#METABOLOMICS WORKBENCH Jung_DNLI_20240919_115027 DATATRACK_ID:5207 STUDY_ID:ST003501 ANALYSIS_ID:AN005749 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        	5 µL of sample was injected on an Imtakt Intrada Organic Acid 3 µm, 2 x 150 mm
CH:CHROMATOGRAPHY_SUMMARY        	(Imtakt USA, Portland, OR USA); using a flow rate of 0.2 mL/min at 60°C. For
CH:CHROMATOGRAPHY_SUMMARY        	negative ionization mode, Mobile phase A consisted of acetonitrile/water/formic
CH:CHROMATOGRAPHY_SUMMARY        	acid = 10/90/0.1%. Mobile phase B consisted of acetonitrile/ 100mM ammonium
CH:CHROMATOGRAPHY_SUMMARY        	formate= 10/90%. The gradient was programmed as follows: 0.0–1.0 min at 0% B;
CH:CHROMATOGRAPHY_SUMMARY        	1.0–7.0 min to 100% B; 7.1 at 0% B; and 7.1-10 min at 0% B.
CH:CHROMATOGRAPHY_TYPE           	Ion exchange
CH:INSTRUMENT_NAME               	Agilent 1290 Infinity II
CH:COLUMN_NAME                   	Imtakt Intrada Organic Acid (150 x 2mm, 3um) )
CH:SOLVENT_A                     	10% acetonitrile/90% water; 0.1% formic acid
CH:SOLVENT_B                     	10% acetonitrile/90% water; 100mM ammonium formate
CH:FLOW_GRADIENT                 	0.0–1.0 min at 0% B; 1.0–7.0 min to 100% B; 7.1 at 0% B; and 7.1-10 min at
CH:FLOW_GRADIENT                 	0% B.
CH:FLOW_RATE                     	0.20 mL/min
CH:COLUMN_TEMPERATURE            	60
#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                      	NEGATIVE
MS:MS_COMMENTS                   	curtain gas at 40 V; collision gas was set at medium; ion spray voltage at -4500
MS:MS_COMMENTS                   	V; temperature at 600°C; ion source Gas 1 at 50 psi; ion source Gas 2 at 60
MS:MS_COMMENTS                   	psi; entrance potential at -10 V; and  collision cell exit potential at -15.0
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-000019574	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
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:APP | condition:high | group:high_disease | 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
13C3-Citric 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
13C4-Fumaric 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
13C4-Malic 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
13C4-Succinic acid	20.696272926743678	20.56548769821013	20.571484588381583	20.60595306722529	20.577617540913213	20.51421135263355	20.547209687416174	20.462518540143712	20.506008677119834	20.458784421344564	20.445906105607094	20.410826096914235	20.43848553113269	20.457611910420837	20.567061915240576	20.449200034610612	20.504149513710068	20.454897047883886	20.44352229956763	20.40123773607129	20.39130874866888	20.376138281188023	20.365287092295667	20.331311244460604	20.443176227409626	20.437544208820817	20.36565686146364	20.368737577144408	20.479123224002883
13C5-Oxoglutaric acid	19.758219507154585	19.70555627828419	19.729502641366466	19.72512586852337	19.702405379193117	19.69865233159412	19.545996543448485	19.635924634356318	19.63275348217121	19.498934065069676	19.68329348992736	19.652699616700815	19.515984648389978	19.479641768798647	19.405045728211824	19.640782344895523	19.52114971204955	19.480172798525686	19.558422981575095	19.557531350936625	19.48890971441678	19.531532975236782	19.541320179707295	19.565246201268273	19.43473686005052	19.436061475071917	19.528497690272143	19.430637199924195	19.536761183773873
13C6-Benzoic acid	21.244384241485037	21.126745786827975	21.21566042356713	21.21196377537931	21.22906608881889	21.278219949178126	21.090638032513844	21.209231086244973	21.237481349599364	21.079199394132882	21.32546241743073	21.273466475140026	21.177547778755155	21.094583082866297	21.017732486709843	21.20351988292637	21.162492971756404	21.155327332502846	21.161675728898043	21.171233068038635	21.115306065706303	21.214812290633528	21.146706780386133	21.221728226839467	21.11027100005672	21.091482090164334	21.19543060041183	21.218147207174095	21.155859230139885
13C8-Octanic acid	24.559944434946996	24.517408730554962	24.585789147734268	24.489152869663805	24.557102947456812	24.64629003618371	24.457801496552367	24.61672305038245	24.599571109999733	24.46979770922719	24.84447467400862	24.656994638232074	24.507629225912336	24.523111638846117	24.420174594029003	24.582709907507468	24.613994646829376	24.560306327111654	24.53717769917855	24.578608995184712	24.46365128076371	24.59046570153508	24.540385836111298	24.622421013624848	24.555562808434676	24.53989737954426	24.581221208447154	24.596252308153694	24.47762227788992
15N5-ADP	21.614297289512496	21.434733231514098	20.522726240071023	20.649786998769134	19.88579182	18.421240616687307	19.855439245656182	18.176646706816317	18.875145525915784	19.55215064110112	15.358328333638793	16.920700443264725	19.031238856175857	19.06555565593994	19.756209147841442	18.036365619502366	18.787432177181028	18.439799654436538	18.353977366289428	18.12430722621877	18.181114059436364	17.60225036541727	17.86204762820679	16.39703459317729	17.926629520837448	18.178789642813427	16.979444377657288	16.143096539585667	17.944409704860075
2-Hydroxyglutarate	NA	NA	NA	NA	NA	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-Phosphoglyceric 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-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-Phosphoglyceric 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
6-Phosphogluconic 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
Acetoacetic 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
Adenosine monophosphate	NA	NA	NA	NA	NA	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 triphosphate	NA	NA	NA	NA	NA	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 triphosphate-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
ADP	NA	NA	NA	NA	NA	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	NA	NA	NA	NA	NA	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-d4	21.615386579176345	21.27622048283794	21.656431846710568	21.547741370100518	21.648713229977812	21.97308631435992	21.442792131695533	21.935266135589792	21.73913465522812	21.43515116015182	22.18160595847872	22.014364793239302	21.526889371072265	21.430094323967623	20.59720958430099	21.832851543070774	21.534066876559052	21.62350982134825	21.604383542769444	21.683808356099707	21.48600724092819	21.834045135247816	21.64571682126857	21.908180754435133	21.614477381970925	21.348451366333965	21.91700418286355	21.970221203005195	21.556290459323286
Arginine	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Arginine-d4C13	25.94338437254793	25.85023156938372	25.95409136261772	25.92129832902276	25.912878670198996	25.931865684628818	25.807916446307132	26.06439717156318	25.918700515873667	25.858296820709736	25.99872426018753	25.97110928781179	25.810703671390772	25.767757868155716	25.44607868801695	25.862951505057488	25.790734045902557	25.75358506553661	25.814678040007408	25.70313965400282	25.689125967323246	25.792966576281813	25.809914341665163	25.864986104675005	25.74173047	25.59392051363478	25.821239847282925	25.82704939	25.668026200767255
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	NA	NA	NA	NA	NA	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-d3	24.56448049943304	24.411441222880207	24.440367358659003	24.361417782094446	24.406289724112895	24.371282262520637	24.24401941991085	24.357755072100435	24.260971655404735	24.162130319331133	24.361873935421045	24.183967158442965	24.15691755	24.184094493245993	24.033897995393957	24.27843148057162	24.164510243859965	24.072013463344597	24.101887652659148	24.134456746741485	24.07755511880683	24.156201572752323	24.077080669977143	24.167677313538636	24.092425468297133	24.033743465691618	24.203110478854757	24.029661113511477	23.94574908033826
cis-Aconitic 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
Sum of Citric acid and Isocitric 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
Dihydroxyacetone phosphate	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Erythose 4-phosphate	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Fructose 1,6-bisphosphate	16.94931551	17.073847008686805	17.03031340567249	17.12977934474663	16.95040562060058	16.21279059081403	17.139546878982976	16.279081683157088	16.703988320625136	17.078328783325755	15.750423337171632	16.11362468808342	17.261831860742934	17.22526055668612	17.33575803	16.46591226567112	17.28644811279494	16.807688133186332	16.903123259875844	16.623047672366713	16.834526475150064	16.574908047985005	16.707226642105958	15.923087376208967	16.971174461083706	17.17440309086494	16.518159420627686	16.127103011275405	17.264404128474993
Fructose 6-phosphate	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Fumaric 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
Glucose 1-phosphate	NA	NA	NA	NA	NA	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 6-phosphate	16.695414622562815	16.963327725154468	16.60193802860686	16.88833176413429	16.092266040240638	15.264891177786424	17.032439334884153	16.187168027020586	16.099426656112435	15.97847753139458	14.781359287745575	16.730411680913765	16.05141856490009	15.537329642145874	16.23516130664381	17.057965332886628	16.730476594034272	17.27583924303307	15.637673327333621	15.888527495393689	16.423351801615333	16.002153700883145	15.87752128614099	15.138507615561265	16.117453384472803	15.907860000049144	16.57597978397044	14.762959378555447	16.33766975000846
Glutamic 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
Glutamic acid-d3	22.68369998136673	22.608184089738465	22.70631943810525	22.634042628577635	22.64296368786774	22.60401898524518	22.479548250361233	22.583578304122934	22.50766014342594	22.48299584219232	22.67355666118105	22.62468155307527	22.43106162008862	22.492871942188366	22.255020303914016	22.530454606941653	22.486253438247125	22.221635413066057	22.427996092053455	22.42834237644278	22.337045030054338	22.454277432763412	22.444048258004127	22.418772630754795	22.406121449063516	22.373164889369516	22.49971498944773	22.416708491217996	22.379260050625152
Glutamine	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Glyceraldehyde 3-phosphate	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Lactic acid	17.195378230638894	15.774453094754179	16.74538879505487	16.122115401832346	16.032770410189972	15.52989571	16.377083481121588	17.243197394099997	15.708553696193125	14.964775560557019	17.40883281276612	17.26204935543534	15.467535224746054	15.648330037246607	15.596573079723203	19.07084460559871	17.07095712676364	16.862191326862245	15.110380766950188	14.727489022884454	17.296038193116445	16.10461583884974	15.084624844198098	15.277055275607275	16.571194127503862	16.203789379921044	15.820271626018814	16.958292795853907	17.03673796177161
Malic 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
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
NADH	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
NADP	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
NADPH	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Oxalacetic 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
Oxoglutaric 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
Phosphocreatine	16.12617234991907	16.87394690190043	16.785514466675536	15.972642568235722	16.17522474583265	13.982386237007377	17.255193660993736	16.26042718550107	15.70122004169764	16.33153261414818	13.32151416952848	17.259156501100357	15.628290720405769	15.587918172444539	16.236490132310454	15.85672981440694	16.16137611155079	17.015373496631362	15.549396341314733	15.746357281592433	15.852108824348452	16.110275287875943	15.15377653684824	16.08364528382903	13.936243374121855	16.395088414044288	15.81162671	14.09122615157264	15.80918798784736
Phosphoenolpyruvic 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
Pyruvic 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
Ribose 5-phosphate	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Ribulose 5-phosphate	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Sedoheptulose 7-phosphate	15.684096057185549	15.764049457348511	15.543463582032592	15.488660546651268	15.554463014277538	14.055593940495486	15.66960856310152	14.812106799349264	15.187963993005194	16.046873045936348	13.655506412633837	15.361074577479886	16.294562794115034	14.417238780546827	14.897173148807683	15.39243470317673	15.303773050612877	15.606885777732597	14.095183817368612	14.485740837694976	16.207154250972962	14.391967620348842	14.769241111454356	14.449427347177355	14.190992830160443	14.478490089745026	15.037922821239622	14.041550733726963	15.20495227495096
Serine	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Succinic acid	19.081376235834163	19.275626447657352	19.38011169590339	19.13389326362427	19.410767158098977	19.010072074351207	19.26240447868939	18.932402049449106	19.071856679844206	18.856869804140654	18.901376068142437	18.801602644992133	18.937999085875962	19.07632531202259	18.728553453922004	19.098369768981588	18.811128617640218	19.04669016307844	19.21816219058364	18.67631903397029	19.341565506739933	18.785321592587724	18.65298594608943	18.69705016730237	18.841941968448825	18.67175992036619	18.695966146780155	18.89221732658571	18.77438311337504
U-13C10,U-15N5-Adenosine monophosphate	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
U-13C3-Pyruvic acid	17.089736248739968	16.926165551215057	17.18011515	17.137269990363855	17.13871728	17.382602073646485	16.75578210505539	17.19360679820826	17.133725101874116	16.918344917797636	17.496910829732784	17.192974831983644	16.98649550187652	16.774085087217134	16.638741831572545	16.93971407375806	16.87476180908621	16.945095534696048	16.941034283054613	16.959833522182016	16.83513056	17.104683952637735	16.968128894401644	17.235494854519278	16.814811452945026	16.80277876239668	16.979108351049806	17.066357298342908	16.73760370523315
U-13C6-Glucose 6-phosphate	23.114845958824638	23.102070882825195	22.75768303	23.027736376017977	22.867167627733956	22.447236993482385	23.106844736899163	22.466802556298305	22.879870913794793	23.324380750168665	21.89485200492282	22.372293978071152	23.392868370602585	23.440491702285385	23.497974512697205	23.052436120571677	23.442426321403886	23.25658314637172	23.25682877596059	23.14966719	23.194762976133028	23.108822195513834	23.334854473271555	22.96748910367867	23.362165405246948	23.388962103767593	23.089631121196376	22.76564368041822	23.271849434498037
Xylulose 5-phosphate	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
Fructose 1-phosphate	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	internal standard	Expected RT	precursor (m/z)	product (m/z)
13C3-Citric acid	NA	3.77	194.2	113
13C4-Fumaric acid	NA	3.28	119.2	74.3
13C4-Malic acid	NA	3.26	137.2	119.2
13C4-Succinic acid	NA	3.07	121.3	76
13C5-Oxoglutaric acid	NA	2.97	150.2	105.3
13C6-Benzoic acid	NA	0.51	127	83
13C8-Octanic acid	NA	1.04	151.1	151.1
15N5-ADP	NA	3.55	431.1	79
2-Hydroxyglutarate	13C4-Succinic acid	2.97	145	101
2-Phosphoglyceric acid	13C4-Succinic acid	3.66	185.5	97.1
3-Hydroxybutyric acid	13C4-Succinic acid	0.94	103.2	59.2
3-Phosphoglyceric acid	13C4-Succinic acid	3.67	185.5	97
6-Phosphogluconic acid	13C4-Succinic acid	3.77	275	97
Acetoacetic acid	13C4-Succinic acid	0.31	101	101
Adenosine monophosphate	U-13C10,U-15N5-Adenosine monophosphate	3.27	346	79
Adenosine triphosphate	Adenosine triphosphate-d4	3.71	506.1	158.9
Adenosine triphosphate-d4	NA	3.7	510	158.9
ADP	15N5-ADP	3.53	426.1	79
Alanine	Alanine-d4	2.18	88	88
Alanine-d4	NA	2	92	92
Arginine	Arginine-d4C13	3.95	173	131
Arginine-d4C13	NA	3.96	178	136
Asparagine	13C4-Succinic acid	2.48	131	114
Aspartic acid	Aspartic acid-d3	3.05	132	88
Aspartic acid-d3	NA	3.06	135	91
cis-Aconitic acid	13C4-Succinic acid	3.29	173	129
Sum of Citric acid and Isocitric acid	13C4-Succinic acid	3.77	191.2	111
Dihydroxyacetone phosphate	13C4-Succinic acid	3.35	169.1	79
Erythose 4-phosphate	13C4-Succinic acid	3.65	199	97
Fructose 1,6-bisphosphate	13C4-Succinic acid	3.48	339.1	79
Fructose 6-phosphate	13C4-Succinic acid	3.5	259	97.1
Fumaric acid	13C4-Succinic acid	6.34	115.2	71.3
Glucose 1-phosphate	13C5-Oxoglutaric acid	3.62	259	241
Glucose 6-phosphate	13C8-Octanic acid	3.64	259	97
Glutamic acid	13C4-Succinic acid	3.06	146	128
Glutamic acid-d3	NA	3.02	149	131
Glutamine	13C4-Succinic acid	2.46	145	127
Glyceraldehyde 3-phosphate	13C4-Succinic acid	3.35	169.1	97
Lactic acid	13C4-Succinic acid	0.87	89.2	43.2
Malic acid	13C4-Succinic acid	3.46	133.2	115.2
NAD	13C4-Succinic acid	3.22	662.1	540.3
NADH	13C4-Succinic acid	3.03	664.1	408.1
NADP	13C4-Succinic acid	3.92	742.1	620
NADPH	13C4-Succinic acid	3.75	744.1	408
Oxalacetic acid	13C5-Oxoglutaric acid	3.63	131	131
Oxoglutaric acid	13C5-Oxoglutaric acid	2.96	145.2	101.3
Phosphocreatine	13C4-Succinic acid	3.68	210	79
Phosphoenolpyruvic acid	13C4-Succinic acid	3.78	167	79
Pyruvic acid	13C8-Octanic acid	0.5	87.2	43.2
Ribose 5-phosphate	13C4-Succinic acid	3.35	229	97
Ribulose 5-phosphate	13C4-Succinic acid	3.42	229	97.1
Sedoheptulose 7-phosphate	13C4-Succinic acid	3.55	289	97
Serine	13C4-Succinic acid	2.44	104	74
Succinic acid	13C4-Succinic acid	3.07	117.2	73.2
U-13C10,U-15N5-Adenosine monophosphate	NA	3.28	361	79
U-13C3-Pyruvic acid	NA	0.49	90.2	45.2
U-13C6-Glucose 6-phosphate	NA	3.71	265	97
Xylulose 5-phosphate	13C4-Succinic acid	3.34	229.1	97
Fructose 1-phosphate	13C4-Succinic acid	3.63	259.1	79
METABOLITES_END
#END