#METABOLOMICS WORKBENCH juliehaines_20240502_073341 DATATRACK_ID:4811 STUDY_ID:ST003185 ANALYSIS_ID:AN005231 PROJECT_ID:PR001983 VERSION 1 CREATED_ON May 3, 2024, 10:13 am #PROJECT PR:PROJECT_TITLE A multimodal drug-diet-immunotherapy combination restrains melanoma progression PR:PROJECT_TITLE and metastasis PR:PROJECT_SUMMARY The genetic landscape of cancer cells can lead to specific metabolic PR:PROJECT_SUMMARY dependencies for tumor growth. Dietary interventions represent an attractive PR:PROJECT_SUMMARY strategy to restrict the availability of key nutrients to tumors. In this study, PR:PROJECT_SUMMARY we identified that growth of a subset of melanoma was severely restricted by a PR:PROJECT_SUMMARY rationally designed combination therapy of a stearoyl-CoA desaturase (SCD) PR:PROJECT_SUMMARY inhibitor with an isocaloric low-oleic acid diet. Despite its importance in PR:PROJECT_SUMMARY oncogenesis, SCD underwent monoallelic co-deletion along with PTEN on chromosome PR:PROJECT_SUMMARY 10q in about 47.5% of melanoma, and the other SCD allele was methylated, PR:PROJECT_SUMMARY resulting in very low SCD expression. While this SCD deficient subset was PR:PROJECT_SUMMARY refractory to SCD inhibitors, the subset of PTEN wildtype melanoma that retained PR:PROJECT_SUMMARY SCD was sensitive. As dietary oleic acid could potentially blunt the effect of PR:PROJECT_SUMMARY SCD inhibitors, a low-oleic acid custom diet was combined with SCD inhibitor. PR:PROJECT_SUMMARY The combination reduced monounsaturated fatty acids and increased saturated PR:PROJECT_SUMMARY fatty acids, inducing robust apoptosis and growth suppression and inhibiting PR:PROJECT_SUMMARY lung metastasis with minimal toxicity in preclinical mouse models of PTEN PR:PROJECT_SUMMARY wildtype melanoma. When combined with anti-PD1 immunotherapy, the SCD inhibitor PR:PROJECT_SUMMARY improved T cell functionality and further constrained melanoma growth in mice. PR:PROJECT_SUMMARY Collectively, these results suggest that optimizing SCD inhibitors with diets PR:PROJECT_SUMMARY low in oleic acid may offer a viable and efficacious therapeutic approach for PR:PROJECT_SUMMARY improving melanoma treatment. PR:INSTITUTE University of Colorado Anschutz Medical Campus PR:LABORATORY Lab of Angelo D'Alessandro in collaboration with lab of Biplab Dasgupta PR:LAST_NAME Haines PR:FIRST_NAME Julie PR:ADDRESS 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA PR:EMAIL julie.haines@cuanschutz.edu PR:PHONE 3037243339 #STUDY ST:STUDY_TITLE A multimodal drug-diet-immunotherapy combination restrains melanoma progression ST:STUDY_TITLE and metastasis - plasma lipidomics ST:STUDY_SUMMARY Lipidomics profiling of immunocompetent B16F10 model of melanoma to examine ST:STUDY_SUMMARY lipid levels in mouse plasma following reduced oleic acid content in diet ST:STUDY_SUMMARY combined with the stearyl CoA desaturase inhibitor CAY10566. ST:INSTITUTE University of Colorado Anschutz Medical Campus ST:LAST_NAME Haines ST:FIRST_NAME Julie ST:ADDRESS 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA ST:EMAIL julie.haines@cuanschutz.edu ST:PHONE 3037243339 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:GENDER Not applicable #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 - DS2-039-021 factor:vehicle + low oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-021 SUBJECT_SAMPLE_FACTORS - DS2-039-022 factor:vehicle + low oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-022 SUBJECT_SAMPLE_FACTORS - DS2-039-023 factor:vehicle + low oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-023 SUBJECT_SAMPLE_FACTORS - DS2-039-024 factor:vehicle + low oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-024 SUBJECT_SAMPLE_FACTORS - DS2-039-025 factor:vehicle + low oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-025 SUBJECT_SAMPLE_FACTORS - DS2-039-026 factor:vehicle + low oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-026 SUBJECT_SAMPLE_FACTORS - DS2-039-027 factor:SCD inhibitor + low oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-027 SUBJECT_SAMPLE_FACTORS - DS2-039-028 factor:SCD inhibitor + low oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-028 SUBJECT_SAMPLE_FACTORS - DS2-039-029 factor:SCD inhibitor + low oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-029 SUBJECT_SAMPLE_FACTORS - DS2-039-030 factor:SCD inhibitor + low oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-030 SUBJECT_SAMPLE_FACTORS - DS2-039-031 factor:SCD inhibitor + low oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-031 SUBJECT_SAMPLE_FACTORS - DS2-039-032 factor:SCD inhibitor + low oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-032 SUBJECT_SAMPLE_FACTORS - DS2-039-033 factor:Vehicle + high oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-033 SUBJECT_SAMPLE_FACTORS - DS2-039-034 factor:Vehicle + high oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-034 SUBJECT_SAMPLE_FACTORS - DS2-039-035 factor:Vehicle + high oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-035 SUBJECT_SAMPLE_FACTORS - DS2-039-036 factor:Vehicle + high oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-036 SUBJECT_SAMPLE_FACTORS - DS2-039-037 factor:Vehicle + high oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-037 SUBJECT_SAMPLE_FACTORS - DS2-039-038 factor:Vehicle + high oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-038 SUBJECT_SAMPLE_FACTORS - DS2-039-039 factor:SCD inhibitor + high oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-039 SUBJECT_SAMPLE_FACTORS - DS2-039-040 factor:SCD inhibitor + high oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-040 SUBJECT_SAMPLE_FACTORS - DS2-039-041 factor:SCD inhibitor + high oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-041 SUBJECT_SAMPLE_FACTORS - DS2-039-042 factor:SCD inhibitor + high oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-042 SUBJECT_SAMPLE_FACTORS - DS2-039-043 factor:SCD inhibitor + high oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-043 SUBJECT_SAMPLE_FACTORS - DS2-039-044 factor:SCD inhibitor + high oleic acid diet | Sample source:plasma RAW_FILE_NAME(raw file name)=DS2-039-044 #COLLECTION CO:COLLECTION_SUMMARY After two weeks of treatment, retroorbital whole blood samples were collected CO:COLLECTION_SUMMARY following Isoflurane sedation. The samples were obtained using heparinized CO:COLLECTION_SUMMARY capillary tubes (Catalog Number: 22-362566). Subsequently, these samples were CO:COLLECTION_SUMMARY placed into tubes containing K2E (Catalog Number: 365974), with a bulb used to CO:COLLECTION_SUMMARY drain the capillary tube (Catalog Number: 22-362566). The tubes were centrifuged CO:COLLECTION_SUMMARY for 15 minutes at 2,000 x g (4°C). The resulting plasma (supernatant) was CO:COLLECTION_SUMMARY collected and aliquoted into 1.5ml Eppendorf tubes and stored at -80°C. CO:SAMPLE_TYPE Blood (plasma) #TREATMENT TR:TREATMENT_SUMMARY All animal procedures were carried out in accordance with the IACUC-approved TR:TREATMENT_SUMMARY protocol of Cincinnati Children’s Hospital Medical Center. Animals were TR:TREATMENT_SUMMARY monitored daily by Veterinary Services. For subcutaneous tumor implantation, TR:TREATMENT_SUMMARY 1x10^6 B16F10 cells were mixed with matrigel 1:1 and implanted subcutaneously TR:TREATMENT_SUMMARY into NOD-SCID IL2Rgnull or C57BL/6 mice, respectively. CAY10566 was suspended in TR:TREATMENT_SUMMARY 0.5% Methyl Cellulose in water with 0.2% Tween 80 at 9 parts per 1 part DMSO TR:TREATMENT_SUMMARY stock. CAY10566 was administered at 30mg/kg via oral gavage, twice daily, with a TR:TREATMENT_SUMMARY drug holiday during the weekends. Treatment began three days after tumor cell TR:TREATMENT_SUMMARY implantation (bilateral tumors in n=4 per group). Mice were euthanized17 days TR:TREATMENT_SUMMARY after tumor cell injection/14 days after the start of treatment. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY For plasma analysis, 20 µL of plasma was aliquoted into 1.5 mL Eppendorf tubes SP:SAMPLEPREP_SUMMARY followed by 480 µL cold MeOH. Samples were then vortexed for 30 minutes, SP:SAMPLEPREP_SUMMARY insoluble material was pelleted by centrifugation (18000g, 10 min) and SP:SAMPLEPREP_SUMMARY supernatants were isolated for analysis by UHPLC-MS. SP:PROCESSING_STORAGE_CONDITIONS 4℃ SP:EXTRACT_STORAGE -80℃ #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Negative C18 global lipidomics CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME Phenomenex Kinetex C18 (30 x 2.1mm,1.7um) CH:SOLVENT_A 75% water/25% acetonitrile; 5 mM ammonium acetate CH:SOLVENT_B 90% isopropanol/10% acetonitrile; 5 mM ammonium acetate CH:FLOW_GRADIENT 0-3 min 10-95% B at 0.3 mL/min, 3-4.2 min hold at 95% B at 0.3 mL/min, 4.2-4.3 CH:FLOW_GRADIENT min drop to 10% B at 0.45 mL/min, 4.3-4.9 min hold at 10%B while lowering flow CH:FLOW_GRADIENT rate to 0.4 mL/min, 4.9-5 min hold at 10%B while lowering flow rate to 0.3 CH:FLOW_GRADIENT mL/min. CH:FLOW_RATE 0.3-0.4 ml/min CH:COLUMN_TEMPERATURE 45 CH:SAMPLE_INJECTION 10 uL #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_COMMENTS The Q Exactive was run independently in positive and negative ion mode, scanning MS:MS_COMMENTS using full MS from 125-1500 m/z at 70,000 resolution and top 10 data-dependent MS:MS_COMMENTS MS2 at 17,500 resolution. Electrospray ionization was achieved with 45 Arb MS:MS_COMMENTS sheath gas, 25 Arb auxiliary gas, and 4 kV spray voltage. Calibration was MS:MS_COMMENTS performed prior to the run using the PierceTM Positive and Negative Ion MS:MS_COMMENTS Calibration Solutions (Thermo Fisher Scientific). Run order of samples was MS:MS_COMMENTS randomized and technical replicates were injected after every 4 samples to MS:MS_COMMENTS assess quality control. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS peak area MS_METABOLITE_DATA_START Samples DS2-039-021 DS2-039-022 DS2-039-023 DS2-039-024 DS2-039-025 DS2-039-026 DS2-039-027 DS2-039-028 DS2-039-029 DS2-039-030 DS2-039-031 DS2-039-032 DS2-039-033 DS2-039-034 DS2-039-035 DS2-039-036 DS2-039-037 DS2-039-038 DS2-039-039 DS2-039-040 DS2-039-041 DS2-039-042 DS2-039-043 DS2-039-044 Factors factor:vehicle + low oleic acid diet | Sample source:plasma factor:vehicle + low oleic acid diet | Sample source:plasma factor:vehicle + low oleic acid diet | Sample source:plasma factor:vehicle + low oleic acid diet | Sample source:plasma factor:vehicle + low oleic acid diet | Sample source:plasma factor:vehicle + low oleic acid diet | Sample source:plasma factor:SCD inhibitor + low oleic acid diet | Sample source:plasma factor:SCD inhibitor + low oleic acid diet | Sample source:plasma factor:SCD inhibitor + low oleic acid diet | Sample source:plasma factor:SCD inhibitor + low oleic acid diet | Sample source:plasma factor:SCD inhibitor + low oleic acid diet | Sample source:plasma factor:SCD inhibitor + low oleic acid diet | Sample source:plasma factor:Vehicle + high oleic acid diet | Sample source:plasma factor:Vehicle + high oleic acid diet | Sample source:plasma factor:Vehicle + high oleic acid diet | Sample source:plasma factor:Vehicle + high oleic acid diet | Sample source:plasma factor:Vehicle + high oleic acid diet | Sample source:plasma factor:Vehicle + high oleic acid diet | Sample source:plasma factor:SCD inhibitor + high oleic acid diet | Sample source:plasma factor:SCD inhibitor + high oleic acid diet | Sample source:plasma factor:SCD inhibitor + high oleic acid diet | Sample source:plasma factor:SCD inhibitor + high oleic acid diet | Sample source:plasma factor:SCD inhibitor + high oleic acid diet | Sample source:plasma factor:SCD inhibitor + high oleic acid diet | Sample source:plasma Cer(d19:1_24:1) 26689 27133 39074 39874 33246 31897 7956 8736 9146 10457 13738 13997 36641 36035 40461 47615 36708 32436 25076 25260 19709 20982 13899 14022 FA(13:0) 185787 179066 183843 185205 181763 182531 182167 185339 186833 183549 191441 189680 178635 183830 191337 190126 187298 184285 183597 196811 186533 187560 187139 188950 FA(14:0) 273190 263346 533480 531349 531987 543771 558206 567812 336826 352857 1031082 995609 195418 223193 89351 242438 263638 233838 805668 911868 806196 936688 354193 340972 FA(14:1) 9733 9280 14850 15627 22672 24988 7587 8210 7645 7770 16904 17141 16989 18515 28017 31656 39682 36884 46538 49509 58984 61562 15581 16069 FA(17:0) 55166 60471 53176 57823 68441 59844 60064 64465 60529 61742 80181 89221 52735 65853 58166 66755 59661 49752 92643 103975 92019 116714 62727 60084 FA(17:1) 14270 13847 18776 21131 23622 22171 14600 12904 12090 12887 19803 22041 16400 15046 18073 22555 23950 23285 20832 23430 22516 24481 17356 16399 FA(19:0) 13182 13658 15503 17582 13814 13706 12394 12876 14223 15381 18796 19447 13754 15602 15171 15732 13937 12948 16726 18237 21150 24326 15422 13555 FA(19:1) 8951 9492 12028 13048 12375 12256 10134 9876 9614 10156 15064 14921 9984 8700 14887 14742 15475 14831 14960 16279 19749 20144 11930 11330 FA(20:0) 58554 47036 56980 56333 43014 105130 107614 83018 65105 64380 115128 193670 51068 69455 38951 48492 41609 72036 138863 148764 153961 215975 55926 52778 FA(20:1) 29887 29363 54492 55646 37314 37271 25822 26260 26160 28034 54143 53830 57355 57800 47837 51120 62094 58584 84903 94931 90379 101105 41504 39420 FA(20:2) 11850 13432 23131 24104 23640 25638 19313 19311 16421 18444 44545 44754 19528 17960 22006 24936 33209 32447 66578 67841 60017 64319 33785 30071 FA(20:3) 24900 25878 48610 51092 33736 35392 39882 41211 35404 34030 94209 83347 24424 33954 21017 21330 38610 36853 117888 122137 124216 133289 62788 56889 FA(20:4) 156336 163117 215850 221426 177290 180935 207186 202312 155536 180641 314207 277427 204755 200169 126678 143711 200365 183306 311610 367712 493267 507624 284768 273293 FA(20:5) 25573 22551 32546 34017 26822 23944 25520 23559 50396 51627 120931 120969 39768 35434 31452 33310 29644 26372 83424 93815 102874 107831 100022 91745 FA(22:0) 30479 27595 27526 28443 25475 61461 53181 31009 27678 29747 27136 71553 38756 44467 34211 40762 34981 48602 26229 29680 29204 52047 29665 21029 FA(22:1) 10438 10656 13791 13922 11071 11191 9566 8914 10065 10152 10289 11216 14580 15959 12344 12851 13841 13477 11537 11947 12078 12094 11088 9972 FA(22:4) 13591 13116 21232 23575 19778 20749 21959 21983 16574 18670 34840 34582 19341 18023 16013 15840 29356 29405 38903 38325 57321 58903 30392 26090 FA(22:5) 24799 24978 40607 41143 38636 44732 48718 50948 51086 56404 130803 120049 43930 41647 46774 48455 57035 56086 121328 134624 152126 163107 93007 89426 FA(22:6) 150073 164119 221585 237172 281067 289606 314384 305824 310965 344757 611859 597111 345007 331279 348635 360013 472827 461778 825892 920255 1288589 1312539 565233 544790 FA(23:0) 8544 12108 9749 8914 8532 8154 9474 10868 9220 8980 8560 9621 7575 11463 12374 12155 9821 8996 7170 7453 7130 7986 11809 6420 FA(24:0) 30014 37723 28458 27631 23804 25932 32472 32836 30300 35802 26052 34358 35316 40438 29926 31782 33544 30841 23869 25871 29860 31653 33578 22998 FA(24:1) 6368 7749 8669 8586 10601 8313 4284 4215 5936 7095 7893 9727 10873 10839 14613 14108 16441 16665 8526 10080 10860 11100 7313 7521 FA(24:5) 1646 1515 2426 2660 2349 2449 4040 4221 3354 3569 12310 11998 2715 2863 2391 2724 3530 3041 15518 18130 14082 14394 6206 6558 FA(24:6) 3585 3713 6091 6657 5649 6061 7857 7373 9421 9559 27589 24907 5992 5788 3563 3985 8621 7032 37796 43479 24707 25445 12426 12426 FA(26:0) 13223 17158 9540 9292 9099 10894 11935 12884 13106 11951 12019 12288 9810 12146 9636 11773 10190 8104 7491 11037 9995 10375 15710 11293 LPC(19:2) 2296888 2245431 2837909 3259754 2722536 2744720 2627126 2482286 2301249 2685206 3588141 3123934 2732325 2783449 2595957 2569063 2965508 2536759 3044556 3616106 2727646 2853006 3005422 3203226 LPC(19:3) 17338 33786 46888 26354 35251 21935 40181 35243 19737 20622 40726 40387 32865 15160 16693 17090 22797 24673 44467 51484 36482 37414 41264 36158 LPC(21:0) 13449 13366 14421 16889 13341 12823 14467 13149 14193 17497 15819 14422 14023 13683 15140 15330 14643 14249 14398 15170 14625 12905 13710 13436 LPC(21:1) 18915 16259 23300 23639 19238 22155 3367 3218 3327 3863 4198 2950 21835 23450 28447 28554 25369 24432 6593 8085 8762 9542 7298 7580 LPC(21:2) 13000 13773 20128 18133 20834 15737 7509 6171 6170 6193 10971 10101 18499 17161 15734 16782 19263 18648 18526 18974 10985 12360 12376 10599 LPC(21:4) 469897 499905 459262 510517 579638 480204 468470 439750 287987 299745 514153 471995 633150 632656 390765 446996 666662 520244 591236 586616 666484 667153 772495 687757 LPC(21:5) 30015 31958 45880 49820 31566 30553 28076 23203 52820 57819 98044 99091 42754 41741 51848 55283 35364 30008 85517 84998 89788 87242 111883 103846 LPC(23:5) 8407 9180 12906 13670 9516 9715 10876 10298 10965 12380 18247 20174 9039 9446 14759 14202 11787 8710 18273 20128 15542 16939 15242 12222 LPC(23:6) 264516 274909 284784 344446 366888 331694 237821 227091 219767 237759 268583 239147 387363 443780 358232 426025 399737 293753 368761 373768 400887 385977 344080 362633 LPC(25:0) 8386 8129 9340 8977 8763 8454 10762 10492 11288 12094 10964 12404 9370 8259 17586 17027 11879 11327 12194 11944 10594 11805 12784 11705 LPI(18:0) 8218 9056 9572 10697 10667 8534 10609 10696 11657 12327 14623 12646 13636 13450 12599 14596 11219 10785 12171 16122 14280 13980 14514 13680 LPI(20:4) 10708 12052 11952 13811 9648 10245 11363 10331 11209 11187 19462 13571 12816 13559 15584 8427 9319 9655 17539 21384 24108 17890 12690 15985 PC(15:0_16:0) 29344 29406 31419 32180 39196 36462 30543 31488 26095 25915 699 976 195 1932 264 12579 131 48 109 2125 424 402 128 82 PC(15:0_18:2) 62799 64804 60236 66339 97173 87331 87498 85460 53577 56134 36477 33902 18961 23339 31960 35491 21974 21416 18430 17415 13652 13172 21901 21000 PC(16:0_17:0) 170503 140965 144643 125071 123890 144307 86538 101431 92663 91053 119782 117505 111194 109755 140339 141413 147369 144152 104318 117421 115008 104930 126508 134155 PC(16:0_18:1) 36680 48974 71334 48980 51615 39239 18851 18240 21269 17614 19849 24428 51105 69450 60116 64873 51480 45494 54356 48940 43928 45346 49790 47638 PC(16:0_18:2) 146339 133015 132513 156107 102165 163199 152014 136834 162139 172434 146860 150148 132180 130084 135744 122578 112848 126602 136388 142083 103240 111539 145149 151484 PC(16:0_19:0) 87498 86546 98586 106774 93268 96910 63416 59725 52658 64155 72000 77982 68151 68155 52648 59620 73773 74276 77228 78024 79691 79647 84442 92775 PC(16:0_20:3) 15191 16020 17309 16048 19244 18712 10152 8855 12112 8533 11343 11044 17751 19152 20501 23257 22020 20589 14351 12609 13221 10835 12985 11416 PC(16:0_20:4) 42897 42518 28152 41137 42552 44127 43240 45907 30722 36632 45348 35223 40090 46816 44760 45970 26583 30885 38659 39536 46325 43240 40334 51331 PC(17:0_16:1) 33547 38615 117239 113596 104934 72813 17457 23982 15249 9283 4872 3289 65101 60488 48007 41098 9031 22171 17411 6158 675 715 7782 4922 PC(17:0_18:1) 1254383 1327566 1645050 1657244 1259916 1151071 685593 703719 564120 595501 665996 852451 1848985 1756449 1798197 1802268 1321004 1201974 1665418 1735685 1463962 1522368 1424947 1510506 PC(17:0_18:2) 3938448 3853423 3890258 4165775 3947152 3962583 4239683 3920477 4287034 4986330 4345146 4340357 3774732 3612658 4906518 4627834 3873396 3378599 3877556 4181517 3201148 3268893 3944420 4270079 PC(17:0_20:3) 932517 966665 1065898 1021731 1057125 1053453 631445 602262 689113 651679 708198 782067 967311 1065068 1021168 1193830 1083660 1066571 884981 914908 647398 683051 722430 748994 PC(17:0_20:5) 211994 177792 195870 192926 181155 165192 136222 137630 296973 334872 418683 427033 220366 227494 359368 364011 180641 168010 328643 327791 294756 275037 480032 481566 PC(17:1_18:2) 258644 154884 256735 276111 321541 296604 147840 150586 148670 166556 149363 149143 252559 264908 271343 274523 243252 224248 163054 154788 114976 103195 153104 160446 PC(18:0_18:1) 28887 29755 38901 32745 27263 34045 13139 14897 16323 15893 9965 11099 38480 41183 46841 49781 37760 35396 27779 28209 19763 20839 27727 26937 PC(18:0_18:2) 145701 155961 166607 170787 167647 164498 143661 130920 177158 183146 133078 132983 161571 141269 269738 264522 185803 172692 104717 129566 88164 98491 116755 121341 PC(18:0_20:4) 44666 65382 30453 31353 36120 37544 41939 44077 30383 30364 30524 28183 46877 60954 48740 47911 53712 67852 22609 43390 29053 39089 38196 37215 PC(18:0_22:6) 24029 25094 22631 22257 22204 22960 17802 18265 19139 20511 16256 17231 28926 30681 36670 40422 33165 32260 19062 13932 17173 21591 22158 16350 PC(18:1_23:6) 108626 109276 106000 103114 124723 135197 42847 43853 32673 36040 43669 25514 149078 170433 166957 185997 168709 161298 56434 63426 76961 74933 73546 59341 PC(18:2_19:2) 1240617 1168625 301369 1036812 1061500 1123768 1140973 1190025 1077012 1063654 290689 970897 1310276 1414988 1164604 1278688 1194292 1121057 1250755 1135066 1132952 1111455 1724842 1460750 PC(18:2_21:4) 1407163 1448032 1531713 1476828 1501633 1444624 1394950 57060 1223916 1137727 1608199 1716688 1797265 1939087 2596564 2896193 1666261 1679034 1629442 1598053 1598038 1733891 1761914 1723677 PC(18:2_21:5) 10346 16579 16271 12578 27567 11625 18141 17349 9731 12975 25281 20465 27497 22532 37783 44217 48374 54442 29683 30072 27170 25345 22669 21824 PC(19:0_18:1) 701144 685397 793398 860991 554418 638217 355792 417439 432133 400471 374795 371682 865935 986685 804754 865685 637213 638305 649541 728334 632661 641183 698780 663445 PC(19:0_18:2) 3593436 3208902 4836409 3410653 5057064 4327652 4209468 4058151 6016781 5854744 4368062 4020395 3115071 4639355 3844759 3678824 3900832 2764193 3367878 3547733 2436674 2725179 2816523 2922887 PC(19:0_20:2) 65802 68399 112581 87411 88860 90024 41505 44291 56479 50843 49061 39542 87602 103473 84468 98365 67722 84431 73792 73173 50610 39179 48880 54036 PC(19:0_20:3) 324844 319053 473964 422540 291981 289718 392875 357219 394151 428299 477483 514024 406639 383466 247202 271574 278573 275041 603513 589391 504082 502754 401210 383856 PC(19:0_20:4) 873403 1036248 934867 810682 904955 718307 941374 1050970 661635 636568 857654 725643 1116606 1323781 890293 902595 975233 1161793 769126 865157 1148927 936363 1000734 1045783 PC(19:0_22:5) 43508 39004 53700 54578 39757 40255 72118 65346 66042 36959 85769 97278 57225 53654 74362 65585 53972 44869 91668 79252 80027 78164 61285 52430 PC(19:0_22:6) 557167 597862 603752 493068 445478 489152 559333 547901 577162 614257 519521 622508 573221 595370 871242 966904 515277 539123 570715 560001 690166 689218 553656 617852 PC(19:1_20:4) 323916 327950 322671 324597 301335 277767 218166 214901 296598 269446 344196 356070 381050 407182 430205 431022 373333 361941 342709 363832 343847 363921 377327 337328 PC(20:0_18:2) 47840 49619 63090 48158 68713 60107 20403 20386 45970 49509 25190 27988 46771 50318 91052 77329 53697 50835 25781 25642 15339 15946 25098 23589 PC(O-16:0_22:6) 176485 156979 176596 161283 132478 139977 247520 239141 225034 266916 195537 189918 123396 128004 307739 333064 154440 139031 186722 195230 197001 201117 225413 255440 PC(O-16:1_18:2) 45476 38893 49282 37013 37557 37354 50631 51010 57016 62885 46268 44441 41530 35731 17306 27036 36863 31383 48854 52215 44106 43966 46401 57133 PC(O-17:0_20:4) 28617 24347 19985 21582 31208 22185 67642 73495 61355 63633 54986 51291 21374 22017 37939 39089 27218 23215 33896 38748 47895 43417 63145 63207 PC(O-17:1_20:4) 21242 21173 15221 12489 13406 15600 38286 36295 29882 27993 25540 22674 13719 14024 31252 33867 21072 19821 24045 23210 26097 24335 37583 33895 PC(O-18:0_18:2) 28329 30578 33617 30205 26091 28185 37537 34578 43633 49962 35040 31656 19806 23142 32382 35225 24699 22954 32674 34361 27236 27665 29512 35399 PC(O-18:0_20:4) 86028 82892 90967 85081 64163 65710 121182 123197 83836 103805 62888 60581 63806 62326 97139 126281 62612 56723 62752 62812 76069 86569 85309 91693 PC(O-19:0_20:4) 20468 20002 20326 17997 17345 18482 68491 71516 53594 69553 46581 54629 15753 15105 28733 28711 17225 16033 43433 42735 50324 52127 58159 69906 PC(O-19:0_22:6) 12495 11458 10399 9887 10765 9471 37574 36967 32814 43133 30687 28694 8696 10526 21619 22493 10756 12303 25058 25461 27506 27194 34746 33451 PC(O-19:1_16:0) 27188 28984 24711 21579 28131 29829 12930 13947 11228 11843 12905 14335 29137 32470 42981 46500 55296 48411 39569 40178 28256 32456 39184 37252 PC(O-20:0_18:1) 14262 14301 14927 15050 15593 15043 12898 14535 14362 17666 21877 17320 13688 14411 19124 23239 20680 19865 18874 20583 13497 15528 18112 18174 PC(O-4:0_13:1) 84055 93534 123360 153347 111256 106912 15074 13016 13294 13412 23851 22598 104976 107060 98832 107414 96783 91953 27934 33502 20600 24411 34495 32199 PC(P-5:0_16:3) 488669 499927 499931 511079 536835 520328 437432 427893 288074 334540 452089 470458 661418 676988 423056 393881 542081 570096 525298 542378 687325 741256 655327 603117 PE(16:0_18:1) 11014 13442 15844 15910 14544 12657 6582 7542 7640 6526 9734 8047 18489 19441 24283 23920 10780 12254 14029 15194 10308 9669 11701 12496 PE(16:0_20:4) 99762 101390 105372 112037 87096 98553 138659 131102 127253 142907 211664 162860 148571 147229 328996 416083 80559 81105 149158 138541 154718 152553 131112 162035 PE(16:0_20:5) 8406 9675 10285 10383 7019 8018 7211 7504 27228 18290 27248 26120 9610 16414 38908 49668 4808 4982 17814 17413 15061 14875 17936 17391 PE(18:0_22:6) 78559 85414 57426 65186 75165 77352 74061 73579 89556 86914 107935 106560 115702 117753 254510 268825 61991 53385 112120 118676 138301 147534 103721 103397 PE(18:1_18:2) 50021 49719 53958 58411 58348 53924 34974 34291 43575 41306 42786 35234 84312 90203 193433 206796 56023 58232 45821 48445 32205 26086 35175 35294 PE(18:1_20:4) 58518 62110 61231 63416 71111 66521 42465 45111 54212 54311 73512 77280 115113 116832 221416 224021 68643 69939 78902 71882 86269 86837 62839 62412 PE(18:1_22:6) 39586 35783 30173 34384 43840 43869 15982 17950 16684 19410 32460 27714 76601 77937 154343 160593 56342 52195 32499 32837 42229 44978 28748 30861 PE(O-16:1_22:6) 150521 145121 112590 128313 138830 113315 166947 178296 140929 153511 163814 159865 110721 108691 152968 165724 116086 92885 158922 172278 127133 131487 179564 193793 PE(O-18:0_18:1) 18504 15793 18232 16275 14945 15150 8912 8801 8944 9435 8661 8061 14307 15107 15509 16514 18131 16715 23157 21613 17297 16840 19440 19678 PE(O-18:0_18:2) 39672 41065 49892 46448 39786 36813 52378 54316 50709 47201 67474 66685 27913 29154 50947 52611 35671 38481 56635 63190 51613 54091 65823 63636 PE(O-18:0_20:4) 92757 78439 103109 65675 65695 62545 145948 132109 95487 104345 85700 85117 63081 64813 117158 134486 70178 84988 83346 95852 99528 105370 101471 148566 PE(O-18:0_22:5) 28616 33091 46460 37845 22188 22793 38114 40360 34649 46060 71263 48675 16351 17700 25608 46300 24367 17360 37248 50522 39050 39664 53044 30783 PE(O-18:0_22:6) 167071 157434 168370 155209 132455 145466 240677 257615 254120 244683 194119 170413 124160 127895 289230 333877 141157 140350 173454 195216 191772 203253 244370 245419 PE(O-18:1_20:4) 165838 148470 140522 159660 140630 128060 226910 233299 162492 205718 170539 183841 125521 130504 128212 142691 112166 93478 133863 138896 143299 165412 195548 188921 PE(O-18:1_22:6) 194243 192686 163711 167644 159733 153887 237328 252907 201086 255290 165532 176929 157193 154787 220080 215923 136871 128158 198317 193589 177315 171059 238174 258845 PE(O-18:2_22:6) 48108 53095 36415 35803 42306 40492 26847 27194 22114 19723 26520 29567 38404 40613 48790 46979 44441 41738 32386 39000 29173 28381 41221 38618 PE(O-20:0_18:2) 28497 30607 32431 31175 26154 24484 35250 34723 40481 47230 33643 30242 20071 23349 34493 31105 20928 23221 32461 31248 25990 26872 34259 33858 PE(O-20:0_20:4) 84650 82879 90970 84630 64155 66573 121417 119679 83516 103847 62859 59712 59647 62252 94395 132951 57651 56659 66328 60160 73367 82612 84803 89897 PE(O-20:0_22:6) 78522 76131 80329 82114 66416 64588 110422 110623 101004 126533 72791 59032 63598 69043 152979 149167 63500 62067 67600 78005 76438 64671 85156 88084 PE(O-20:1_20:4) 54901 60139 80236 65757 45670 46085 101170 108140 50358 65566 97297 49433 44868 40741 43577 56018 35612 29657 35438 38352 37615 34927 66828 54176 PE(O-20:1_22:6) 67334 56253 56906 54930 46140 45371 54030 49817 50107 57553 31034 36666 47081 52379 77787 85758 38323 35824 35848 36267 41277 38427 51882 52615 PI(16:0_18:2) 73967 72739 58762 65427 85594 80066 53799 50815 90160 98396 60918 61404 58191 59489 87248 95449 60745 54968 44671 48873 31184 30766 60753 60413 PI(16:0_20:4) 146479 157897 142283 153945 185424 159254 97255 96093 127970 137147 98301 97760 153273 172344 222358 209376 123821 114391 103149 108893 93989 98529 124593 132495 PI(16:0_22:6) 24517 25648 22156 21568 29742 29770 19206 17486 24641 25349 21420 21323 28615 29406 46360 44754 24429 24334 20979 21432 16361 17143 26582 26168 PI(17:0_20:4) 11592 11608 9710 10512 14992 14614 5118 4830 7359 8498 5106 5676 13946 13427 23770 22835 16627 15892 5783 5939 4175 4483 7387 7039 PI(18:0_18:2) 196134 202997 193656 212370 242011 231634 127506 130033 221143 227401 124609 127341 178464 190243 231686 234226 235537 215211 104288 109229 63054 69481 130915 137857 PI(18:0_20:4) 1670999 1711098 1340951 1618057 1718417 1601566 1052738 1077419 1293030 1352887 1084275 1096958 1892253 2083336 2381620 2686389 1938100 1742771 1249676 1393464 1347690 1325799 1404138 1295119 PI(18:0_22:6) 52555 50130 40573 46197 59923 53131 37510 35503 51910 51902 35812 36911 58964 63518 105309 108699 64634 62607 35016 35039 28848 28876 40417 40401 PI(O-18:0_20:4) 4587 4456 4746 4674 3719 3305 15417 16250 11700 12560 10521 10007 2043 2404 9453 9950 3523 3374 8769 9960 10853 10627 11201 9241 PS(P-8:0_18:4) 272595 272003 278727 324601 366495 331381 237803 226715 217819 237751 268553 268782 441019 445825 379029 427701 418274 422084 368651 387684 401002 385838 416576 362516 SM(d18:1_23:0) 111843 135418 196347 170148 88338 84569 217201 200512 281340 317936 233740 216126 120960 104170 133702 142945 126770 115049 202027 229112 199651 189252 182941 186011 SM(d35:2) 60973 59544 59671 60441 51186 46577 54442 51172 51091 57971 67631 72754 55878 55225 81880 92100 60463 58099 56917 61769 64476 63239 60789 59135 SM(d37:2) 16617 15806 14045 12628 9830 11564 44599 43766 30740 26895 48728 50391 11143 14662 18951 15537 14483 13441 32968 33693 48348 50264 41117 38011 SM(d42:1) 123381 121922 145169 144987 96850 99042 74688 71929 100698 114380 105525 96386 86760 94254 113894 121889 83651 83528 74472 84652 85058 80140 82237 90262 SM(d43:3) 152928 132547 149807 125981 138222 136499 69694 68811 59499 62314 79341 78946 101098 113696 160896 180584 134322 136539 65774 73204 69051 74753 63837 72671 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Lipid Class m/z rt Cer(d19:1_24:1) Cer 706.6354975 3.656524078 FA(13:0) FA 213.1860035 2.225849503 FA(14:0) FA 257.1758335 1.510239072 FA(14:1) FA 225.1860035 2.196380256 FA(17:0) FA 269.2486035 2.760183383 FA(17:1) FA 267.2329535 2.590696688 FA(19:0) FA 297.2799035 2.973498305 FA(19:1) FA 295.2642535 2.819803225 FA(20:0) FA 311.2955535 3.0673209 FA(20:1) FA 309.2799035 2.907626158 FA(20:2) FA 307.2642535 2.764487915 FA(20:3) FA 305.2486035 2.633931597 FA(20:4) FA 303.2329535 2.746131462 FA(20:5) FA 301.2173035 2.366562096 FA(22:0) FA 339.3268535 3.225798751 FA(22:1) FA 337.3112035 3.08335478 FA(22:4) FA 331.2642535 2.716847075 FA(22:5) FA 329.2486035 2.583296765 FA(22:6) FA 327.2329535 2.465128943 FA(23:0) FA 353.3425035 3.294387225 FA(24:0) FA 367.3581535 3.361490552 FA(24:1) FA 365.3425035 3.23274616 FA(24:5) FA 357.2799035 2.784414874 FA(24:6) FA 355.2642535 2.671580859 FA(26:0) FA 395.3894535 3.476083515 LPC(19:2) LPC 578.3463455 2.211988584 LPC(19:3) LPC 576.3306955 2.11378699 LPC(21:0) LPC 610.4089455 2.788115563 LPC(21:1) LPC 608.3932955 2.617677096 LPC(21:2) LPC 606.3776455 2.476267437 LPC(21:4) LPC 602.3463455 2.200765057 LPC(21:5) LPC 600.3306955 2.089843248 LPC(23:5) LPC 628.3619955 2.297241745 LPC(23:6) LPC 626.3463455 2.201287281 LPC(25:0) LPC 666.4715455 3.116772271 LPI(18:0) LPI 599.3201915 2.388138276 LPI(20:4) LPI 619.2888915 2.015530999 PC(15:0_16:0) PC 764.5447105 3.266636874 PC(15:0_18:2) PC 788.5447105 3.211374514 PC(16:0_17:0) PC 792.5760105 3.365807067 PC(16:0_18:1) PC 744.5548805 3.378567063 PC(16:0_18:2) PC 742.5392305 3.30481091 PC(16:0_19:0) PC 820.6073105 3.46404105 PC(16:0_20:3) PC 768.5548805 3.345039618 PC(16:0_20:4) PC 766.5392305 3.303807068 PC(17:0_16:1) PC 790.5603605 3.291812201 PC(17:0_18:1) PC 818.5916605 3.385218983 PC(17:0_18:2) PC 816.5760105 3.316212381 PC(17:0_20:3) PC 842.5916605 3.34192557 PC(17:0_20:5) PC 838.5603605 3.247263951 PC(17:1_18:2) PC 814.5603605 3.253139726 PC(18:0_18:1) PC 832.6073105 3.430199407 PC(18:0_18:2) PC 830.5916605 3.366054171 PC(18:0_20:4) PC 854.5916605 3.35689957 PC(18:0_22:6) PC 878.5916605 3.34745297 PC(18:1_23:6) PC 890.5916605 3.304577041 PC(18:2_19:2) PC 840.5760105 3.300647414 PC(18:2_21:4) PC 864.5760105 3.291937253 PC(18:2_21:5) PC 862.5603605 3.238595085 PC(19:0_18:1) PC 846.6229605 3.477831906 PC(19:0_18:2) PC 844.6073105 3.414740712 PC(19:0_20:2) PC 872.6386105 3.491843982 PC(19:0_20:3) PC 870.6229605 3.443506961 PC(19:0_20:4) PC 868.6073105 3.403174828 PC(19:0_22:5) PC 894.6229605 3.439039719 PC(19:0_22:6) PC 892.6073105 3.386916711 PC(19:1_20:4) PC 866.5916605 3.336535134 PC(20:0_18:2) PC 858.6229605 3.453912173 PC(O-16:0_22:6) PC 776.5599655 3.472200668 PC(O-16:1_18:2) PC 726.5443155 3.487418379 PC(O-17:0_20:4) PC 826.5967455 3.382675781 PC(O-17:1_20:4) PC 824.5810955 3.362203054 PC(O-18:0_18:2) PC 756.5912655 3.571646062 PC(O-18:0_20:4) PC 780.5912655 3.562042793 PC(O-19:0_20:4) PC 854.6280455 3.465793525 PC(O-19:0_22:6) PC 878.6280455 3.44957684 PC(O-19:1_16:0) PC 804.6123955 3.451299848 PC(O-20:0_18:1) PC 846.6593455 3.636453722 PC(O-4:0_13:1) PC 552.3306955 2.183250117 PC(P-5:0_16:3) PC 602.3463455 2.20057302 PE(16:0_18:1) PE 716.5235805 3.410846691 PE(16:0_20:4) PE 738.5079305 3.3335338 PE(16:0_20:5) PE 736.4922805 3.286918817 PE(18:0_22:6) PE 790.5392305 3.417946341 PE(18:1_18:2) PE 740.5235805 3.361998752 PE(18:1_20:4) PE 764.5235805 3.351366031 PE(18:1_22:6) PE 788.5235805 3.334261399 PE(O-16:1_22:6) PE 746.5130155 3.376849123 PE(O-18:0_18:1) PE 730.5756155 3.549966275 PE(O-18:0_18:2) PE 728.5599655 3.495985566 PE(O-18:0_20:4) PE 752.5599655 3.488686326 PE(O-18:0_22:5) PE 778.5756155 3.494582341 PE(O-18:0_22:6) PE 776.5599655 3.472666073 PE(O-18:1_20:4) PE 750.5443155 3.423189222 PE(O-18:1_22:6) PE 774.5443155 3.461369859 PE(O-18:2_22:6) PE 772.5286655 3.387925061 PE(O-20:0_18:2) PE 756.5912655 3.572198725 PE(O-20:0_20:4) PE 780.5912655 3.56247352 PE(O-20:0_22:6) PE 804.5912655 3.548588296 PE(O-20:1_20:4) PE 778.5756155 3.551417362 PE(O-20:1_22:6) PE 802.5756155 3.535363412 PI(16:0_18:2) PI 833.5185565 3.104124087 PI(16:0_20:4) PI 857.5185565 3.106403744 PI(16:0_22:6) PI 881.5185565 3.085490919 PI(17:0_20:4) PI 871.5342065 3.155938301 PI(18:0_18:2) PI 861.5498565 3.208447992 PI(18:0_20:4) PI 885.5498565 3.205133104 PI(18:0_22:6) PI 909.5498565 3.190420222 PI(O-18:0_20:4) PI 871.5705915 3.25428476 PS(P-8:0_18:4) PS 626.3463455 2.187366407 SM(d18:1_23:0) SM 845.6753295 3.55100549 SM(d35:2) SM 759.5657795 3.176304261 SM(d37:2) SM 787.5970795 3.288972515 SM(d42:1) SM 859.6909795 3.586352966 SM(d43:3) SM 869.6753295 3.491993457 METABOLITES_END #END