#METABOLOMICS WORKBENCH wongw24_20240815_110239 DATATRACK_ID:5110 STUDY_ID:ST003410 ANALYSIS_ID:AN005600 PROJECT_ID:PR002111 VERSION 1 CREATED_ON August 15, 2024, 11:17 am #PROJECT PR:PROJECT_TITLE Inhibition of GPX4 enhances CDK4/6 inhibitor and endocrine therapy activity in PR:PROJECT_TITLE breast cancer. PR:PROJECT_TYPE MS quantitative analysis PR:PROJECT_SUMMARY CDK4/6 inhibition in combination with endocrine therapy is the standard of care PR:PROJECT_SUMMARY for estrogen receptor (ER+) breast cancer, and although cytostasis is frequently PR:PROJECT_SUMMARY observed, new treatment strategies that enhance efficacy are required. We PR:PROJECT_SUMMARY performed two independent genome-wide CRISPR screens to identify genetic PR:PROJECT_SUMMARY determinants of CDK4/6 and endocrine therapy sensitivity. Genes involved in PR:PROJECT_SUMMARY oxidative stress and ferroptosis modulated sensitivity, with GPX4 the top PR:PROJECT_SUMMARY sensitiser in both screens. Depletion or inhibition of GPX4 increased PR:PROJECT_SUMMARY sensitivity to palbociclib and giredestrant, and their combination, in ER+ PR:PROJECT_SUMMARY breast cancer models, with GPX4 null xenografts being highly sensitive to PR:PROJECT_SUMMARY palbociclib. GPX4 perturbation additionally sensitised triple negative breast PR:PROJECT_SUMMARY cancer models to palbociclib. Palbociclib and giredestrant induced oxidative PR:PROJECT_SUMMARY stress and disordered lipid metabolism, leading to a ferroptosis-sensitive PR:PROJECT_SUMMARY state. Lipid peroxidation was promoted by a peroxisome AGPAT3-dependent pathway PR:PROJECT_SUMMARY in ER+ breast cancer models, rather than the classical ACSL4 pathway. Our data PR:PROJECT_SUMMARY demonstrate that CDK4/6 and ER inhibition creates vulnerability to ferroptosis PR:PROJECT_SUMMARY induction, that could be exploited through combination with GPX4 inhibitors, to PR:PROJECT_SUMMARY enhance sensitivity to the current therapies in breast cancer. PR:INSTITUTE Genentech Inc. PR:LAST_NAME Wong PR:FIRST_NAME Weng Ruh PR:ADDRESS 1 DNA Way, South San Francisco, CA 94080, USA PR:EMAIL wongw24@gene.com PR:PHONE 4089048962 PR:CONTRIBUTORS Herrera-Abrey MT, Guan J, Khalid U, Ning J, Costa MR, Chan J, Li Q, Fortin J-P, PR:CONTRIBUTORS Perampalam P, Biton A, Sandoval W, Vijay J, Hafner M, Cutts R, Wilson G, Frankum PR:CONTRIBUTORS J, Roumeliotis TI, Alexander J, Hickman O, Brough R, Haider S, Choudhary J, Lord PR:CONTRIBUTORS CJ, Swain, A, Metcalfe C, Tuner NC #STUDY ST:STUDY_TITLE Lipidomics Analysis of ER+ Breast Cancer Cells Treated with Giredestrant and ST:STUDY_TITLE Palbociclib ST:STUDY_SUMMARY We observed in a previous experiment that giredestrant treatment had a profound ST:STUDY_SUMMARY impact on the lipid profile of MCF-7 cells, in particular through elevating ST:STUDY_SUMMARY PUFAs at the apparent expense of MUFAs. We hypothesize that this shift in ST:STUDY_SUMMARY PUFA/MUFA ratio underlies giredestrant-induced sensitivity to GPX4 inhibition. ST:STUDY_SUMMARY Emerging data from our lab and other suggests that palbociclib, a key ST:STUDY_SUMMARY combination partner for giredestrant in the clinic, also sensitizes to GPX4 ST:STUDY_SUMMARY inhibition, and that the combination of giredestrant and palbo may synergize to ST:STUDY_SUMMARY creating an even higher sensitivity to GPX4i. Here, we aim to directly compare ST:STUDY_SUMMARY the effects on the lipidome of giredestrant and palbociclib, in MCF-7 cells (the ST:STUDY_SUMMARY discovery cell line where we already have some lipidomics data), and also T-47D ST:STUDY_SUMMARY cells, in which giredestrant, palbociclib and their combination drive a very ST:STUDY_SUMMARY profound sensitization to GPX4i, that exceeds what was observed in MCF-7 cells. ST:STUDY_SUMMARY The cells were treated with DMSO, 1 nM giredestrant, 200 nM palbociclib, or 1nM ST:STUDY_SUMMARY giredestrant plus 200nM palbociclib in quadruplicates, and collected on Day 7 ST:STUDY_SUMMARY for lipid analysis. Despite their differences under basal conditions, drug ST:STUDY_SUMMARY treatments altered the lipid profiles of MCF7 and T47D cells in a similar ST:STUDY_SUMMARY manner, with 200nM palbociclib at the 7 day time point having a less pronounced ST:STUDY_SUMMARY effect than giredestrant, and with the greatest lipid changes occurring with the ST:STUDY_SUMMARY combination of palbociclib plus giredestrant. PUFA-ePLs were likewise elevated ST:STUDY_SUMMARY by giredestrant and/or palbociclib in both cell lines, with the combined action ST:STUDY_SUMMARY of both drugs generally driving greatest increases in individual PUFA-linked ePL ST:STUDY_SUMMARY species. Palbociclib combination with giredestrant enhance the accumulation of ST:STUDY_SUMMARY PUFAs-phospholipids compared to the single treatments. ST:INSTITUTE Genentech Inc. ST:LAST_NAME Wong ST:FIRST_NAME Weng Ruh ST:ADDRESS 1 DNA Way, South San Francisco, CA 94080, USA ST:EMAIL wongw24@gene.com ST:PHONE 4089048962 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens SU:GENOTYPE_STRAIN MCF-7 and T-47D #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 - MCF7_DMSO_1 Sample source:MCF7 breast cancer cells | Treatment:Control | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-01.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-01.mzML SUBJECT_SAMPLE_FACTORS - MCF7_9545_1 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-02.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-02.mzML SUBJECT_SAMPLE_FACTORS - MCF7_Palbo_1 Sample source:MCF7 breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-03.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-03.mzML SUBJECT_SAMPLE_FACTORS - MCF7_9plusP_1 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-04.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-04.mzML SUBJECT_SAMPLE_FACTORS - T47D_DMSO_1 Sample source:T47D breast cancer cells | Treatment:Control | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-05.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-05.mzML SUBJECT_SAMPLE_FACTORS - T47D_9545_1 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-06.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-06.mzML SUBJECT_SAMPLE_FACTORS - T47D_Palbo_1 Sample source:T47D breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-07.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-07.mzML SUBJECT_SAMPLE_FACTORS - T47D_9plusP_1 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-08.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-08.mzML SUBJECT_SAMPLE_FACTORS - MCF7_DMSO_2 Sample source:MCF7 breast cancer cells | Treatment:Control | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-09.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-09.mzML SUBJECT_SAMPLE_FACTORS - MCF7_9545_2 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-10.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-10.mzML SUBJECT_SAMPLE_FACTORS - MCF7_Palbo_2 Sample source:MCF7 breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-11.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-11.mzML SUBJECT_SAMPLE_FACTORS - MCF7_9plusP_2 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-12.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-12.mzML SUBJECT_SAMPLE_FACTORS - T47D_DMSO_2 Sample source:T47D breast cancer cells | Treatment:Control | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-13.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-13.mzML SUBJECT_SAMPLE_FACTORS - T47D_9545_2 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-14.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-14.mzML SUBJECT_SAMPLE_FACTORS - T47D_Palbo_2 Sample source:T47D breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-15.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-15.mzML SUBJECT_SAMPLE_FACTORS - T47D_9plusP_2 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-16.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-16.mzML SUBJECT_SAMPLE_FACTORS - MCF7_DMSO_3 Sample source:MCF7 breast cancer cells | Treatment:Control | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-17.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-17.mzML SUBJECT_SAMPLE_FACTORS - MCF7_9545_3 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-18.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-18.mzML SUBJECT_SAMPLE_FACTORS - MCF7_Palbo_3 Sample source:MCF7 breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-19.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-19.mzML SUBJECT_SAMPLE_FACTORS - MCF7_9plusP_3 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-20.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-20.mzML SUBJECT_SAMPLE_FACTORS - T47D_DMSO_3 Sample source:T47D breast cancer cells | Treatment:Control | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-21.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-21.mzML SUBJECT_SAMPLE_FACTORS - T47D_9545_3 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-22.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-22.mzML SUBJECT_SAMPLE_FACTORS - T47D_Palbo_3 Sample source:T47D breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-23.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-23.mzML SUBJECT_SAMPLE_FACTORS - T47D_9plusP_3 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-24.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-24.mzML SUBJECT_SAMPLE_FACTORS - MCF7_DMSO_4 Sample source:MCF7 breast cancer cells | Treatment:Control | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-25.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-25.mzML SUBJECT_SAMPLE_FACTORS - MCF7_9545_4 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-26.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-26.mzML SUBJECT_SAMPLE_FACTORS - MCF7_Palbo_4 Sample source:MCF7 breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-27.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-27.mzML SUBJECT_SAMPLE_FACTORS - MCF7_9plusP_4 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-28.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-28.mzML SUBJECT_SAMPLE_FACTORS - T47D_DMSO_4 Sample source:T47D breast cancer cells | Treatment:Control | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-29.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-29.mzML SUBJECT_SAMPLE_FACTORS - T47D_9545_4 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-30.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-30.mzML SUBJECT_SAMPLE_FACTORS - T47D_Palbo_4 Sample source:T47D breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-31.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-31.mzML SUBJECT_SAMPLE_FACTORS - T47D_9plusP_4 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 RAW_FILE_NAME_1=Lipidomics - 20240129 - 1-32.mzML; RAW_FILE_NAME_2=Lipidomics - 20240129 - 2-32.mzML #COLLECTION CO:COLLECTION_SUMMARY All cell lines were obtained from American Type Culture Collection (ATCC) or CO:COLLECTION_SUMMARY Asterand and maintained according to the supplier's instructions. MCF-7 and T47D CO:COLLECTION_SUMMARY cells were seeded at same density, 4x106 cells in RPMI medium in T175 flask (16 CO:COLLECTION_SUMMARY flasks each for each cell line) overnight. On day 0, the cells were treated with CO:COLLECTION_SUMMARY DMSO, 1 nM giredestrant, 200 nM palbociclib, or 1nM giredestrant plus 200nM CO:COLLECTION_SUMMARY palbociclib in quadruplicates. On day 4, after the cells were passaged, and CO:COLLECTION_SUMMARY 4x106 cells from each flask were reseeded into another T175, and continued with CO:COLLECTION_SUMMARY the same treatment for 3 more days. On day 7, the cells were trypsinized and CO:COLLECTION_SUMMARY counted, and 1.5-2 x106 cells from each flask were collected and frozen for CO:COLLECTION_SUMMARY lipid analysis. CO:SAMPLE_TYPE Breast cancer cells #TREATMENT TR:TREATMENT_SUMMARY Time-points (n = 4; 2x10^6 cells for pelleting and submission) - Time: 7 days - TR:TREATMENT_SUMMARY Treatment: DMSO; 1 nM Giredestrant (GDC-9545); 200nM Palbociclib; Giredestrant TR:TREATMENT_SUMMARY (GDC-9545) + Palbo Total samples: 32 #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Cells were extracted with dichloromethane and methanol #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY DMS on with switching pos/neg polarity CH:CHROMATOGRAPHY_TYPE None (Direct infusion) CH:INSTRUMENT_NAME Sciex QTRAP 6500+ with SelexION CH:COLUMN_NAME none CH:SOLVENT_A dichloromethane/methanol (1:1), 10 mM ammonium acetate CH:SOLVENT_B dichloromethane/methanol (1:1), 10 mM ammonium acetate CH:FLOW_GRADIENT none CH:FLOW_RATE 7 ul/min CH:COLUMN_TEMPERATURE none CH:SAMPLE_INJECTION 50 ul CH:CHROMATOGRAPHY_COMMENTS Method 1 with DMS on with switching pos/neg polarity #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME ABI Sciex 6500+ MS:INSTRUMENT_TYPE QTRAP MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS DMS on Data processing with Lipidyzer platform #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS nmol/250 ug protein MS_METABOLITE_DATA_START Samples MCF7_DMSO_1 MCF7_9545_1 MCF7_Palbo_1 MCF7_9plusP_1 T47D_DMSO_1 T47D_9545_1 T47D_Palbo_1 T47D_9plusP_1 MCF7_DMSO_2 MCF7_9545_2 MCF7_Palbo_2 MCF7_9plusP_2 T47D_DMSO_2 T47D_9545_2 T47D_Palbo_2 T47D_9plusP_2 MCF7_DMSO_3 MCF7_9545_3 MCF7_Palbo_3 MCF7_9plusP_3 T47D_DMSO_3 T47D_9545_3 T47D_Palbo_3 T47D_9plusP_3 MCF7_DMSO_4 MCF7_9545_4 MCF7_Palbo_4 MCF7_9plusP_4 T47D_DMSO_4 T47D_9545_4 T47D_Palbo_4 T47D_9plusP_4 Factors Sample source:MCF7 breast cancer cells | Treatment:Control | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Control | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Control | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Control | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Control | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Control | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Control | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 Sample source:MCF7 breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Control | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Palbociclib_200nM | Time:Day_7 Sample source:T47D breast cancer cells | Treatment:Giredestrant_1nM_plus_Palbociclib_200nM | Time:Day_7 SM(14:0) 0.160891517 0.146025811 0.124746636 0.126233596 0.13579425 0.169685032 0.134454961 0.187386933 0.15170748 0.132800288 0.120575376 0.114625 0.134944425 0.167210656 0.149305772 0.185755901 0.169272663 0.124003181 0.141424614 0.12401161 0.128763893 0.156311793 0.144093882 0.156102085 0.172046602 0.12905167 0.156426055 0.129798493 0.150034545 0.146961959 0.151610106 0.169981199 SM(16:0) 3.549036527 3.745378644 3.480530543 3.735850087 4.857670887 7.142757804 4.818175423 7.733266323 3.533678634 3.465170959 3.551561999 3.37002316 4.880109115 7.005283434 5.041672423 7.289287078 3.758980885 3.283479277 3.791142963 3.545980363 4.805859625 6.2864477 5.094941367 6.257992898 3.942292687 3.341110582 4.14337019 3.567747383 5.286080622 6.186667402 4.98892884 6.812208521 SM(18:0) 0.282357777 0.301768104 0.281870457 0.29020699 0.182769773 0.15584693 0.225051187 0.160921133 0.275120886 0.288978346 0.273161849 0.25809025 0.187636518 0.144129068 0.233894255 0.160871817 0.26987923 0.259370166 0.30795589 0.273740378 0.178408806 0.140223723 0.238058101 0.140858135 0.294753855 0.280632274 0.323878652 0.266545564 0.194921038 0.148528683 0.232426659 0.15413468 SM(18:1) 0.044043407 0.057916477 0.051717961 0.057536035 0.043056706 0.032834161 0.057037249 0.037008568 0.043803515 0.049979436 0.051357136 0.056492977 0.036926322 0.032798711 0.056094351 0.034374562 0.041375813 0.043187633 0.057674158 0.053764087 0.042233614 0.031583082 0.055614609 0.030832402 0.048263576 0.048328216 0.061180896 0.059359776 0.044007803 0.032233717 0.052796046 0.033301566 SM(20:0) 0.342409373 0.358675957 0.289887171 0.28631742 0.195525337 0.193659736 0.245748902 0.196758444 0.313369824 0.320015763 0.297575098 0.27730833 0.215353632 0.182077362 0.259215038 0.212332727 0.344701113 0.30616888 0.341004903 0.284158596 0.186354295 0.170524118 0.25467162 0.203279668 0.363905802 0.340798624 0.386635688 0.273979638 0.247826841 0.215643807 0.273075173 0.223289734 SM(20:1) 0.036767728 0.043984056 0.026956608 0.034391954 0.013743329 0.012920302 0.023333851 0.019423676 0.034473499 0.036064285 0.028674092 0.031617493 0.014142747 0.013182683 0.02585481 0.018408174 0.034838322 0.033208447 0.031672454 0.030216913 0.013478257 0.012363133 0.023682022 0.020836253 0.034132393 0.037518689 0.037360937 0.031396474 0.018140243 0.013949324 0.024267862 0.019168375 SM(22:0) 0.743048126 1.114109692 0.70029371 0.939467429 0.592263771 0.496052621 0.60747275 0.465056924 0.665778137 1.001870031 0.735656497 0.870658413 0.671425924 0.538770285 0.656715162 0.531306109 0.774083096 0.946626376 0.837491341 0.880498494 0.584217375 0.480538983 0.630976594 0.471772403 0.814348901 1.023116878 0.927938893 0.888431723 0.77874696 0.599933276 0.671879946 0.511565387 SM(22:1) 0.241851907 0.301051025 0.209750369 0.285098751 0.137026109 0.154180732 0.20750442 0.211694651 0.233898824 0.266904954 0.2204063 0.269951926 0.137325695 0.157004686 0.215696181 0.231202942 0.254595288 0.256000225 0.241398992 0.273366887 0.127942565 0.139514119 0.213026459 0.195239921 0.27042787 0.278220902 0.276006096 0.266325097 0.154393896 0.172160043 0.222556581 0.227331177 SM(24:0) 1.032566771 2.093170414 1.512011621 2.171412998 0.867003825 0.796834042 0.987721425 1.068104562 0.955280809 1.9858874 1.520306106 1.96404768 0.887286953 0.782301923 1.001712683 1.070416073 1.05170539 1.79667226 1.700559839 1.93776551 0.821996203 0.703829489 0.997414144 0.928970422 1.110521094 1.912768238 1.854888965 1.9913711 0.964072876 0.755311627 0.983164012 0.98140806 SM(24:1) 2.519422174 2.531784325 2.62519902 2.37761041 0.94545045 0.743130527 1.273739619 0.978298135 2.403162118 2.481865219 2.514781027 2.090341638 0.943003497 0.727203763 1.244327925 1.01175371 2.550962982 2.20905256 2.820838798 2.060090947 0.894490423 0.667766227 1.21353306 0.882034434 2.719282472 2.213884239 3.087343048 2.115595743 1.041671109 0.720174879 1.198448841 0.915898434 SM(26:0) 0.294432997 0.760894244 0.567288914 0.840163863 0.126216534 0.0993717 0.118519656 0.088020982 0.266479849 0.720281221 0.576767695 0.816866084 0.137286552 0.089897771 0.124923514 0.087815859 0.297863478 0.683486008 0.652464231 0.761530614 0.111177936 0.08538942 0.114048072 0.081165859 0.287639833 0.722514021 0.689909055 0.773897719 0.134489806 0.08775555 0.120481225 0.084303466 SM(26:1) 0.701036111 0.94812317 0.994276421 0.840925908 0.121658329 0.090699845 0.130627293 0.080729002 0.665924912 0.95036002 0.990861063 0.799023451 0.118405364 0.084791094 0.138888909 0.084579656 0.73394971 0.874437985 1.075338823 0.749876116 0.115896481 0.074067537 0.134117677 0.07322044 0.736590571 0.906063208 1.208359674 0.759222981 0.131112237 0.084733431 0.13531164 0.072172207 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Q1 Q3 SM(14:0) 675.5 184.1 SM(16:0) 703.6 184.1 SM(18:0) 731.6 184.1 SM(18:1) 729.6 184.1 SM(20:0) 759.6 184.1 SM(20:1) 757.6 184.1 SM(22:0) 787.7 184.1 SM(22:1) 785.7 184.1 SM(24:0) 815.7 184.1 SM(24:1) 813.7 184.1 SM(26:0) 843.7 184.1 SM(26:1) 841.7 184.1 METABOLITES_END #END