#METABOLOMICS WORKBENCH jad2033_20230615_184322 DATATRACK_ID:4093 STUDY_ID:ST002745 ANALYSIS_ID:AN004452 PROJECT_ID:PR001509
VERSION             	1
CREATED_ON             	June 26, 2023, 11:30 am
#PROJECT
PR:PROJECT_TITLE                 	Biomolecular condensates create phospholipid-enriched microenvironments
PR:PROJECT_TYPE                  	Metabolomics of in vitro condensates
PR:PROJECT_SUMMARY               	Proteins and RNA are able to phase separate from the aqueous cellular
PR:PROJECT_SUMMARY               	environment to form sub-cellular compartments called condensates. This process
PR:PROJECT_SUMMARY               	results in a protein-RNA mixture that is chemically distinct from the
PR:PROJECT_SUMMARY               	surrounding aqueous phase. Here we use mass spectrometry to characterize the
PR:PROJECT_SUMMARY               	metabolomes of condensates. To test this, we prepared mixtures of
PR:PROJECT_SUMMARY               	phase-separated proteins and cellular metabolites and identified metabolites
PR:PROJECT_SUMMARY               	enriched in the condensate phase. These proteins included SARS-CoV-2
PR:PROJECT_SUMMARY               	nucleocapsid, as well as low complexity domains of MED1 and HNRNPA1.
PR:INSTITUTE                     	Cornell University
PR:DEPARTMENT                    	Department of Pharmacology
PR:LABORATORY                    	Dr. Samie Jaffrey
PR:LAST_NAME                     	Dumelie
PR:FIRST_NAME                    	Jason
PR:ADDRESS                       	1300 York Ave, LC-524, New York City, NY
PR:EMAIL                         	srj2003@med.cornell.edu
PR:PHONE                         	6465690174
PR:FUNDING_SOURCE                	This work was supported by the National Institutes of Health grants R35NS111631
PR:FUNDING_SOURCE                	and R01CA186702 (S.R.J.); R01AR076029, R21ES032347 and R21NS118633 (Q.C.); and
PR:FUNDING_SOURCE                	NIH P01 HD067244 and support from the Starr Cancer Consortium I13-0037 (S.S.G.).
PR:PUBLICATIONS                  	Under revision
PR:CONTRIBUTORS                  	Jason G. Dumelie, Qiuying Chen, Dawson Miller, Nabeel Attarwala, Steven S. Gross
PR:CONTRIBUTORS                  	and Samie R. Jaffrey1
#STUDY
ST:STUDY_TITLE                   	Biomolecular condensates create phospholipid-enriched microenvironments (Part 6)
ST:STUDY_SUMMARY                 	Proteins and RNA are able to phase separate from the aqueous cellular
ST:STUDY_SUMMARY                 	environment to form sub-cellular compartments called condensates. This process
ST:STUDY_SUMMARY                 	results in a protein-RNA mixture that is chemically distinct from the
ST:STUDY_SUMMARY                 	surrounding aqueous phase. Here we use mass spectrometry to characterize the
ST:STUDY_SUMMARY                 	metabolomes of condensates. To test this, we prepared mixtures of
ST:STUDY_SUMMARY                 	phase-separated proteins and cellular metabolites and identified metabolites
ST:STUDY_SUMMARY                 	enriched in the condensate phase. Here, we quantified the concentration of a
ST:STUDY_SUMMARY                 	select set of phospholipids in the aqueous and condensate phase of condensates
ST:STUDY_SUMMARY                 	formed from the low complexity domain of MED1 by comparison with
ST:STUDY_SUMMARY                 	isotopic-labeled phospholipid standards.
ST:INSTITUTE                     	Cornell University
ST:DEPARTMENT                    	Department of Pharmacology
ST:LABORATORY                    	Dr. Samie Jaffrey
ST:LAST_NAME                     	Dumelie
ST:FIRST_NAME                    	Jason
ST:ADDRESS                       	1300 York Ave, LC-524, New York City, NY
ST:EMAIL                         	srj2003@med.cornell.edu
ST:STUDY_TYPE                    	Metabolomes of in vitro synthesized condensates
ST:PHONE                         	6465690174
#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           	-	MED1 PE Aqueous Sample 5	fraction:aqueous | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=5; RAW_FILE_NAME=PE52T.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PE Aqueous Sample 6	fraction:aqueous | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=5; RAW_FILE_NAME=PE53T.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PE Aqueous Sample 9	fraction:aqueous | Extraction from condensate:standard	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=Metabolites added after 10 min incubation; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=5; RAW_FILE_NAME=PE63T.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PE Condensate Sample 5	fraction:condensate | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=5; RAW_FILE_NAME=PE52B.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PE Condensate Sample 6	fraction:condensate | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=5; RAW_FILE_NAME=PE53B.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PE Condensate Sample 9	fraction:condensate | Extraction from condensate:standard	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=Metabolites added after 10 min incubation; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=5; RAW_FILE_NAME=PE63B.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PE Input Sample 5	fraction:input | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=5; RAW_FILE_NAME=PE52I.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PE Input Sample 6	fraction:input | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=5; RAW_FILE_NAME=PE53I.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PE Input Sample 9	fraction:input | Extraction from condensate:standard	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=Metabolites added after 10 min incubation; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=5; RAW_FILE_NAME=PE63I.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PI Aqueous Sample 5	fraction:aqueous | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=3; RAW_FILE_NAME=PI52T.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PI Aqueous Sample 6	fraction:aqueous | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=3; RAW_FILE_NAME=PI53T.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PI Aqueous Sample 9	fraction:aqueous | Extraction from condensate:standard	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=Metabolites added after 10 min incubation; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=3; RAW_FILE_NAME=PI63T.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PI Condensate Sample 5	fraction:condensate | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=3; RAW_FILE_NAME=PI52B.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PI Condensate Sample 6	fraction:condensate | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=3; RAW_FILE_NAME=PI53B.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PI Condensate Sample 9	fraction:condensate | Extraction from condensate:standard	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=Metabolites added after 10 min incubation; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=3; RAW_FILE_NAME=PI63B.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PI Input Sample 5	fraction:input | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=3; RAW_FILE_NAME=PI52I.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PI Input Sample 6	fraction:input | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 20; Sample injection volume (µL)=3; RAW_FILE_NAME=PI53I.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PI Input Sample 9	fraction:input | Extraction from condensate:standard	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=Metabolites added after 10 min incubation; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 300; Sample injection volume (µL)=3; RAW_FILE_NAME=PI63I.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PO Aqueous Sample 5	fraction:aqueous | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 300; Sample injection volume (µL)=5; RAW_FILE_NAME=PO52T.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PO Aqueous Sample 6	fraction:aqueous | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 300; Sample injection volume (µL)=5; RAW_FILE_NAME=PO53T.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PO Aqueous Sample 9	fraction:aqueous | Extraction from condensate:standard	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=Metabolites added after 10 min incubation; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 300; Sample injection volume (µL)=5; RAW_FILE_NAME=PO63T.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PO Condensate Sample 5	fraction:condensate | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 300; Sample injection volume (µL)=5; RAW_FILE_NAME=PO52B.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PO Condensate Sample 6	fraction:condensate | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 300; Sample injection volume (µL)=5; RAW_FILE_NAME=PO53B.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PO Condensate Sample 9	fraction:condensate | Extraction from condensate:standard	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=Metabolites added after 10 min incubation; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 300; Sample injection volume (µL)=5; RAW_FILE_NAME=PO63B.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PO Input Sample 5	fraction:input | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 300; Sample injection volume (µL)=5; RAW_FILE_NAME=PO52I.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PO Input Sample 6	fraction:input | Extraction from condensate:No heat step	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=standard; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 300; Sample injection volume (µL)=5; RAW_FILE_NAME=PO53I.mzdata.xml
SUBJECT_SAMPLE_FACTORS           	-	MED1 PO Input Sample 9	fraction:input | Extraction from condensate:standard	Protein=MED1; RNA=150 nM; timing of metabolite extract addition=Metabolites added after 10 min incubation; SPLASH™ LIPIDOMIX® Quantitative Mass Spec Internal Standard dilution=1 in 300; Sample injection volume (µL)=5; RAW_FILE_NAME=PO63I.mzdata.xml
#COLLECTION
CO:COLLECTION_SUMMARY            	Mouse metabolites were collected from the liver of female mice using methanol
CO:COLLECTION_SUMMARY            	extraction. After euthanizing a mouse, the liver was immediately frozen in
CO:COLLECTION_SUMMARY            	liquid nitrogen. We then used cold 80% methanol to extract metabolites. First, 1
CO:COLLECTION_SUMMARY            	ml of 80% methanol was added to the liver and incubated for 10 min at -20oC.
CO:COLLECTION_SUMMARY            	Glass beads were added to the liver and then the liver was lysed by bead-beating
CO:COLLECTION_SUMMARY            	for 45 s using a Tissuelyser cell disrupter (Qiagen). The lysate was incubated
CO:COLLECTION_SUMMARY            	for 10 min at -20oC and centrifuged (13200 rpm, 5 min) to separate metabolites
CO:COLLECTION_SUMMARY            	from macromolecules. The supernatant was collected and 200 µl of 80% methanol
CO:COLLECTION_SUMMARY            	was added to the pellet. The incubation, shaking and centrifugation steps were
CO:COLLECTION_SUMMARY            	repeated twice to extract more metabolites from the pellet. The three
CO:COLLECTION_SUMMARY            	supernatants were combined and centrifuged (14000 rpm, 10 min) to separate any
CO:COLLECTION_SUMMARY            	remaining macromolecules from the metabolites. The combined supernatants were
CO:COLLECTION_SUMMARY            	dried using a SpeedVac Concentrator (Savant, SPD131DDA) at 25oC and the dried
CO:COLLECTION_SUMMARY            	metabolite samples were stored at -80oC. The amount of protein in the pellet was
CO:COLLECTION_SUMMARY            	measured using the Quick Start Bradford assay to calculate the metabolites’
CO:COLLECTION_SUMMARY            	protein equivalent mass. Mouse metabolites were initially re-suspended in
CO:COLLECTION_SUMMARY            	condensate buffer (50 mM NH4HCO3 pH 7.5, 50 mM NaCl, 1 mM DTT) to a protein
CO:COLLECTION_SUMMARY            	equivalent concentration of 938 g/l. The chosen final concentration of
CO:COLLECTION_SUMMARY            	metabolites is slightly lower than the 200-300 g/l protein concentration
CO:COLLECTION_SUMMARY            	observed in cells. Metabolites that were not fully soluble in condensate buffer
CO:COLLECTION_SUMMARY            	were removed by centrifugation (2x5 min, 16,000 g each), in which only the
CO:COLLECTION_SUMMARY            	supernatant was retained. Purified mCherry tagged MED1 low-complexity domain
CO:COLLECTION_SUMMARY            	(37.5 μM) was centrifuged (1 min, 1,000 g) to disrupt any existing condensates
CO:COLLECTION_SUMMARY            	and to remove any precipitated proteins. The MED1 (final concentration, 30 μM)
CO:COLLECTION_SUMMARY            	was then combined with metabolites (final concentration, 150 g/l protein
CO:COLLECTION_SUMMARY            	equivalent) and then phage lambda RNA (final concentration, 0.15 μM) in a total
CO:COLLECTION_SUMMARY            	volume of 300 µl. An input sample (10 µl) was saved and then the sample was
CO:COLLECTION_SUMMARY            	allowed to incubate for 10 min at 25oC. Condensates were then separated from the
CO:COLLECTION_SUMMARY            	aqueous environment by centrifugation (10 min, 12,500 g, 25oC). The aqueous
CO:COLLECTION_SUMMARY            	phase was removed from the condensate phase and then equal volumes (usually ~ 2
CO:COLLECTION_SUMMARY            	µl) of the aqueous fraction, condensate fraction and input sample were
CO:COLLECTION_SUMMARY            	processed for metabolomics using identical approaches as described below. First
CO:COLLECTION_SUMMARY            	the samples were diluted in ammonium bicarbonate buffer (50 mM NH4HCO3 pH 7.5)
CO:COLLECTION_SUMMARY            	and briefly heated (2 min, 65oC) to disrupt condensates before being added
CO:COLLECTION_SUMMARY            	immediately to 4x volume of ice-cold 100% methanol to precipitate protein and
CO:COLLECTION_SUMMARY            	RNA. This heating step was excluded for some samples where noted. Protein and
CO:COLLECTION_SUMMARY            	RNA were separated from metabolites by vortexing the samples (2 min), followed
CO:COLLECTION_SUMMARY            	by incubation at -25oC (10 min) and then centrifugation (5 min, 13,000 rpm). The
CO:COLLECTION_SUMMARY            	supernatant was saved and the process was repeated on the pellet two more times
CO:COLLECTION_SUMMARY            	after adding 200 µl of 80% methanol each time to the pellet. The three
CO:COLLECTION_SUMMARY            	supernatants were combined and centrifuged (10 min, 14000 rpm) to remove any
CO:COLLECTION_SUMMARY            	additional macromolecules. The final supernatant was collected and dried using a
CO:COLLECTION_SUMMARY            	SpeedVac Concentrator run at 25oC. Notably, in one subset of experiments,
CO:COLLECTION_SUMMARY            	metabolites were added to MED1 condensates after the 10 min incubation rather
CO:COLLECTION_SUMMARY            	than prior to the incubation.
CO:SAMPLE_TYPE                   	Liver
CO:COLLECTION_METHOD             	80% methanol
CO:STORAGE_CONDITIONS            	-80℃
#TREATMENT
TR:TREATMENT_SUMMARY             	Mouse liver metabolites were combined with the condensate-forming low-complexity
TR:TREATMENT_SUMMARY             	domain of MED1. Condensates were stimulated with 150 nM RNA and then incubated
TR:TREATMENT_SUMMARY             	for 10 min. In a subset of samples, RNA addition occurred 10 min before
TR:TREATMENT_SUMMARY             	metabolite addition. Next, condensates were centrifuged to the bottom of a 600
TR:TREATMENT_SUMMARY             	ul tube. Equal fractions from the input sample, aqueous phase and condensate
TR:TREATMENT_SUMMARY             	phases were collected separately. Metabolites were extracted from each fraction
TR:TREATMENT_SUMMARY             	using 80% methanol in steps that involved disrupting condensates with heat. In a
TR:TREATMENT_SUMMARY             	subset of samples, this heat step was omitted.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Dried-down extracts were reconstituted in 150 µl 70% acetonitrile, at a
SP:SAMPLEPREP_SUMMARY            	relative protein concentration of ~ 2 µg/µl. These were stored until used at
SP:SAMPLEPREP_SUMMARY            	-20C. SPLASH® LIPIDOMIX® Quantitative Mass Spec Standard was diluted 1/30 or
SP:SAMPLEPREP_SUMMARY            	1/200, combined with the reconstituted extract and then either 3 µl (for PIs
SP:SAMPLEPREP_SUMMARY            	samples) or 5 µl (all other samples) were injected for LC/MS-based targeted
SP:SAMPLEPREP_SUMMARY            	metabolite profiling.
SP:PROCESSING_STORAGE_CONDITIONS 	-80℃
SP:EXTRACT_STORAGE               	-20℃
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	Chromatography of metabolites utilized reversed phase chromatography on a
CH:CHROMATOGRAPHY_SUMMARY        	Agilent ZORBAX Eclipse Plus C18, 100 × 2.1 mm, 1.8 μm. Mobile phases consisted
CH:CHROMATOGRAPHY_SUMMARY        	of (A) 10 mM ammonium formate with 5 μM Agilent deactivator additive in 5:3:2
CH:CHROMATOGRAPHY_SUMMARY        	water:acetonitrile:2-propanol and (B) 10 mM ammonium formate in 1:9:90
CH:CHROMATOGRAPHY_SUMMARY        	water:acetonitrile:2-propanol. Column temperature was set at 60°C and
CH:CHROMATOGRAPHY_SUMMARY        	autosampler temperature was at 20°C. The flow rate was 0.4 mL/min. The
CH:CHROMATOGRAPHY_SUMMARY        	following gradient was applied: 0 min, 15% B; 0-2.5 min, to 50% B; 2.5-2.6 min,
CH:CHROMATOGRAPHY_SUMMARY        	to 57%, 2.6-9 min, to 70% B; 9-9.1 min, to 93% B; 9.1-11.1 min, to 96%; 11.1-
CH:CHROMATOGRAPHY_SUMMARY        	15min, 100% B; 15-20 min, 15% B.
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	Agilent Model 1290 Infinity II liquid chromatography system
CH:COLUMN_NAME                   	Cogent Diamond Hydride (150 × 2.1 mm, 4um)
CH:SOLVENT_A                     	50% water/30% acetonitrile/20% isopropanol;10 mM ammonium formate with 5 µM
CH:SOLVENT_A                     	Agilent deactivator additive
CH:SOLVENT_B                     	1% water/9% acetonitrile/90% isopropanol;10 mM ammonium formate
CH:FLOW_GRADIENT                 	0 min, 15% B; 0-2.5 min, to 50% B; 2.5-2.6 min, to 57%, 2.6-9 min, to 70% B;
CH:FLOW_GRADIENT                 	9-9.1 min, to 93% B; 9.1-11.1 min, to 96%; 11.1- 15min, 100% B; 15-20 min, 15%
CH:FLOW_GRADIENT                 	B.
CH:FLOW_RATE                     	0.4 mL/min
CH:COLUMN_TEMPERATURE            	60
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Agilent 6460 QQQ
MS:INSTRUMENT_TYPE               	Triple quadrupole
MS:MS_TYPE                       	Other
MS:ION_MODE                      	POSITIVE
MS:MS_COMMENTS                   	(PI) LC/MS-based targeted metabolite profiling. MS mode was a Agilent Jet Stream
MS:MS_COMMENTS                   	ESI. To quantify phospholipid concentrations, we used stable isotope standards
MS:MS_COMMENTS                   	and dynamic multiple reaction monitoring (dMRM). The transitions for lipid
MS:MS_COMMENTS                   	standards were monitored as recommended by the supplier.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Ion abundance (peak area)
MS_METABOLITE_DATA_START
Samples	MED1 PI Aqueous Sample 5	MED1 PI Input Sample 5	MED1 PI Condensate Sample 5	MED1 PI Aqueous Sample 6	MED1 PI Input Sample 6	MED1 PI Condensate Sample 6	MED1 PI Aqueous Sample 9	MED1 PI Input Sample 9	MED1 PI Condensate Sample 9
Factors	fraction:aqueous | Extraction from condensate:No heat step	fraction:input | Extraction from condensate:No heat step	fraction:condensate | Extraction from condensate:No heat step	fraction:aqueous | Extraction from condensate:No heat step	fraction:input | Extraction from condensate:No heat step	fraction:condensate | Extraction from condensate:No heat step	fraction:aqueous | Extraction from condensate:standard	fraction:input | Extraction from condensate:standard	fraction:condensate | Extraction from condensate:standard
PI 32:1	956	450	16296	902	662	16451	366	536	7287
PI 34:1	4250	2656	71791	4007	3308	65820	1080	2277	33563
PI 32:0	4716	2894	70826	2922	3555	61030	1398	2615	32966
PI 15:0/18:1-d7	1233	653	1268	1130	556	3623	758	1219	1629
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	Formula	Mass (actual)	Monitored Transition	Retention time (min)
PI 32:1	C41H77O13P	808.5102	(824.5-->255.2)	4.647
PI 34:1	C43H81O13P	836.5415	(850.6-->255.2)	4.8
PI 32:0	C41H79O13P	810.5258	(826.5-->255.2)	4.872
PI 15:0/18:1-d7	C42H75D7NO13P	846.596	(845.6--> 288.3)	4.291
METABOLITES_END
#END