#METABOLOMICS WORKBENCH westcoastmetabolomics_20230727_154209 STUDY_ID:ST002817 ANALYSIS_ID:AN004586 #ANALYSIS TYPE: MS; ION MODE: Reversed phase POSITIVE ION MODE; (Institute: University of California, San Francisco) VERSION 1 CREATED_ON 10-16-2024 #PROJECT PR:PROJECT_TITLE Investigation of metabolism in hypertrophic cardiomyopathy PR:PROJECT_SUMMARY We propose the use of targeted metabolomics to define the metabolic and PR:PROJECT_SUMMARY molecular pathways altered in 2 mouse models (R92W-TnT and R403Q-MHC) of PR:PROJECT_SUMMARY hypertrophic cardiomyopathy (HCM) that span the spectrum of human disease (heart PR:PROJECT_SUMMARY failure and sudden death), with the goal of identifying treatment targets. PR:PROJECT_SUMMARY Parallel targeted metabolomics studies will be performed in heart tissue and PR:PROJECT_SUMMARY plasma at rest and following inotrope stimulation. Since energy compromise is PR:PROJECT_SUMMARY expected to be most marked when the heart is subject to increased workload, as PR:PROJECT_SUMMARY is the case during high-intensity exercise or inotropic stimulation, we propose PR:PROJECT_SUMMARY metabolomics studies in heart tissue and plasma, at rest and following inotrope PR:PROJECT_SUMMARY stimulation. We anticipate that the results of these studies will allow us to PR:PROJECT_SUMMARY move forward with further investigations into specific metabolites of interest PR:PROJECT_SUMMARY as biomarkers, to be tested in HCM patients in future studies. PR:INSTITUTE University of California, San Francisco PR:DEPARTMENT Hypertrophic Cardiomyopathy Center of Excellence PR:LABORATORY UCSF Smith Cardiovascular Research Building PR:LAST_NAME Abraham PR:FIRST_NAME Maria Roselle PR:ADDRESS 555 Mission Bay Boulevard South, San Francisco, CA 94158 PR:EMAIL Roselle.Abraham@ucsf.edu PR:PHONE 415-502-3911 PR:DOI http://dx.doi.org/10.21228/M8RQ7M PR:CONTRIBUTORS Arpana Vaniya (avaniya@ucdavis.edu), Anja Karlstaedt (Anja.Karlstaedt@cshs.org) #STUDY ST:STUDY_TITLE Investigation of metabolism in hypertrophic cardiomyopathy - Lipidomics ST:STUDY_SUMMARY We propose the use of targeted metabolomics to define the metabolic and ST:STUDY_SUMMARY molecular pathways altered in 2 mouse models (R92W-TnT and R403Q-MHC) of ST:STUDY_SUMMARY hypertrophic cardiomyopathy (HCM) that span the spectrum of human disease (heart ST:STUDY_SUMMARY failure and sudden death), with the goal of identifying treatment targets. ST:STUDY_SUMMARY Parallel targeted metabolomics studies will be performed in heart tissue and ST:STUDY_SUMMARY plasma at rest and following inotrope stimulation. Since energy compromise is ST:STUDY_SUMMARY expected to be most marked when the heart is subject to increased workload, as ST:STUDY_SUMMARY is the case during high-intensity exercise or inotropic stimulation, we propose ST:STUDY_SUMMARY metabolomics studies in heart tissue and plasma, at rest and following inotrope ST:STUDY_SUMMARY stimulation. We anticipate that the results of these studies will allow us to ST:STUDY_SUMMARY move forward with further investigations into specific metabolites of interest ST:STUDY_SUMMARY as biomarkers, to be tested in HCM patients in future studies. ST:INSTITUTE University of California, San Francisco ST:DEPARTMENT Hypertrophic Cardiomyopathy Center of Excellence ST:LABORATORY UCSF Smith Cardiovascular Research Building ST:LAST_NAME Abraham ST:FIRST_NAME Maria Roselle ST:ADDRESS 555 Mission Bay Boulevard South, San Francisco, CA 94158 ST:EMAIL Roselle.Abraham@ucsf.edu ST:PHONE 415-502-3911 ST:SUBMIT_DATE 2023-07-27 ST:NUM_GROUPS 2 groups of 2 (i.e., mutant vs control of two mouse models of HCM (R402Q-MyHC, ST:NUM_GROUPS R92W-TnT) ST:TOTAL_SUBJECTS 32 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS - M438 Treatment:Control MHC Sample_Data:RAW_FILE_NAME=Abraham026_MX441683_posCSH_M438-011_2.d; RAW_FILE_NAME=Abraham026_MX441683_negCSH_M438-011_2.d SUBJECT_SAMPLE_FACTORS - M440 Treatment:Control MHC Sample_Data:RAW_FILE_NAME=Abraham053_MX441683_posCSH_M440-012_2.d; RAW_FILE_NAME=Abraham053_MX441683_negCSH_M440-012_2.d SUBJECT_SAMPLE_FACTORS - M447 Treatment:Control MHC Sample_Data:RAW_FILE_NAME=Abraham028_MX441683_posCSH_M447-009_2.d; RAW_FILE_NAME=Abraham028_MX441683_negCSH_M447-009_2.d SUBJECT_SAMPLE_FACTORS - M485 Treatment:Control MHC Sample_Data:RAW_FILE_NAME=Abraham023_MX441683_posCSH_M485-013_2.d; RAW_FILE_NAME=Abraham023_MX441683_negCSH_M485-013_2.d SUBJECT_SAMPLE_FACTORS - M487 Treatment:Control MHC Sample_Data:RAW_FILE_NAME=Abraham008_MX441683_posCSH_M487-014_2.d; RAW_FILE_NAME=Abraham008_MX441683_negCSH_M487-014_2.d SUBJECT_SAMPLE_FACTORS - M492 Treatment:Control MHC Sample_Data:RAW_FILE_NAME=Abraham045_MX441683_posCSH_M492-016_2.d; RAW_FILE_NAME=Abraham045_MX441683_negCSH_M492-016_2.d SUBJECT_SAMPLE_FACTORS - M499 Treatment:Control MHC Sample_Data:RAW_FILE_NAME=Abraham034_MX441683_posCSH_M499-010_2.d; RAW_FILE_NAME=Abraham034_MX441683_negCSH_M499-010_2.d SUBJECT_SAMPLE_FACTORS - M503 Treatment:Control MHC Sample_Data:RAW_FILE_NAME=Abraham015_MX441683_posCSH_M503-025_2.d; RAW_FILE_NAME=Abraham015_MX441683_negCSH_M503-025_2.d SUBJECT_SAMPLE_FACTORS - T515 Treatment:Control TNT Sample_Data:RAW_FILE_NAME=Abraham043_MX441683_posCSH_T515-041_2.d; RAW_FILE_NAME=Abraham043_MX441683_negCSH_T515-041_2.d SUBJECT_SAMPLE_FACTORS - T518 Treatment:Control TNT Sample_Data:RAW_FILE_NAME=Abraham047_MX441683_posCSH_T518-042_2.d; RAW_FILE_NAME=Abraham047_MX441683_negCSH_T518-042_2.d SUBJECT_SAMPLE_FACTORS - T520 Treatment:Control TNT Sample_Data:RAW_FILE_NAME=Abraham059_MX441683_posCSH_T520-043_2.d; RAW_FILE_NAME=Abraham059_MX441683_negCSH_T520-043_2.d SUBJECT_SAMPLE_FACTORS - T522 Treatment:Control TNT Sample_Data:RAW_FILE_NAME=Abraham022_MX441683_posCSH_T522-044_2.d; RAW_FILE_NAME=Abraham022_MX441683_negCSH_T522-044_2.d SUBJECT_SAMPLE_FACTORS - T524 Treatment:Control TNT Sample_Data:RAW_FILE_NAME=Abraham039_MX441683_posCSH_T524-045_2.d; RAW_FILE_NAME=Abraham039_MX441683_negCSH_T524-045_2.d SUBJECT_SAMPLE_FACTORS - T544 Treatment:Control TNT Sample_Data:RAW_FILE_NAME=Abraham005_MX441683_posCSH_T544-046_2.d; RAW_FILE_NAME=Abraham005_MX441683_negCSH_T544-046_2.d SUBJECT_SAMPLE_FACTORS - T545 Treatment:Control TNT Sample_Data:RAW_FILE_NAME=Abraham060_MX441683_posCSH_T545-047_2.d; RAW_FILE_NAME=Abraham060_MX441683_negCSH_T545-047_2.d SUBJECT_SAMPLE_FACTORS - T547 Treatment:Control TNT Sample_Data:RAW_FILE_NAME=Abraham025_MX441683_posCSH_T547-048_2.d; RAW_FILE_NAME=Abraham025_MX441683_negCSH_T547-048_2.d SUBJECT_SAMPLE_FACTORS - MtdBlank001 Treatment:Method Blank Sample_Data:RAW_FILE_NAME=MtdBlank001_MX441683_posCSH_preAbraham001_2.d; RAW_FILE_NAME=MtdBlank001_MX441683_negCSH_preAbraham001_2.d SUBJECT_SAMPLE_FACTORS - MtdBlank002 Treatment:Method Blank Sample_Data:RAW_FILE_NAME=MtdBlank002_MX441683_posCSH_postAbraham010_2.d; RAW_FILE_NAME=MtdBlank002_MX441683_negCSH_postAbraham010_2.d SUBJECT_SAMPLE_FACTORS - MtdBlank003 Treatment:Method Blank Sample_Data:RAW_FILE_NAME=MtdBlank003_MX441683_posCSH_postAbraham020_2.d; RAW_FILE_NAME=MtdBlank003_MX441683_negCSH_postAbraham020_2.d SUBJECT_SAMPLE_FACTORS - MtdBlank004 Treatment:Method Blank Sample_Data:RAW_FILE_NAME=MtdBlank004_MX441683_posCSH_postAbraham030_2.d; RAW_FILE_NAME=MtdBlank004_MX441683_negCSH_postAbraham030_2.d SUBJECT_SAMPLE_FACTORS - MtdBlank005 Treatment:Method Blank Sample_Data:RAW_FILE_NAME=MtdBlank005_MX441683_posCSH_postAbraham040_2.d; RAW_FILE_NAME=MtdBlank005_MX441683_negCSH_postAbraham040_2.d SUBJECT_SAMPLE_FACTORS - MtdBlank006 Treatment:Method Blank Sample_Data:RAW_FILE_NAME=MtdBlank006_MX441683_posCSH_postAbraham050_2.d; RAW_FILE_NAME=MtdBlank006_MX441683_negCSH_postAbraham050_2.d SUBJECT_SAMPLE_FACTORS - MtdBlank007 Treatment:Method Blank Sample_Data:RAW_FILE_NAME=MtdBlank007_MX441683_posCSH_postAbraham060_2.d; RAW_FILE_NAME=MtdBlank007_MX441683_negCSH_postAbraham060_2.d SUBJECT_SAMPLE_FACTORS - MtdBlank008 Treatment:Method Blank Sample_Data:RAW_FILE_NAME=MtdBlank008_MX441683_posCSH_postAbraham064_2.d; RAW_FILE_NAME=MtdBlank008_MX441683_negCSH_postAbraham064_2.d SUBJECT_SAMPLE_FACTORS - M439 Treatment:MHC Sample_Data:RAW_FILE_NAME=Abraham044_MX441683_posCSH_M439-026_2.d; RAW_FILE_NAME=Abraham044_MX441683_negCSH_M439-026_2.d SUBJECT_SAMPLE_FACTORS - M441 Treatment:MHC Sample_Data:RAW_FILE_NAME=Abraham017_MX441683_posCSH_M441-027_2.d; RAW_FILE_NAME=Abraham017_MX441683_negCSH_M441-027_2.d SUBJECT_SAMPLE_FACTORS - M483 Treatment:MHC Sample_Data:RAW_FILE_NAME=Abraham014_MX441683_posCSH_M483-029_2.d; RAW_FILE_NAME=Abraham014_MX441683_negCSH_M483-029_2.d SUBJECT_SAMPLE_FACTORS - M486 Treatment:MHC Sample_Data:RAW_FILE_NAME=Abraham032_MX441683_posCSH_M486-030_2.d; RAW_FILE_NAME=Abraham032_MX441683_negCSH_M486-030_2.d SUBJECT_SAMPLE_FACTORS - M498 Treatment:MHC Sample_Data:RAW_FILE_NAME=Abraham052_MX441683_posCSH_M498-032_2.d; RAW_FILE_NAME=Abraham052_MX441683_negCSH_M498-032_2.d SUBJECT_SAMPLE_FACTORS - M500 Treatment:MHC Sample_Data:RAW_FILE_NAME=Abraham048_MX441683_posCSH_M500-015_2.d; RAW_FILE_NAME=Abraham048_MX441683_negCSH_M500-015_2.d SUBJECT_SAMPLE_FACTORS - M504 Treatment:MHC Sample_Data:RAW_FILE_NAME=Abraham035_MX441683_posCSH_M504-028_2.d; RAW_FILE_NAME=Abraham035_MX441683_negCSH_M504-028_2.d SUBJECT_SAMPLE_FACTORS - M540 Treatment:MHC Sample_Data:RAW_FILE_NAME=Abraham030_MX441683_posCSH_M540-031_2.d; RAW_FILE_NAME=Abraham030_MX441683_negCSH_M540-031_2.d SUBJECT_SAMPLE_FACTORS - Pool001 Treatment:Pool QC Sample_Data:RAW_FILE_NAME=Pool001_MX441683_posCSH_preAbraham001_2.d; RAW_FILE_NAME=Pool001_MX441683_negCSH_preAbraham001_2.d SUBJECT_SAMPLE_FACTORS - Pool002 Treatment:Pool QC Sample_Data:RAW_FILE_NAME=Pool002_MX441683_posCSH_postAbraham010_2.d; RAW_FILE_NAME=Pool002_MX441683_negCSH_postAbraham010_2.d SUBJECT_SAMPLE_FACTORS - Pool003 Treatment:Pool QC Sample_Data:RAW_FILE_NAME=Pool003_MX441683_posCSH_postAbraham020_2.d; RAW_FILE_NAME=Pool003_MX441683_negCSH_postAbraham020_2.d SUBJECT_SAMPLE_FACTORS - Pool004 Treatment:Pool QC Sample_Data:RAW_FILE_NAME=Pool004_MX441683_posCSH_postAbraham030_2.d; RAW_FILE_NAME=Pool004_MX441683_negCSH_postAbraham030_2.d SUBJECT_SAMPLE_FACTORS - Pool005 Treatment:Pool QC Sample_Data:RAW_FILE_NAME=Pool005_MX441683_posCSH_postAbraham040_2.d; RAW_FILE_NAME=Pool005_MX441683_negCSH_postAbraham040_2.d SUBJECT_SAMPLE_FACTORS - Pool006 Treatment:Pool QC Sample_Data:RAW_FILE_NAME=Pool006_MX441683_posCSH_postAbraham050_2.d; RAW_FILE_NAME=Pool006_MX441683_negCSH_postAbraham050_2.d SUBJECT_SAMPLE_FACTORS - Pool007 Treatment:Pool QC Sample_Data:RAW_FILE_NAME=Pool007_MX441683_posCSH_postAbraham060_2.d; RAW_FILE_NAME=Pool007_MX441683_negCSH_postAbraham060_2.d SUBJECT_SAMPLE_FACTORS - Pool008 Treatment:Pool QC Sample_Data:RAW_FILE_NAME=Pool008_MX441683_posCSH_postAbraham064_2.d; RAW_FILE_NAME=Pool008_MX441683_negCSH_postAbraham064_2.d SUBJECT_SAMPLE_FACTORS - Biorec001 Treatment:QC Sample_Data:RAW_FILE_NAME=Biorec001_MX441683_posCSH_preAbraham001_2.d; RAW_FILE_NAME=Biorec001_MX441683_negCSH_preAbraham001_2.d SUBJECT_SAMPLE_FACTORS - Biorec002 Treatment:QC Sample_Data:RAW_FILE_NAME=Biorec002_MX441683_posCSH_postAbraham010_2.d; RAW_FILE_NAME=Biorec002_MX441683_negCSH_postAbraham010_2.d SUBJECT_SAMPLE_FACTORS - Biorec003 Treatment:QC Sample_Data:RAW_FILE_NAME=Biorec003_MX441683_posCSH_postAbraham020_2.d; RAW_FILE_NAME=Biorec003_MX441683_negCSH_postAbraham020_2.d SUBJECT_SAMPLE_FACTORS - Biorec004 Treatment:QC Sample_Data:RAW_FILE_NAME=Biorec004_MX441683_posCSH_postAbraham030_2.d; RAW_FILE_NAME=Biorec004_MX441683_negCSH_postAbraham030_2.d SUBJECT_SAMPLE_FACTORS - Biorec005 Treatment:QC Sample_Data:RAW_FILE_NAME=Biorec005_MX441683_posCSH_postAbraham040_2.d; RAW_FILE_NAME=Biorec005_MX441683_negCSH_postAbraham040_2.d SUBJECT_SAMPLE_FACTORS - Biorec006 Treatment:QC Sample_Data:RAW_FILE_NAME=Biorec006_MX441683_posCSH_postAbraham050_2.d; RAW_FILE_NAME=Biorec006_MX441683_negCSH_postAbraham050_2.d SUBJECT_SAMPLE_FACTORS - Biorec007 Treatment:QC Sample_Data:RAW_FILE_NAME=Biorec007_MX441683_posCSH_postAbraham060_2.d; RAW_FILE_NAME=Biorec007_MX441683_negCSH_postAbraham060_2.d SUBJECT_SAMPLE_FACTORS - Biorec008 Treatment:QC Sample_Data:RAW_FILE_NAME=Biorec008_MX441683_posCSH_postAbraham064_2.d; RAW_FILE_NAME=Biorec008_MX441683_negCSH_postAbraham064_2.d SUBJECT_SAMPLE_FACTORS - T519 Treatment:TNT Sample_Data:RAW_FILE_NAME=Abraham018_MX441683_posCSH_T519-057_2.d; RAW_FILE_NAME=Abraham018_MX441683_negCSH_T519-057_2.d SUBJECT_SAMPLE_FACTORS - T521 Treatment:TNT Sample_Data:RAW_FILE_NAME=Abraham002_MX441683_posCSH_T521-058_2.d; RAW_FILE_NAME=Abraham002_MX441683_negCSH_T521-058_2.d SUBJECT_SAMPLE_FACTORS - T523 Treatment:TNT Sample_Data:RAW_FILE_NAME=Abraham031_MX441683_posCSH_T523-059_2.d; RAW_FILE_NAME=Abraham031_MX441683_negCSH_T523-059_2.d SUBJECT_SAMPLE_FACTORS - T525 Treatment:TNT Sample_Data:RAW_FILE_NAME=Abraham029_MX441683_posCSH_T525-060_2.d; RAW_FILE_NAME=Abraham029_MX441683_negCSH_T525-060_2.d SUBJECT_SAMPLE_FACTORS - T527 Treatment:TNT Sample_Data:RAW_FILE_NAME=Abraham062_MX441683_posCSH_T527-061_2.d; RAW_FILE_NAME=Abraham062_MX441683_negCSH_T527-061_2.d SUBJECT_SAMPLE_FACTORS - T540 Treatment:TNT Sample_Data:RAW_FILE_NAME=Abraham061_MX441683_posCSH_T540-062_2.d; RAW_FILE_NAME=Abraham061_MX441683_negCSH_T540-062_2.d SUBJECT_SAMPLE_FACTORS - T542 Treatment:TNT Sample_Data:RAW_FILE_NAME=Abraham058_MX441683_posCSH_T542-063_2.d; RAW_FILE_NAME=Abraham058_MX441683_negCSH_T542-063_2.d SUBJECT_SAMPLE_FACTORS - T546 Treatment:TNT Sample_Data:RAW_FILE_NAME=Abraham001_MX441683_posCSH_T546-064_2.d; RAW_FILE_NAME=Abraham001_MX441683_negCSH_T546-064_2.d #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #COLLECTION CO:COLLECTION_SUMMARY Excision while the heart still beating and flash freeze within 15 seconds of CO:COLLECTION_SUMMARY excision CO:SAMPLE_TYPE Heart #TREATMENT TR:TREATMENT_SUMMARY Saline IP and heparine SC injection in control & mutant group. After 10 minutes TR:TREATMENT_SUMMARY of saline injection we performed cervical dislocation, whole heart excision and TR:TREATMENT_SUMMARY flash freeze within 15 seconds of excision. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY 2 mg of lyophilized tissue extracted with 225 uL MeOH + 188 uL H2O + 750 uL SP:SAMPLEPREP_SUMMARY MTBE. 350 uL of the organic layer was dried and resuspended 90:10 MeOH + Toluene SP:SAMPLEPREP_SUMMARY with internal standards. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Low pH polar (LC/MS Pos early) CH:INSTRUMENT_NAME Waters Acquity CH:COLUMN_NAME Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) CH:COLUMN_TEMPERATURE - CH:FLOW_GRADIENT - CH:FLOW_RATE - CH:SOLVENT_A - CH:SOLVENT_B - CH:CHROMATOGRAPHY_TYPE Reversed phase #ANALYSIS AN:ANALYSIS_TYPE MS AN:ANALYSIS_DISPLAY Reversed phase POSITIVE ION MODE AN:NUM_FACTORS 1 AN:NUM_METABOLITES 217 AN:UNITS raw area counts rescaled to set the median equal to 1 #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:MS_COMMENTS Metabolon (LC/MS Pos early) MS:ION_MODE POSITIVE #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS MS_METABOLITE_DATA_START Samples Factors MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name pubchem_id inchi_key kegg_id other_id other_id_type ri ri_type moverz_quant METABOLITES_END