22.81473081416146 22.71762875911599 22.739475750539253 22.789319081781507 23.060111777501128 22.732765470682203 22.66701171836958 22.908971582475512 23.011379230348833 23.028913067613292 23.082565670908135 23.04254474644885 23.06676182855222 23.10223253470835 23.113680055157957 23.12126155106361 23.08308297525358 23.012125751828496 23.10738949755962 23.235983642482278 23.100489524187307 23.032213249886226 23.168934317265077 23.531395697616215 Palmitoylcarnitine 15.191634620428362 14.057777274641294 13.949533708898688 15.913528581191935 13.981653319047942 15.658600551668094 15.347833438592374 15.098267846190678 15.666595258094675 14.550890070562803 14.60933450207689 14.882222444441886 14.45108818433534 14.331468276157619 16.282344909996738 15.43402510792255 15.053325326423629 13.87408057241706 14.391513608287767 15.448460302387788 14.483620584432131 14.812697134112408 14.404721412651401 16.12921474521018 13.405992179878481 16.252404369511716 14.626739175815926 14.996849655586225 14.28660330147302 Palmitoylcarnitine-d3 25.12797460774381 25.108211721202554 25.169249685398132 25.098872343613362 25.170829733359952 25.224966397702953 25.04346920482061 25.066951520200575 25.103837587454738 24.95555044950941 25.098293252754956 25.06175942911732 25.10823850196443 25.072774916370182 25.094254297364717 25.07620797730169 25.00509870633524 25.066197491149328 25.09507538195256 24.953448821376398 25.047740313877394 25.100138847871246 25.039152756686924 25.048502593944104 24.998437383849907 25.094884344171074 25.150899174114215 25.040782731251035 25.000614258222484 Paraxanthine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Phenylalanine 18.694315766469664 17.57274262 17.636148955801048 17.937306902763847 17.551428521478392 17.038379217734693 18.93058309 18.75899117849839 17.607773102835477 18.47252985191611 18.248817597155657 18.252526779038405 18.45225385856452 16.815165007315088 19.89819695990639 18.700300799639326 18.276181481934508 16.509356547438514 17.430871611505793 19.23251841245537 18.60764877 17.34558224012195 17.231927877002594 17.91280699202132 17.876078981732032 17.84582048223067 17.92474796 18.715250972661355 17.176869936803104 Piperanine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Piperine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Pipernonaline NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Piperyline NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Proline NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Propionylcarnitine 17.768663598682167 17.858951851670103 17.518895490605157 18.23004554516977 17.42457726457905 17.350258176523006 18.179672094206996 17.598041412222234 17.57471963619205 16.958494409495856 16.74610644580124 18.226728602101602 17.02935662 17.462616374919932 18.50286507 17.77064780296091 18.242145091713304 17.26348933139263 17.582292978353685 17.447748037530488 17.305210690314205 17.420390969108045 16.98093690978077 17.753310718380042 17.18388322167488 18.178242300517425 16.67064292139351 17.665361399783055 17.257815763164306 Propionylcartinine-d3 27.881791687406103 27.867837827219915 27.87186654510036 27.854762028504865 27.903589187092045 27.87210076754671 27.83133091919535 27.888812009396364 27.88511464 27.820884867711396 27.903000590502714 27.90655702393185 27.856651672925295 27.873472068122037 27.890964184253487 27.86444232 27.85516025652687 27.833049341675117 27.83859411749068 27.842990341849706 27.849567060686816 27.824858374328606 27.86361667317862 27.842145857748722 27.812873600000493 27.872956718947894 27.86901864267373 27.797466960818134 27.759064472658277 Putrescine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Pyridoxamine 16.770851701428366 16.877107464638538 17.036713197451874 16.64290817 16.872199294587542 16.909778937695815 17.16428472 16.876006125730868 16.961027928959428 16.457854746149714 16.663749530469087 16.671151268809314 17.15079502123068 16.41944545719545 16.44080438272598 16.615640504641842 16.60309589171671 16.663874017779886 17.195531669594708 16.878408623417766 16.649316895633657 16.64819613392695 16.6299999 16.729030395243832 16.783617187350963 16.31507009 16.729936960094854 16.478239740833324 16.613636730949334 Pyroglutamic acid 21.031087344187405 19.72178425307336 19.68955689410325 20.11814740734795 19.141417028057965 19.49151468228407 21.010402005184396 21.240445888850086 19.839196477828065 19.125290582056522 21.157000735174844 21.00793836912146 19.423245210309176 19.536357967716633 22.735358225572092 21.06666896152675 20.192594769464435 18.703068731944494 19.784023505677347 21.250657051810798 19.544810875112727 18.386301699855103 18.382989154639535 20.82894052122298 20.24532304933756 19.545951831721165 21.06887924 21.00143192152905 20.29061675534026 S-Adenosylhomocysteine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA S-Adenosylmethionine 17.190430750832245 18.209431603951526 17.903612053105427 17.725597 17.88470831371839 15.372626931984712 19.272734672326905 18.41436867797366 17.109616519645527 19.16834510070418 16.58166291066007 18.49856281 18.715521750375938 17.49882255973777 18.177995789515563 18.977687168068165 18.810928312737385 17.662802004909718 17.655881739224732 20.433843513587114 19.616301091384774 18.07432485144493 17.52520040497399 16.966364396008682 18.817068377433948 18.233057987170305 16.407609286096317 19.154586682146263 20.20352323408698 Sarcosine 13.164743251837857 13.626864233835086 12.490866656492253 12.915373223090484 12.570300767298281 12.831550513491667 14.397312740367065 13.878942059386992 13.455125979874413 14.360589702805568 NA 13.778238391560976 13.93949054878213 NA 13.668923852434682 13.814501883091635 13.662874449971335 12.051986697959673 13.440164981738263 15.688352244114812 14.080242055263449 12.585477847792667 13.702971562158506 NA NA 12.735718588222452 12.20920908658852 14.259010302079012 14.459574120330883 Serine 16.477861895447827 15.923909810661586 16.068790536560428 15.20255977969368 15.218587973273033 15.025398472529135 16.414402573284057 15.799463619778436 14.738377918689915 15.886834393081156 15.67713315385886 16.490689519071275 15.753882055815488 14.98559449 17.793880990867855 16.38814157 16.308550236782615 14.73671646158938 14.983053731327212 16.820695489907592 15.452665859462869 14.714242538321454 14.870683316228986 15.386649309098047 15.596743199635661 14.858850754559112 15.987775831071604 16.31147253 15.676005197416792 Serotonin NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Spermidine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Spermine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Stearoylcarnitine 15.270329056009343 15.230943816212507 14.83044342 15.769991771763028 14.305030975112068 15.537151634261823 14.98633654927152 14.75389638678343 15.43328702349707 14.44160880964316 16.036272161419692 15.648576016509917 14.286602140302103 13.87078392306265 15.718169002755412 14.977561141832467 15.512087672604196 14.497278030682176 14.595607140608731 15.52931642267121 15.310627052665398 15.109603351114304 14.70927864995735 16.066376590573554 13.521696119361057 15.911447086346781 14.737957091842711 15.30103108890966 14.417219802534841 Sucrose 22.194774413506654 19.98821777567629 24.490927482256502 21.522126725894353 20.94151992577741 20.413415753080635 23.105914829184876 26.515532981364053 21.600242259210788 20.14823191 23.24395215978659 22.667139753728147 20.561467284108936 20.282429870164517 22.932903773951352 22.447874293719902 22.324074326632243 19.963926220323998 19.681290637421075 22.78920156467674 21.44405794 19.935559634037205 19.990892378482837 23.457103734803297 20.59254020619336 20.69340595029825 21.966167643914844 22.417519764526883 21.904661919885204 Taurine 23.018537247460188 22.967032079182477 23.88905939150687 23.279254681245593 23.81136075090847 24.634080725460944 23.04842005675611 24.498134420148048 24.21409694224033 23.199814 24.89589607565214 24.616931341573828 23.444608003629842 23.335519701857603 24.132921294416693 23.448753512127052 23.639816261545572 23.598071040305637 23.83789731388961 23.56152673824326 24.16296562145127 23.808896878556848 24.534049493179758 23.67679776991848 23.401826181005006 24.340149209671097 24.431225640806705 23.496859929884952 21.83439109 Tetrahydrocurcumin NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Theobromine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Theophylline NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Thiamine 11.517268598360147 11.96671363129216 NA 12.04447073845219 12.044945770164844 11.383802992890722 12.636326535204558 12.152847254365431 12.935313002834857 12.24807578111116 12.325998232563201 12.285230672068703 11.248075809122778 12.597053907901904 12.93613081 12.326069576039693 13.162842596732528 NA 12.663099880922617 13.689610442847368 12.936131802854039 12.247626279585957 NA 13.599423828531027 11.984453147186697 12.389243555617789 NA 13.03234709273348 10.885505680904243 Threonine 14.471270819479233 13.54328029394651 12.87709005506391 13.327025136065462 12.783027439060808 12.922429216083827 13.44755427677447 13.88260502143603 13.340953661737286 13.200214161366253 13.71437371444469 13.845302212226482 12.267286115121623 13.06475385544961 15.005417650987477 13.555240908307066 12.45830644557612 NA 11.34230289587512 14.111999344299985 13.165613637364793 12.96259846422409 13.326078304325613 12.50541560527115 12.720297298891342 13.74964331064747 13.417905638731611 12.851401003793804 13.47621218549226 Trigonelline NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Trimethylamine-d9 N-oxide 27.338937065140453 27.324095384449418 27.353112732034752 27.33889473802184 27.370134453506825 27.332784896050615 27.29196043112212 27.35414167254354 27.358008236005197 27.318829603995628 27.357370583122705 27.327674134946836 27.328316438754495 27.320769403198497 27.312906291698145 27.319950829992298 27.320056966684824 27.292128881041386 27.328015050540543 27.33957906798232 27.335913181647815 27.29750238306234 27.375024462052586 27.28397095284962 27.298957089789997 27.328804101245325 27.29771917934276 27.285908359596583 27.293684725582246 Trimethylamine-N-oxide 17.476101631139795 17.21150219 17.52949764844393 17.64028274706613 17.268903941790313 17.306214924149785 17.335597192636293 17.142441551485838 17.34008383437222 17.411356511266202 17.07632615564186 17.41725528320483 17.163273691653355 17.316947872209152 17.715190026218536 17.416489477469568 17.403417744739123 17.037950273453603 17.37516163337256 17.363593880657092 17.598986636927062 17.384927399711227 17.414240722757135 17.523237294749826 17.436975983524263 17.410931013075825 16.683374289624105 17.38071645358941 17.421926814685804 Tryptophan 15.052675632556669 13.542081862125565 12.341698877662019 13.487536151539409 12.959757135900642 12.792510399928709 13.969535292416563 15.335444996555102 12.980586135502055 13.716744343607195 14.558542795401392 14.202443495361155 13.424822937659146 13.431542578750157 16.593939891167626 14.944768537437348 14.291150117664909 12.37478522235185 12.59651239847551 15.189515094724943 13.78409877730921 13.34545612563995 NA 13.909465015977123 13.604078525849587 13.631607833534156 14.978908513146765 14.795997413896432 12.397568450706471 Tyrosine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Uracil NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Ureidopropionic acid NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Uric acid NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Uridine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Valerobetaine 19.233799096816558 18.267694987108765 19.396699654678066 19.67848759196121 19.045138272604813 18.395748075371827 20.16460755853803 18.599553580760627 17.774313653217046 19.64704993 16.470827464146904 19.41293919225296 19.580016365228797 17.50828869576348 20.332964066520333 19.312112643745994 20.005778894924635 18.580468437949268 17.304266637590818 20.181273423534407 18.209896523231915 19.19608227845664 18.490101487150078 18.949217576374803 17.085093640473513 18.635477021908976 16.85758218475904 19.15849383722197 17.400736499278292 Valerobetaine-d9 25.995014325946322 25.952501411299597 25.994456428956383 26.01534812889487 26.02842664632914 26.020378567437632 25.97423790695906 26.014980962348407 26.027597217142617 25.95926540095608 26.074425100908982 26.023542780035378 25.994978790206208 26.00596407907255 26.052770340890635 26.03685373658489 25.98897387349746 26.026190108212166 26.065569883160034 25.927124465827454 26.026681008820006 25.990042914434348 26.027130296527282 26.030914388750734 25.99788671823839 26.063608263316535 26.084646258334377 26.00913276618143 25.95545391719377 Valine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Valine-d8 23.018537247460188 22.967032079182477 23.88905939150687 23.279254681245593 23.81136075090847 24.634080725460944 23.04842005675611 24.498134420148048 24.21409694224033 23.199814 24.89589607565214 24.616931341573828 23.444608003629842 23.335519701857603 24.132921294416693 23.448753512127052 23.639816261545572 23.598071040305637 23.83789731388961 23.56152673824326 24.16296562145127 23.808896878556848 24.534049493179758 23.67679776991848 23.401826181005006 24.340149209671097 24.431225640806705 23.496859929884952 21.83439109 Xanthine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Xanthosine 18.950921677296776 18.92771740552729 18.864210737592014 19.000456465421436 18.947723163098086 19.004119029116094 18.828304983485403 18.83092961763884 18.836428418074547 18.834361715707825 18.92234408645054 18.918321019649948 18.814572693127744 19.043409735922634 19.105860727674063 18.87813198949658 18.843192167027304 18.907533922331574 18.99638782216611 18.955663567085708 18.887983645987774 18.986596894441043 18.83092282609428 18.869956137318926 19.03895885 18.921999061333725 19.10974227402501 18.83012040945353 18.58531935551724 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name internal standard Expected RT precursor (m/z) product (m/z) 1-Methylhistidine Arginine-d4C13 6.61 170 124 1-Methylnicotinamide 6C13-Phenylalanine 4.31 137 94 1-Methylxanthine 13C5-Hypoxanthine 2.9 167 110 1-Methylxanthosine 13C5-Hypoxanthine 2.79 299 167.1 1,3-15N2-Uric acid NA 5.29 171.1 143 13C10,15N5-Adenosine NA 4.09 283 146.1 13C3-Thiamine NA 5.09 268 122.1 13C5-Hypoxanthine NA 3.94 142.2 124 13C5-Xanthosine NA 4.72 290 153 15N4-Inosine NA 4.37 273.1 141 2-Aminobenzoic acid 6C13-Phenylalanine 1.05 138.1 92 3-Hydroxy-N6,N6,N6-Trimethyllysine Arginine-d4C13 6.77 205.2 128.1 3-Hydroxybutyric acid Methionine-d3 1.3 105 87 3-Hydroxykynurenine 6C13-Phenylalanine 0.95 225.1 179.1 3-Hydroxytyrosol 13C5-Hypoxanthine 3.71 137.1 119 3-Methoxytyrosine Methionine-d3 5.32 212.1 166.1 3-Methylxanthine 13C5-Hypoxanthine 3.1 167 69 3-Methylxanthosine 13C5-Hypoxanthine 2.98 299.1 167.1 4-Hydroxyproline 6C13-Tyrosine 5.9 132 68.1 4-Trimethylammoniobutanal Arginine-d4C13 6.86 130.1 71.1 5-Glutamylalanine 6C13-Phenylalanine 7 219.1 90.1 5-Hydroxyindoleacetic acid 6C13-Phenylalanine 1.6 192.1 146.1 5-Hydroxytryptophan Methionine-d3 4.9 221.1 175 5'-Methylthioadenosine 6C13-Phenylalanine 2.82 298 136 6-Aminouracil 6C13-Phenylalanine 4.3 128 85 6C13-Phenylalanine NA 4.92 172.1 126.1 6C13-Tyrosine NA 5.25 188.1 142.1 7-alpha-Hydroxy-3-oxo-4-cholestenoate 6C13-Phenylalanine 1.52 431.3 395.3 7-Methylguanine 6C13-Phenylalanine 4.32 166.1 124.1 7-Methylguanosine 6C13-Phenylalanine 5.48 298 166 7-Methylxanthine 13C5-Hypoxanthine 3.3 167.1 69 7-Methylxanthosine 13C5-Hypoxanthine 3.2 299.2 167.1 8-Hydroxy-deoxyguanosine 6C13-Phenylalanine 5.18 284.1 140 8-Oxo-deoxyguanosine-13C,15N2 NA 4.8 300 168 8-Hydroxyguanosine 6C13-Phenylalanine 4.93 287.3 171 9-Hexadecenoylcarnitine Palmitoylcarnitine-d3 3.12 398.3 85 Acetylcarnitine Acetylcarnitine-d3 4.08 204.1 85 Acetylcarnitine-d3 NA 4.24 207.1 85 Adenine 13C5-Hypoxanthine 4.05 136.1 119 Adenosine 6C13-Phenylalanine 3.86 268.2 136.1 Adenosine diphosphate ribose Arginine-d4C13 7.31 560.1 136.1 Adenosylcobalamin 6C13-Phenylalanine 6 801.5 676.3 AICA-riboside 6C13-Phenylalanine 4.43 259 110 Alanine Alanine-d4 5.68 90.1 44.2 Alanine-d4 NA 5.68 94.1 48.1 alpha-Tocopherol 6C13-Phenylalanine 0.81 431.4 165.1 Arabitol 6C13-Phenylalanine 5.05 153.1 153.1 Arginine Arginine-d4C13 6.86 175.1 70 Arginine-d4C13 NA 6.85 180.1 75 Ascorbate 13C5-Hypoxanthine 3.8 177 95 Asparagine N15C13-Glycine 6.29 133.1 74 Aspartic acid Aspartic acid-d3 6.33 134 74 Aspartic acid-d3 NA 6.46 137 75 Asymmetric dimethylarginine N15C13-Glycine 6.35 203.2 70.3 Betaine Betaine-d11 4.88 118.1 59.1 Betaine-d11 NA 4.92 129.1 68.1 Bilirubin 6C13-Phenylalanine 1.01 585.3 299.1 Butyrobetaine Carnitine-d9 4.3 146.1 87 Butyrylcarnitine Butyrylcarnitine-d3 3.7 232.2 85 Butyrylcarnitine-d3 NA 3.83 235.2 85 Cadaverine 6C13-Phenylalanine 7.21 102.9 86.1 cADPRibose Arginine-d4C13 7.4 542.1 136.1 Caffeine 6C13-Phenylalanine 1.26 195.1 138 Capsaicin 6C13-Phenylalanine 1.28 306.2 137.1 Carnitine Carnitine-d9 4.94 162.1 103.1 Carnitine-d9 NA 4.95 171.2 85 Choline Acetylcarnitine-d3 4.12 104 60 Citrulline Citrulline-d2 6.36 176.1 113.1 Citrulline-d2 NA 6.21 178.1 115.1 Cotinine 6C13-Phenylalanine 1.77 177.1 80 Creatine Alanine-d4 5.57 132 90 Creatinine 6C13-Phenylalanine 4.27 114 44.1 Creatinine-d3 NA 4.33 117 86 Curcumin 6C13-Phenylalanine 1.01 369 177 Cyanocobalamin 6C13-Phenylalanine 6.09 678.5 997.5 Cystathionine 6C13-Phenylalanine 7 223.1 134 Cysteine Alanine-d4 5.65 122 76 Cysteinylglycine 6C13-Phenylalanine 6.86 179.1 162.2 Cystine Arginine-d4C13 7.25 241 74 Cytosine 6C13-Phenylalanine 4.94 112.1 94.9 Decanoylcarnitine Octanoylcarnitine-d3 3.45 316.2 85 Demethoxycurcumin 6C13-Phenylalanine 1.31 339.1 255.2 Deoxyadenosine 13C5-Hypoxanthine 3.67 252.1 136 Deoxyguanosine 6C13-Phenylalanine 4.67 268.1 152 Deoxyinosine 13C5-Hypoxanthine 3.6 253 137 Dimethylethanolamine 6C13-Phenylalanine 4.25 90 72 Dimethylglycine Alanine-d4 5.5 104 58 DNL201 6C13-Phenylalanine 1.08 340.3 313.2 Dodecanoylcarnitine Isovalerylcarnitine-d9 3.85 343.3 85 Dopa Alanine-d4 5.62 198 152 Dopamine 6C13-Phenylalanine 4.72 154 137 Dopamine 3-o-sulfate 13C5-Hypoxanthine 3.7 234 137.1 Dopamine 4-o-sulfate 13C5-Hypoxanthine 3.9 234.1 137.2 Epinephrine 6C13-Phenylalanine 4.92 166 107 Ergothioneine Methionine-d3 5.5 230.1 127 Ethanolamine Methionine-d3 5.23 62 44.2 Formylanthranilic acid 6C13-Phenylalanine 1.3 166 120 gamma-Aminobutyric acid 6C13-Phenylalanine 5.08 104.1 87 Gamma-Glutamylcysteine 6C13-Phenylalanine 6.46 251.1 122 Glucosamine Glutamic acid-d3 6.45 180 162 Glucose 6C13-Phenylalanine 4.95 202.8 202.8 Glutamic acid-d3 NA 5.91 151 133.1 Glutamic acid Glutamic acid-d3 5.92 148.1 84 Glutamine Glutamic acid-d3 6.05 147.1 84 Glutathione Glutamic acid-d3 6.01 308.1 179.1 Glutathione disulfide Arginine-d4C13 7.48 613.2 355.1 Glutathione-(glycine-13C2,15N) NA 6.3 311.3 182.1 Glycerophosphocholine N15C13-Glycine 6.04 258.1 104 Glycine N15C13-Glycine 5.89 76 30 Guanine 6C13-Phenylalanine 4.72 152.2 110 Guanosine 6C13-Phenylalanine 5.09 284.1 152 Hexanoylcarnitine Propionylcartinine-d3 3.47 260.2 85 Histamine N15C13-Glycine 6.47 112.1 95 Histidine Arginine-d4C13 6.93 156.1 110.1 Homocysteine Valine-d8 5.04 136.1 90.1 Homoserine N15C13-Glycine 5.84 120.2 56.2 Hydroxybutyrylcarnitine Carnitine-d9 4.58 248.2 85 Hydroxyhexanoylcarnitine Carnitine-d9 4.5 276.2 85 Hydroxyisovaleroyl carnitine Carnitine-d9 4.22 262.2 85 Hydroxypropionylcarnitine Propionylcartinine-d3 4.9 234.1 85 Hypoxanthine 13C5-Hypoxanthine 3.7 137.2 118.8 Imidazoleacetic acid Alanine-d4 5.3 127 81 Indole 6C13-Phenylalanine 1 118 91 Inosine 6C13-Phenylalanine 4.32 269.1 137 Isovalerylcarnitine Propionylcartinine-d3 3.58 246.2 85 Isovalerylcarnitine-d9 NA 3.7 255.2 85 Kynurenic acid 6C13-Phenylalanine 4.27 190.1 116 Kynurenine 6C13-Phenylalanine 4.81 209 146 Leucine Leucine-d3 4.73 132.1 86 Leucine-d3 NA 4.73 135.1 89.1 Linoleyl carnitine Palmitoylcarnitine-d3 2.96 424.3 85 LPC(18:1(d7)) NA 3.79 529.3 184.1 Lysine Arginine-d4C13 6.93 147.1 84 Mannitol 6C13-Phenylalanine 5.44 183 69 Mannose 6C13-Phenylalanine 5.5 202.8 202.8 Melatonin 6C13-Phenylalanine 3.84 233.1 174.1 Methionine Methionine-d3 5.03 150.1 104.1 Methionine S-oxide N15C13-Glycine 6.04 166.1 74 Methionine-d3 NA 5.03 153.1 107 Methylcobalamin 6C13-Phenylalanine 6.04 673 971.5 Myristoylcarnitine Myristoylcarnitine-d9 2.9 372 85 Myristoylcarnitine-d9 NA 3.15 381.4 85 N-Acetylalanine Octanoylcarnitine-d3 1.8 160.1 72.1 N-Acetylaspartic acid 13C5-Hypoxanthine 3.41 176.1 176.1 N-Acetylcysteine 6C13-Phenylalanine 1.3 163 121.2 N-Acetylglutamic acid Glutamic acid-d3 3.49 189 130 N-Acetylneuraminic acid N15C13-Glycine 6.69 310.1 274 N-Acetylputrescine Leucine-d3 4.89 131.1 114 N-Acetylserine 6C13-Phenylalanine 3.54 148 106 N-Alpha-acetyllysine Alanine-d4 5.69 189 84 N,N'-Bis(gamma-glutamyl)cystine 6C13-Phenylalanine 7 499.1 453.1 N1-Acetylspermidine N15C13-Glycine 6.5 188.2 171 N1-Acetylspermidine-d6 NA 6.5 194.3 106.2 N1-Acetylspermine Arginine-d4C13 7.7 245.2 100.1 N1-N12-Diacetylspermine N15C13-Glycine 6.1 287.2 100.1 N1-N8-Diacetylspermidine N15C13-Glycine 4.93 230.5 100.2 N1-N8-Diacetylspermidine-d6 NA 4.69 236.2 103.2 N15C13-Glycine NA 5.89 78 32 N6,N6,N6-Trimethyllysine Arginine-d4C13 6.55 189.2 84.1 NAD 6C13-Phenylalanine 7 664.1 428.2 Niacinamide 6C13-Phenylalanine 1.78 123.1 80 Niacinamide-d4 NA 1.88 127 84 Nicotinamide mononucleotide Valine-d8 6.6 335.2 123.1 Nicotinamide riboside Alanine-d4 5.48 255 123 Nicotinic acid 6C13-Phenylalanine 1.87 124.1 78 Nitrotyrosine 6C13-Phenylalanine 4.78 227.1 210 Nonanoylcarnitine Isovalerylcarnitine-d9 3.3 302.2 85 Norepinephrine 6C13-Phenylalanine 5.1 152 107 Octanoylcarnitine Octanoylcarnitine-d3 3.31 288.2 85 Octanoylcarnitine-d3 NA 3.44 291.2 85 Ornithine Ornithine-d2 6.98 133 70 Ornithine-d2 NA 6.98 135.1 117.2 Palmitoylcarnitine Palmitoylcarnitine-d3 3 400 85 Palmitoylcarnitine-d3 NA 3.08 403.4 85 Paraxanthine 6C13-Phenylalanine 1.85 181.1 124 Phenylalanine 6C13-Phenylalanine 4.72 166.1 120.1 Piperanine 6C13-Phenylalanine 1.34 288.2 135.2 Piperine 6C13-Phenylalanine 1.04 286.1 201.1 Pipernonaline 6C13-Phenylalanine 1.3 342.1 229.2 Piperyline 6C13-Phenylalanine 1.39 272.2 201.1 Proline 6C13-Tyrosine 5.46 116 70.1 Propionylcarnitine Propionylcartinine-d3 3.84 218.1 85 Propionylcartinine-d3 NA 3.84 221.2 85 Putrescine N15C13-Glycine 6.3 89 72 Pyridoxamine Alanine-d4 6.02 169 152 Pyroglutamic acid Octanoylcarnitine-d3 3.03 130 84 S-Adenosylhomocysteine N15C13-Glycine 6.35 385.1 136 S-Adenosylmethionine Arginine-d4C13 7.13 399 250 Sarcosine Alanine-d4 5.57 90 44.1 Serine N15C13-Glycine 6.11 106 60 Serotonin 6C13-Phenylalanine 4.42 177 160 Spermidine Arginine-d4C13 7.8 146.2 72 Spermine 6C13-Phenylalanine 4.95 203.1 129.1 Stearoylcarnitine Isovalerylcarnitine-d9 3.02 428.4 85 Sucrose 6C13-Phenylalanine 5.97 364.8 202.8 Taurine 6C13-Tyrosine 5.17 126 80.1 Tetrahydrocurcumin 6C13-Phenylalanine 1.38 355 137.1 Theobromine 6C13-Phenylalanine 2.1 181 138.3 Theophylline 6C13-Phenylalanine 1.7 181.1 124 Thiamine 13C3-Thiamine 5.07 265 122 Threonine N15C13-Glycine 5.86 120 74 Trigonelline Methionine-d3 5.3 138.1 94.1 Trimethylamine-d9 N-oxide NA 4.17 85 66 Trimethylamine-N-oxide Trimethylamine-d9 N-oxide 4.07 76.1 58.1 Tryptophan 6C13-Phenylalanine 4.73 205 146.1 Tyrosine 6C13-Phenylalanine 5.4 182.1 136 Uracil Palmitoylcarnitine-d3 2.47 113 70 Ureidopropionic acid Palmitoylcarnitine-d3 3.24 133 115 Uric acid 1,3-15N2-Uric acid 5.28 169.1 141 Uridine 13C5-Hypoxanthine 3.91 245 113 Valerobetaine Valerobetaine-d9 3.96 160 101.1 Valerobetaine-d9 NA 4.09 169.1 101.1 Valine 6C13-Phenylalanine 5.37 118.1 55 Valine-d8 NA 5.17 126 80.1 Xanthine 6C13-Phenylalanine 4.23 153 110 Xanthosine 6C13-Phenylalanine 5.03 285 153 METABOLITES_END #END