#METABOLOMICS WORKBENCH boryana_ptrva_20240115_150616 DATATRACK_ID:4571 STUDY_ID:ST003079 ANALYSIS_ID:AN005037 PROJECT_ID:PR001918
VERSION             	1
CREATED_ON             	February 16, 2024, 10:25 am
#PROJECT
PR:PROJECT_TITLE                 	Metabolomics of Mouse Embryonic CSF Following Maternal Immune Activation
PR:PROJECT_SUMMARY               	The embryonic cerebrospinal fluid (eCSF) is critical for the developing central
PR:PROJECT_SUMMARY               	nervous system (CNS), from neurogenesis to lifelong cognitive functions. Changes
PR:PROJECT_SUMMARY               	in eCSF composition due to inflammation can impact brain function. We recently
PR:PROJECT_SUMMARY               	identified an abnormal cytokine signature in eCSF following maternal immune
PR:PROJECT_SUMMARY               	activation (MIA), a mouse model of autism spectrum disorder (ASD). We
PR:PROJECT_SUMMARY               	hypothesized that MIA leads to other alterations in eCSF composition and
PR:PROJECT_SUMMARY               	employed untargeted metabolomics to profile changes in the eCSF metabolome in
PR:PROJECT_SUMMARY               	mice after inducing MIA with polyI:C. We report these data here as a resource,
PR:PROJECT_SUMMARY               	including a comprehensive MS1 and MS2 reference dataset, and present additional
PR:PROJECT_SUMMARY               	datasets comparing two mouse strains (CD-1 and C57Bl/6) and two developmental
PR:PROJECT_SUMMARY               	time points (E12.5 and E14.5). Targeted metabolomics further validated changes
PR:PROJECT_SUMMARY               	in eCSF upon MIA. We show a significant elevation of glucocorticoids and
PR:PROJECT_SUMMARY               	kynurenine pathway related metabolites. Both pathways are relevant for
PR:PROJECT_SUMMARY               	suppressing inflammation or could be informative as disease biomarkers. Our
PR:PROJECT_SUMMARY               	resource should inform future mechanistic studies regarding the etiology of MIA
PR:PROJECT_SUMMARY               	neuropathology and roles and contributions of eCSF metabolites to brain
PR:PROJECT_SUMMARY               	development.
PR:INSTITUTE                     	Boston Childrens Hospital
PR:LAST_NAME                     	Petrova
PR:FIRST_NAME                    	Boryana
PR:ADDRESS                       	300 Longwood Av, Boston, MA, 2115, USA
PR:EMAIL                         	boryana.petrova@childrens.harvard.edu
PR:PHONE                         	6173557433
#STUDY
ST:STUDY_TITLE                   	Metabolome changes in embryonic CSF (Part 1)
ST:STUDY_SUMMARY                 	Targeted MS analysis of maternal liver and serum and embryonic CSF and liver, 3h
ST:STUDY_SUMMARY                 	post saline or PolyI:C administrated to mother. Metabolome changes in embryonic
ST:STUDY_SUMMARY                 	CSF (E12.5), embryonic liver (E12.5), maternal liver or maternal serum 3h hours
ST:STUDY_SUMMARY                 	following PolyI:C or saline injection in mother. Older experiment run included
ST:STUDY_SUMMARY                 	of embryonic CSF at 48 hour collection point, mice at E14.5
ST:INSTITUTE                     	Boston Children's Hospital, Harvard Medical School
ST:LABORATORY                    	Kanarek Lab
ST:LAST_NAME                     	Petrova
ST:FIRST_NAME                    	Boryana
ST:ADDRESS                       	Enders 1116.2 300 Longwood Ave
ST:EMAIL                         	Boryana.Petrova@childrens.harvard.edu
ST:PHONE                         	6179197352
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
#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           	-	1	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP986; Sample source inrormation=embryonic CSF2
SUBJECT_SAMPLE_FACTORS           	-	2	Sample source:Embryonic CSF | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP987; Sample source inrormation=embryonic CSF3
SUBJECT_SAMPLE_FACTORS           	-	3	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP988; Sample source inrormation=embryonic CSF4
SUBJECT_SAMPLE_FACTORS           	-	4	Sample source:Embryonic CSF | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP989; Sample source inrormation=emryonic CSF5
SUBJECT_SAMPLE_FACTORS           	-	5	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP990; Sample source inrormation=embryonic CSF6
SUBJECT_SAMPLE_FACTORS           	-	6	Sample source:Embryonic CSF | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP991; Sample source inrormation=embryonic CSF7
SUBJECT_SAMPLE_FACTORS           	-	7	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP992; Sample source inrormation=embryonic CSF8
SUBJECT_SAMPLE_FACTORS           	-	8	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP993; Sample source inrormation=embryonic CSF10
SUBJECT_SAMPLE_FACTORS           	-	9	Sample source:mock | Maternal Treatment (injection):N/A | Developmental Timepoint:N/A | Collection Time:N/A	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP994; Sample source inrormation=mock 1
SUBJECT_SAMPLE_FACTORS           	-	10	Sample source:mock | Maternal Treatment (injection):N/A | Developmental Timepoint:N/A | Collection Time:N/A	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP995; Sample source inrormation=mock 2
SUBJECT_SAMPLE_FACTORS           	-	11	Sample source:mock | Maternal Treatment (injection):N/A | Developmental Timepoint:N/A | Collection Time:N/A	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP996; Sample source inrormation=mock 3
SUBJECT_SAMPLE_FACTORS           	-	12	Sample source:mock | Maternal Treatment (injection):N/A | Developmental Timepoint:N/A | Collection Time:N/A	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP997; Sample source inrormation=mock 5
SUBJECT_SAMPLE_FACTORS           	-	13	Sample source:mock | Maternal Treatment (injection):N/A | Developmental Timepoint:N/A | Collection Time:N/A	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP998; Sample source inrormation=mock 6
SUBJECT_SAMPLE_FACTORS           	-	14	Sample source:mock | Maternal Treatment (injection):N/A | Developmental Timepoint:N/A | Collection Time:N/A	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP999; Sample source inrormation=mock 7
SUBJECT_SAMPLE_FACTORS           	-	15	Sample source:maternal serum | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP976; Sample source inrormation=maternal serum 1
SUBJECT_SAMPLE_FACTORS           	-	16	Sample source:maternal serum | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP977; Sample source inrormation=maternal serum2
SUBJECT_SAMPLE_FACTORS           	-	17	Sample source:maternal serum | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP978; Sample source inrormation=maternal serum 3
SUBJECT_SAMPLE_FACTORS           	-	18	Sample source:maternal serum | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP979; Sample source inrormation=maternal serum 4
SUBJECT_SAMPLE_FACTORS           	-	19	Sample source:maternal serum | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP980; Sample source inrormation=maternal serum 5
SUBJECT_SAMPLE_FACTORS           	-	20	Sample source:maternal serum | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP981; Sample source inrormation=maternal serum 6
SUBJECT_SAMPLE_FACTORS           	-	21	Sample source:maternal serum | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP982; Sample source inrormation=maternal serum 7
SUBJECT_SAMPLE_FACTORS           	-	22	Sample source:maternal serum | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP983; Sample source inrormation=maternal serum 8
SUBJECT_SAMPLE_FACTORS           	-	23	Sample source:maternal serum | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220527_QEF1-HILIC_MIAshortRepeat_BP984; Sample source inrormation=maternal serum 10
SUBJECT_SAMPLE_FACTORS           	-	24	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1006; Sample source inrormation=Embyronic CSF C-1
SUBJECT_SAMPLE_FACTORS           	-	25	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1007; Sample source inrormation=Embryonic CSF C-2
SUBJECT_SAMPLE_FACTORS           	-	26	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1008; Sample source inrormation=Embryonic CSF C-3
SUBJECT_SAMPLE_FACTORS           	-	27	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1009; Sample source inrormation=Embryonic CSF C-4
SUBJECT_SAMPLE_FACTORS           	-	28	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1010; Sample source inrormation=Embryonic CSF C-5
SUBJECT_SAMPLE_FACTORS           	-	29	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1011; Sample source inrormation=Embryonic CSF C-6
SUBJECT_SAMPLE_FACTORS           	-	30	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1012; Sample source inrormation=Embryonic CSF C-7
SUBJECT_SAMPLE_FACTORS           	-	31	Sample source:Maternal Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1016; Sample source inrormation=Maternal Liver Chunk-1
SUBJECT_SAMPLE_FACTORS           	-	32	Sample source:Maternal Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1017; Sample source inrormation=Maternal Liver Chunk-2
SUBJECT_SAMPLE_FACTORS           	-	33	Sample source:Maternal Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1018; Sample source inrormation=Maternal Liver Chunk-3
SUBJECT_SAMPLE_FACTORS           	-	34	Sample source:Maternal Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1019; Sample source inrormation=Maternal Liver Chunk-4
SUBJECT_SAMPLE_FACTORS           	-	35	Sample source:Maternal Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1020; Sample source inrormation=Maternal Liver Chunk-5
SUBJECT_SAMPLE_FACTORS           	-	36	Sample source:Maternal Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1021; Sample source inrormation=Maternal Liver Chunk-6
SUBJECT_SAMPLE_FACTORS           	-	37	Sample source:Maternal Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1022; Sample source inrormation=Maternal Liver Chunk-7
SUBJECT_SAMPLE_FACTORS           	-	38	Sample source:Maternal Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1023; Sample source inrormation=Maternal Liver Chunk-8
SUBJECT_SAMPLE_FACTORS           	-	39	Sample source:Maternal Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1024; Sample source inrormation=Maternal Liver Chunk-10
SUBJECT_SAMPLE_FACTORS           	-	40	Sample source:Embyronic Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1028; Sample source inrormation=Embyronic Liver Chunk-1
SUBJECT_SAMPLE_FACTORS           	-	41	Sample source:Embyronic Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1029; Sample source inrormation=Embyronic Liver Chunk-2
SUBJECT_SAMPLE_FACTORS           	-	42	Sample source:Embyronic Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1030; Sample source inrormation=Embyronic Liver Chunk-3
SUBJECT_SAMPLE_FACTORS           	-	43	Sample source:Embyronic Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1031; Sample source inrormation=Embyronic Liver Chunk-4
SUBJECT_SAMPLE_FACTORS           	-	44	Sample source:Embyronic Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1032; Sample source inrormation=Embyronic Liver Chunk-5
SUBJECT_SAMPLE_FACTORS           	-	45	Sample source:Embyronic Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1033; Sample source inrormation=Embyronic Liver Chunk-6
SUBJECT_SAMPLE_FACTORS           	-	46	Sample source:Embyronic Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1034; Sample source inrormation=Embyronic Liver Chunk-7
SUBJECT_SAMPLE_FACTORS           	-	47	Sample source:Embyronic Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1035; Sample source inrormation=Embyronic Liver Chunk-8
SUBJECT_SAMPLE_FACTORS           	-	48	Sample source:Embyronic Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	RAW_FILE_NAME=20220620_QEF1_HILIC_oldeCSF_mLiver_eLiver_BP1036; Sample source inrormation=Embyronic Liver Chunk-10
#COLLECTION
CO:COLLECTION_SUMMARY            	All animal studies were performed under the protocol approved by the
CO:COLLECTION_SUMMARY            	Institutional Animal Care and Use Committee (IACUC) of Boston Children’s
CO:COLLECTION_SUMMARY            	Hospital (BCH). All mice were housed in a 12h light-dark cycle with ad libitum
CO:COLLECTION_SUMMARY            	access to food and water. CSF, eCSF, was collected from the cisterna magna of
CO:COLLECTION_SUMMARY            	the pup embryos and mother, and centrifuged at 5,000g for 10 min. at 4 °C to
CO:COLLECTION_SUMMARY            	remove any tissue debris. CSF samples were kept on ice and analyzed the same day
CO:COLLECTION_SUMMARY            	as collection.
CO:SAMPLE_TYPE                   	CSF, Liver, serum
#TREATMENT
TR:TREATMENT_SUMMARY             	For polyI:C experiments: Pregnant female mice were injected intraperitoneally
TR:TREATMENT_SUMMARY             	(route of administration) with a single dose of 20 mg/kg polyI:C (sigma aldrich)
TR:TREATMENT_SUMMARY             	and controls received an injection of 0.9% saline embryonic day 12.5-14.5.
TR:TREATMENT_SUMMARY             	Samples were collected 3hrs post injection.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Per condition, 5uL of maternal serum, CSF, were extracted by brief sonication in
SP:SAMPLEPREP_SUMMARY            	200/100μl (serum/csf) 80% methanol, supplemented with isotopically labeled
SP:SAMPLEPREP_SUMMARY            	internal standards (17 amino acids and reduced glutathione, Cambridge Isotope
SP:SAMPLEPREP_SUMMARY            	Laboratories, MSK-A2-1.2 and CNLM-6245-10). 10uL Embryonic CSF (eCSF) was
SP:SAMPLEPREP_SUMMARY            	extracted per condition using the previously described buffer quantity, and the
SP:SAMPLEPREP_SUMMARY            	flash frozen liver chunks were extracted in 300uL of the previously described
SP:SAMPLEPREP_SUMMARY            	buffer. After centrifugation for 10min. at maximum speed on a benchtop
SP:SAMPLEPREP_SUMMARY            	centrifuge (Eppendorf) the cleared supernatant from CSF and eCSF was dried using
SP:SAMPLEPREP_SUMMARY            	a nitrogen dryer. Samples were reconstituted in LCMS water by brief sonication.
SP:SAMPLEPREP_SUMMARY            	Extracted metabolites were spun again and cleared supernatant was transferred in
SP:SAMPLEPREP_SUMMARY            	LC-MS microvials. Serum followed the same protocol, except that an additional
SP:SAMPLEPREP_SUMMARY            	20-minute centrifugation was administered, and homogenization for 5 minutes.
SP:SAMPLEPREP_SUMMARY            	Final LCMS water reconstitution values for tissue type were 50uL (maternal and
SP:SAMPLEPREP_SUMMARY            	embryonic serum), 15uL (maternal CSF and eCSF),. A small amount of each sample
SP:SAMPLEPREP_SUMMARY            	was pooled and serially diluted 3 and 10-fold to be used as quality controls
SP:SAMPLEPREP_SUMMARY            	throughout the batch run. Two microliters (equivalent to 0.2 ul of CSF) of
SP:SAMPLEPREP_SUMMARY            	reconstituted sample were injected into a ZIC-pHILIC 150 × 2.1 mm
SP:SAMPLEPREP_SUMMARY            	(5 µm particle size) column (EMD Millipore) operated on a Dionex UltiMate
SP:SAMPLEPREP_SUMMARY            	3000 UPLC system (Thermo Fisher Scientific). Chromatographic separation was
SP:SAMPLEPREP_SUMMARY            	achieved using the following conditions: buffer A was acetonitrile; buffer B was
SP:SAMPLEPREP_SUMMARY            	20 mM ammonium carbonate, 0.1% ammonium hydroxide. Gradient conditions were:
SP:SAMPLEPREP_SUMMARY            	linear gradient from 20% to 80% B; 20–20.5 min: from 80% to 20% B; 20.5–28
SP:SAMPLEPREP_SUMMARY            	min: hold at 20% B. The column oven and autosampler tray were held at 25 °C
SP:SAMPLEPREP_SUMMARY            	and 4 °C, respectively. The MS data acquisition was on a QExactive benchtop
SP:SAMPLEPREP_SUMMARY            	orbitrap mass spectrometer equipped with an Ion Max source and a HESI II probe
SP:SAMPLEPREP_SUMMARY            	and was performed in a range of m/z= 70–1000, with the resolution set at
SP:SAMPLEPREP_SUMMARY            	70,000, the AGC target at 1x106, and the maximum injection time (Max IT) at 20
SP:SAMPLEPREP_SUMMARY            	msec. For tSIM scans, the resolution was set at 70,000, the AGC target was
SP:SAMPLEPREP_SUMMARY            	1x105, and the max IT was 100 msec. Relative quantitation of polar metabolites
SP:SAMPLEPREP_SUMMARY            	was performed with TraceFinder 4.1 (Thermo Fisher Scientific) using a 5 ppm mass
SP:SAMPLEPREP_SUMMARY            	tolerance and referencing an in-house library of chemical standards. Pooled
SP:SAMPLEPREP_SUMMARY            	samples and fractional dilutions were prepared as quality controls and only
SP:SAMPLEPREP_SUMMARY            	those metabolites were taken for further analysis, for which the correlation
SP:SAMPLEPREP_SUMMARY            	between the dilution factor and the peak area was >0.95 (high confidence
SP:SAMPLEPREP_SUMMARY            	metabolites).
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	ZIC-pHILIC
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	SeQuant ZIC- pHILIC (150 x 2.1mm, 5um)
CH:SOLVENT_A                     	100% acetonitrile
CH:SOLVENT_B                     	100% water; 20mM ammonium carbonate, 0.1% ammonium hydroxide
CH:FLOW_GRADIENT                 	0-20 min: linear gradient from 20% to 80% B; 20–20.5 min: from 80% to 20% B;
CH:FLOW_GRADIENT                 	20.5–28 min: hold at 20% B.
CH:FLOW_RATE                     	0.150mL/minute
CH:COLUMN_TEMPERATURE            	25
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Plus Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	POSITIVE
MS:MS_COMMENTS                   	HESI
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	a.u.
MS_METABOLITE_DATA_START
Samples	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40	41	42	43	44	45	46	47	48
Factors	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:mock | Maternal Treatment (injection):N/A | Developmental Timepoint:N/A | Collection Time:N/A	Sample source:mock | Maternal Treatment (injection):N/A | Developmental Timepoint:N/A | Collection Time:N/A	Sample source:mock | Maternal Treatment (injection):N/A | Developmental Timepoint:N/A | Collection Time:N/A	Sample source:mock | Maternal Treatment (injection):N/A | Developmental Timepoint:N/A | Collection Time:N/A	Sample source:mock | Maternal Treatment (injection):N/A | Developmental Timepoint:N/A | Collection Time:N/A	Sample source:mock | Maternal Treatment (injection):N/A | Developmental Timepoint:N/A | Collection Time:N/A	Sample source:maternal serum | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:maternal serum | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:maternal serum | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:maternal serum | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:maternal serum | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:maternal serum | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:maternal serum | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:maternal serum | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:maternal serum | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	Sample source:Embryonic CSF | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E14.5 | Collection Time:48 Hrs	Sample source:Maternal Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Maternal Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Maternal Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Maternal Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Maternal Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Maternal Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Maternal Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Maternal Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Maternal Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embyronic Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embyronic Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embyronic Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embyronic Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embyronic Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embyronic Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embyronic Liver | Maternal Treatment (injection):saline | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embyronic Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs	Sample source:Embyronic Liver | Maternal Treatment (injection):PolyIC | Developmental Timepoint:E12.5 | Collection Time:3 Hrs
SODIUM PALMITATE_U-13C16	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F
Alpha-Ketoglutarate	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	11572723	10032528	N/F	N/F	N/F	N/F	3209392	N/F	N/F	N/F	N/F	N/F	N/F	N/F	10983766	10074763	N/F	13829957	N/F	N/F	5199454	N/F
isoleucine	667155349	4561211703	603803793	868617100	653826532	865497269	670438512	350410751	5131144	N/F	6140350	N/F	N/F	N/F	1179469802	530731235	660771862	583568161	720127796	647369582	704216766	613897832	725614484	827736484	1064483231	1236595069	976291437	1256180034	722019547	1434167217	939685433	388027885	613939805	555643491	613358699	819525665	765883469	1061760044	706945340	189080538	328621024	462503647	294560631	521164571	315395901	325983598	167529184	440968393
leucine-13C6-15N	308511798	311698843	244056429	243738630	260088952	229695676	303931067	282024036	178381377	227392360	304182060	201692362	298282130	220920040	194193899	159230310	194141388	183166534	221638760	215124749	171752608	199682993	181529834	449221835	386141638	408259691	356433817	396428359	429757268	380939879	40584155	47722897	43949019	42822110	43410774	34615497	42833019	32299061	40402035	55465072	47300491	42294568	49187022	48685947	44335480	50841736	55911152	45771617
NICOTINAMIDE_13C6	1487966	6278039	1647950	1198413	1921714	488482	540986	1760953	1877707	1766402	5405329	N/F	4135237	1268153	N/F	7898584	10237219	10533736	10784917	10795994	7529542	8535064	9594622	1709911	1838177	1448694	1654581	1549516	1721363	1702254	N/F	241954	N/F	N/F	N/F	N/F	N/F	N/F	N/F	1852759	1335737	1079998	1115443	1196198	1308764	1322272	1702189	167157
"ETHANOLAMINE_1,1,2,2-D4"	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F
methionine	352851663	1205463633	142605345	217247786	151301659	239040454	131324598	10049781	N/F	N/F	N/F	N/F	N/F	N/F	307149316	9617799	1831371	103816266	13504787	47019198	24947714	60335919	53636921	384727078	1705399930	3425087345	1030279580	2745391657	2733560929	1853627087	1333710228	210512724	1522353950	582761580	985810684	1008010873	1091116264	1361374581	777929492	274419583	827289064	890309850	721349053	1338025433	786745370	896126983	237334479	743667830
L-TYROSINE_RING-13C6	10244156	11564044	11456389	10255837	11245347	11027856	12062274	15916926	16381168	20293353	31055709	18599879	26478164	21638629	N/F	32543265	39267477	41367150	45475131	44809250	33926335	42171359	39956623	31848836	23185151	23586307	24262684	24280697	24317420	21574975	13360418	16518916	15058937	19695890	16148296	14082061	15855949	13125284	16834353	25701307	18683112	17249455	19584188	15575353	17162327	19096231	24320461	14715012
hypoxanthine	1939329134	3175168891	1792493985	1185758670	811446973	976447020	812868443	448916315	1654458	1939648	2878202	1213283	2540483	1769449	4679972163	1729101292	2528730223	4210500707	1747550086	878244892	1009143337	1272901018	1664632666	1137756810	1408351605	1452873703	1331909374	878834402	1296661692	1257476870	8985567535	3644421207	14046678677	4106535901	6774517924	5867593730	7044306823	8325176652	4269437487	2431909715	5401522401	2443398772	2800051612	2307833356	2388443834	2029526931	1326227957	3085705080
histidine-13C6-15N3	119297850	282860771	260955955	280757576	255294851	266513640	260307146	377531468	173950875	189396661	360840263	213241047	354394378	236916032	160850120	317180373	387653869	176714877	349231840	367996936	396182016	308401870	267773682	204675279	92127041	110999151	110346385	107292342	102317457	95588521	12202299	22873530	20558480	23965647	14761658	10505853	12137375	8508467	14898077	42357311	15710757	16709044	20518768	15006006	14821424	19990430	40762038	10513032
arginine-13C6-15N4	646560395	463397139	555357402	524572586	529290671	528174901	575396452	798751435	438908305	834836832	1094147514	845903241	1037361433	947298113	775974040	655781348	696359472	796136773	859352906	859594981	668635076	780365042	781460530	540699724	370665584	344880214	340939095	353161073	380782064	339044807	375993	81935372	23481016	69552730	2909135	1693093	4142913	1165949	16691585	155891697	90704911	77319057	94857635	76417454	86917117	88878706	152573835	72056092
arginine	6469385567	8462736588	6442252239	8001204144	6693309825	7872599353	7341990783	3394412095	6401319	12228151	18317552	18583560	15394569	21670418	3830783422	4502516586	5516444036	5142768255	5213341596	4349812799	4487290038	4874975755	4506660271	5744752741	9619628132	12077273698	9689736400	10618824832	9367654446	10815232882	28345140	72348608	68531986	85375433	25480693	17531629	34522036	18917283	28465472	2019093245	3308520316	3172123142	3321541862	3729543114	2940838662	2509184373	2002237758	3401946639
tryptophan	451514914	936575435	466599725	685315098	448498996	729632161	559351424	294344912	N/F	171838	505260	N/F	208563	220956	705270443	610391815	962252299	422826782	607610674	556041844	884601475	694131725	875464082	628281051	1460349500	2351583344	1153217974	1678448027	2996859609	1921667533	831148603	69539409	568012062	377104097	592001315	536147406	660126307	846579717	576492428	135550795	475619111	429321802	300408315	546861743	327665936	419163090	140407170	665405408
lysine	4656250070	6290500927	5006770757	6637787126	5847246619	6450953809	6606925726	2326639361	N/F	N/F	N/F	N/F	2475489	2317098	2036294517	1366140171	1820181888	1946738932	1722174476	1771800004	1609752592	1793449399	1558121355	4752454085	11265740198	12668012654	9804959746	11169303419	10493818097	11680718428	2477065303	643611446	1808168800	1426216600	2143817601	2164309932	2302474658	2630889718	1594581532	492660386	1291392949	1211388612	1215433995	1717206987	1247933508	950245355	609496664	1840396534
THYMINE	53683325	60221891	50958724	31434168	29704120	32112775	42775158	14859953	N/F	N/F	N/F	2037714	N/F	N/F	23106242	8579519	10810256	11137930	10691473	10304691	7348102	11829477	8803122	32120303	71467900	58146459	87199496	65106907	79981688	58093658	9327099	3996851	5299099	974949	6214814	4993847	5377530	7247582	1775141	24189166	27209311	5231750	12048580	7649624	4510055	4903383	3598245	21987158
L-ALANINE_13C3	18358378	17465147	17411402	19632045	15404569	16744431	17404175	32090561	29952875	39822830	51389762	36113944	47434671	43079268	7975811	16843241	18080125	10014794	19669805	20472797	16888601	17106983	14391357	30301797	22533112	22383249	20260368	23026600	21973246	19468364	1596352	4452014	3546424	3971143	2853640	1188750	3186715	1497471	2495701	6729282	3736110	3958874	3822660	3393170	2767232	4020472	6388195	2178871
cysteine_unc	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F
pyruvate	7418538	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	387424	229484	331929	N/F	N/F	N/F	N/F	134588692	5910721	18209951	75573755	78138602	85902454	60308362	87586096	34576097	1571587	10877879	14146889	16235588	25277460	38420766	9387033	1877880	31263427
PYRUVATE_13C3	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	713795	654993	505776	686865	764244	584328	643155	639916	667095	507853	497361	508830	604914	534938	478906	662345	470327	523435
threonine	847713291	1708691258	1860218599	1376106233	1190483215	1225402290	1112460167	449182427	5509722	N/F	N/F	16549076	12400389	11726247	626114961	625775691	922105515	799228480	633699062	675123374	582018587	671516548	417051903	1002658737	1799855262	1475308196	1503681209	1417983224	1003448838	1126372178	869490623	332710754	829176287	547324613	776455801	645580464	578264717	968385701	476070982	233347355	714063220	851585563	794744194	893524337	688535154	555299051	296165748	776709812
guanosine	9144639	14066079	9871390	4713609	4329586	3536392	2764141	2554796	N/F	N/F	N/F	N/F	N/F	N/F	8749855	930668	8821757	8737829	15112133	5080027	10375010	4471500	3627145	3825096	3942463	4121666	4298816	2199421	3679830	2669342	260185462	48820375	312037367	75952410	172507118	123483575	149120100	200960856	70413499	12462104	39500198	18328277	29376110	24354849	21420966	16234613	7307139	30451309
GUANOSINE_15N5	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	116056	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	149081	N/F	N/F
CREATININE_N-METHYL-D3	308555664	497828109	320543623	311126688	338659706	282443028	310046919	353088135	291027640	324797707	458529973	248392440	418060043	331054876	211450	637704800	729354744	793938763	838523540	819748108	721800922	806323865	777522345	703297987	679047651	637559915	646118258	646902244	607641280	597367487	534968123	231315000	531485287	553491336	536583683	536563358	591081766	547810884	544809509	599022609	588996794	528713776	609894871	556690967	566737341	606657916	583226929	534151087
fumarate	25110281	24509409	21944802	23452043	24422943	23649178	20851216	10702684	N/F	N/F	N/F	494705	N/F	N/F	104517661	56780064	28761784	101886182	22717185	35823165	25312376	33245512	62001529	17783075	35735073	38991672	33408325	35284450	38922419	33092436	339192395	65734198	217860241	193592055	244213561	314581736	248785809	318611802	208747016	42105836	103221135	96304922	98240018	113040839	111738883	97185384	46753533	150003057
phenylalanine	467240594	686209697	530653464	639687170	609647205	659282624	637298923	230296332	N/F	N/F	1388105	N/F	972263	1504489	408118321	119579217	126593598	121008720	142593487	152014280	130242608	146180773	192084937	433339176	842708406	1003146949	978720249	836645581	1286199486	1203815137	666846912	152116262	463788827	202888466	380797758	369421839	405361291	653986211	322141665	85861182	225699455	249655727	209498958	356174615	224613661	221068405	87167027	398514707
FUMARIC ACID_13C4	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	206229	198081	234374	368454	389528	302759	408990	162670	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F
glutamate	14439706	22887431	21539233	19967351	16604003	18194569	11619357	13495017	1893663	1322873	2253846	3199068	2292908	4710714	285715501	72237417	41314870	191557841	54404354	75999799	47027126	116860489	112443348	14856438	23446954	18396368	17549712	12474152	248308	11734769	1028065903	325091486	787576900	446416504	990633173	767541375	949896630	1350607099	770595600	775410979	1855830478	1794017565	1444082299	2335826173	1740415514	1851575994	805464732	3270170719
PALMITATE_U-13C16	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F
palmitate	328695043	250043343	371808121	301294512	294607291	327117318	296498062	137563642	N/F	2514575	N/F	N/F	N/F	N/F	4219867293	704281448	488682515	962688832	1196531436	798651681	589524049	737118421	1329022794	150888336	322923237	364344171	341107736	293320501	381505419	291430451	1684508839	283098515	873112441	544254806	1140480393	1184287040	1151767211	1633179427	725591568	45487955	283967978	116084023	187899103	216706257	72474070	135773910	60130954	325841068
"ALPHA-KETOGLUTARIC ACID_1,2,3,4- 13C4"	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	1855905	1188122	713866	1504579	837589	705010	1137644	N/F	1703447	N/F	N/F	N/F	N/F	N/F	N/F	N/F	5021539	936670	2052002	2219407	N/F	397175	1761743	5019813	N/F
aspartate	5888339	6952596	5055656	2641060	2218321	2525133	3297623	2397020	398617	N/F	1519118	1786379	943842	2055282	132100038	20417170	18767069	75011955	19600571	29080858	15305687	40236536	29488457	4368898	4471957	5808740	4270883	4953474	4998549	5820938	354213438	113257529	278842201	138104195	249800188	269275795	300328574	345032521	207875076	398707746	718104141	784682516	594751868	902603050	656048633	694959995	365307383	1060660147
glycine_13C2-15N	2224964	2003704	2512176	2240945	1912438	2214705	2362844	3270839	1461851	1906907	2455754	1790448	2350910	2124379	915077	1101655	1183623	1127754	1308485	1589153	1202310	1494479	1157238	4034355	3513869	3876393	3017471	3448472	3534277	3631652	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F
"CITRIC ACID_1,5,6-CARBOXYL-13C3"	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F
Isoleucine-13C6-15N	184991929	266867889	201246204	213577347	147414993	202227415	148375722	294262023	223270047	258919111	444500075	272556576	393097718	311607379	189545096	176880939	215666283	259564002	246464017	256511996	192886868	228695013	219839150	272202572	164103116	158497209	161750645	179491679	144456930	173196759	9891715	28594952	13941121	27150530	13142027	21207733	14494550	14843336	25033864	38761547	24541878	26995014	24066841	22181083	22125717	31083776	37427723	21208012
citrate	3095645206	3285736031	3051278083	3091095282	3286950939	3161378928	3475207474	1749395497	12345728	36710272	22727345	30718476	29294973	30495935	1702592662	1336955019	1598663380	1761965301	1695815644	1728961231	1831271317	1689686700	1265365383	2408666149	4789694300	4935502793	4246971893	4959277723	4785247186	5642382752	1081110934	164448667	194321316	730353063	1202266798	1040429754	643991590	1285042846	679956151	221668194	1036115407	741253384	966598130	1170304029	1101661834	872475976	353844748	1968067518
L-TRYPTOPHAN_13C11	13121291	23630955	19740008	20907843	20862294	17716522	21293719	22827290	16985324	17900686	33250181	19634977	30305031	21792664	N/F	43444539	54704774	56081426	62425180	62693097	45787255	52697214	51545170	50837166	46611149	45799427	41226667	47891614	42778348	41144151	19194340	22254987	20455373	29617024	24299220	22253725	22389481	22238940	26210411	33743945	31067712	30735275	32650145	29746563	31166218	33563109	32553534	27122756
serine	156054697	317046070	235591157	312528890	203935374	285484076	196560926	126826249	2387850	3104499	3801558	2951269	3875638	3028204	107519141	28066084	55188343	42641580	48662436	31019509	47073242	39535598	34477605	289485117	540480803	732727365	456345214	569590812	504997004	473712821	163340562	87813486	190123186	45651794	150968176	92358785	153111183	127795983	65277015	89864744	173716211	227847631	131422865	302444048	163455721	189075767	86788008	304570198
leucine	1957128565	3547378468	2167186203	2580020543	2480892242	2640427957	2657765807	885201319	N/F	2987774	5210387	N/F	4454991	N/F	2032372381	705272522	815971336	677151077	915578109	867490162	915916136	881569658	1020154848	2387468453	5937922898	6340168903	5698768537	5080031355	3909071161	5707991066	4199147828	981106311	3443397909	1522112052	2551064362	2401996557	3219366069	3939943237	2209225257	518593636	1336444585	1446184352	1199292393	1984904360	1337274450	1293441325	558244406	2049110382
lysine-13C6-15N2	125040102	106671309	110041948	110259143	103490850	111362811	121898565	125535950	44244627	67939280	89842095	65244132	86968028	69958552	81082535	68838005	78765921	75585085	88820742	86568144	74766610	85633521	78114070	128950944	110313506	112298293	101411355	112281516	109332589	102730031	6899601	10405509	9333768	12057570	8308858	6814499	7486213	6410277	9044521	14543179	11176908	10447152	10783466	10742342	10025664	10631063	14347464	10101631
cystine	44466334	72756577	70136649	77250317	89014690	78316651	80592105	27703297	N/F	N/F	N/F	N/F	N/F	N/F	33169487	95284570	133343596	124240392	68395390	188101107	111036101	187866945	159790091	44412773	106307913	121724135	102856795	102221422	99632219	120506554	N/F	784055	N/F	N/F	N/F	N/F	N/F	N/F	N/F	2162297	1377704	1675914	1019954	2147585	962229	909122	1361732	1041010
alanine	1068636773	1256588635	1242762381	1193436362	1347732007	1241940338	1337642350	620901214	1835881	N/F	3933663	2555753	2916061	3566479	1138678928	532556596	484174436	961290848	533471735	579557939	528698015	720359107	672885419	1020287191	2121108532	2074644862	1844794660	1991291290	1881507337	2088078835	2256106932	903972395	1798449212	1325055020	1631668163	2116703909	1728233492	2271337052	1453436623	396977638	1033909896	1013676845	796126870	1247782291	1124479218	893424649	494988078	1554528726
threonine-13C4-15N	72707423	86037549	82751527	86814966	79905118	78093506	87442997	146861968	106408651	121107509	208466273	123353673	199667696	145129642	42020904	53181903	52191765	44091756	57689819	69678299	54764668	59680554	55403554	79059315	49039204	50984726	47416543	52261752	49981032	49203392	4465089	9254549	5532864	6602906	5580627	3878519	4476813	2922117	4374772	9067982	5318589	6422356	6723815	5440792	5982402	6615677	9739121	5889841
proline-13C5-15N	1088873853	1111847403	995997300	927725883	923255250	876145634	956405897	1314685268	711349852	988524910	1323732290	987122723	1217483879	1111490850	654513125	748025763	850922781	924104185	943195402	961223237	748012853	907117483	877094194	1127111446	728591403	696825505	698316119	722535746	742564911	648579140	92703569	142767450	105566323	145769098	120929502	107618668	116839500	84299813	127823114	174178030	118298496	106942909	128408339	99779939	104192753	128546059	164177393	101000510
niacinamide	801092492	1073812873	715378977	343830411	613218879	345495801	504411956	413512990	N/F	N/F	3605582	N/F	N/F	N/F	1819982867	1164224385	577304663	3088247682	746436684	1176994406	502398854	1246223811	1889067544	354775664	1223793305	861366576	1135155360	616326864	589658420	766730213	42936875221	14274217164	25907659032	20722123829	34479515137	37473790051	36640392643	42856349773	27211886172	3224332015	8045239834	5653783353	7256466529	7642255717	7883644331	6736580992	3491765441	9757207975
tyrosine	556991794	1201161740	760261746	944838585	851411629	1010382726	900983450	401093289	2103236	2212101	2959799	3130806	2813226	3811383	953406625	291463632	375949364	312138143	362933323	337421190	365047118	326380790	458219959	1052329963	1565921543	2078822263	1594513639	1635953308	2590949505	1976396433	1524309652	281852264	1342380773	719198241	1017457890	950165616	1179181827	1378037504	895635045	319557009	553069662	637740106	515272698	776860082	540665176	598995530	287745463	778343834
methionine-13C5-15N	103629693	173162947	30799355	27245961	26867214	29954596	25490041	10886436	N/F	N/F	2610053	N/F	2303231	140623	63722201	5749015	214334	57380970	5287441	32344905	6703792	40249664	35545816	62313406	137035076	157250840	78912034	139178459	152217315	97934609	23195498	27803872	28614646	42401534	28923979	28869846	26531520	26798720	36429608	35496702	41612710	34827495	43072479	35464836	38473632	41556805	37315070	36899196
proline	8542539003	14156166283	11101432845	12232447573	13067732174	11310064227	12109733316	4712653601	20196506	21112585	40644328	42406750	33284106	43684165	3678087238	1648529872	2753279459	2495637517	2313371515	1967059361	2480223046	1749331000	1902209097	9492468810	16603987070	17360689027	15645815030	16964112915	15224262497	17560976928	7216772076	2353643366	5737878567	3601232395	5016417971	5346869646	5750012881	6866123826	4823639943	3264283852	7220956612	7313293678	6252565669	8895421001	8159922761	6681483034	3890560851	10895837211
creatinine	933629478	1585005888	1290818048	1177210892	1081051479	1184441549	1106556374	570488514	N/F	N/F	N/F	N/F	N/F	N/F	1132257650	544245433	670779491	954508776	772770049	617552910	834258645	694900961	736118411	945940240	2206349907	2508442339	2042616742	2371709153	2222847696	2281637334	1048365039	46049916	490997350	330449768	814400511	614531693	1074984417	797415622	393892017	99970037	352549628	276888838	358623605	461765545	341984318	302857051	125575284	637314824
valine	1223707555	2260996469	1424398407	1627081809	1890053621	1765684224	1850664957	832364721	N/F	N/F	15565033	N/F	6931036	N/F	1161383237	583295584	751086794	723531701	785531904	872644550	764488837	844082095	1043306257	1839374491	3589232996	3900520611	3724383699	3385446871	3221817725	3790660751	1925161746	586257962	1606419439	844198876	2295497434	1378634104	1516746709	2341059743	1343881489	399948481	890310329	1157537263	860001066	1306897891	1233921206	844915456	450991397	1575162143
"glutamate-13C5,15N"	24959147	22393909	22505799	24625449	21502977	23812339	24722309	24474015	12065816	16112926	16810694	16670546	16934426	16298202	14823878	11474223	12145821	13144742	13884771	14089925	12443487	14457541	12370177	38972599	36129859	37272766	35591749	39274300	38008054	38674125	275063	3360187	2203226	2682945	313359	689329	1074691	580551	1736327	4855321	3039382	3428982	3633035	3085647	2861952	3522656	4965824	2997138
tyrosine-13C9-15N	235959757	246693386	240863521	225234887	225507529	212005710	247006235	312293032	191143281	239715740	363257115	234896537	329090237	262383144	179468092	187316227	228432501	229162115	254851613	251272582	194299588	238299561	228873992	351821697	261698316	251610897	252659890	272844607	268566324	239571726	22577962	31532698	27882168	34538317	28079659	24109313	28162029	20516784	28705208	52467088	36425962	32066845	37961765	31225443	31881534	37857454	49769900	30332429
cysteine_13C3_15N1	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F
"1,4-BUTANEDIAMINE_13C4"	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F
alanine-13C3-15N	18358378	17465147	17467384	19632045	15404569	16744431	17404175	32090561	29952875	39822830	51389762	36113944	47434671	43079268	7975811	16843241	18080125	10014794	19669805	20472797	16888601	17106983	14391357	30301797	22533112	22383249	20260368	23026600	21973246	19468364	1596352	4452014	3546424	3971143	2853640	1188750	3186715	1497471	2495701	6729282	3736110	3958874	3822660	3393170	2767232	4020472	6388195	2178871
cystine-13C6-15N2	24100491	33065900	39551177	38688970	36860593	37592165	40756262	45865378	27095449	27442295	37113782	25341909	35206027	29041995	22561357	24013017	27958875	26488078	27491781	29098911	22320655	28093704	23753627	21803152	18440481	19210790	18764003	19329728	20204565	18677297	N/F	1158696	N/F	N/F	N/F	N/F	N/F	N/F	N/F	1411789	595630	868816	679108	298423	397342	956920	1474349	N/F
phenylalanine-13C9-15N	983785568	1281317266	890518838	859996661	813455003	761628579	913906496	1032537407	695710835	734799389	1305359833	564549285	1119663685	855999930	614048930	564452686	760580604	772631258	851959667	804665786	641328569	721730079	697593750	1345831761	1000218782	930253354	920390490	1044713144	948957736	952262339	97776306	121441354	115193619	123455383	110645637	104408909	113561490	91230578	117934738	156669778	129667268	106432711	135820674	118509710	114841356	133916599	149875792	113692116
histidine	1067646368	4196364470	2751203772	4690560754	3522859036	4717496250	3829902656	2159184779	1860483	N/F	N/F	5568605	10084742	15410228	1161123380	1273505923	2112970183	665683867	1595596821	1612638360	1635515057	1216231115	1406502233	3363219104	2233970484	3333852838	2675153342	2552435413	3065187551	4696366401	9741698023	3105633093	9121431289	4938680403	7331927456	6900237476	8718188801	8418989045	6605761928	1390800208	1604848489	1920151596	1676611843	2237841684	1845713398	1804399435	1380932538	1973674072
"1,4-BUTANEDIAMINE"	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F
valine-13C5-15N	126400014	144742393	125046100	115442691	127409253	115657829	125529265	171232417	118062684	151353788	209762042	152284643	191612841	174639903	105119814	102901377	119031982	131088672	139397148	129870111	109485206	124431287	122172049	173727297	128502976	117041163	112368150	122148752	123127390	104395216	15536749	20067287	17383175	20796920	18685304	16782021	17095706	15027206	18678274	27269394	22197025	18127795	21487898	19794257	19513382	21404627	24526301	19737964
serine-13C3-15N	13756300	14906714	16950405	15631823	16995471	15110754	16361571	24131226	10005434	10916603	15458406	10613516	15307402	12842663	7884726	8053985	7852636	8371442	10534501	10368424	8180257	10203420	7758139	20769545	17630389	19477026	13988608	17548993	17147366	16269217	N/F	866044	N/F	N/F	N/F	N/F	N/F	N/F	N/F	1131811	770384	403744	767160	527092	473715	537222	1171885	579892
HYPOXANTHINE_13C5	2267548	12228227	966231	570526	2404660	737739	1425225	2244655	5146721	2432672	17747404	1002507	11521255	5987472	N/F	11677546	17141160	15430831	22217720	20963609	14704409	12081973	16775264	9972682	7325641	7208244	6522823	7483899	8647030	7145639	10679225	10804644	6953810	9928700	10834553	13659164	9517905	11441108	11121033	9804631	7604202	6439755	8143865	8507740	8231039	10581889	10741470	5667058
INDOLE-3-ACETIC ACID	436198	2761382	787435	2110057	638533	2963611	2012716	251702	N/F	N/F	N/F	56140	N/F	401014	1990210	7093594	9323691	4028261	7957266	7166261	7670258	6990634	8092572	1301057	3553356	6959068	2888699	5271934	8010939	7621013	362020	44865	299560	64696	164574	246697	275209	375858	433309	40493	188176	35303	65654	171399	95725	123768	10550	272243
aspartate-13C6-15N4	20973525	20262522	20065440	21792568	19075074	20224533	21946582	20894669	11773327	14730496	16134689	14614372	16045219	15354032	11465447	9909784	10830618	10566665	11308787	12002207	10719473	12261572	10871878	36240210	33487125	33225718	33015743	35181342	34042830	34909606	144955	2952518	2216827	2361824	N/F	392450	999196	735910	1363207	6411942	4657943	4088030	4723075	3724643	3917644	4634186	6727774	3625137
INDOLE-3-ACETIC ACID_PHENYL-13C6	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F	N/F
"THYMINE_1,3-15N2"	1279817	1815201	1359506	1641999	1595312	1383904	1276636	1601482	1101689	1636810	1974952	892710	1751710	1566678	N/F	2053764	2274177	2515093	2657668	2962102	2397893	2512776	2552013	2713120	2544090	2547360	2835313	2501326	2382178	2575699	1253212	1621672	1464326	1630395	1539396	1285376	1516960	1411666	1353377	1323897	1396046	1375657	1478175	1440177	1275915	1526161	1514738	1436516
L-LEUCINE_13C6	N/F	1110447	272871	862054	N/F	N/F	N/F	1046323	1133751	1191007	2367220	546421	2526085	1504798	N/F	2686022	2875145	2653673	3115910	3392575	2663730	3005071	2624074	3768956	2727902	2098661	2050381	2420304	2848203	1389327	1031024	1793395	1503604	1836501	1341301	1092615	1652689	645090	1403163	2152644	1851614	1841291	1950756	1747854	1748243	2050932	1922876	1399406
L-PHENYLALANINE_RING-13C6	54507774	84366656	46630364	44979712	49326697	38777037	44834658	61676421	66466401	66972987	138505647	39390039	113893827	78595563	N/F	119890702	166612520	170935815	190120546	180736778	143336465	157464007	152174922	147889374	115524009	102648014	105562706	111222170	102711988	103093907	68465056	72654704	69376026	79558375	72033934	70301235	75765502	70017344	75711122	89294951	78713572	68118260	85751420	70735076	73743864	80733990	86637544	62638628
glycine	12648448	9806330	9620720	10472762	10389176	9699573	9709244	7861095	N/F	1084551	1493217	1011049	1739265	1444784	14126882	5296961	5585538	8712766	6806474	4563670	4574584	7179222	8027663	15138271	30483699	35964084	24730277	35112574	28652011	35223103	156115724	34265176	116901469	51907198	135002414	112827165	136952290	127332836	79334083	37842633	94345108	88210509	89272650	101625241	88053042	80701532	49609950	129653633
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name
SODIUM PALMITATE_U-13C16
Alpha-Ketoglutarate
isoleucine
leucine-13C6-15N
NICOTINAMIDE_13C6
"ETHANOLAMINE_1,1,2,2-D4"
methionine
L-TYROSINE_RING-13C6
hypoxanthine
histidine-13C6-15N3
arginine-13C6-15N4
arginine
tryptophan
lysine
THYMINE
L-ALANINE_13C3
cysteine_unc
pyruvate
PYRUVATE_13C3
threonine
guanosine
GUANOSINE_15N5
CREATININE_N-METHYL-D3
fumarate
phenylalanine
FUMARIC ACID_13C4
glutamate
PALMITATE_U-13C16
palmitate
"ALPHA-KETOGLUTARIC ACID_1,2,3,4- 13C4"
aspartate
glycine_13C2-15N
"CITRIC ACID_1,5,6-CARBOXYL-13C3"
Isoleucine-13C6-15N
citrate
L-TRYPTOPHAN_13C11
serine
leucine
lysine-13C6-15N2
cystine
alanine
threonine-13C4-15N
proline-13C5-15N
niacinamide
tyrosine
methionine-13C5-15N
proline
creatinine
valine
"glutamate-13C5,15N"
tyrosine-13C9-15N
cysteine_13C3_15N1
"1,4-BUTANEDIAMINE_13C4"
alanine-13C3-15N
cystine-13C6-15N2
phenylalanine-13C9-15N
histidine
"1,4-BUTANEDIAMINE"
valine-13C5-15N
serine-13C3-15N
HYPOXANTHINE_13C5
INDOLE-3-ACETIC ACID
aspartate-13C6-15N4
INDOLE-3-ACETIC ACID_PHENYL-13C6
"THYMINE_1,3-15N2"
L-LEUCINE_13C6
L-PHENYLALANINE_RING-13C6
glycine
METABOLITES_END
#END