#METABOLOMICS WORKBENCH hormel101_20170407_140053_mwtab.txt DATATRACK_ID:884 STUDY_ID:ST000588 ANALYSIS_ID:AN000903 PROJECT_ID:PR000430
VERSION             	1
CREATED_ON             	April 12, 2017, 12:18 pm
#PROJECT
PR:PROJECT_TITLE                 	Mayo Metabolomics Pilot and Feasibility Award: Metabolomics of Exhaled Breath
PR:PROJECT_TITLE                 	Condensate in Decompensated Heart Failure
PR:PROJECT_SUMMARY               	Metabolomics is a large-scale approach to monitoring as many as possible of the
PR:PROJECT_SUMMARY               	compounds involved in cellular processes in a single assay to derive metabolic
PR:PROJECT_SUMMARY               	profiles. Compared with genomics or proteomics, metabolomics reflects changes in
PR:PROJECT_SUMMARY               	phenotype and therefore function. Nearly all the blood volume-cardiac output in
PR:PROJECT_SUMMARY               	humans flows through the lungs at a rate of 5L/min and traverses through
PR:PROJECT_SUMMARY               	capillaries with a very thin blood-gas barrier (approximately 2μm, 600–800
PR:PROJECT_SUMMARY               	nm; in some places <200 nm) to allow sufficient gas diffusion. However, there is
PR:PROJECT_SUMMARY               	evidence that many other biochemicals from the blood can be found in the exhaled
PR:PROJECT_SUMMARY               	air. Collection of exhaled breath condensate (EBC) is a relatively new,
PR:PROJECT_SUMMARY               	noninvasive method that allows assessment of biochemical profiles that may not
PR:PROJECT_SUMMARY               	only link to airway physiology, but also to other changing processes in the
PR:PROJECT_SUMMARY               	body. The aims of this study are: (1) Working with the Mayo Clinic Metabolomics
PR:PROJECT_SUMMARY               	Resource Core Laboratory to develop the optimal method for performing
PR:PROJECT_SUMMARY               	metabolomics of EBC, (2) Collecting and metabolomic profiling of the EBCs from
PR:PROJECT_SUMMARY               	patients with heart failure; (2) Comparing the profiles of these patients
PR:PROJECT_SUMMARY               	obtained during stable and acute exacerbation periods as well as during recovery
PR:PROJECT_SUMMARY               	from a decompensation; (3) Comparing the profiles of these patients with age and
PR:PROJECT_SUMMARY               	gender matched controls; (4) Correlation of EBC metabolomic profiles with
PR:PROJECT_SUMMARY               	clinical phenotypes. The proposed metabolomics profiles would be obtained from
PR:PROJECT_SUMMARY               	patients involved in IRB approved, ongoing, primarily NIH funded studies focused
PR:PROJECT_SUMMARY               	on understanding pulmonary congestion in heart failure patients. This includes a
PR:PROJECT_SUMMARY               	recently started project capturing patients as they present in the emergency
PR:PROJECT_SUMMARY               	room with decompensated heart failure. Phenotyping for this study includes novel
PR:PROJECT_SUMMARY               	measures of pulmonary capillary recruitment, alveolar-capillary conductance,
PR:PROJECT_SUMMARY               	pulmonary capillary blood volume, thoracic CT imaging combined with in-hospital
PR:PROJECT_SUMMARY               	clinical data, including blood biomarkers such as BNP and catecholamines.
PR:PROJECT_SUMMARY               	Measurements are performed upon admission (within 24hours) and then repeated
PR:PROJECT_SUMMARY               	just prior to dismissal. In addition, we would collect EBC on stable HF patients
PR:PROJECT_SUMMARY               	and in age and gender matched controls healthy controls from our other ongoing
PR:PROJECT_SUMMARY               	studies. The overall aim will be to identify novel patterns or biomarkers for
PR:PROJECT_SUMMARY               	developing a point-of-care test (POC) for tracking disease status in HF
PR:PROJECT_SUMMARY               	patients.
PR:INSTITUTE                     	Mayo Clinic
PR:DEPARTMENT                    	Cardiovascular Diseases
PR:LABORATORY                    	Mayo Metabolomics Core
PR:LAST_NAME                     	Johnson
PR:FIRST_NAME                    	Bruce
PR:ADDRESS                       	200 First St. SW, Rochester, Minnesota, 55905, USA
PR:EMAIL                         	johnson.bruce@mayo.edu
PR:PHONE                         	507-284-4441
#STUDY
ST:STUDY_TITLE                   	Metabolomics of Saliva in Decompensated Heart Failure
ST:STUDY_SUMMARY                 	The aim of the study was to test weather characteristic differences or changes
ST:STUDY_SUMMARY                 	in metabolic profile exist between exhaled breath condensate (EBC) and saliva of
ST:STUDY_SUMMARY                 	healthy individuals and heart failure patients. Salival NMR profiling was
ST:STUDY_SUMMARY                 	performed.
ST:INSTITUTE                     	Mayo Clinic
ST:DEPARTMENT                    	Cardiovascular Diseases
ST:LABORATORY                    	Mayo Metabolomics Core
ST:LAST_NAME                     	Johnson
ST:FIRST_NAME                    	Bruce
ST:ADDRESS                       	200 First Street SW, Rochester, MN 55905
ST:EMAIL                         	johnson.bruce@mayo.edu
ST:PHONE                         	507-284-4441
#SUBJECT
SU:SUBJECT_TYPE                  	Human
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
#SUBJECT_SAMPLE_FACTORS:         	SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data
SUBJECT_SAMPLE_FACTORS           	-	C10	Group:Control	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	C11	Group:Control	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	C14	Group:Control	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	C15	Group:Control	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	C16	Group:Control	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	C18	Group:Control	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	C19	Group:Control	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	C20	Group:Control	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	C21	Group:Control	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	C22	Group:Control	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	C23	Group:Control	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	C24	Group:Control	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	HF01	Group:Heart failure	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	HF02	Group:Heart failure	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	HF03	Group:Heart failure	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	HF04	Group:Heart failure	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	HF05	Group:Heart failure	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	HF06	Group:Heart failure	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	HF07	Group:Heart failure	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	HF08	Group:Heart failure	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	HF09	Group:Heart failure	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	HF12	Group:Heart failure	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	HF13	Group:Heart failure	Type=saliva
SUBJECT_SAMPLE_FACTORS           	-	HF17	Group:Heart failure	Type=saliva
#COLLECTION
CO:COLLECTION_SUMMARY            	The samples were collected in Dr. Bruce Johnson lab, at the Department of
CO:COLLECTION_SUMMARY            	Cardiovascular Diseases, Mayo Clinic. EBC samples were collected using Jaeger
CO:COLLECTION_SUMMARY            	EcoScreen cooling unit (-20°C). Patients were breathing through mouth piece
CO:COLLECTION_SUMMARY            	while wearing a nose clip during 30 minutes. Saliva was collected from the same
CO:COLLECTION_SUMMARY            	patients during last 15 minutes. The samples were frozen immediately after
CO:COLLECTION_SUMMARY            	collection.
#TREATMENT
TR:TREATMENT_SUMMARY             	We will focus initially on patients with classic systolic HF who are admitted to
TR:TREATMENT_SUMMARY             	St Mary’s Hospital with decompensated disease. These patients are currently
TR:TREATMENT_SUMMARY             	being studied to quantify changes in lung water during the “recompensation”
TR:TREATMENT_SUMMARY             	diuresis in the hospital and the related changes in alveolar gas conductance and
TR:TREATMENT_SUMMARY             	breathing pattern to develop a predictive algorithm for likelihood of
TR:TREATMENT_SUMMARY             	readmission, but also to obtain a better understanding of fluid regulation in
TR:TREATMENT_SUMMARY             	the lungs. As these subjects are recruited, we will recruit age and sex matched
TR:TREATMENT_SUMMARY             	stable HF patients going through similar testing in parallel running studies as
TR:TREATMENT_SUMMARY             	well as age and sex matched control subjects. We will target 12 subjects per
TR:TREATMENT_SUMMARY             	group and in addition to the EBC collection we will obtain saliva samples and
TR:TREATMENT_SUMMARY             	blood at the same time points.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Saliva: Allow samples to thaw on ice at 4 °C for 30–60 min. Transfer 250 μl
SP:SAMPLEPREP_SUMMARY            	aliquots of saliva samples into 1.5ml EP tubes, centrifuge each sample at
SP:SAMPLEPREP_SUMMARY            	13,300g for 10 min. Transfer 200μl of supernatant of saliva samples into 1.5 ml
SP:SAMPLEPREP_SUMMARY            	EP tubes, add 150 μl of phosphate buffer and 150 μl of 4mM TSP-d4 solution in
SP:SAMPLEPREP_SUMMARY            	D2O. Vortex for 20 s. Transfer the solution to 5 mm NMR tube.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	-
CH:INSTRUMENT_NAME               	-
CH:COLUMN_NAME                   	-
#ANALYSIS
AN:ANALYSIS_TYPE                 	NMR
#NMR
NM:INSTRUMENT_NAME               	Bruker 600 MHz Avance III HD spectrometer
NM:INSTRUMENT_TYPE               	FT-NMR
NM:NMR_EXPERIMENT_TYPE           	1D-1H
NM:SPECTROMETER_FREQUENCY        	600 MHz
#NMR_METABOLITE_DATA
NMR_METABOLITE_DATA:UNITS        	uM
NMR_METABOLITE_DATA_START
Samples	C10	C11	C14	C15	C16	C18	C19	C20	C21	C22	C23	C24	HF01	HF02	HF03	HF04	HF05	HF06	HF07	HF08	HF09	HF12	HF13	HF17
Factors	Group:Control	Group:Control	Group:Control	Group:Control	Group:Control	Group:Control	Group:Control	Group:Control	Group:Control	Group:Control	Group:Control	Group:Control	Group:Heart failure	Group:Heart failure	Group:Heart failure	Group:Heart failure	Group:Heart failure	Group:Heart failure	Group:Heart failure	Group:Heart failure	Group:Heart failure	Group:Heart failure	Group:Heart failure	Group:Heart failure
5-Aminopentanoate	138.1	208.7	48.7	147.4	36	190.9	74.8	73.7	12.1	39.1	20.6	297.6	232.1	469.2	22.8	18.2	224.4	122.9	369.3	202.7	33.6	11	32.2	
Acetate	3781	8567.6	1756.7	1925.6	4130	3307.2	2036.9	2330.9	619	842.9	849.2	4779.8	5534.4	14386.1	1967.4	1769.6	3156.7	2462.4	11955.4	8881.7	3265.4	2291	383.1	4721.5
Acetoin	19.5	37.1	13.2	5.2	37.4	11	5	11.8	4.7	8.8	7.7	42.1	16.5	89.4	3.3	11.8	8.8	12.4	16.2	106.2	577	18.7	0.6	29.7
Acetone	12.7	11.8	18.7	6.6	15.7	14.3	34.9	11.8	27	9.9	10.2	15.4	20.6	66.8	29.4	13.8	20.9	51.7	7.2	12.4	9.4	12.9	32.7	18.7
Alanine	23.1	38	10.2	5.5	36.3	8	6.6	9.1	12.7	9.1	17.3	44	36.3	84.4	21.5	26.4	33.3	10.7	94.6	20.1	55.6	15.1	30.8	26.7
Butyrate	64.6	118.8	12.9	58.6	9.6	85.5	26.7	33	8	18.2	6.1	41.3	53.4	95.4	26.1	12.9	84.7	28.1	115.8	102.6	3.6	8.8	2.2	
Choline	6.9	7.7	3.3	2.5	11.6	4.7	1.9	2.5	2.2	2.2	1.9	22.3	7.4	25	8.8	6.6	8.8	3	14.3	13.2	11.8	4.1	4.7	36.9
Citrate	35.2	11	47	65.7	46.8	53.1	34.7	42.9	40.4	50.6	72.1	29.2	12.7	29.4	67.1	47.3	58	57.8	34.9	14	71.2	13.8	25	204.1
Creatine	18.2	14	10.7	7.7	30	11.6	8.8	9.6	12.4	6.6	13.8	59.4	4.7	22.8	17.6	16.8	15.7	21.2	26.7	24.2	36.6	10.7	35.8	25.9
Creatinine			8		5.5	6.9	4.4	4.7		1.9					14.6		9.1	5.2	63	6.9	27		13.2	9.6
Dimethyl sulfone	17.3	6.9	16.8	10.2	23.9	17.9	22.8	11.6	394.1	9.6	20.4	17.3	9.1	25.9	34.1	23.7	10.2	21.5	53.9	8.5	18.2	16.8	23.7	4.1
Dimethylamine	3.9	4.1	3.6	3.9	7.2	3	4.1	4.7	1.4	2.5	2.8	13.5	3.9	11.6	10.7	8.5	9.4	3.6	7.4	6.3	32.7	1.9	12.4	14.6
Ethanol	54.7	74.3	23.7	16.5	25.3	24.8	15.7	19.5	10.2	15.4	14.3	26.4	72.9	78.1	13.5	21.2	23.4	69.6	193.6	47	39.3	28.9	13.8	25.3
Ethanolamine	46.5	89.9	16.8	11.6	130.6		13.8	20.1	4.7	12.1	40.2	57.8	47.9	106.2	16.5	31.4	71.2	30.8	77.8	207.1	30.5	30	29.7	
Formate	530.2	13.5	207.6	349	1614.8	241.5	149.6	153.7	54.7	115.5	143	214.2	118.3	231.3	30.3	702.1	172.4	285.7	3189.5	167.8	535.2	29.7	25.9	13.2
Fucose	60	57.2	28.6		31.6	11.3	22.6	34.4	10.7	16.8		69.3	79.5	89.4	69.3	32.2	81.1	23.9	33.3	45.9	33.3	12.7	17.1	
Fumarate					2.5						3							2.5			5.8		3	
Galactose	57.2							61.1				115.5		93.5										
Glucose	75.4		29.7	33.6	112.5	34.4	19.5	56.4	46.5	196.1	124.3	92.7		38.2	101.2	192	119.4	131.2	325.6		1152		105.6	43.7
Glycine	118.5	94.9	37.1	31.1	96.3	91.9	37.7	34.1	20.9	28.6	36.6	303.1	97.6	492.8	66	58.3	82	45.9	162.3	92.4	218.9	35.8	60.5	122.7
Histidine	30.3	22.8	10.7	41	47		8	18.4	15.4		25.6	49	17.9	138.1	37.4	28.1	24.2	19.8	71.5	46.5	81.1	31.9	13.8	76.2
Hypoxanthine					18.2														31.1					
Isoleucine		6.6			5.8							13.2	11.3	19.5			6.6		8	9.4	9.6			37.4
Isopropanol	8.5	3.6	4.4	3.6	4.7	5.5	7.7	6.1	4.1	3	3.6	4.7	8	12.4	5.2	10.7	10.7	7.4	23.7	6.9	9.1	8.5	5.8	5.2
Isovalerate		13.8					5.8						17.1	11						7.2				3.6
Lactate	455.1	61.9	245.6	152.9	471.4	128.4	101.5	396.8	206.3	341.8	360	694.1	48.1	141.4	212.3	271.7	263.7	693.8	1591.2	397.7	6357.7	202.1	517.3	13.2
Leucine		15.7		11.8	13.2		6.1					23.4	31.4	25			9.6		30.5	12.4	12.7		8.5	33
Maltose			20.9		45.1	17.9		34.7	23.7	87.7	46.2							108.4			584.1		57.5	
Methanol	68.2	59.4	97.4	59.4	99.6	72.9	68.5	86.1	81.4	83.9	59.1	69.6	96.8	108.4	72.6	82	83.6	60.5	96.8	86.4	84.7	64.1	61.3	79.2
Methylamine	6.9	23.9	4.7	1.9	7.4	4.1	5	5.8		1.4		9.1	10.5	7.7	18.4	3.6	7.2	4.1	17.6	23.4	6.1	2.8	2.5	8.5
O-Phosphocholine	12.4	10.7	9.1	5.5	14.6	6.9	6.6	7.4	5.5	6.3	12.9	16.5	4.1	21.5	8.8	17.3	14.6	15.1	27.8	18.2	30	14.9	10.5	43.7
O-Phosphoethanolamine	121.8	44.8	97.1	68.5	85	86.1	55.8	116.6	106.2	78.4	308	60.2	18.2	95.4	130.6	312.7	76.5	292.1	55.8	59.4	265.4	83.1	127.3	409.5
Ornithine							11.8					24.8							58.3	22.3	27.2	5.2		
Phenol													26.1											
Phenylalanine	16	27.8	4.7	9.6	24.8	9.4	7.4	6.1		9.1	16.8	40.4	38.8	74.5	10.2	25.9	31.1	13.5	50.9	31.6	33.3	15.7	7.4	47.9
Proline	52.8	36	14.9	44	51.7	50.3	66.8	16.5		24.8	22.8	244.2	41.8	207.1	33.6	28.6	64.1	32.2	87.5	49.8	296.5	13.2	16.5	25.6
Propionate	471.9	1574.9	172.4	269.2	484.3	467.2	162	347.6	74	91.9	133.7	576.1	1053.8	2025.7	147.4	244.2	492.8	485.1	2614.2	1191	507.7	209	9.6	19.8
Propylene glycol	28.9	19.8	27.5	8.5	17.9	7.4	4.7	47.6	9.9	45.4	9.9	9.4	11.8	53.4	31.1	19	20.1	13.5	64.4	59.4	162.3	3.9	3.6	36.9
Putrescine	35.2	50.1		30.3		52.5	38.5	7.4				108.1	107.3	146	25.9		49.8			58.9		11.8		41.3
Pyruvate	91.6	153.5	60.2	45.9	338.3	54.2	56.1	53.1	24.5	81.1	86.9	302.8	35.2	161.2	87.2	18.7	81.4	87.7	369.9	394.9	1310.4	78.1	36.3	
Succinate	12.1	39.3	28.3	33	191.7	36	29.7	14	13.8	46.8	39.6	97.4	38	49.2	6.1	39.3	73.7	55.3	281.9	60.5	229.4	44.6	11	423.8
Sucrose	14.3							14.3		21.2	61.1			10.7				36.9	46.2		367.1		11.3	
Taurine	176.3	166.4	51.2	35.5	245	60.8	44.8	53.6	61.9	41	78.7	285.7	76.2	194.7	95.2	175.5	98.7	51.4	284.1	207.4	94.1	78.7	126.2	110
Tyrosine	38.2	58	20.4	14.9	49.8	16.8	14.9	14.9	8.5	13.5	36.3	69	48.7	135	34.4	59.1	40.7	18.2	129.8	70.7	65.2	35.8	19.5	118.8
Uracil					25.6														31.9					
Urea	330.6	361.1	423.5	316	452.4	429.6	100.1	461.5		344.9	766.4	415.8		409.5	974.3	380.1	270.1	690.5	449.6	206.5	966.1	361.9	750.5	709
Valine		10.2		7.7	12.1		6.6					26.4	27	18.4			11.8		22	7.4	11.8		7.7	30.3
sn-Glycero-3-phosphocholine	1.7	1.7	3.3		16	3.9		2.8		3.6	3.9	2.5	0.6	3.3		8.3	1.9	3.9	18.2		25.3		11.6	
NMR_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name
5-Aminopentanoate
Acetate
Acetoin
Acetone
Alanine
Butyrate
Choline
Citrate
Creatine
Creatinine
Dimethyl sulfone
Dimethylamine
Ethanol
Ethanolamine
Formate
Fucose
Fumarate
Galactose
Glucose
Glycine
Histidine
Hypoxanthine
Isoleucine
Isopropanol
Isovalerate
Lactate
Leucine
Maltose
Methanol
Methylamine
O-Phosphocholine
O-Phosphoethanolamine
Ornithine
Phenol
Phenylalanine
Proline
Propionate
Propylene glycol
Putrescine
Pyruvate
Succinate
Sucrose
Taurine
Tyrosine
Uracil
Urea
Valine
sn-Glycero-3-phosphocholine
METABOLITES_END
#END