#METABOLOMICS WORKBENCH Jung_DNLI_20250214_171815 DATATRACK_ID:5629 STUDY_ID:ST003737 ANALYSIS_ID:AN006132 PROJECT_ID:PR002323 VERSION 1 CREATED_ON February 16, 2025, 11:41 am #PROJECT PR:PROJECT_TITLE PILRA regulates microglial neuroinflammation and lipid metabolism as a candidate PR:PROJECT_TITLE therapeutic target for Alzheimer’s disease PR:PROJECT_TYPE Cellular studies PR:PROJECT_SUMMARY The Alzheimer’s disease (AD) human genetic landscape identified microglia as a PR:PROJECT_SUMMARY key disease-modifying brain cell type. A common loss-of-function coding variant PR:PROJECT_SUMMARY in paired immunoglobulin-like type 2 receptor alpha (PILRA) associated with PR:PROJECT_SUMMARY reduced AD risk, was found enriched in a cohort of healthy centenarians and PR:PROJECT_SUMMARY rescued APOE4 AD risk, however the mechanisms underlying protection are PR:PROJECT_SUMMARY undefined. Here we identify biological functions of PILRA, an immunoreceptor PR:PROJECT_SUMMARY tyrosine-based inhibitory motif (ITIM)-containing receptor, in human PR:PROJECT_SUMMARY iPSC-derived microglia (iMG) and chimeric AD mice. CRISPR-mediated PILRA PR:PROJECT_SUMMARY knockout (KO) in iMG rescued ApoE4-induced immunometabolic deficits. Moreover, PR:PROJECT_SUMMARY loss of PILRA confers a signature of metabolic resilience in microglia with PR:PROJECT_SUMMARY increased mitochondrial capacity in tandem with elevated antioxidants, reduced PR:PROJECT_SUMMARY ROS and toxic lipid species. Additionally, PILRA KO iMG exhibit improved PR:PROJECT_SUMMARY lysosomal degradation, enhanced migration, and attenuated cytokine responses. We PR:PROJECT_SUMMARY show PPAR and STAT1/3 act as master regulators that mediate downstream signaling PR:PROJECT_SUMMARY and regulate PILRA-dependent microglial functions. Importantly, AD mice PR:PROJECT_SUMMARY transplanted with human PILRA KO microglia showed reduced amyloid pathology and PR:PROJECT_SUMMARY rescued levels of synaptic markers. Finally, we identify a high-affinity human PR:PROJECT_SUMMARY PILRA-specific antagonist antibody that phenocopies PILRA KO. Together, these PR:PROJECT_SUMMARY findings suggest a therapeutic approach to modulate microglial immunometabolism PR:PROJECT_SUMMARY by inhibiting PILRA, thus identifying a pharmacologically tractable target for PR:PROJECT_SUMMARY AD. PR:INSTITUTE Denali Therapeutics PR:LAST_NAME Suh PR:FIRST_NAME Jung PR:ADDRESS 161 Oyster Point Blvd, South San Francisco, CA 94080 PR:EMAIL suh@dnli.com PR:PHONE +1 6507973837 #STUDY ST:STUDY_TITLE PILRA regulates microglial neuroinflammation and lipid metabolism as a candidate ST:STUDY_TITLE therapeutic target for Alzheimer’s disease ST:STUDY_TYPE In vitro study ST:STUDY_SUMMARY The Alzheimer’s disease (AD) human genetic landscape identified microglia as a ST:STUDY_SUMMARY key disease-modifying brain cell type. A common loss-of-function coding variant ST:STUDY_SUMMARY in paired immunoglobulin-like type 2 receptor alpha (PILRA) associated with ST:STUDY_SUMMARY reduced AD risk, was found enriched in a cohort of healthy centenarians and ST:STUDY_SUMMARY rescued APOE4 AD risk, however the mechanisms underlying protection are ST:STUDY_SUMMARY undefined. Here we identify biological functions of PILRA, an immunoreceptor ST:STUDY_SUMMARY tyrosine-based inhibitory motif (ITIM)-containing receptor, in human ST:STUDY_SUMMARY iPSC-derived microglia (iMG) and chimeric AD mice. CRISPR-mediated PILRA ST:STUDY_SUMMARY knockout (KO) in iMG rescued ApoE4-induced immunometabolic deficits. Moreover, ST:STUDY_SUMMARY loss of PILRA confers a signature of metabolic resilience in microglia with ST:STUDY_SUMMARY increased mitochondrial capacity in tandem with elevated antioxidants, reduced ST:STUDY_SUMMARY ROS and toxic lipid species. Additionally, PILRA KO iMG exhibit improved ST:STUDY_SUMMARY lysosomal degradation, enhanced migration, and attenuated cytokine responses. We ST:STUDY_SUMMARY show PPAR and STAT1/3 act as master regulators that mediate downstream signaling ST:STUDY_SUMMARY and regulate PILRA-dependent microglial functions. Importantly, AD mice ST:STUDY_SUMMARY transplanted with human PILRA KO microglia showed reduced amyloid pathology and ST:STUDY_SUMMARY rescued levels of synaptic markers. Finally, we identify a high-affinity human ST:STUDY_SUMMARY PILRA-specific antagonist antibody that phenocopies PILRA KO. Together, these ST:STUDY_SUMMARY findings suggest a therapeutic approach to modulate microglial immunometabolism ST:STUDY_SUMMARY by inhibiting PILRA, thus identifying a pharmacologically tractable target for ST:STUDY_SUMMARY AD. ST:INSTITUTE Denali Therapeutics ST:LAST_NAME Suh ST:FIRST_NAME Jung ST:ADDRESS 161 Oyster Point Blvd, South San Francisco, CA 94080 ST:EMAIL suh@dnli.com ST:PHONE +1 06507973837 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:GENOTYPE_STRAIN WT, PILRA KO SU:CELL_BIOSOURCE_OR_SUPPLIER University of California Irvine SU:CELL_STRAIN_DETAILS Induced pluripotent stem cells derived microglia cells SU:CELL_PRIMARY_IMMORTALIZED no SU:CELL_COUNTS 500,000 SU:SPECIES_GROUP human #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 - HSA-000033340 genotype:PILRAKO | treatment:LPS | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_002.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_002.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_002.mzML; cell_line=Line 2 MBJ; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_002.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033323 genotype:PILRAKO | treatment:Vehicle | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_003.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_003.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_003.mzML; cell_line=Line 1 DNLI; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_003.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033319 genotype:WT | treatment:Vehicle | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_004.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_004.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_004.mzML; cell_line=Line 1 DNLI; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_004.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033335 genotype:PILRAKO | treatment:Vehicle | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_005.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_005.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_005.mzML; cell_line=Line 2 MBJ; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_005.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033332 genotype:WT | treatment:LPS | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_006.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_006.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_006.mzML; cell_line=Line 2 MBJ; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_006.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033327 genotype:PILRAKO | treatment:LPS | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_007.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_007.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_007.mzML; cell_line=Line 1 DNLI; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_007.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033331 genotype:WT | treatment:Vehicle | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_008.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_008.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_008.mzML; cell_line=Line 2 MBJ; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_008.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033329 genotype:WT | treatment:Vehicle | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_009.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_009.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_009.mzML; cell_line=Line 2 MBJ; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_009.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033326 genotype:PILRAKO | treatment:LPS | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_010.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_010.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_010.mzML; cell_line=Line 1 DNLI; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_010.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033334 genotype:WT | treatment:LPS | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_011.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_011.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_011.mzML; cell_line=Line 2 MBJ; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_011.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033324 genotype:PILRAKO | treatment:Vehicle | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_012.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_012.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_012.mzML; cell_line=Line 1 DNLI; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_012.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033322 genotype:WT | treatment:LPS | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_013.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_013.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_013.mzML; cell_line=Line 1 DNLI; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_013.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033320 genotype:WT | treatment:LPS | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_015.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_015.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_015.mzML; cell_line=Line 1 DNLI; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_015.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033337 genotype:PILRAKO | treatment:Vehicle | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_016.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_016.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_016.mzML; cell_line=Line 2 MBJ; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_016.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033317 genotype:WT | treatment:Vehicle | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_017.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_017.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_017.mzML; cell_line=Line 1 DNLI; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_017.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033339 genotype:PILRAKO | treatment:LPS | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_018.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_018.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_018.mzML; cell_line=Line 2 MBJ; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_018.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033330 genotype:WT | treatment:Vehicle | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_019.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_019.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_019.mzML; cell_line=Line 2 MBJ; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_019.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033328 genotype:PILRAKO | treatment:LPS | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_020.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_020.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_020.mzML; cell_line=Line 1 DNLI; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_020.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033325 genotype:PILRAKO | treatment:Vehicle | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_021.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_021.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_021.mzML; cell_line=Line 1 DNLI; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_021.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033321 genotype:WT | treatment:LPS | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_022.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_022.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_022.mzML; cell_line=Line 1 DNLI; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_022.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033336 genotype:PILRAKO | treatment:Vehicle | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_023.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_023.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_023.mzML; cell_line=Line 2 MBJ; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_023.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033338 genotype:PILRAKO | treatment:LPS | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_024.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_024.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_024.mzML; cell_line=Line 2 MBJ; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_024.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033318 genotype:WT | treatment:Vehicle | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_025.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_025.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_025.mzML; cell_line=Line 1 DNLI; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_025.mzML SUBJECT_SAMPLE_FACTORS - HSA-000033333 genotype:WT | treatment:LPS | Sample source:iPSC microglia RAW_FILE_NAME(Met_Neg)=20230911_TW_HEX-000666_Met_Neg_026.mzML; RAW_FILE_NAME(Lipid_Pos)=20230908_TW_HEX-000666_Lipid_Pos_026.mzML; RAW_FILE_NAME(Lipid_Neg)=20230909_TW_HEX-000666_Lipid_Neg_026.mzML; cell_line=Line 2 MBJ; RAW_FILE_NAME(Met_Pos)=20230909_TW_HEX-000666_Met_Pos_026.mzML #COLLECTION CO:COLLECTION_SUMMARY WT and PILRA KO microglia cells (500,000) were pelleted, and washed 1x with 0.9% CO:COLLECTION_SUMMARY sodium chloride and collected in collected in Lobind 1.5 mL Eppendorf tubes and CO:COLLECTION_SUMMARY snap frozen. CO:SAMPLE_TYPE iPSC cells CO:STORAGE_CONDITIONS -80℃ CO:COLLECTION_VIALS Lobind 1.5 mL Eppendorf tubes CO:STORAGE_VIALS Lobind 1.5 mL Eppendorf tubes #TREATMENT TR:TREATMENT_SUMMARY WT and PILRA KO microglia cells were cultured in iPSC-complete media without TR:TREATMENT_SUMMARY TGFBeta and plated on matrigel-coated 12-well plate. Wells were supplemented TR:TREATMENT_SUMMARY with PBS (vehicle) or endotoxin (LPS) (100ng/ml, Sigma-Aldrich, 055-B5) for 48 TR:TREATMENT_SUMMARY hours and harvested for metabolite extraction. TR:TREATMENT_COMPOUND endotoxin (LPS; Sigma-Aldrich, 055-B5) TR:TREATMENT_DOSE 100 ng/mL TR:TREATMENT_DOSEDURATION 48 hours TR:TREATMENT_VEHICLE PBS #SAMPLEPREP SP:SAMPLEPREP_SUMMARY On the day of lipid and metabolite extraction, cell pellets were reconstituted SP:SAMPLEPREP_SUMMARY with 400 μL MS grade methanol spiked with internal standards.Samples were SP:SAMPLEPREP_SUMMARY vortexed and volumes were adjusted to 800 μL with MS grade H2O, vortexed again, SP:SAMPLEPREP_SUMMARY then 600 μL tert-butyl methyl ether (MTBE) was added, vortexed, then centrifuged SP:SAMPLEPREP_SUMMARY at 21,000 g for 10 min at 4C. The two phases generated by centrifugation were SP:SAMPLEPREP_SUMMARY separated. Each phase (top: non-polar lipids, bottom: polar metabolites) was SP:SAMPLEPREP_SUMMARY transferred to glass vials and dried overnight using a Genevac EZ3. Non-polar SP:SAMPLEPREP_SUMMARY lipids were resuspended MS grade methanol and polar metabolites were resuspended SP:SAMPLEPREP_SUMMARY in 90% methanol:water mixture. SP:PROCESSING_STORAGE_CONDITIONS On ice SP:EXTRACT_STORAGE -20℃ #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Agilent 1290 Infinity II CH:COLUMN_NAME Waters ACQUITY UPLC BEH Amide (150 x 2.1 mm, 1.7 μm) CH:SOLVENT_A 60:40 acetonitrile/water (v/v) with 10 mM ammonium formate + 0.1% formic CH:SOLVENT_A acid CH:SOLVENT_B 90:10 isopropyl alcohol/acetonitrile (v/v) with 10 mM ammonium formate + CH:SOLVENT_B 0.1% formic acid CH:FLOW_GRADIENT 0.0-8.0 min from 45% B to 99% B, 8.0-9.0 min at 99% B, 9.0-9.1 min to 45% B, and CH:FLOW_GRADIENT 9.1-10.0 min at 45% B. CH:FLOW_RATE 0.25 CH:COLUMN_TEMPERATURE 55°C #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME ABI Sciex Triple Quad 6500+ 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 area MS_METABOLITE_DATA_START Samples HSA-000033340 HSA-000033323 HSA-000033319 HSA-000033335 HSA-000033332 HSA-000033327 HSA-000033331 HSA-000033329 HSA-000033326 HSA-000033334 HSA-000033324 HSA-000033322 HSA-000033320 HSA-000033337 HSA-000033317 HSA-000033339 HSA-000033330 HSA-000033328 HSA-000033325 HSA-000033321 HSA-000033336 HSA-000033338 HSA-000033318 HSA-000033333 Factors genotype:PILRAKO | treatment:LPS | Sample source:iPSC microglia genotype:PILRAKO | treatment:Vehicle | Sample source:iPSC microglia genotype:WT | treatment:Vehicle | Sample source:iPSC microglia genotype:PILRAKO | treatment:Vehicle | Sample source:iPSC microglia genotype:WT | treatment:LPS | Sample source:iPSC microglia genotype:PILRAKO | treatment:LPS | Sample source:iPSC microglia genotype:WT | treatment:Vehicle | Sample source:iPSC microglia genotype:WT | treatment:Vehicle | Sample source:iPSC microglia genotype:PILRAKO | treatment:LPS | Sample source:iPSC microglia genotype:WT | treatment:LPS | Sample source:iPSC microglia genotype:PILRAKO | treatment:Vehicle | Sample source:iPSC microglia genotype:WT | treatment:LPS | Sample source:iPSC microglia genotype:WT | treatment:LPS | Sample source:iPSC microglia genotype:PILRAKO | treatment:Vehicle | Sample source:iPSC microglia genotype:WT | treatment:Vehicle | Sample source:iPSC microglia genotype:PILRAKO | treatment:LPS | Sample source:iPSC microglia genotype:WT | treatment:Vehicle | Sample source:iPSC microglia genotype:PILRAKO | treatment:LPS | Sample source:iPSC microglia genotype:PILRAKO | treatment:Vehicle | Sample source:iPSC microglia genotype:WT | treatment:LPS | Sample source:iPSC microglia genotype:PILRAKO | treatment:Vehicle | Sample source:iPSC microglia genotype:PILRAKO | treatment:LPS | Sample source:iPSC microglia genotype:WT | treatment:Vehicle | Sample source:iPSC microglia genotype:WT | treatment:LPS | Sample source:iPSC microglia 1-Methylhistidine 1007749.508 2298884.97 2241832.492 924644.5051 1258205.153 2257285.248 757933.9331 648461.2789 2960935.633 560131.148 1751414.875 3675552.361 3235431.868 1118144.106 2492952.74 865971.5192 706768.553 2341241.21 1719233.778 2568422.625 1420863.375 1109849.885 2458339.999 671623.5872 1-Methylnicotinamide 16993969.92 14668590.96 29257436 12243829.79 14289469.5 21485519.98 21988795.23 9499726.508 10015647.81 6939264.68 16464727.55 30598708.75 21681166.87 28308692.82 13348492.69 15986059.05 8611982.947 23743074.97 22826957.41 26877724.96 19593321.56 10846705.58 17255747.5 24257505.41 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 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 1,3-15N2-Uric acid 4493889.264 5135224.813 5110109.213 4127852.167 4396224.921 4353144.777 3366556.064 4182195.277 4094225.345 3257471.625 4869754.293 4609804.1 4750737.771 4311886.06 3766989.917 4801327.393 4903734.72 4324110.459 4860205.412 5509290.4 4158186.187 4763132.339 4864183.54 3612165.582 13C10,15N5-Adenosine 122163066.1 119414480.6 108401072.4 124041078 118952173.3 116668471.6 118754286.3 122823317.8 117756902 106444346.7 120468256.2 102808637.9 100596621.9 123701259.2 108642255.9 125026317.8 131706300.7 115435718.9 121135165.3 105794028.1 122245169.2 124923106.2 110382550.7 120854181.9 13C3-Thiamine 58980841.61 65854342.04 57588262.43 64004393.64 65340136.62 63291174.84 63931600.01 61914442.95 55877091.17 51086752.39 74448510.51 58308074.71 37425437.89 56616967.95 61638661.23 59250951.3 67746972.13 63659891.75 66126110.95 62179225.57 53791761.14 52265314.31 63759471.42 67132166.84 13C5-Hypoxanthine 18008823.69 16888615.92 15339985.47 17448248.79 16947208.68 16997550.35 16811840.14 17526110.78 16013615.08 12841393.17 16576339.17 16321760.98 15237424.99 17940041.86 15983716.05 17039184.92 18690814.9 16563039.06 17988857.09 15209707.89 17595686.53 17152226.73 14087902.27 17234849.67 13C5-Xanthosine 4130355.939 9542801.317 6648637.634 7846075.542 4658896.788 7056775.555 3783820.838 5565704.535 5996285.8 2254740.837 4342313.858 2813441.829 4160748.554 6322199.596 4623116.091 5900589.218 7294726.475 4445310.22 3655550.026 7780193.676 7895062.779 4857894.347 5588964.986 6762708.345 15N4-Inosine 31603005.9 30683727.69 29296262.29 31202272.53 29082516.02 28310388.34 29821595.38 27805208.56 29670377.51 23155738.19 26819715.18 27493834.71 27858321.97 29026099.23 29664269.52 27320638.24 29485770.21 27676035.97 28461609.84 28933462.6 31253852.88 27852927.72 25090571.74 26360081.81 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 3-Hydroxy-N6,N6,N6-Trimethyllysine 3994259.475 4636416.932 6916506.354 4576762.703 4372381.444 4284029.942 4306223.486 4162617.902 3980206.646 982899.7176 3729275.717 5780011.197 6119897.004 4745126.774 7541724.927 3125903.264 3390012.873 3291121.682 3667011.591 4894900.562 4098041.271 1800549.914 6199832.863 3003338.857 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 3-Hydroxykynurenine 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-Hydroxytyrosol 6113311.32 3712197.2 7492017.498 4983653.608 6087856.375 6126113.34 5781230.154 2832724.155 3582914.501 2599326.601 4440599.831 9990394.114 8200753.951 6295371.518 4348248.058 6592784.378 4716219.877 5764322.854 5795582.582 7201050.989 6891020.833 4439728.301 5343342.268 4921179.741 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 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 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 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 4-Trimethylammoniobutanal 17774442.64 10680930.12 14659042.48 11864871.95 13490387.46 17468262.14 14167217.95 8088633.364 11177480.53 3437576.459 11117395.79 23113175.75 19462918.59 16313971.33 14454599.67 20254332.98 11482231.19 12328520.05 16112232.67 16319759.74 17962824.79 11693337.42 11508641.73 8751254.327 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 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 5-Hydroxytryptophan 2611350.308 1736374.003 1657577.519 2104223.588 1523175.361 2360393.487 1867854.36 1012746.665 1403585.548 931530.6875 1840670.81 2149256.374 1394096.436 1922892.341 1593900.99 2786429.577 1777967.893 1233588.395 2745161.616 2056246.786 2551680.039 1389031.03 1084901.164 1040378.241 5'-Methylthioadenosine 48822876.39 51047381.94 68460250.08 46615627.23 56233329.89 73025451.28 44378728 45124741.45 60175846.66 23436167.15 74121861.41 75753755.58 73852791.02 47152028.56 76915060.84 49386692.64 59123082.59 63101248.46 52360224.64 109410533.7 62378936.85 48157290.26 87433688.55 57930709.22 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 6C13-Phenylalanine 144496880.8 147932546.9 141454182 148955218.4 145405167.2 141651108.4 143984058.4 148764895.5 142305415.2 106841484.4 146038747 132331317.6 130304144.8 145879605.5 142973422.3 139211431.1 146461421.2 141629020.1 136043706.3 142653885.3 140383604.4 142431955.5 141751766 139754684.2 6C13-Tyrosine 25952783.42 26995515.42 23664176.44 24374743.2 26306327.09 22673304.56 25078098.85 30526223.49 25241010.95 21016171.95 25371204.04 25460332 22692581.69 24240286.04 27572028.11 24993268.53 27179498.71 22596885.55 24323115.92 24622364.22 22405959.75 23851770.01 26155792.84 23073727.06 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 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 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 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 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 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 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 8-Hydroxyguanosine 2186157.065 1687270.533 1616479.725 3387824.903 2008758.352 1579703.736 1599193.601 1645488.81 2313713.135 1368240.773 2877935.551 2679651.747 2611132.501 1739628.02 2498362.482 4550214.756 2043418.291 2309346.456 2850000.373 2509363.552 2323900.315 3876498.008 2608059.896 2097735.854 9-Hexadecenoylcarnitine 774905.9371 901259.0268 1024267.499 625999.8725 1717629.776 1181870.049 836680.7025 1987906.826 779618.6518 246289.4147 940723.4977 414255.0878 509211.9648 708711.5406 1119395.134 629640.3773 688088.7863 699857.8546 654262.0224 601425.8603 612546.4839 673031.7418 1284183.632 1006559.783 Acetylcarnitine 46234262.15 53832063.68 77876041.82 42623636.24 55293427.77 52525575.36 43965974.34 45594270.11 56335051.21 28152118.58 50744474.72 98738156.25 97812336.11 48463970.95 84168990.7 42691061.79 44353783.33 44971851.48 50284071.56 94920987.69 42311559.25 37947609.58 74601353.36 44341283 Acetylcarnitine-d3 476296527 483681758.1 441157646.9 449046017.5 443366395.4 433514403.2 435842085.7 443399457.8 454192580.5 356747424 442393966.5 438346356.2 426723833.4 473558746.2 464571737.8 439034150.6 448234761.5 444525093.2 443054912.9 452232998.1 444559177.2 442228886 424624263.3 426108104.1 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 Adenosine 45290134.24 38877824.54 64920643.7 33012693.57 31919394.48 35067457.16 56943172.9 28538867.39 30415224.13 34534287.5 49279108.36 54861557.37 43369519.33 62822538.94 46056677.62 38474183.14 40331162.93 38414633.25 53874439.41 42491788.5 41087702.38 24730472.65 54947190.33 39562342.27 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 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 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 Alanine 28028229.16 18524682.66 23993373.09 21871127.56 23930112.26 23419169.62 21046005.19 17948084.75 20185586.08 8928874.429 19378850.95 30190550.66 30498056.47 23574826.67 25557801.93 26321331.06 21996222.54 20005802.79 21429565.8 27940388.94 24803669.74 18875744.31 23478180.46 18433205.34 Alanine-d4 25033251.89 25659485.15 25708464 24344959.4 25396505.05 25781510.58 25558201.34 25491748.19 26115906.36 16485475.98 25317136.99 24877594.01 23777451.93 25751772.08 25122879.24 25011302.89 27011210.59 26218723.15 25142491.21 25199892.96 25024150.24 24449113.7 23180032.97 23898563.44 alpha-Tocopherol 3728067.115 5392511.132 7757394.542 4644861.411 7064412.809 4507811.815 6086919.583 7477917.639 4609338.57 1105229.543 5343335.677 7938716.549 9369137.872 4516358.42 7608865.049 5728440.645 4686515.143 3903150.003 3488087.949 6932672.406 5164575.328 3652719.569 6108292.583 5040394.968 Arabitol 44104040.18 63751111.74 62908075.29 48662514.22 42943672.41 62886853.28 37771060 32377932.65 45418077.81 22870470.2 50040651.7 35112925.37 50165133.29 54677964.06 42455541.82 45649148.46 48002722.13 44892048.24 47250723.42 57791039.24 57064956.5 42223629.13 38302769.85 50144432.84 Arginine 166972940.4 119921851.9 146591237.9 134918470.9 132699725.7 153816060 128834624.4 93028863.83 124900924.6 62313177.59 115619826.7 177162986.9 168846471.3 139091851.1 128027849 165663065.6 119228131.5 126692528.7 144396404.3 144239563.3 151503169.1 110241895.6 120761497.2 96154920.46 Arginine-d4C13 209675422.3 210812877.3 205707927.3 199133211 199679330.5 192944455.2 197748484.2 186151266.5 191447321 140494216.2 182080857.2 206672656.7 195108979.5 187763917.5 205101022.9 175457900.5 180643036.3 169689849 177213373.3 196212305.1 171214887.9 166509311.6 180990036.7 169908046.8 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 Asparagine 6899796.873 4007987.251 7369397.44 6908465.372 5741633.814 6876681.201 5665718.535 4831826.637 4518292.665 1889287.435 4533049.248 7226869.297 6934035.288 6003727.753 5166873.642 7216116.579 5527727.134 5692000.459 6692020.54 7436260.52 6955584.063 4462782.984 5767234.855 4792401.352 Aspartic acid 60901825.23 69376974.63 77107861 66943366.93 57610833.41 66278299.06 49748040.4 54218684.98 67033865.14 29499833.16 63906573.93 65487668.09 65674751.96 64216342.48 85413177.66 58784023.8 48764711.36 56569954.81 61429568.29 69527997.26 59405703.56 47995745.08 75557515.65 53394403.35 Aspartic acid-d3 37860488.41 34054493.88 35233095.16 35854270.42 35508251.9 34843479.59 34388873.7 36427866.18 34924631.26 22649174.11 35265642.62 35662318.88 33170664.6 34441987.23 35444312.2 34820314.94 37910431.85 35792904.89 34466049.6 34042670.88 34717558.32 32935426.92 32830333.78 35028299.07 Asymmetric dimethylarginine 27557773.81 24689343.79 41779142.5 23663280.53 24831209.66 28371552.63 27434502.8 20395642.2 23848418.49 9203138.436 22572256.14 40270992.7 36042956.2 24968292.78 36074117.27 26394358.25 23596965.86 21604232.7 21233100.9 39804659.72 23999380.04 18482011.96 34735721.28 24460947.2 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 Betaine-d11 31922632.3 28657436 26509024.74 31500483.74 30381012.78 29077444.33 30604125.29 31416554.1 29993879.61 22928748.44 29869464.25 25948099.67 24189175.84 30787764.81 25617703.28 31761675.61 33040520.1 29506048.21 30909646.35 27835149.35 30848636.11 30478835.37 24453230.49 30231458.8 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 Butyrobetaine 15223138.4 29587244.39 32194557.41 16793910.98 20659553.26 25842483.1 17967442.83 22561775.49 26568082.32 11648326.76 26726460.06 32993609.82 31068498.72 16219612.12 39380936.81 13139746.25 16893001.37 22663938.91 25576331.92 32258781.75 14315903.07 10479591.98 35273644.49 18481183.53 Butyrylcarnitine 46949281.63 34225659.14 51146722.61 35028919.72 43287845.19 50261484.2 27610980.65 30371887.36 49434871.98 24754001.3 33388346.17 75187127.88 67503972.82 35838667.14 52343262.02 43785060.2 28319228.61 40104972.3 28755385.66 72883000.38 34173122.37 40962311.01 48131687.78 38539281.68 Butyrylcarnitine-d3 257264738.4 233675140.8 216802841.4 239806829.3 229197161.7 233035829.5 260643741.5 271546474.9 260358650.6 200965620.1 261901949 225555796.7 212192974.7 275833893.8 230544430 253300337.9 264344746.6 260321234.6 247763801.3 238563512 243754439.2 251346912.6 240907951.6 266595502.3 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 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 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 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 Carnitine 56405597.88 47063503.06 65832757.68 52998351.46 58477209.97 49450083.17 49993319.78 49963700.47 47960023.5 28214104.26 45940666.73 66336653.35 65613433.99 53302173.66 68564861.12 53069733.82 48863510.21 42637505.2 45252054.09 69840412.94 52712492.25 43253381.28 63764834.47 50732043.75 Carnitine-d9 86525998.78 82367809.83 77003861.56 82222252.31 82863114.3 79931369.13 84782889.32 82759706.36 83203536.77 61857791.28 82884968.65 77571009.62 75050566.49 83894212.32 79700286.52 82681188.21 85674433.31 81272299.5 82994139.15 79037845.53 81557021.56 79995956.59 73660646.5 81427528.26 Choline 249365606.8 210458496.6 253017331 239954225.5 254752476 245703154.6 242749948 223921045.3 239336157.9 172758467.3 203699313 280988052.9 284614491.2 255080502 244826591.7 249372047.2 231082287.3 226754924.3 208114630.2 276358023.7 252274295.8 206432712 241040900.7 244206845.1 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 Citrulline-d2 7594562.658 7656143.597 7642644.063 8412762.891 8252818 7378138.34 7698364.799 8420715.667 7840520.001 3671952.694 7845716.227 7464468.451 7277628.064 7675044.788 7529164.207 7010409.984 8416635.213 7511231.445 8254492.862 7490775.725 7310764.697 7279115.124 7512587.202 7565554.375 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 Creatine 98432394.1 57585096.3 81746918.05 80352498.65 95554384.73 59126616.16 80188062.67 90904760.45 58564991.13 54268722.02 52628455.06 93672895.31 88849751.53 86532398.68 92734565.7 79110388.19 70340012.82 51252259.48 53226116.41 82107611.54 69197286.18 66122646.99 83298893.23 78823946.69 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 Creatinine-d3 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Curcumin NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 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 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 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 Cysteinylglycine 9773037.732 8989143.568 9505832.668 9843002.563 10066110.29 8500811.339 8834483.017 9422345.092 9321094.705 4982096.684 7968618.737 9743311.354 7434048.584 9196992.835 9139600.881 6659986.685 7479006.442 7490567.417 8541366.456 8612376.172 8095998.123 8498869.813 7053422.36 9306166.754 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 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 Decanoylcarnitine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 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 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 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 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 Dimethylethanolamine 12045994.15 12191063.48 10337411.17 10295136.37 9344061.85 13320012.16 13995781.59 10945718 12183125.62 7154121.605 8262530.213 9978617.506 11508388.37 13550433.17 14915781.15 7754642.878 8982272.554 11247439.61 10889189.99 9965229.879 10099241.43 11165196.85 10659168.8 9678784 Dimethylglycine 16281866.97 14216902.53 21791110.24 14479011.58 15606743.33 19274452.02 14374787.22 11068034.31 16843207.75 3939693.623 15337759.77 28657743.29 30192882.52 14659795.61 22710049.43 17354766.45 11753114.42 15002479.95 18855865.29 30861555.06 14605628.18 9810495.941 19568137.87 13034722.28 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 Dodecanoylcarnitine 200313.3625 359178.4181 500816.887 311420.6032 270444.0988 429732.3593 250589.1041 402531.699 312027.6027 113386.1574 480613.9777 267156.7481 457964.7431 402812.7655 680540.5083 313700.9873 385855.6122 277382.844 464272.5387 742779.4857 303235.9703 130519.8409 910403.315 355055.2279 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 Dopamine 4826950.404 7844663.853 8640505.187 6513938.712 4470428.372 10250255.71 5200069.155 3613331.663 6195137.339 2631760.197 6598585.999 4705264.599 5611172.672 7901763.045 6192373.866 7661884.231 6838144.88 7627277.956 7292136.298 9514699.347 8214073.002 6275043.992 4867711.803 7116182.152 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 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 Epinephrine 11035047.63 7985035.941 11170234.58 8295972.095 8739520.85 9522372.389 9510184.625 5815150.793 7629734.416 1853524.035 8327207.929 12170445.94 11907126.47 9148836.809 9300632.759 11741687.04 9100115.969 8805903.797 9824907.398 11180108.56 10767676.61 8983292.394 8592551.454 6895826.416 Ergothioneine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Ethanolamine 1683476.419 1380796.557 2574861.84 1194105.782 1800044.652 1206168.574 1581447.563 1845796.951 1401267.794 616206.5271 1232670.532 2319787.988 2500937.631 1099548.342 2262796.68 1379174.964 1137263.62 1176709.732 1324730.713 2553816.109 1179501.762 1010972.408 2389587.679 1228452.811 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 gamma-Aminobutyric acid 1242648.627 911198.1576 1755104.364 916674.0841 2397671.582 1090845.408 994809.4627 951810.8038 1361739.088 364583.2408 780175.9618 2686774.552 2259736.915 745061.2104 2261646.808 1195397.04 864765.9077 890449.7631 532648.6421 2797190.991 929034.2991 769762.7461 1955804.592 1493315.74 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 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 Glucose NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Glutamic acid-d3 16992558.57 15787773.1 15134379.99 15300899 13968828.42 15487452.68 16071891.04 16558035.25 15062180.5 10457739.1 16058198.07 14937455.21 12288958.47 14493396.74 16612648.43 16193264.29 19372639.07 18676620.16 17889923.12 14434651.36 15526485.97 16773180.11 14538334.27 14337035.88 Glutamic acid 148931148.1 131345164 168708708.2 140328455.8 154519518.3 135958947.4 132205598 133811044.3 142244515.7 79205702.47 138562373.9 172778908.2 176814610.7 141729463.3 183545114.4 140137213.1 113548696.7 116433698.8 117672973.2 176328138.2 136189112.9 112153022.4 162786616.3 134433379.6 Glutamine 85917388.84 64934216 77777587.54 68374517.55 69505968.03 78794971.27 63386274.73 49908650.7 70671063.31 33139162.5 64761744.02 99121093.39 98010495.58 74342807.6 76338764.17 89124444.47 68058986.85 68282174.99 80107964.73 91036083.17 78653994.47 64764000.95 73429742.68 56836934.83 Glutathione 46987460.68 41674689.68 69215141.45 51478464 45130544.03 66780597.4 42452001.82 32854668.45 69161231.3 23246515.42 55495770 96537819.84 105746769.4 49906550.27 74153169.27 53878534.2 38099553.17 53320256.76 57751243.69 151293679 40749037.46 40147156.24 70663768.23 48138353.03 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 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 Glycerophosphocholine 115045041.3 71356755.56 98501318.35 85391890.17 151856027.8 122129545.2 99201837.08 94816647.91 145177277.3 63617902.68 72217853.57 175989273 174359615.3 93005627.42 98238445.74 102627968.1 89863456.4 99549728.48 67517632.87 170712969.4 107433131.9 78852121.32 93359898.94 113043652.4 Glycine 1749724.375 1610420.937 1637484.84 1769442.107 1681223.59 2225717.354 1198806.094 1613507.049 1897213.94 666865.0871 1387405.986 2419473.082 2003981.781 1929474.191 1967862.083 1838544.954 896708.5112 1491728.72 1281127.445 2049587.623 1321840.072 1715525.385 1812566.347 2170254.909 Guanine 12011431.23 14744886.19 16864168.08 14152142.51 11840531.72 16229251.89 10570736.59 9972410.509 12470918.54 6952351.782 12518405.75 11961174.37 13878472.73 15969930.15 10348102.2 12674921.64 14824384.85 13645796.85 12942561.96 16828325.59 15439212.3 12531030.9 11620086.91 15934564.59 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 Hexanoylcarnitine 5122610.107 3826618.663 4691475.612 3484334.704 4631416.608 4627744.223 2874349.613 2831382.617 4350109.253 2409304.033 2976547.33 5651295.285 4183791.421 4353007.43 5301232.56 4423580.9 2985474.298 4421543.83 3406230.893 4863719.088 3662565.045 4912575.969 3991468.989 3931195.888 Histamine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Histidine 62639432.57 48892658.49 58977785.5 51593441.29 52070856 55470602.83 48342504.8 38016571.9 51900571.83 22205593.76 46933094.6 73266948.92 71667057.01 54377461.97 58941848.95 61474169.01 47923221.69 51360429 54029626.43 62569277 56286204.24 43946603.91 52583404.27 39939491.18 Homocysteine 28391910.73 28851169.25 28223013.53 29079519.75 28583443.51 30323052.28 30082463.53 30658535.72 28642331.76 20367300.11 30563666.55 28310902.63 27181457.54 30433928.56 30976775.29 29184367.64 31119076.73 29151874.38 29011193.85 28378813.67 28381167.29 28796135.62 27976562.09 29579728.55 Homoserine 23753121.2 17217967.82 22085384.01 19360355.18 20334613.72 22893124.02 18726969.03 15889722.44 20207393.38 8692016.299 18367291.98 26638376.48 25511704.15 20421646.26 20536490.55 23946320.19 19888370.9 19399830.91 21528405.49 24985504.36 21846883.13 18095237.6 19923382.13 16892775.4 Hydroxybutyrylcarnitine 22142874.88 21720247.57 26835953.95 22568662.83 24993795.99 24046791.46 21851528.27 23164812.66 26539686.29 11899329.93 21029048.68 37484627.48 37656682.83 23481854.2 28584188.98 21118867.97 21161667.08 19671512.05 18665809.21 37947040.31 23407296.78 19455015.23 24856956.62 23990811.26 Hydroxyhexanoylcarnitine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Hydroxyisovaleroyl carnitine 25942830.71 17505588.41 26737015.96 27080537.9 31849549.67 23953441.58 20540379.43 27784442.62 26660512.42 14316438.4 18789130.87 43236246.09 42438178.92 25203175.87 29361409.11 22283442.36 21621898.36 21551917.87 17388570.52 43260494.12 23476903.28 22722648.54 25365434.58 25667135.94 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 Hypoxanthine 3091415.984 2034725.952 4355511 2437053.639 2349872.453 3486550.091 3609926.681 1388467.09 1804968.23 992048.7133 1906220.384 7109016.292 5120531.985 3699594.914 2989425.709 3571685.099 3078737.539 3083445.808 3799290.783 4792356.394 2991552.251 1682034.602 2432056.794 3346789.851 Imidazoleacetic acid 7132755.587 5428996.167 5417036.67 3725273.152 9244408.75 3251068.876 6392052.222 10584709.3 5310656.25 6076317.975 6585326.362 5221013.616 4017433.784 5122907.928 9548362.497 5910654.036 7217531.649 5108620.693 6667339.388 3963392.316 3990450.841 5473894.556 8228092.079 4722402.392 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 Inosine 8094282.395 7697495.818 14622918.41 6212525.775 6139703.63 8812235.414 8770492.537 4648679.634 5901692.784 4047623.253 7633492.867 11818817.88 9904514.209 11921125.63 6098229.797 6032996.553 5035491.877 10276125.54 10513525.39 10887394.7 8186557.41 4538270.305 7448558.273 9407420.703 Isovalerylcarnitine 44763638.99 31579507.28 33676157 36830355.45 45967386.7 39149683.69 37742130.19 39704129.1 40490158.3 30206146.98 31066920.17 51728487.27 51637428.19 43620767.63 35264344.55 40184343.05 37616923.97 35707697.55 30105128.14 45814639.05 40837675.04 39817736.89 30694276.35 41254939.61 Isovalerylcarnitine-d9 355257761.6 341357379.7 315568484.5 354890333.5 343572306.2 338304014.6 351421278.1 344398192 334794131.6 277593081.9 337343611.9 322109865.7 299801808.5 357143340 315495556 346950765.2 367605251.7 331071747.6 335583339.7 303612001.5 350467445.6 350036992.3 305358930.6 344253521.3 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 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 Leucine 111461813.8 92977870.74 105438428.4 93131064.57 93779041.73 103988070.4 91437550.88 76628631.89 96294785.44 50521106.65 95565397.07 113665786.4 116197144 98818135.55 99227417.42 116319356.2 102623007.1 97005291.81 106539438.2 109174712.5 108645122.9 90552988.13 95893045.94 79686674.56 Leucine-d3 145493527.7 142871860.8 139020860.1 142813444.4 137925819.7 134150066.1 137964281.2 147119172.2 140653569.3 106866615.2 144785379.6 140145164.2 125475343.5 142940713.8 140321799.6 138933653.3 143974884.9 138934906.3 133274712 143373910.3 133767251.3 135443172.6 135900041.7 139118346.4 Linoleyl carnitine 718614.5507 666768.7182 1217035.911 714829.3787 2894253.389 1235598.667 1329568.752 2010167.653 953472.9314 360065.7407 1263472.117 1172328.614 1183296.549 1064851.433 1132777.944 1209732.413 1995528.822 1055015.179 777080.0126 905081.2641 403409.633 1173638.889 1071299.722 1579023.003 LPC(18:1(d7)) 242995965.8 258560220.5 265770810.8 240083517.3 251304362.5 260297569 241218486.5 253978488.6 266275751.8 158997064.5 257791450.7 263964173.2 261657944.4 254701619.8 276112981.6 247436374.5 244968450.5 246459998.3 245477101.9 269333973.9 247378301.6 238951829.1 274553252.3 246638282.4 Lysine 20357796.76 14187882.34 18734678.98 14958589.61 16294811.07 18422228.06 15641679.63 11715382.07 14390064.77 6601311.326 15926331.96 22407963.83 20983964.03 17813596.83 16121327.13 21258548.27 17287367.09 15133797.9 18541405.79 18926959.95 18396547.87 14768776.51 14072142.82 13332439.24 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 Mannose 21806580.01 9527422.215 15331212.94 15428573.32 17304622.04 20398978.88 15862029.58 8064489.863 13596529.35 3680988.395 14420071.97 18669890.63 20866645.91 18380411.91 11512690.89 28821531.59 19040521.73 17353121.83 23737614.67 13708795.88 22890750.71 17600461.68 12430508.03 11000261.05 Melatonin 2714048.086 1443178.933 2368451.799 1975658.918 2223529.654 2978000.932 1239731.864 1191445.711 3317165.289 1042321.484 1543026.239 4988910.915 5006072.553 2066301.658 3727307.119 2350366.383 1104939.027 2085368.232 876141.0466 5449541.227 1494983.475 2703460.101 2290447.266 1736599.93 Methionine 6761753.201 4659545.611 7745096.096 5456841.373 5549942.354 6814028.29 5038952.821 3307212.768 5934635.493 1844753.315 5100994.062 9975943.183 8912572.777 5745690.321 7966063.76 8115307.112 5802601.983 5792185.382 6343923.096 8817591.593 7483242.969 4874108.911 7106552.643 5071079.163 Methionine S-oxide 4064850.829 3198895.283 3787518.571 4260321.874 3247055.127 3960747.783 3225240.985 2492414.931 3490055.17 1740220.133 3372690.276 3889451.91 3429846.846 3916671.889 3279845.299 6216179.847 3769435.426 3363220.214 4626358.55 3622472.725 4565297.603 3401916.896 4429776.191 2621136.581 Methionine-d3 51917128.19 49726861.98 50510276.18 49528446.32 51280204.13 49847627.02 51263479.16 53029503.2 51516712.33 38061160.07 52077113.54 51064799.81 48203075.29 51559071.92 53648934.52 49853914.54 52789017.45 50573606.73 51585143.31 51843669.7 49750245.44 49539341.71 50004972.35 50777623.81 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 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 Myristoylcarnitine-d9 77065386.65 70532917.28 66708680.29 76159541.71 78831083.22 68205918.81 57908746.82 70484314.21 47772260.2 53725302.76 68881173.13 78743840.55 64990251.39 74111278.44 64790262.9 81856440.96 74778810.95 69064110.56 54032802.16 72954021.72 69042743.13 54646496.22 68955699.22 73775309.29 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 N-Acetylaspartic acid 24432357.55 24796330.75 27987056.97 22719986.59 23164649.3 31260727.32 22408197.02 23223934.81 28065188.03 19719207.77 27296461.07 29584601.96 29717264.09 23937596.95 28728080.36 25154770.16 26616900.74 26163594.32 25866813.5 30284280.26 25851592.77 24055586.95 28543325.14 23804030.25 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 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 N-Acetylneuraminic acid 13067683.11 4755109.647 6869588.124 5527007.485 5566732.34 7675148.11 4758101.274 1900591.904 5335601.561 342369.91 4251103.748 12093702.91 10383865.41 9271699.55 5350626.439 15303833.23 4798198.354 5694025.759 8034272.832 6409343.863 12407057.12 5016432.668 4830064.817 3091248.886 N-Acetylputrescine 700731.6165 190376.7439 247296.8814 352497.0718 688419.4584 333875.5021 296765.9764 532175.716 300631.0727 478498.9547 274925.4422 411676.1492 752278.0665 349530.0508 337791.6581 441732.4928 309186.6386 468030.9139 243167.6889 678662.8036 658151.7721 678373.7893 140477.5702 684124.7837 N-Acetylserine 5170351.681 9386494.159 10793072.41 5773711.346 6959251.029 9556996.556 3499569.089 5332932.782 8902258.39 1783151.404 7819697.722 13771381.21 13899882.32 5697952.809 14822185.24 5439962.496 3653780.932 7578263.127 5818024.461 15613762.06 5356679.307 4791560.026 10525315.98 6125043.083 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 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 N1-Acetylspermidine 5956423.135 9246815.404 14120347.32 4738951.185 5451523.67 14758766.8 4163535.553 2393329.075 11873731.68 1482245.443 6622195.037 21900616.97 25205557.31 6143781.136 10633495.97 4191587.784 2604349.939 10210237.81 5886757.983 23636052.73 4485546.285 5613057.509 8657830.48 6223553.709 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 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 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 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 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 N15C13-Glycine 6453676.796 6303522.848 5917795.145 6206745.253 5343341 5728505.6 5711413.11 6341969.252 5901555.953 4209283.41 6079681.563 5862037.457 4762428.674 5429045.946 5401194.345 6018628.716 6353153.048 6011031.295 6113882.744 6104782.859 5525834.265 5481312.311 5312679.953 5464482.842 N6,N6,N6-Trimethyllysine 12480171.28 14001147.23 19017890.27 12696349.28 12297191.43 14387375.79 11154643.8 11707214.1 12205324.64 3558518.491 11517909 16554233.01 16272029.06 13255495.23 18709933.23 10534691 10677758.05 10336214.64 10264559.08 15976345.85 11664426.47 8388783.632 16286563.75 10130757.58 NAD 409983.6892 845053.5326 997224.5223 629366.848 450611.2754 1276703.061 436286.9872 599345.2228 887763.2395 135000.685 543158.1673 1098568.5 1173523.062 407972.3573 1435809.316 372355.8191 246937.548 341142.156 688760.5926 1469217.07 366837.5023 352761.3615 1181361.177 466616.4668 Niacinamide 49449495.54 44790548.62 52490378.78 39352533.04 45374233.71 68237850.5 41847565.35 33686410.53 55620208.4 23944554.54 55326167.07 78797128.74 75900399.32 44347359 48606272.47 70431243.57 57806222.78 57432325.41 51133151.81 124959973.1 65100999.38 42396941.11 63419400.75 52354094.78 Niacinamide-d4 401302142.9 399755553.1 391092090 397763516.4 398647006.8 394548490 404297351.3 389327512.3 389790316.9 289610832 394659157.6 402406351.2 386967585.6 408356880 396036761.6 380533617 382748200.6 367418181.5 364898494.8 385376130.3 383914783.8 363955171.5 388864042.4 391238982.6 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 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 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 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 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 Norepinephrine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Octanoylcarnitine 1874919.964 1983460.255 1839825.337 1816209.626 1278138.207 1792608.594 744792.8593 955251.0051 753897.2896 1357411.837 1396016.849 1403903.654 1236089.498 1834879.91 1383257.241 1413042.67 1249385.85 920472.9402 1080376.335 1194648.973 1714951.977 1305004.459 1692716.55 1519084.128 Octanoylcarnitine-d3 201943833.8 180211932.4 161797467.4 189607791.4 181587849.1 168785466.6 176762066.9 185261100.1 170365788.9 159641736.6 188253015.4 166943132.8 151161534.4 188346737.3 156537588 184362036.4 209238711.3 181999874.4 187675146.5 153850364.1 191997059.5 195098975.6 159641242.3 180254847.3 Ornithine 2035776.622 1058466.395 1232255.536 1118092.627 878940.5951 1274467.302 1240406.309 575393.7027 1940886.447 300223.0695 949408.2231 2484533.064 2955099.717 1087434.301 2036744.34 1128936.147 1002051.107 1006564.406 781276.0628 2613474.193 1086675.685 831113.3121 1820981.408 918046.9339 Ornithine-d2 16213625.1 15543004.23 16904538.82 15181617.75 16329491.51 15567423.94 14744676.11 15710469.08 16075144.71 10044368.64 13368745.58 18086405.47 14831220.77 15692985.03 16500357.88 14211162.97 14772690.14 15190579.71 15553301.67 18029970.78 13944839.42 14435781.74 14693485.56 14888226.08 Palmitoylcarnitine 381982.9099 870688.5023 794274.9733 385817.2486 851005.0411 591811.2385 707533.8215 910074.688 755811.1768 333173.7836 574698.3444 738531.6621 823588.2888 535268.8728 1217664.297 806920.2826 480047.3031 343740.8582 525697.8339 605664.1976 551086.6523 423247.5049 1019352.763 761521.4135 Palmitoylcarnitine-d3 35329233.25 36420615.67 34671583.88 32187421.75 34617229.46 23744933.99 28426623.55 43257414.34 32266227.05 30002997.15 35050825.27 25471151.97 24910276.15 27101115.74 29726545.04 27439519.54 28417897.72 37967000.37 26986950.01 35092113.58 26453231.75 25777544.77 25625700.65 32995315.11 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 Phenylalanine 103028568 80617295.53 103721415.6 84171635.2 82426044.11 102015493.1 79534018.69 60339293.88 82988695.48 38046354.82 82779970.94 116477502.8 110249152.9 93716361.2 92344356.02 113114782.3 87836397.29 85682441.04 99080999.96 111324100.3 107854546.8 80699976.08 90388730.3 71430940.7 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 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 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 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 Proline 21378369.28 8282252.945 13227616.87 12882395.91 16370953.83 9224102.902 11374940.19 10949312.41 9972169.416 4417120.98 9529445.807 16122925.99 14812766.92 12945521.26 16391628.96 21505255.77 11922351.66 8704327.833 11295832.7 17331560.61 17098971.77 14032557.26 10645713.58 10109922.16 Propionylcarnitine 54366844.28 74919669.5 97131933.67 68755615.71 61947696.23 63240321.12 50704483.66 54903464.86 67334435.8 49356979.92 61710548.23 105018517 100291093.5 61335167.87 104153986.3 49458806.78 48733993.31 61939881.32 61472596.97 109590233.1 58137938.77 54460220.49 98596293.4 65843341.4 Propionylcartinine-d3 180829404.1 177229174.3 169263339 175367284.2 172683674.2 176407234.7 171702012 178577050.8 174729597.3 141997274.6 178181703.7 169950783.4 160063633.3 178740200.5 173814350.3 177609249.1 185929513.8 177913044.9 184937694.9 169669697.4 180263563.7 181630889.3 167990160.9 173564796.7 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 Pyridoxamine 18161250.25 13085608.25 11521959.61 17259897.35 15065764.5 12471621.94 12869017.58 13268289.22 11039060.76 6546178.369 10606538.42 13019353.29 10111338.43 19076606.53 10792983.74 19666703.98 15912449.13 13807653.79 12731434.88 11706841.04 20176099.32 14697111.98 10515977.56 13322517.75 Pyroglutamic acid 274800668 186297323.3 228069820.6 223491495.9 218316006.6 257615596 209508237.7 156748465.6 223615928.9 113383631.8 201365255 298876956.4 307255478.9 242181460.6 209928917.8 305192616.8 223299450.4 234219401 254764042.8 282401071.3 287006661.5 229620412.3 201474516.6 183351896.3 S-Adenosylhomocysteine 1041344.017 1080925.706 1356895.204 676296.3218 1312033.348 1239238.568 844301.9522 652168.6069 1002782.931 447826.3231 759666.8208 1688522.087 2128278.973 1101868.631 1489977.033 931145.6595 745572.7347 444546.4716 967859.8382 2068705.407 663329.774 632217.0462 1110779.077 800185.6739 S-Adenosylmethionine 12485578.91 15192610.83 24748374.41 13183357.59 15157967.29 11914107.36 7967135.48 9350495.962 15877740.69 3044136.988 7260088.827 28609706.28 28695738.62 12489221.72 22575572.04 7209890.994 4117704.396 11362525.86 9146728.127 19807748.69 5917300.277 7292901.283 13045503.23 8153846.617 Sarcosine 23675863.95 17034244.34 21726185.67 19069613.04 21810475.26 20512837.01 19061946.78 15949699.35 18704110.42 8793365.102 16555650.24 26068897.19 26677161.59 20406942.07 22631862.08 23682762.27 17455568.25 16788103.02 19071902.73 25307312.67 21714958.77 17678043.98 20349276.88 17299711.07 Serine 13943657.45 9645019.267 10629565.48 11752672.65 11904133.43 12466524.83 12141179.62 9013953.76 9108117.67 5231309.924 10376560.24 13450660.52 10239012.08 12966630.51 9455205.914 15371951.85 12421017.8 10255495.85 12712922.3 11216097.33 14162097.41 11191516.77 10661663.13 10442243.68 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 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 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 Stearoylcarnitine NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Sucrose 17908760.31 14075218.07 13816844.18 18333018.96 13371037.31 10957688.17 16402102.47 14716097.12 19562567.01 14141598.84 17326076.7 23261242.49 10362453.2 18185364.71 10672889.03 17675548.42 12200689.31 13818434.99 15487888.44 10028035.01 16233582.03 17118069.23 13236375.61 14452388.28 Taurine 53795767.06 49939236.54 45356039.6 43278986.78 59920666.57 40505013.87 54291898.52 72127439.97 46109096.82 50260586.83 56943324.41 50196600.45 43651038.53 45453313.53 63056424.7 51034002.62 54321646.13 46772183.45 50280305.96 44294015.23 38307520.22 48423876.73 59035031.67 45825826.04 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 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 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 Thiamine 33982536.42 30443374.94 41856459.56 29566447.41 34679500.49 39010762.04 26646939.64 26886830.81 28807356.05 19185725.41 36504464.65 46479573.68 49980428.09 32753784.39 33179502.64 46301225.35 32716773.83 36752949.65 38926775.06 45053484.65 41625078.93 30638833.58 31026639.48 27743065.86 Threonine 14284297.68 10425626.4 12661410.09 10483261.42 11481672.58 14031025.44 10403603.65 7867217.47 11794406.85 3853382.395 9965869.197 15639920.88 15657080.12 11375597.2 12524812.19 14759575.16 11211665.88 11242132.11 12320909.27 14504777.66 13090472.4 9228745.156 11426584.19 8676082.129 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 Trimethylamine-d9 N-oxide 156650894.9 155648225.3 148341375.3 157551672.9 148666213.7 155978381.8 153483153.9 149134070 150542778.5 119931146.2 153724578.4 146962534.3 142290190.2 159382888.1 151700778.5 155290473 159419526.3 156406811.5 156973953.5 147427220.2 156508731.6 155327235.2 144255972.1 147667445.8 Trimethylamine-N-oxide 6964541.014 7520117.569 6968997.288 7574483.344 8083600.552 7375084.024 5453946.272 7694353.275 6894846.002 4167546.942 7888903.885 6201704.197 5458262.318 5872968.516 7709285.92 6717865.943 7421695.253 7734122.323 6945182.743 7454643.574 6737980.003 7650088.281 6783059.458 7995697.173 Tryptophan 7128532.644 4884453.352 5824351.577 5175430.408 5615883.459 6419870.099 5309775.315 4261636.41 5593417.724 2007841.762 4859523.425 6394581.645 6897890.752 6132789.387 7190063.568 8504581.93 4271157.013 6205164.592 6843426.202 6362321.591 6421683.071 4941802.572 6675967.17 4911596.911 Tyrosine 8268361.417 5727785.657 6900839.788 5193780.392 7181838.492 6889401.548 6295588.335 4240778.027 5493258.341 2552651.808 5426497.938 9364920.066 9261266.872 6191318.055 8539090.258 9321071.693 6457714.651 5395986.433 7969835.227 9166819.605 7830633.252 5619632.595 7799064.453 4286606.778 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 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 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 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 Valerobetaine 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-d9 62541472.17 68239935.74 61980632.28 63047588.76 60967325.04 63804828.28 60435485.57 61585314.76 63843116.95 56213761.62 65912558.3 55811703.05 54147884.25 63304862.01 61341567.9 61325128.31 69689765.53 64818598.6 68167482.41 62837517.96 61784905.76 66198179.71 57635129.66 58990000.9 Valine 8357909.109 5350421.327 5242294.444 4178111.203 8433113.836 3677684.077 6658156.499 7007775.307 4796241.839 3915008.445 6496484.242 8178446.486 8269942.261 4667312.561 9063615.643 8710252.312 6898482.886 5000546.029 7613442.336 6284887.024 4377220.567 4688973.1 9728714.416 3420909.422 Valine-d8 53795767.06 49939236.54 45356039.6 43278986.78 59920666.57 40505013.87 54291898.52 72127439.97 46109096.82 50260586.83 56943324.41 50196600.45 43651038.53 45453313.53 63056424.7 51034002.62 54321646.13 46772183.45 50280305.96 44294015.23 38307520.22 48423876.73 59035031.67 45825826.04 Xanthine 3069673.477 2416616.253 3205871.232 3040673.605 2360585.519 3486100.815 2252054.76 2254481.094 2925905.207 1610365.131 2210710.419 2912636.457 2972117.81 3136494.84 2622764.208 2648802.233 2592579.74 2711922.093 2699454.876 3135750.001 3182065.773 2564971.148 2690298.559 2633290.995 Xanthosine 5079925.502 8733582.327 7648896.009 6936642.809 4052884.834 9176959.871 5205181.522 5394133.271 7671387.67 3800482.257 7097288.456 5836951.39 6371064.477 8644410.864 5672638.234 7027768.878 6755430.202 7756283.683 6315727.396 8912849.908 7851038.078 6005372.528 5689763.891 8208111.809 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Expected RT MS1_mz MS2_mz 1-Methylhistidine 6.35 170 124 1-Methylnicotinamide 4.34 137 94 1-Methylxanthine 2.9 167 110 1-Methylxanthosine 2.79 299 167.1 1,3-15N2-Uric acid 5.17 171.1 143 13C10,15N5-Adenosine 3.88 283 146.1 13C3-Thiamine 5.12 268 122.1 13C5-Hypoxanthine 3.74 142.2 124 13C5-Xanthosine 4.56 290 153 15N4-Inosine 4.35 273.1 141 2-Aminobenzoic acid 1.05 138.1 92 3-Hydroxy-N6,N6,N6-Trimethyllysine 6.77 205.2 128.1 3-Hydroxybutyric acid 1.3 105 87 3-Hydroxykynurenine 0.95 225.1 179.1 3-Hydroxytyrosol 3.74 137.1 119 3-Methoxytyrosine 5.32 212.1 166.1 3-Methylxanthine 3.1 167 69 3-Methylxanthosine 2.98 299.1 167.1 4-Hydroxyproline 5.9 132 68.1 4-Trimethylammoniobutanal 6.86 130.1 71.1 5-Glutamylalanine 7 219.1 90.1 5-Hydroxyindoleacetic acid 1.6 192.1 146.1 5-Hydroxytryptophan 4.9 221.1 175 5'-Methylthioadenosine 2.83 298 136 6-Aminouracil 4.3 128 85 6C13-Phenylalanine 4.92 172.1 126.1 6C13-Tyrosine 5.42 188.1 142.1 7-alpha-Hydroxy-3-oxo-4-cholestenoate 1.52 431.3 395.3 7-Methylguanine 4.32 166.1 124.1 7-Methylguanosine 5.48 298 166 7-Methylxanthine 3.3 167.1 69 7-Methylxanthosine 3.2 299.2 167.1 8-Hydroxy-deoxyguanosine 5.18 284.1 140 8-Oxo-deoxyguanosine-13C,15N2 4.8 300 168 8-Hydroxyguanosine 4.76 287.3 171 9-Hexadecenoylcarnitine 3.12 398.3 85 Acetylcarnitine 4.2 204.1 85 Acetylcarnitine-d3 4.24 207.1 85 Adenine 4.05 136.1 119 Adenosine 3.87 268.2 136.1 Adenosine diphosphate ribose 7.33 560.1 136.1 Adenosylcobalamin 6 801.5 676.3 AICA-riboside 4.43 259 110 Alanine 5.87 90.1 44.2 Alanine-d4 5.82 94.1 48.1 alpha-Tocopherol 1 431.4 165.1 Arabitol 4.7 153.1 153.1 Arginine 6.86 175.1 70 Arginine-d4C13 6.85 180.1 75 Ascorbate 3.8 177 95 Asparagine 6.21 133.1 74 Aspartic acid 6.33 134 74 Aspartic acid-d3 6.46 137 75 Asymmetric dimethylarginine 6.44 203.2 70.3 Betaine 5.17 118.1 59.1 Betaine-d11 4.94 129.1 68.1 Bilirubin 1.01 585.3 299.1 Butyrobetaine 4.3 146.1 87 Butyrylcarnitine 3.68 232.2 85 Butyrylcarnitine-d3 3.83 235.2 85 Cadaverine 7.21 102.9 86.1 cADPRibose 7.14 542.1 136.1 Caffeine 1.26 195.1 138 Capsaicin 1.05 306.2 137.1 Carnitine 4.99 162.1 103.1 Carnitine-d9 4.99 171.2 85 Choline 3.97 104 60 Citrulline 6.36 176.1 113.1 Citrulline-d2 6.24 178.1 115.1 Cotinine 1.77 177.1 80 Creatine 5.76 132 90 Creatinine 4.27 114 44.1 Creatinine-d3 4.24 117 86 Curcumin 1.01 369 177 Cyanocobalamin 6.09 678.5 997.5 Cystathionine 7 223.1 134 Cysteine 5.65 122 76 Cysteinylglycine 6.86 179.1 162.2 Cystine 7.25 241 74 Cytosine 4.94 112.1 94.9 Decanoylcarnitine 3.33 316.2 85 Demethoxycurcumin 1.31 339.1 255.2 Deoxyadenosine 3.67 252.1 136 Deoxyguanosine 4.67 268.1 152 Deoxyinosine 3.6 253 137 Dimethylethanolamine 4.25 90 72 Dimethylglycine 5.41 104 58 DNL201 1.08 340.3 313.2 Dodecanoylcarnitine 3.85 343.3 85 Dopa 5.62 198 152 Dopamine 4.54 154 137 Dopamine 3-o-sulfate 3.7 234 137.1 Dopamine 4-o-sulfate 3.9 234.1 137.2 Epinephrine 4.73 166 107 Ergothioneine 5.71 230.1 127 Ethanolamine 5.23 62 44.2 Formylanthranilic acid 1.3 166 120 gamma-Aminobutyric acid 5.08 104.1 87 Gamma-Glutamylcysteine 6.46 251.1 122 Glucosamine 6.45 180 162 Glucose 5.31 202.8 202.8 Glutamic acid-d3 5.97 151 133.1 Glutamic acid 6.07 148.1 84 Glutamine 6.22 147.1 84 Glutathione 6.11 308.1 179.1 Glutathione disulfide 7.48 613.2 355.1 Glutathione-(glycine-13C2,15N) 6.1 311.3 182.1 Glycerophosphocholine 6.24 258.1 104 Glycine 5.92 76 30 Guanine 4.72 152.2 110 Guanosine 5.09 284.1 152 Hexanoylcarnitine 3.46 260.2 85 Histamine 6.5 112.1 95 Histidine 6.93 156.1 110.1 Homocysteine 5.05 136.1 90.1 Homoserine 5.88 120.2 56.2 Hydroxybutyrylcarnitine 4.65 248.2 85 Hydroxyhexanoylcarnitine 4.71 276.2 85 Hydroxyisovaleroyl carnitine 4.3 262.2 85 Hydroxypropionylcarnitine 4.9 234.1 85 Hypoxanthine 3.75 137.2 118.8 Imidazoleacetic acid 5.18 127 81 Indole 1 118 91 Inosine 4.33 269.1 137 Isovalerylcarnitine 3.56 246.2 85 Isovalerylcarnitine-d9 3.55 255.2 85 Kynurenic acid 4.27 190.1 116 Kynurenine 4.81 209 146 Leucine 4.94 132.1 86 Leucine-d3 4.74 135.1 89.1 Linoleyl carnitine 3.05 424.3 85 LPC(18:1(d7)) 3.85 529.3 184.1 Lysine 6.93 147.1 84 Mannitol 5.44 183 69 Mannose 5.5 202.8 202.8 Melatonin 3.67 233.1 174.1 Methionine 5.04 150.1 104.1 Methionine S-oxide 6.05 166.1 74 Methionine-d3 5.23 153.1 107 Methylcobalamin 6.04 673 971.5 Myristoylcarnitine 2.9 372 85 Myristoylcarnitine-d9 3.15 381.4 85 N-Acetylalanine 1.8 160.1 72.1 N-Acetylaspartic acid 3.42 176.1 176.1 N-Acetylcysteine 1.3 163 121.2 N-Acetylglutamic acid 3.49 189 130 N-Acetylneuraminic acid 6.69 310.1 274 N-Acetylputrescine 4.89 131.1 114 N-Acetylserine 3.38 148 106 N-Alpha-acetyllysine 5.69 189 84 N,N'-Bis(gamma-glutamyl)cystine 7 499.1 453.1 N1-Acetylspermidine 6.4 188.2 171 N1-Acetylspermidine-d6 6.5 194.3 106.2 N1-Acetylspermine 7.7 245.2 100.1 N1-N12-Diacetylspermine 6.1 287.2 100.1 N1-N8-Diacetylspermidine 4.93 230.5 100.2 N1-N8-Diacetylspermidine-d6 4.93 236.2 103.2 N15C13-Glycine 5.92 78 32 N6,N6,N6-Trimethyllysine 6.62 189.2 84.1 NAD 7.13 664.1 428.2 Niacinamide 1.86 123.1 80 Niacinamide-d4 1.88 127 84 Nicotinamide mononucleotide 6.6 335.2 123.1 Nicotinamide riboside 5.48 255 123 Nicotinic acid 1.87 124.1 78 Nitrotyrosine 4.78 227.1 210 Nonanoylcarnitine 3.3 302.2 85 Norepinephrine 5.1 152 107 Octanoylcarnitine 3.31 288.2 85 Octanoylcarnitine-d3 3.44 291.2 85 Ornithine 6.98 133 70 Ornithine-d2 6.98 135.1 117.2 Palmitoylcarnitine 3 400 85 Palmitoylcarnitine-d3 3.08 403.4 85 Paraxanthine 1.85 181.1 124 Phenylalanine 4.91 166.1 120.1 Piperanine 1.34 288.2 135.2 Piperine 1.04 286.1 201.1 Pipernonaline 1.3 342.1 229.2 Piperyline 1.39 272.2 201.1 Proline 5.27 116 70.1 Propionylcarnitine 3.84 218.1 85 Propionylcartinine-d3 4 221.2 85 Putrescine 6.3 89 72 Pyridoxamine 6.06 169 152 Pyroglutamic acid 3.29 130 84 S-Adenosylhomocysteine 6.23 385.1 136 S-Adenosylmethionine 7.13 399 250 Sarcosine 5.75 90 44.1 Serine 6.14 106 60 Serotonin 4.42 177 160 Spermidine 7.8 146.2 72 Spermine 4.95 203.1 129.1 Stearoylcarnitine 3.02 428.4 85 Sucrose 6 364.8 202.8 Taurine 5.37 126 80.1 Tetrahydrocurcumin 1.38 355 137.1 Theobromine 2.1 181 138.3 Theophylline 1.7 181.1 124 Thiamine 5.11 265 122 Threonine 5.87 120 74 Trigonelline 5.3 138.1 94.1 Trimethylamine-d9 N-oxide 4.17 85 66 Trimethylamine-N-oxide 4.03 76.1 58.1 Tryptophan 4.75 205 146.1 Tyrosine 5.26 182.1 136 Uracil 2.47 113 70 Ureidopropionic acid 3.24 133 115 Uric acid 5.28 169.1 141 Uridine 3.91 245 113 Valerobetaine 4.09 160 101.1 Valerobetaine-d9 4.09 169.1 101.1 Valine 5.18 118.1 55 Valine-d8 5.32 126 80.1 Xanthine 4.05 153 110 Xanthosine 4.71 285 153 METABOLITES_END #END