#METABOLOMICS WORKBENCH biswapriya_20180912_075107 DATATRACK_ID:1502 STUDY_ID:ST001053 ANALYSIS_ID:AN001722 PROJECT_ID:PR000706 VERSION 1 CREATED_ON September 17, 2018, 2:29 pm #PROJECT PR:PROJECT_TITLE Skin and Blubber Metabolomics PR:PROJECT_TYPE Multi-institutional Metabolomics PR:PROJECT_SUMMARY The common bottlenose dolphin (Tursiops truncatus) is carnivorous cetacean PR:PROJECT_SUMMARY thriving in marine environment are one of the most common apex predators found PR:PROJECT_SUMMARY in coastal and estuarine ecosystems. Although recent studies have focused on PR:PROJECT_SUMMARY capturing the circulating metabolomes of these organisms, with respect to PR:PROJECT_SUMMARY pollutants and exposures of the marine environment, the skin and blubber are PR:PROJECT_SUMMARY important protective organs that have not been probed. Using 1HNMR based PR:PROJECT_SUMMARY untargeted metabolomics we quantified 51 metabolites belonging to 74 different PR:PROJECT_SUMMARY metabolic pathways in the skin and blubber of bottle nose dolphins (n=5) samples PR:PROJECT_SUMMARY collected in 2017 from the coast of Mexico. Results indicate that the skin and PR:PROJECT_SUMMARY blubber metabolism are quantitatively different. These metabolite abundances PR:PROJECT_SUMMARY could help discriminate the tissue-types using supervised and unsupervised PCA PR:PROJECT_SUMMARY and PLSDA analysis. Heat maps and random forest analysis point to unique PR:PROJECT_SUMMARY metabolites that are important classifiers of the tissue-type. The altered PR:PROJECT_SUMMARY metabolic patterns, mainly linking fatty acid metabolism and ketogenic amino PR:PROJECT_SUMMARY acids, seem to constitute a characteristic of blubber, while the skin showed PR:PROJECT_SUMMARY diverse metabolites involved in gluceoneogenic pathways. 1H NMR spectra allowed PR:PROJECT_SUMMARY the identification of metabolites associated with these organ types, such as PR:PROJECT_SUMMARY pyruvic acid, arginine, ornithine, 2-hydroxybutyric acid, 3-hydroxyisobutyric PR:PROJECT_SUMMARY acid, and acetic acid, as discriminatory and classifying metabolites. These PR:PROJECT_SUMMARY results would lead to further understanding of dolphin skin and blubber PR:PROJECT_SUMMARY metabolism for better efforts in their conservation as well as a measure of PR:PROJECT_SUMMARY marine pollution and ecotoxicology. PR:INSTITUTE Wake Forest Baptist Medical Center PR:DEPARTMENT Department of Internal Medicine PR:LAST_NAME Misra PR:FIRST_NAME Biswapriya PR:ADDRESS Medical Center Boulevard NRC Building, G#43, Medical Center Boulevard, Winston PR:ADDRESS Salem, NC, 27157, USA PR:EMAIL bbmisraccb@gmail.com PR:PHONE 3522156040 PR:FUNDING_SOURCE NA PR:PROJECT_COMMENTS NA PR:PUBLICATIONS In process PR:CONTRIBUTORS Biswapriya B. Misra, Ixchel Mariel Ruiz Hernandez, Gloria Ivonne Hernández PR:CONTRIBUTORS Bolio, Emanuel Hernandez, Colli Dula Reyna Cristina #STUDY ST:STUDY_TITLE 1H-NMR Analysis of Skin and Blubber of Nose Dolphin Metabolome Reveal the ST:STUDY_TITLE Functional Metabolomic Dichotomy of The Organs ST:STUDY_TYPE Dolphin Skin and Blubber ST:STUDY_SUMMARY The common bottlenose dolphin (Tursiops truncatus) is carnivorous cetacean ST:STUDY_SUMMARY thriving in marine environment are one of the most common apex predators found ST:STUDY_SUMMARY in coastal and estuarine ecosystems. Although recent studies have focused on ST:STUDY_SUMMARY capturing the circulating metabolomes of these organisms, with respect to ST:STUDY_SUMMARY pollutants and exposures of the marine environment, the skin and blubber are ST:STUDY_SUMMARY important protective organs that have not been probed. Using 1HNMR based ST:STUDY_SUMMARY untargeted metabolomics we quantified 51 metabolites belonging to 74 different ST:STUDY_SUMMARY metabolic pathways in the skin and blubber of bottle nose dolphins (n=5) samples ST:STUDY_SUMMARY collected in 2017 from the coast of Mexico. Results indicate that the skin and ST:STUDY_SUMMARY blubber metabolism are quantitatively different. These metabolite abundances ST:STUDY_SUMMARY could help discriminate the tissue-types using supervised and unsupervised PCA ST:STUDY_SUMMARY and PLSDA analysis. Heat maps and random forest analysis point to unique ST:STUDY_SUMMARY metabolites that are important classifiers of the tissue-type. The altered ST:STUDY_SUMMARY metabolic patterns, mainly linking fatty acid metabolism and ketogenic amino ST:STUDY_SUMMARY acids, seem to constitute a characteristic of blubber, while the skin showed ST:STUDY_SUMMARY diverse metabolites involved in gluceoneogenic pathways. 1H NMR spectra allowed ST:STUDY_SUMMARY the identification of metabolites associated with these organ types, such as ST:STUDY_SUMMARY pyruvic acid, arginine, ornithine, 2-hydroxybutyric acid, 3-hydroxyisobutyric ST:STUDY_SUMMARY acid, and acetic acid, as discriminatory and classifying metabolites. These ST:STUDY_SUMMARY results would lead to further understanding of dolphin skin and blubber ST:STUDY_SUMMARY metabolism for better efforts in their conservation as well as a measure of ST:STUDY_SUMMARY marine pollution and ecotoxicology. ST:INSTITUTE Wake Forest Baptist Medical Center ST:DEPARTMENT Department of Internal Medicine ST:LAST_NAME Misra ST:FIRST_NAME Biswapriya ST:ADDRESS Medical Center Boulevard NRC Building, G#43, Medical Center Boulevard, Winston ST:ADDRESS Salem, NC, 27157, USA ST:EMAIL bbmisraccb@gmail.com ST:PHONE 3522156040 ST:NUM_GROUPS 2 ST:TOTAL_SUBJECTS 4 ST:NUM_MALES 3 ST:NUM_FEMALES 1 ST:STUDY_COMMENTS NA ST:PUBLICATIONS In process #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Tursiops truncatus SU:TAXONOMY_ID 9739 SU:GENDER Male and female #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS - G7_1 Tissue:Blubber SUBJECT_SAMPLE_FACTORS - G7_2 Tissue:Blubber SUBJECT_SAMPLE_FACTORS - G7_3 Tissue:Blubber SUBJECT_SAMPLE_FACTORS - G10_1 Tissue:Blubber SUBJECT_SAMPLE_FACTORS - G10_2 Tissue:Blubber SUBJECT_SAMPLE_FACTORS - G10_3 Tissue:Blubber SUBJECT_SAMPLE_FACTORS - G14_1 Tissue:Blubber SUBJECT_SAMPLE_FACTORS - G14_2 Tissue:Blubber SUBJECT_SAMPLE_FACTORS - G14_3 Tissue:Blubber SUBJECT_SAMPLE_FACTORS - G15_1 Tissue:Blubber SUBJECT_SAMPLE_FACTORS - G15_2 Tissue:Blubber SUBJECT_SAMPLE_FACTORS - G15_3 Tissue:Blubber SUBJECT_SAMPLE_FACTORS - P7_1 Tissue:Skin SUBJECT_SAMPLE_FACTORS - P7_2 Tissue:Skin SUBJECT_SAMPLE_FACTORS - P7_3 Tissue:Skin SUBJECT_SAMPLE_FACTORS - P10_1 Tissue:Skin SUBJECT_SAMPLE_FACTORS - P10_2 Tissue:Skin SUBJECT_SAMPLE_FACTORS - P10_3 Tissue:Skin SUBJECT_SAMPLE_FACTORS - P14_1 Tissue:Skin SUBJECT_SAMPLE_FACTORS - P14_2 Tissue:Skin SUBJECT_SAMPLE_FACTORS - P14_3 Tissue:Skin SUBJECT_SAMPLE_FACTORS - P15_1 Tissue:Skin SUBJECT_SAMPLE_FACTORS - P15_2 Tissue:Skin SUBJECT_SAMPLE_FACTORS - P15_3 Tissue:Skin #COLLECTION CO:COLLECTION_SUMMARY Environmental samples. CO:SAMPLE_TYPE Skin and Blubber CO:COLLECTION_METHOD NA CO:COLLECTION_TUBE_TEMP 4 C #TREATMENT TR:TREATMENT_SUMMARY None. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY A portion (about 20 mg) of each tissue extract was dissolved in 500 ml of SP:SAMPLEPREP_SUMMARY phosphate buffer (pH = 7.0) and then 500 ml of deuterium oxide containing 0.05 % SP:SAMPLEPREP_SUMMARY v/v trimethylsilane was added. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE - CH:INSTRUMENT_NAME - CH:COLUMN_NAME - #ANALYSIS AN:DATA_FORMAT .fid AN:ANALYSIS_TYPE NMR #NMR NM:INSTRUMENT_NAME Varian 600 MHz AR Premium Compact NM:INSTRUMENT_TYPE FT-NMR NM:NMR_EXPERIMENT_TYPE 1D-1H NM:SPECTROMETER_FREQUENCY 600 MHz NM:NMR_PROBE OneProbe NM:NMR_SOLVENT D2O NM:NMR_TUBE_SIZE 5 mm NM:SHIMMING_METHOD Gradient shimming NM:PULSE_SEQUENCE PRESAT NM:WATER_SUPPRESSION Yes, satmode NM:PULSE_WIDTH 5.90 (90°) NM:POWER_LEVEL 63 NM:RECEIVER_GAIN 20 NM:PRESATURATION_POWER_LEVEL 20 NM:CHEMICAL_SHIFT_REF_CPD 0 ppm (TSP) NM:TEMPERATURE 25 NM:NUMBER_OF_SCANS 128 NM:ACQUISITION_TIME 3 NM:RELAXATION_DELAY 2 NM:SPECTRAL_WIDTH 9615.4 NM:NUM_DATA_POINTS_ACQUIRED 64000 NM:REAL_DATA_POINTS 57692 NM:CHEMICAL_SHIFT_REF_STD TSP #NMR_METABOLITE_DATA NMR_METABOLITE_DATA:UNITS Relative abundance NMR_METABOLITE_DATA_START Samples G7_1 G7_2 G7_3 G10_2 G10_3 G14_1 G14_2 G14_3 G15_1 G15_2 G15_3 P7_1 P7_2 P7_3 P10_2 P10_3 P14_1 P14_2 P14_3 P15_1 P15_2 P15_3 Factors Tissue:Blubber Tissue:Blubber Tissue:Blubber Tissue:Blubber Tissue:Blubber Tissue:Blubber Tissue:Blubber Tissue:Blubber Tissue:Blubber Tissue:Blubber Tissue:Blubber Tissue:Skin Tissue:Skin Tissue:Skin Tissue:Skin Tissue:Skin Tissue:Skin Tissue:Skin Tissue:Skin Tissue:Skin Tissue:Skin Tissue:Skin Succinate 318 246.2 229 12.5 4.6 5.8 0 11 0 3.6 1.7 1.8 1.7 4.5 0 4.2 30.8 5.7 10.4 0 0 0 Acetic acid 3483.3 2619.3 2058.4 123.6 202.9 41.1 11.7 89.9 103.6 37.4 0 0 20.6 1055 233.3 0 38 0.1 17.8 131.2 109.5 109.5 Xanthine 733.8 598 994.6 0 5.1 70.8 32.3 0 0.8 12.4 25.9 0 1.9 383.3 3.3 24.6 143.9 33.9 0 5.9 0 0 Propylene glycol 2.1 0 2.6 1.1 0 0 0 0 0 1.1 0 0 0 0 0.1 0 0.9 0.8 0 0 0 0 2-Hydroxyisovalerate 38.4 87.4 42.7 20.3 1.4 0 0 10.7 30.2 0.1 0 0 0.3 17.6 9.8 0 6.5 2.6 3.8 18.2 5.5 5.5 Fructose 0 0 0 9.4 0 22.7 0 0 55.2 461.4 626.6 0 0 31.8 0 0 0 24.6 84.4 121.6 77.3 77.3 2-Hydroxybutyric acid 69.5 125.6 67.9 305.6 403.6 48.9 0 16 238.6 277.8 261.4 51.5 0 0 138.8 290.8 17 0 48.7 35.9 0 0 Formate 200.2 154.6 128.8 74.6 127.8 1.8 2.8 10.1 52.3 17.9 3.4 20.2 2 34.6 65.5 45.3 7.3 0.9 1.7 33.4 41 41 Hypoxanthine 0.7 0.5 3.8 1.8 1.9 0.2 1.5 0.6 4.8 6.5 5.9 1 0.2 1.4 0.4 0.6 0.7 0.3 0.3 3.2 2.2 2.2 3-Hydroxyisovaleric acid 11.8 0 9.4 3.6 0 1 2.5 3.6 4.9 30.1 23.1 0 0 30.6 0 0 4.2 1.4 0 0.2 0 0 L-Proline 0 0 0 180.4 0 90.6 254.9 120.1 112 0 315.8 0 43.7 0 101 177.2 0 114.3 0 0 0 0 Isobutyric acid 406.1 300.4 231.1 122.4 105.6 110.3 237.5 198.8 360.6 499.8 511.1 128 10.9 203.6 61.4 99.9 109.8 116.1 119.1 264.8 207.9 207.9 L-Leucine 214.5 154 107.7 202.9 188.7 132.8 324.4 230.6 486.4 745.9 657.2 140.5 22.3 114 81.3 172.2 178.2 157.9 173.3 235.1 333.9 333.9 Glycine 317.5 299.2 243.3 206.1 306.4 117.6 448 314.9 439.5 306 269.1 29.3 81.6 318.2 234.6 47.8 164.1 25.7 119.7 408.1 154.3 154.3 Valine 345.5 316.2 198.2 82.5 140.8 100.9 192.1 145.9 413.7 322.6 246.3 128.6 11.8 221.7 46.4 75.8 142.9 133.7 116.2 205.5 189.1 189.1 D-Glucose 46.8 0 451.8 0 6.2 0 0 0 21 0 0 0 0 0 0 0 0 0 223.9 45.4 0 0 Isoleucine 94.6 109.6 50.4 402.8 391.7 172.3 401.9 307.7 888.9 1341.6 1294.9 379.8 28.5 551.5 192.1 284.2 164 158.8 205.2 601.5 422.8 422.8 L-Alanine 236.6 196.2 119.9 199.7 221.8 73.6 174 148.4 174 273 251.4 47.8 21.6 146.3 163.9 222.5 101.4 71.5 65.2 173.3 136.5 136.5 Acetone 58.8 524.6 86.8 33 100.9 6.7 1.9 5.2 9 1.1 5.3 63.8 5.2 228.8 41.8 61.8 33 0.8 32.1 0 0 0 L-Lactic acid 157.8 58.8 62 136.9 133.7 43.4 79.1 93.8 60.6 389.8 217.5 94.6 8.6 297.3 65.3 40.7 71.3 53.4 30 113.3 45.4 45.4 L-Glutamic acid 4138.4 2747.1 2994 1239.2 1561 343.3 1021 544.1 824.9 1279.5 1616.4 2251.8 360.9 2429.1 920.4 1909 462.8 524.8 544.4 787.1 346 346 Glycerol 57.2 359.7 93.8 286.7 306.3 588 1225.9 888.3 1749.4 1103.1 2579.5 510.9 149.7 304 80.1 379.1 595.2 486.1 996.5 762.7 1092 1092 L-Lysine 1009.3 898.6 540.2 69.7 0 95.4 324 120.3 295.1 203 550.5 1316 34.4 0 179.3 249.4 155.6 142.1 187.1 150.9 0 0 Tyrosine 34.8 40.5 36.9 30.6 41.1 14.8 27.1 24.5 29.8 30.3 65.2 24.9 2 53.4 13.7 28 12.8 13.6 6 32.5 36.9 36.9 Creatine 117.9 152.2 62.1 98.3 220.9 23.9 75.3 0 101.1 61.8 154.6 126.6 26.4 0 91.1 97.1 47.7 29.7 110.4 17.3 115.3 115.3 3-Hydroxybutyric acid 42.6 24.2 45.9 55 54.3 83.9 119.3 53.4 39.6 48.8 58.2 57.5 3.3 43.7 19.3 50.1 50.9 31.8 74.8 32.4 23.9 23.9 Creatinine 0 87 0 122.6 24.1 36.9 54.9 86.3 1.9 126.2 33.9 15.7 0 0 0 71.7 118.3 45.3 86.9 17 34.6 34.6 L-Phenylalanine 285.4 200.2 158.5 104.1 138.1 25.8 63.8 47.4 33.8 79 59.5 185.9 8.1 268.6 54.8 110.1 47.6 37.1 33.4 34.8 49.1 49.1 L-Threonine 29.6 34.7 64.1 76.7 55.9 13.3 25.7 28.2 121.9 24.9 153.6 19.2 3.8 197.4 23.2 40.8 16.9 6.2 34.3 78.5 44.4 44.4 Malonate 113 129.2 86.4 0 0 28.4 46.1 17.9 23.1 99.4 352.9 9.3 0 337.6 0 4.6 43.9 7.7 165.9 13.4 82.3 82.3 Dimethylamine 19.7 29 10.2 20.8 19.4 11.6 29.7 24 41.2 36.3 19.6 14 2.1 90.2 8.3 12.3 8.8 12.3 10.8 24.5 11 11 Ethanol 126.3 106.4 101.3 9.3 0 96.2 142.6 47.4 41.1 60.3 0 61.6 5.1 252.6 0 34.3 66.1 23.7 55 49.8 0 0 Isopropyl alcohol 13.6 6.2 18.1 4.5 5.2 5.1 5 9.7 8.2 13.6 13.3 10.2 0.8 30.5 3.2 4.3 6 2.6 1.3 13.2 5.2 5.2 Urea 0 6.1 56.7 5.2 22.7 65.7 142.9 120.9 4.3 103.6 157.3 17.2 7.3 15.8 84.9 24.2 63.3 103.7 0 24.4 225.8 225.8 Methionine 81 0 48 39.7 35.8 11.7 10.7 22.9 13.9 35.3 29.7 99.5 9.5 86.8 36 57 24 10.3 0 5.8 0 0 Myo-inositol 39.1 0 43.4 3.9 0 1.1 24.6 0 93.1 0 338.9 0 0.5 0 0 169 0 0 378.3 0 0 0 L-Histidine 821.1 1427.2 0 3941.8 3208.6 848.7 2108.8 3369.1 3067.8 2737.5 1182.6 3763.6 531.2 5836.5 4177.8 3133.2 1262.8 296.1 484.7 2662.9 2396.8 2396.8 Methanol 10851.9 109799.6 17722.2 17387 17291.1 12581.1 64315.8 17068.3 5461.6 64058.6 71668.3 36794.3 77.4 162013.8 6627.9 34708.2 82658.4 2420 58462 32987 60112 60112 Aspartate 232.2 619.6 106.1 298.4 266.9 42.5 55.1 0 116.5 140.8 207.1 227.3 25.4 1420.4 150.4 151.4 195.9 37.7 134.1 112.5 156.5 156.5 L-Arginine 0 0 0 161.1 476.3 20.5 132.4 27.1 16.3 534.1 441 1083 0 0 179.5 1194.5 0 0 0 0 0 0 Dimethyl sulfone 12.3 57.1 13 30 38.5 12.1 10.6 7.4 15.3 19.9 79.1 39.9 5.4 201.5 27.7 37 19 5.9 41.4 3.1 36.4 36.4 3-Hydroxyisobutyrate 5.6 0 0 152.2 209.6 69.6 56 159.2 134.9 157 218.7 290.3 14.9 601.7 149.1 175.9 77.9 12.2 109.4 158.1 56.2 56.2 Citric acid 105.1 80.3 28.3 50.4 61.6 9.2 37.2 19.7 47.9 52.8 64.6 87 6.2 514.2 34.4 77.2 24.9 8.8 15.9 24.2 17.1 17.1 Betaine 60.2 496.2 125.9 144.3 41.4 94.7 97.7 120.3 25.9 46.7 153 0.4 0 759.3 29.4 138.8 642 0 37 558 367.3 367.3 Choline 0.7 10 8 0 0 0.2 4.1 0.2 0 0 31.4 1 0.7 54.1 0.9 1.1 5.2 0 19.3 4.5 21.1 21.1 L-Ornithine 403 0 0 1219.4 1397.3 182.4 381 362.7 1051.6 1546.7 1427.8 2044.5 221.9 8120 939.6 1837.4 185.2 162.9 257.7 1443.6 811.2 811.2 L-Glutamine 627.5 88.3 236.5 0 183.7 4.6 294.3 0 24 0 0 429.5 0 2195.7 0 165.9 94.2 108.8 0 0.8 125.3 125.3 Pyruvic acid 0 0 0 116.1 0 45.8 73.3 102.4 45.9 114.1 119.7 252.2 20 653.1 95.5 75.5 90 59.6 51.3 80.2 57.4 57.4 Pyroglutamic acid 46.2 0 14.5 94.6 37.9 0 4.3 0 16.2 0 23.9 67.6 0.9 428.6 83.8 78.9 0 2.2 24.2 13.6 2 2 Acetoacetate 8.4 0 3.8 36.7 3 14.4 14.5 5.4 17.4 50.1 13.7 71 3.4 392.5 5.4 30.5 47.7 1.4 38.4 2.3 10 10 Carnitine 6.8 0 35.1 0 0 2.4 7 0.7 0 2.4 53.8 0 0 390.3 0 0 0 7.7 14.4 9.8 18.4 18.4 NMR_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Succinate Acetic acid Xanthine Propylene glycol 2-Hydroxyisovalerate Fructose 2-Hydroxybutyric acid Formate Hypoxanthine 3-Hydroxyisovaleric acid L-Proline Isobutyric acid L-Leucine Glycine Valine D-Glucose Isoleucine L-Alanine Acetone L-Lactic acid L-Glutamic acid Glycerol L-Lysine Tyrosine Creatine 3-Hydroxybutyric acid Creatinine L-Phenylalanine L-Threonine Malonate Dimethylamine Ethanol Isopropyl alcohol Urea Methionine Myo-inositol L-Histidine Methanol Aspartate L-Arginine Dimethyl sulfone 3-Hydroxyisobutyrate Citric acid Betaine Choline L-Ornithine L-Glutamine Pyruvic acid Pyroglutamic acid Acetoacetate Carnitine METABOLITES_END #END