#METABOLOMICS WORKBENCH efahy_20180114_131319 DATATRACK_ID:1299 STUDY_ID:ST000917 ANALYSIS_ID:AN001499 PROJECT_ID:PR000633 VERSION 1 CREATED_ON January 14, 2018, 1:13 pm #PROJECT PR:PROJECT_TITLE Biomarkers of NAFLD progression: a lipidomics approach to an epidemic PR:PROJECT_TYPE Lipidomics Study PR:PROJECT_SUMMARY The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, PR:PROJECT_SUMMARY nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely PR:PROJECT_SUMMARY diagnosis of these different stages, particularly NASH, is important for both PR:PROJECT_SUMMARY potential reversibility and limitation of complications. Liver biopsy remains PR:PROJECT_SUMMARY the clinical standard for definitive diagnosis. Diagnostic tools minimizing the PR:PROJECT_SUMMARY need for invasive procedures or that add information to histologic data are PR:PROJECT_SUMMARY important in novel management strategies for the growing epidemic of NAFLD. We PR:PROJECT_SUMMARY describe an 'omics' approach to detecting a reproducible signature of lipid PR:PROJECT_SUMMARY metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a PR:PROJECT_SUMMARY double-blinded study of patients with different stages of NAFLD that involves PR:PROJECT_SUMMARY profiling liver biopsies, plasma, and urine samples. Using linear discriminant PR:PROJECT_SUMMARY analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, PR:PROJECT_SUMMARY sphingolipids, sterols, and various aqueous small molecular weight components PR:PROJECT_SUMMARY involved in cellular metabolic pathways, can be used to differentiate between PR:PROJECT_SUMMARY NASH and steatosis. This identification of differential biomolecular signatures PR:PROJECT_SUMMARY has the potential to improve clinical diagnosis and facilitate therapeutic PR:PROJECT_SUMMARY intervention of NAFLD. PR:INSTITUTE University of California, San Diego PR:DEPARTMENT Bioengineering PR:LAST_NAME Fahy PR:FIRST_NAME Eoin PR:ADDRESS 9500 Gilman, La Jolla, CA, 92093, USA PR:EMAIL efahy@ucsd.edu PR:PHONE 858-534-4076 PR:FUNDING_SOURCE NIGMS Grant GM U54069338 PR:PUBLICATIONS https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340319/ PR:CONTRIBUTORS LIPID MAPS Consortium #STUDY ST:STUDY_TITLE Biomarkers of NAFLD progression: a lipidomics approach to an epidemic. Part ST:STUDY_TITLE 3:Urine ST:STUDY_TYPE Lipidomics Study ST:STUDY_SUMMARY The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, ST:STUDY_SUMMARY nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely ST:STUDY_SUMMARY diagnosis of these different stages, particularly NASH, is important for both ST:STUDY_SUMMARY potential reversibility and limitation of complications. Liver biopsy remains ST:STUDY_SUMMARY the clinical standard for definitive diagnosis. Diagnostic tools minimizing the ST:STUDY_SUMMARY need for invasive procedures or that add information to histologic data are ST:STUDY_SUMMARY important in novel management strategies for the growing epidemic of NAFLD. We ST:STUDY_SUMMARY describe an 'omics' approach to detecting a reproducible signature of lipid ST:STUDY_SUMMARY metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a ST:STUDY_SUMMARY double-blinded study of patients with different stages of NAFLD that involves ST:STUDY_SUMMARY profiling liver biopsies, plasma, and urine samples. Using linear discriminant ST:STUDY_SUMMARY analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, ST:STUDY_SUMMARY sphingolipids, sterols, and various aqueous small molecular weight components ST:STUDY_SUMMARY involved in cellular metabolic pathways, can be used to differentiate between ST:STUDY_SUMMARY NASH and steatosis. This identification of differential biomolecular signatures ST:STUDY_SUMMARY has the potential to improve clinical diagnosis and facilitate therapeutic ST:STUDY_SUMMARY intervention of NAFLD. ST:INSTITUTE University of California, San Diego ST:DEPARTMENT Bioengineering ST:LAST_NAME Fahy ST:FIRST_NAME Eoin ST:ADDRESS 9500 Gilman, La Jolla, CA, 92093, USA ST:EMAIL efahy@ucsd.edu ST:PHONE 858-534-4076 ST:PUBLICATIONS https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340319/ #SUBJECT SU:SUBJECT_TYPE Human clinical study SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:AGE_OR_AGE_RANGE 23-83 SU:GENDER Male and Female SU:HUMAN_ETHNICITY Black/White #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS - NASH005 Diagnosis:Cirrhosis GENDER=M; BMI=31; ETHNICITY=White; AGE=45; AST=55; ALT=20; ALKP=171; TBIL=8.2; GLUCOSE=- SUBJECT_SAMPLE_FACTORS - NASH007 Diagnosis:Cirrhosis GENDER=F; BMI=40.3; ETHNICITY=White; AGE=64; AST=39; ALT=20; ALKP=102; TBIL=3; GLUCOSE=92 SUBJECT_SAMPLE_FACTORS - NASH009 Diagnosis:Cirrhosis GENDER=M; BMI=40; ETHNICITY=White; AGE=49; AST=162; ALT=66; ALKP=123; TBIL=10.5; GLUCOSE=119 SUBJECT_SAMPLE_FACTORS - NASH013 Diagnosis:Cirrhosis GENDER=M; BMI=35; ETHNICITY=White; AGE=59; AST=44; ALT=32; ALKP=95; TBIL=2.9; GLUCOSE=100 SUBJECT_SAMPLE_FACTORS - NASH016 Diagnosis:Cirrhosis GENDER=M; BMI=26; ETHNICITY=Asian; AGE=66; AST=223; ALT=100; ALKP=149; TBIL=5.2; GLUCOSE=117 SUBJECT_SAMPLE_FACTORS - NASH022 Diagnosis:Cirrhosis GENDER=M; BMI=27; ETHNICITY=White; AGE=63; AST=55; ALT=34; ALKP=91; TBIL=6.5; GLUCOSE=220 SUBJECT_SAMPLE_FACTORS - NASH026 Diagnosis:Cirrhosis GENDER=M; BMI=26.5; ETHNICITY=White; AGE=57; AST=18; ALT=38; ALKP=37; TBIL=4.2; GLUCOSE=122 SUBJECT_SAMPLE_FACTORS - NASH027 Diagnosis:Cirrhosis GENDER=M; BMI=31; ETHNICITY=-; AGE=58; AST=30; ALT=36; ALKP=105; TBIL=3.4; GLUCOSE=131 SUBJECT_SAMPLE_FACTORS - NASH028 Diagnosis:Cirrhosis GENDER=F; BMI=31; ETHNICITY=White; AGE=48; AST=46; ALT=47; ALKP=192; TBIL=2.4; GLUCOSE=173 SUBJECT_SAMPLE_FACTORS - NASH029 Diagnosis:Cirrhosis GENDER=F; BMI=21.5; ETHNICITY=White; AGE=49; AST=92; ALT=54; ALKP=277; TBIL=41.7; GLUCOSE=113 SUBJECT_SAMPLE_FACTORS - NASH040 Diagnosis:Cirrhosis GENDER=F; BMI=44; ETHNICITY=White; AGE=63; AST=36; ALT=26; ALKP=62; TBIL=1.7; GLUCOSE=65 SUBJECT_SAMPLE_FACTORS - NASH047 Diagnosis:Cirrhosis GENDER=M; BMI=-; ETHNICITY=White; AGE=60; AST=51; ALT=24; ALKP=57; TBIL=11.3; GLUCOSE=241 SUBJECT_SAMPLE_FACTORS - NASH048 Diagnosis:Cirrhosis GENDER=M; BMI=26; ETHNICITY=White; AGE=66; AST=44; ALT=23; ALKP=100; TBIL=4.5; GLUCOSE=79 SUBJECT_SAMPLE_FACTORS - NASH049 Diagnosis:Cirrhosis GENDER=M; BMI=35; ETHNICITY=White; AGE=71; AST=42; ALT=21; ALKP=82; TBIL=3.8; GLUCOSE=145 SUBJECT_SAMPLE_FACTORS - NASH052 Diagnosis:Cirrhosis GENDER=M; BMI=-; ETHNICITY=-; AGE=63; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=- SUBJECT_SAMPLE_FACTORS - NASH055 Diagnosis:Cirrhosis GENDER=M; BMI=36.8; ETHNICITY=White; AGE=67; AST=35; ALT=24; ALKP=91; TBIL=0.9; GLUCOSE=135 SUBJECT_SAMPLE_FACTORS - NASH064 Diagnosis:Cirrhosis GENDER=F; BMI=27.9; ETHNICITY=White; AGE=67; AST=67; ALT=31; ALKP=113; TBIL=5.5; GLUCOSE=82 SUBJECT_SAMPLE_FACTORS - NASH065 Diagnosis:Cirrhosis GENDER=M; BMI=41.9; ETHNICITY=White; AGE=36; AST=32; ALT=17; ALKP=44; TBIL=0.2; GLUCOSE=91 SUBJECT_SAMPLE_FACTORS - NASH068 Diagnosis:Cirrhosis GENDER=M; BMI=23; ETHNICITY=White; AGE=55; AST=46; ALT=21; ALKP=67; TBIL=1.4; GLUCOSE=96 SUBJECT_SAMPLE_FACTORS - NASH069 Diagnosis:Cirrhosis GENDER=M; BMI=29.9; ETHNICITY=White; AGE=56; AST=74; ALT=57; ALKP=258; TBIL=3.1; GLUCOSE=84 SUBJECT_SAMPLE_FACTORS - NASH010 Diagnosis:NASH GENDER=F; BMI=43.3; ETHNICITY=White; AGE=46; AST=33; ALT=35; ALKP=71; TBIL=0.4; GLUCOSE=175 SUBJECT_SAMPLE_FACTORS - NASH012 Diagnosis:NASH GENDER=F; BMI=49; ETHNICITY=White; AGE=38; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=89 SUBJECT_SAMPLE_FACTORS - NASH015 Diagnosis:NASH GENDER=M; BMI=44; ETHNICITY=White; AGE=58; AST=27; ALT=39; ALKP=41; TBIL=0.2; GLUCOSE=125 SUBJECT_SAMPLE_FACTORS - NASH018 Diagnosis:NASH GENDER=F; BMI=51; ETHNICITY=Black; AGE=44; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=96 SUBJECT_SAMPLE_FACTORS - NASH019 Diagnosis:NASH GENDER=M; BMI=34; ETHNICITY=White; AGE=73; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=107 SUBJECT_SAMPLE_FACTORS - NASH021 Diagnosis:NASH GENDER=M; BMI=28; ETHNICITY=White; AGE=59; AST=30; ALT=39; ALKP=63; TBIL=0.9; GLUCOSE=185 SUBJECT_SAMPLE_FACTORS - NASH030 Diagnosis:NASH GENDER=F; BMI=41.6; ETHNICITY=White; AGE=28; AST=24; ALT=24; ALKP=77; TBIL=0.1; GLUCOSE=89 SUBJECT_SAMPLE_FACTORS - NASH031 Diagnosis:NASH GENDER=F; BMI=41.5; ETHNICITY=White; AGE=46; AST=17; ALT=23; ALKP=94; TBIL=0.2; GLUCOSE=135 SUBJECT_SAMPLE_FACTORS - NASH035 Diagnosis:NASH GENDER=M; BMI=74.7; ETHNICITY=White; AGE=45; AST=23; ALT=30; ALKP=72; TBIL=0.3; GLUCOSE=84 SUBJECT_SAMPLE_FACTORS - NASH037 Diagnosis:NASH GENDER=M; BMI=44; ETHNICITY=White; AGE=53; AST=52; ALT=83; ALKP=98; TBIL=0.3; GLUCOSE=165 SUBJECT_SAMPLE_FACTORS - NASH038 Diagnosis:NASH GENDER=M; BMI=45; ETHNICITY=White; AGE=65; AST=36; ALT=37; ALKP=67; TBIL=0.3; GLUCOSE=97 SUBJECT_SAMPLE_FACTORS - NASH039 Diagnosis:NASH GENDER=M; BMI=48; ETHNICITY=White; AGE=35; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=- SUBJECT_SAMPLE_FACTORS - NASH044 Diagnosis:NASH GENDER=M; BMI=61; ETHNICITY=Black; AGE=41; AST=22; ALT=24; ALKP=57; TBIL=0.6; GLUCOSE=89 SUBJECT_SAMPLE_FACTORS - NASH057 Diagnosis:NASH GENDER=F; BMI=47.3; ETHNICITY=White; AGE=53; AST=25; ALT=18; ALKP=71; TBIL=0.6; GLUCOSE=99 SUBJECT_SAMPLE_FACTORS - NASH072 Diagnosis:NASH GENDER=M; BMI=77.3; ETHNICITY=White; AGE=50; AST=29; ALT=12; ALKP=85; TBIL=0.8; GLUCOSE=207 SUBJECT_SAMPLE_FACTORS - NASH074 Diagnosis:NASH GENDER=F; BMI=31; ETHNICITY=White; AGE=52; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=169 SUBJECT_SAMPLE_FACTORS - NASH084 Diagnosis:NASH GENDER=F; BMI=63; ETHNICITY=White; AGE=48; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=120 SUBJECT_SAMPLE_FACTORS - NASH087 Diagnosis:NASH GENDER=F; BMI=52; ETHNICITY=Black; AGE=58; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=175 SUBJECT_SAMPLE_FACTORS - NASH088 Diagnosis:NASH GENDER=F; BMI=40; ETHNICITY=Black; AGE=27; AST=15; ALT=19; ALKP=134; TBIL=0.4; GLUCOSE=133 SUBJECT_SAMPLE_FACTORS - NASH090 Diagnosis:NASH GENDER=F; BMI=35; ETHNICITY=White; AGE=32; AST=15; ALT=20; ALKP=69; TBIL=-; GLUCOSE=110 SUBJECT_SAMPLE_FACTORS - NASH003 Diagnosis:Normal GENDER=F; BMI=47.3; ETHNICITY=White; AGE=46; AST=36; ALT=54; ALKP=76; TBIL=-; GLUCOSE=90 SUBJECT_SAMPLE_FACTORS - NASH004 Diagnosis:Normal GENDER=M; BMI=-; ETHNICITY=White; AGE=23; AST=106; ALT=95; ALKP=-; TBIL=0.7; GLUCOSE=97 SUBJECT_SAMPLE_FACTORS - NASH006 Diagnosis:Normal GENDER=F; BMI=-; ETHNICITY=White; AGE=40; AST=68; ALT=72; ALKP=74; TBIL=0.5; GLUCOSE=93 SUBJECT_SAMPLE_FACTORS - NASH011 Diagnosis:Normal GENDER=M; BMI=29.1; ETHNICITY=White; AGE=54; AST=40; ALT=22; ALKP=42; TBIL=0.9; GLUCOSE=101 SUBJECT_SAMPLE_FACTORS - NASH014 Diagnosis:Normal GENDER=F; BMI=36; ETHNICITY=Black; AGE=63; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=139 SUBJECT_SAMPLE_FACTORS - NASH017 Diagnosis:Normal GENDER=M; BMI=45; ETHNICITY=White; AGE=59; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=101 SUBJECT_SAMPLE_FACTORS - NASH020 Diagnosis:Normal GENDER=M; BMI=29; ETHNICITY=White; AGE=33; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=91 SUBJECT_SAMPLE_FACTORS - NASH024 Diagnosis:Normal GENDER=F; BMI=35; ETHNICITY=Black; AGE=43; AST=20; ALT=13; ALKP=71; TBIL=0.9; GLUCOSE=95 SUBJECT_SAMPLE_FACTORS - NASH034 Diagnosis:Normal GENDER=F; BMI=51.5; ETHNICITY=White; AGE=49; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=172 SUBJECT_SAMPLE_FACTORS - NASH036 Diagnosis:Normal GENDER=F; BMI=39; ETHNICITY=Black; AGE=45; AST=21; ALT=23; ALKP=111; TBIL=0.2; GLUCOSE=99 SUBJECT_SAMPLE_FACTORS - NASH041 Diagnosis:Normal GENDER=F; BMI=63; ETHNICITY=Black; AGE=27; AST=21; ALT=19; ALKP=86; TBIL=0.3; GLUCOSE=106 SUBJECT_SAMPLE_FACTORS - NASH042 Diagnosis:Normal GENDER=F; BMI=42; ETHNICITY=White; AGE=58; AST=18; ALT=16; ALKP=98; TBIL=0.4; GLUCOSE=105 SUBJECT_SAMPLE_FACTORS - NASH043 Diagnosis:Normal GENDER=F; BMI=52; ETHNICITY=White; AGE=39; AST=13; ALT=12; ALKP=76; TBIL=0.3; GLUCOSE=104 SUBJECT_SAMPLE_FACTORS - NASH045 Diagnosis:Normal GENDER=F; BMI=48; ETHNICITY=Black; AGE=43; AST=13; ALT=15; ALKP=90; TBIL=0.3; GLUCOSE=104 SUBJECT_SAMPLE_FACTORS - NASH046 Diagnosis:Normal GENDER=F; BMI=40; ETHNICITY=White; AGE=36; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=104 SUBJECT_SAMPLE_FACTORS - NASH050 Diagnosis:Normal GENDER=F; BMI=52.5; ETHNICITY=Black; AGE=38; AST=15; ALT=12; ALKP=75; TBIL=0.1; GLUCOSE=96 SUBJECT_SAMPLE_FACTORS - NASH051 Diagnosis:Normal GENDER=F; BMI=50.6; ETHNICITY=White; AGE=29; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=99 SUBJECT_SAMPLE_FACTORS - NASH053 Diagnosis:Normal GENDER=F; BMI=25.1; ETHNICITY=White; AGE=56; AST=26; ALT=14; ALKP=180; TBIL=0.8; GLUCOSE=140 SUBJECT_SAMPLE_FACTORS - NASH054 Diagnosis:Normal GENDER=F; BMI=30.8; ETHNICITY=White; AGE=83; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=90 SUBJECT_SAMPLE_FACTORS - NASH060 Diagnosis:Normal GENDER=F; BMI=39.7; ETHNICITY=Black; AGE=36; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=115 SUBJECT_SAMPLE_FACTORS - NASH066 Diagnosis:Normal GENDER=F; BMI=40.3; ETHNICITY=Black; AGE=52; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=95 SUBJECT_SAMPLE_FACTORS - NASH067 Diagnosis:Normal GENDER=F; BMI=39.2; ETHNICITY=Black; AGE=33; AST=17; ALT=14; ALKP=73; TBIL=0.2; GLUCOSE=87 SUBJECT_SAMPLE_FACTORS - NASH070 Diagnosis:Normal GENDER=F; BMI=25.7; ETHNICITY=White; AGE=53; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=- SUBJECT_SAMPLE_FACTORS - NASH077 Diagnosis:Normal GENDER=M; BMI=33; ETHNICITY=White; AGE=67; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=193 SUBJECT_SAMPLE_FACTORS - NASH078 Diagnosis:Normal GENDER=F; BMI=45; ETHNICITY=Black; AGE=40; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=101 SUBJECT_SAMPLE_FACTORS - NASH080 Diagnosis:Normal GENDER=F; BMI=50; ETHNICITY=White; AGE=57; AST=26; ALT=28; ALKP=54; TBIL=0.3; GLUCOSE=155 SUBJECT_SAMPLE_FACTORS - NASH082 Diagnosis:Normal GENDER=M; BMI=34; ETHNICITY=White; AGE=73; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=- SUBJECT_SAMPLE_FACTORS - NASH085 Diagnosis:Normal GENDER=F; BMI=32; ETHNICITY=White; AGE=63; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=- SUBJECT_SAMPLE_FACTORS - NASH086 Diagnosis:Normal GENDER=F; BMI=38; ETHNICITY=White; AGE=35; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=99 SUBJECT_SAMPLE_FACTORS - NASH089 Diagnosis:Normal GENDER=F; BMI=52; ETHNICITY=White; AGE=49; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=- SUBJECT_SAMPLE_FACTORS - NASH091 Diagnosis:Normal GENDER=F; BMI=29; ETHNICITY=White; AGE=68; AST=14; ALT=18; ALKP=66; TBIL=0.4; GLUCOSE=107 SUBJECT_SAMPLE_FACTORS - NASH001 Diagnosis:Steatosis GENDER=M; BMI=52.3; ETHNICITY=Black; AGE=37; AST=16; ALT=19; ALKP=58; TBIL=0.4; GLUCOSE=236 SUBJECT_SAMPLE_FACTORS - NASH002 Diagnosis:Steatosis GENDER=F; BMI=34.9; ETHNICITY=White; AGE=57; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=91 SUBJECT_SAMPLE_FACTORS - NASH023 Diagnosis:Steatosis GENDER=M; BMI=34; ETHNICITY=White; AGE=56; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=97 SUBJECT_SAMPLE_FACTORS - NASH032 Diagnosis:Steatosis GENDER=F; BMI=45; ETHNICITY=White; AGE=58; AST=27; ALT=20; ALKP=83; TBIL=0.9; GLUCOSE=89 SUBJECT_SAMPLE_FACTORS - NASH033 Diagnosis:Steatosis GENDER=F; BMI=40; ETHNICITY=White; AGE=58; AST=38; ALT=29; ALKP=102; TBIL=0.5; GLUCOSE=109 SUBJECT_SAMPLE_FACTORS - NASH056 Diagnosis:Steatosis GENDER=F; BMI=45.1; ETHNICITY=White; AGE=51; AST=38; ALT=28; ALKP=45; TBIL=0.5; GLUCOSE=99 SUBJECT_SAMPLE_FACTORS - NASH058 Diagnosis:Steatosis GENDER=M; BMI=42.7; ETHNICITY=Black; AGE=53; AST=28; ALT=34; ALKP=72; TBIL=0.6; GLUCOSE=174 SUBJECT_SAMPLE_FACTORS - NASH059 Diagnosis:Steatosis GENDER=F; BMI=49.8; ETHNICITY=White; AGE=45; AST=16; ALT=16; ALKP=84; TBIL=0.3; GLUCOSE=92 SUBJECT_SAMPLE_FACTORS - NASH061 Diagnosis:Steatosis GENDER=F; BMI=56.7; ETHNICITY=White; AGE=29; AST=64; ALT=50; ALKP=68; TBIL=0.8; GLUCOSE=91 SUBJECT_SAMPLE_FACTORS - NASH062 Diagnosis:Steatosis GENDER=F; BMI=56.6; ETHNICITY=White; AGE=51; AST=15; ALT=16; ALKP=58; TBIL=0.5; GLUCOSE=90 SUBJECT_SAMPLE_FACTORS - NASH071 Diagnosis:Steatosis GENDER=F; BMI=40; ETHNICITY=White; AGE=33; AST=15; ALT=12; ALKP=59; TBIL=0.4; GLUCOSE=85 SUBJECT_SAMPLE_FACTORS - NASH073 Diagnosis:Steatosis GENDER=F; BMI=80.2; ETHNICITY=Black; AGE=34; AST=11; ALT=11; ALKP=90; TBIL=0.4; GLUCOSE=163 SUBJECT_SAMPLE_FACTORS - NASH075 Diagnosis:Steatosis GENDER=M; BMI=33; ETHNICITY=White; AGE=67; AST=22; ALT=34; ALKP=96; TBIL=0.5; GLUCOSE=191 SUBJECT_SAMPLE_FACTORS - NASH076 Diagnosis:Steatosis GENDER=F; BMI=50; ETHNICITY=White; AGE=51; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=92 SUBJECT_SAMPLE_FACTORS - NASH079 Diagnosis:Steatosis GENDER=F; BMI=43; ETHNICITY=White; AGE=37; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=85 SUBJECT_SAMPLE_FACTORS - NASH081 Diagnosis:Steatosis GENDER=F; BMI=46; ETHNICITY=White; AGE=65; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=119 SUBJECT_SAMPLE_FACTORS - NASH083 Diagnosis:Steatosis GENDER=M; BMI=39; ETHNICITY=White; AGE=41; AST=-; ALT=-; ALKP=-; TBIL=-; GLUCOSE=106 #COLLECTION CO:COLLECTION_SUMMARY Human samples were collected according to a protocol approved by Vanderbilt CO:COLLECTION_SUMMARY University Medical Center's Internal Review Board (#120829) and under informed CO:COLLECTION_SUMMARY written patients' consent prior to inclusion in this study. Sample sizes were CO:COLLECTION_SUMMARY selected to minimize the invasive procedures. Plasma samples were obtained from CO:COLLECTION_SUMMARY patients' blood collected during standard of care surgical procedures. Urine CO:COLLECTION_SUMMARY samples were collected from patients' Foley catheters placed for standard of CO:COLLECTION_SUMMARY care procedure. Liver samples were obtained from the excess tissue collected as CO:COLLECTION_SUMMARY part of the standard of care liver biopsies performed at the time of surgery CO:COLLECTION_SUMMARY that would otherwise be discarded. Subsequently, studies at University of CO:COLLECTION_SUMMARY California, San Diego were conducted under further auspices of University of CO:COLLECTION_SUMMARY California, San Diego Internal Review Board #121220. CO:SAMPLE_TYPE Urine #TREATMENT TR:TREATMENT_SUMMARY - #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Urine sample extraction. Five hundred microliters of thawed urine containing 4 SP:SAMPLEPREP_SUMMARY µl of internal standard mix were extracted with 500 µl cold (-20°C) CH3OH by SP:SAMPLEPREP_SUMMARY incubation in an ice bath for 30 min. After mixing by vortex at 4°C for 1 min SP:SAMPLEPREP_SUMMARY and centrifugation (4°C, 18,000 g, 10 min), the solvent was evaporated from the SP:SAMPLEPREP_SUMMARY supernatant and the residue was dissolved in 400 µl of resuspension solvent, SP:SAMPLEPREP_SUMMARY vortexed to mix (1 min at 4°C), and centrifuged (4°C, 18,000 g, 10 min) to SP:SAMPLEPREP_SUMMARY remove any insoluble material. GPLs: GPLs from liver samples were extracted and SP:SAMPLEPREP_SUMMARY analyzed by MS essentially as described in (20, 21). Extraction and analysis of SP:SAMPLEPREP_SUMMARY plasma samples was according to previously published procedures (22). SP:SAMPLEPREP_SUMMARY Cardiolipin, coenzyme Q, and dolichol: Lipid extractions were performed based on SP:SAMPLEPREP_SUMMARY the Bligh and Dyer method with minor modifications (23-25). FAs and eicosanoids: SP:SAMPLEPREP_SUMMARY FFAs were extracted essentially as previously described after supplementation SP:SAMPLEPREP_SUMMARY with deuterated internal standards (Cayman Chemicals) (26, 27). Eicosanoids were SP:SAMPLEPREP_SUMMARY isolated via solid phase extraction, utilizing 25 deuterated internal standards SP:SAMPLEPREP_SUMMARY (28, 29). Sterols and oxysterols: Sterols and oxysterols were extracted using SP:SAMPLEPREP_SUMMARY previously described methods (30). Neutral lipids: Cholesteryl esters (CEs), SP:SAMPLEPREP_SUMMARY TAGs, and DAGs were extracted from weighed liver tissue (0.5-1 mg) suspended in SP:SAMPLEPREP_SUMMARY 0.5 ml PBS that had been homogenized by sonication. Extractions of plasma (0.05 SP:SAMPLEPREP_SUMMARY ml diluted to 0.1 ml with PBS), urine (1 ml), and tissue sonicates were carried SP:SAMPLEPREP_SUMMARY out using 1 ml hexane:methyl t-butyl ether (1:1, v/v), essentially as previously SP:SAMPLEPREP_SUMMARY described (31). Sphingolipids: Sphingolipids from liver, plasma, and urine were SP:SAMPLEPREP_SUMMARY extracted following previously published procedures (32, 33), with the exception SP:SAMPLEPREP_SUMMARY that methylene chloride was substituted for chloroform for the single-phase SP:SAMPLEPREP_SUMMARY extraction of sphingoid bases. 20. Ivanova P. T., Milne S. B., Byrne M. O., SP:SAMPLEPREP_SUMMARY Xiang Y., Brown H. A. 2007. Glycerophospholipid identification and quantitation SP:SAMPLEPREP_SUMMARY by electrospray ionization mass spectrometry. Methods Enzymol. 432: 21-57. 21. SP:SAMPLEPREP_SUMMARY Myers D. S., Ivanova P. T., Milne S. B., Brown H. A. 2011. Quantitative analysis SP:SAMPLEPREP_SUMMARY of glycerophospholipids by LC-MS: acquisition, data handling, and SP:SAMPLEPREP_SUMMARY interpretation. Biochim. Biophys. Acta. 1811: 748-757. 22. Quehenberger O., SP:SAMPLEPREP_SUMMARY Armando A. M., Brown H. A., Milne S. B., Myers D. S., Merrill A. H., Jr, SP:SAMPLEPREP_SUMMARY Bandyopadhyay S., Jones K. N., Kelly S., Shaner R. L., et al. 2010. Lipidomics SP:SAMPLEPREP_SUMMARY reveals a remarkable diversity of lipids in human plasma. J. Lipid Res. 51: SP:SAMPLEPREP_SUMMARY 3299-3305. 23. Guan Z., Li S., Smith D., Shaw W., Raetz C. 2007. Identification SP:SAMPLEPREP_SUMMARY of N-acylphosphatidylserine molecules in eukaryotic cells. Biochemistry. 46: SP:SAMPLEPREP_SUMMARY 14500-14513. 24. Tan B. K., Bogdanov M., Zhao J., Dowhan W., Raetz C. R., Guan SP:SAMPLEPREP_SUMMARY Z. 2012. Discovery of cardiolipin synthase utilizing phosphatidylethanolamine SP:SAMPLEPREP_SUMMARY and phosphatidylglycerol as substrates. Proc. Natl. Acad. Sci. USA. 109: SP:SAMPLEPREP_SUMMARY 16504-16509. 25. Wen R., Lam B., Guan Z. 2013. Aberrant dolichol chain lengths SP:SAMPLEPREP_SUMMARY as biomarkers for retinitis pigmentosa caused by impaired dolichol biosynthesis. SP:SAMPLEPREP_SUMMARY J. Lipid Res. 54: 3516-3522. 26. Quehenberger O., Armando A., Dumlao D., SP:SAMPLEPREP_SUMMARY Stephens D. L., Dennis E. A. 2008. Lipidomics analysis of essential fatty acids SP:SAMPLEPREP_SUMMARY in macrophages. Prostaglandins Leukot. Essent. Fatty Acids. 79: 123-129. 27. SP:SAMPLEPREP_SUMMARY Quehenberger O., Armando A. M., Dennis E. A. 2011. High sensitivity quantitative SP:SAMPLEPREP_SUMMARY lipidomics analysis of fatty acids in biological samples by gas SP:SAMPLEPREP_SUMMARY chromatography-mass spectrometry. Biochim. Biophys. Acta. 1811: 648-656. 28. SP:SAMPLEPREP_SUMMARY Deems R., Buczynski M. W., Bowers-Gentry R., Harkewicz R., Dennis E. A. 2007. SP:SAMPLEPREP_SUMMARY Detection and quantitation of eicosanoids via high performance liquid SP:SAMPLEPREP_SUMMARY chromatography-electrospray ionization-mass spectrometry. Methods Enzymol. 432: SP:SAMPLEPREP_SUMMARY 59-82. 29. Dumlao D. S., Buczynski M. W., Norris P. C., Harkewicz R., Dennis E. SP:SAMPLEPREP_SUMMARY A. 2011. High-throughput lipidomic analysis of fatty acid derived eicosanoids SP:SAMPLEPREP_SUMMARY and N-acylethanolamines. Biochim. Biophys. Acta. 1811: 724-736. 30. McDonald J. SP:SAMPLEPREP_SUMMARY G., Smith D. D., Stiles A. R., Russell D. W. 2012. A comprehensive method for SP:SAMPLEPREP_SUMMARY extraction and quantitative analysis of sterols and secosteroids from human SP:SAMPLEPREP_SUMMARY plasma. J. Lipid Res. 53: 1399-1409. 31. Hutchins P. M., Barkley R. M., Murphy SP:SAMPLEPREP_SUMMARY R. C. 2008. Separation of cellular nonpolar neutral lipids by normal-phase SP:SAMPLEPREP_SUMMARY chromatography and analysis by electrospray ionization mass spectrometry. J. SP:SAMPLEPREP_SUMMARY Lipid Res. 49: 804-813. 32. Shaner R. L., Allegood J. C., Park H., Wang E., SP:SAMPLEPREP_SUMMARY Kelly S., Haynes C. A., Sullards M. C., Merrill A. H., Jr 2009. Quantitative SP:SAMPLEPREP_SUMMARY analysis of sphingolipids for lipidomics using triple quadrupole and quadrupole SP:SAMPLEPREP_SUMMARY linear ion trap mass spectrometers. J. Lipid Res. 50: 1692-1707. 33. Sullards SP:SAMPLEPREP_SUMMARY M. C., Liu Y., Chen Y., Merrill A. H., Jr 2011. Analysis of mammalian SP:SAMPLEPREP_SUMMARY sphingolipids by liquid chromatography tandem mass spectrometry (LC-MS/MS) and SP:SAMPLEPREP_SUMMARY tissue imaging mass spectrometry (TIMS). Biochim. Biophys. Acta. 1811: 838-853. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Cardiolipin analysis was achieved with normal phase LC coupled with CH:CHROMATOGRAPHY_SUMMARY high-resolution MS performed on a TripleTOF 5600 system (AB SCIEX, Foster City, CH:CHROMATOGRAPHY_SUMMARY CA) (24). Dolichol and coenzyme Q were analyzed by reverse phase LC coupled with CH:CHROMATOGRAPHY_SUMMARY multiple reaction monitoring (MRM) MS utilizing a 4000 Q-Trap hybrid triple CH:CHROMATOGRAPHY_SUMMARY quadrupole linear ion-trap mass spectrometer (AB SCIEX) (22, 23). For dolichol CH:CHROMATOGRAPHY_SUMMARY analysis, MRM was performed in negative ion mode, with the precursor ions being CH:CHROMATOGRAPHY_SUMMARY the (M+acetate)- adduct ions and the product ions being the acetate ions (m/z CH:CHROMATOGRAPHY_SUMMARY 59). For coenzyme Q analysis, MRM was carried out in positive ion mode, with CH:CHROMATOGRAPHY_SUMMARY ammonium adducts (M+NH4)+ as precursor ions and the proton adducts of the CH:CHROMATOGRAPHY_SUMMARY quinone ring of coenzyme Q (m/z 197) as product ions. For quantitation, an CH:CHROMATOGRAPHY_SUMMARY internal standard mixture composed of a cardiolipin mix (Avanti Polar Lipids, CH:CHROMATOGRAPHY_SUMMARY Inc.), nor-dolichol (13-22) (Avanti Polar Lipids, Inc.), and yeast coenzyme Q6 CH:CHROMATOGRAPHY_SUMMARY (Sigma) was added during the first step of lipid extraction (22). 22. CH:CHROMATOGRAPHY_SUMMARY Quehenberger O., Armando A. M., Brown H. A., Milne S. B., Myers D. S., Merrill CH:CHROMATOGRAPHY_SUMMARY A. H., Jr, Bandyopadhyay S., Jones K. N., Kelly S., Shaner R. L., et al. 2010. CH:CHROMATOGRAPHY_SUMMARY Lipidomics reveals a remarkable diversity of lipids in human plasma. J. Lipid CH:CHROMATOGRAPHY_SUMMARY Res. 51: 3299-3305. 23. Guan Z., Li S., Smith D., Shaw W., Raetz C. 2007. CH:CHROMATOGRAPHY_SUMMARY Identification of N-acylphosphatidylserine molecules in eukaryotic cells. CH:CHROMATOGRAPHY_SUMMARY Biochemistry. 46: 14500-14513. 24. Tan B. K., Bogdanov M., Zhao J., Dowhan W., CH:CHROMATOGRAPHY_SUMMARY Raetz C. R., Guan Z. 2012. Discovery of cardiolipin synthase utilizing CH:CHROMATOGRAPHY_SUMMARY phosphatidylethanolamine and phosphatidylglycerol as substrates. Proc. Natl. CH:CHROMATOGRAPHY_SUMMARY Acad. Sci. USA. 109: 16504-16509. CH:INSTRUMENT_NAME Multiple CH:COLUMN_NAME Multiple CH:CHROMATOGRAPHY_TYPE Core K #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:MS_COMMENTS - MS:INSTRUMENT_NAME - MS:INSTRUMENT_TYPE - MS:MS_TYPE Other MS:ION_MODE UNSPECIFIED #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS pmol/ml MS_METABOLITE_DATA_START Samples NASH001 NASH002 NASH003 NASH004 NASH005 NASH006 NASH007 NASH009 NASH010 NASH011 NASH012 NASH013 NASH014 NASH015 NASH016 NASH017 NASH018 NASH019 NASH020 NASH021 NASH022 NASH023 NASH024 NASH026 NASH027 NASH028 NASH029 NASH030 NASH031 NASH032 NASH033 NASH034 NASH035 NASH036 NASH037 NASH038 NASH039 NASH040 NASH041 NASH042 NASH043 NASH044 NASH045 NASH046 NASH047 NASH048 NASH049 NASH050 NASH051 NASH052 NASH053 NASH054 NASH055 NASH056 NASH057 NASH058 NASH059 NASH060 NASH061 NASH062 NASH064 NASH065 NASH066 NASH067 NASH068 NASH069 NASH070 NASH071 NASH072 NASH073 NASH074 NASH075 NASH076 NASH077 NASH078 NASH079 NASH080 NASH081 NASH082 NASH083 NASH084 NASH085 NASH086 NASH087 NASH088 NASH089 NASH090 NASH091 Factors Diagnosis:Steatosis Diagnosis:Steatosis Diagnosis:Normal Diagnosis:Normal Diagnosis:Cirrhosis Diagnosis:Normal Diagnosis:Cirrhosis Diagnosis:Cirrhosis Diagnosis:NASH Diagnosis:Normal Diagnosis:NASH Diagnosis:Cirrhosis Diagnosis:Normal Diagnosis:NASH Diagnosis:Cirrhosis Diagnosis:Normal Diagnosis:NASH Diagnosis:NASH Diagnosis:Normal Diagnosis:NASH Diagnosis:Cirrhosis Diagnosis:Steatosis Diagnosis:Normal Diagnosis:Cirrhosis Diagnosis:Cirrhosis Diagnosis:Cirrhosis Diagnosis:Cirrhosis Diagnosis:NASH Diagnosis:NASH Diagnosis:Steatosis Diagnosis:Steatosis Diagnosis:Normal Diagnosis:NASH Diagnosis:Normal Diagnosis:NASH Diagnosis:NASH Diagnosis:NASH Diagnosis:Cirrhosis Diagnosis:Normal Diagnosis:Normal Diagnosis:Normal Diagnosis:NASH Diagnosis:Normal Diagnosis:Normal Diagnosis:Cirrhosis Diagnosis:Cirrhosis Diagnosis:Cirrhosis Diagnosis:Normal Diagnosis:Normal Diagnosis:Cirrhosis Diagnosis:Normal Diagnosis:Normal Diagnosis:Cirrhosis Diagnosis:Steatosis Diagnosis:NASH Diagnosis:Steatosis Diagnosis:Steatosis Diagnosis:Normal Diagnosis:Steatosis Diagnosis:Steatosis Diagnosis:Cirrhosis Diagnosis:Cirrhosis Diagnosis:Normal Diagnosis:Normal Diagnosis:Cirrhosis Diagnosis:Cirrhosis Diagnosis:Normal Diagnosis:Steatosis Diagnosis:NASH Diagnosis:Steatosis Diagnosis:NASH Diagnosis:Steatosis Diagnosis:Steatosis Diagnosis:Normal Diagnosis:Normal Diagnosis:Steatosis Diagnosis:Normal Diagnosis:Steatosis Diagnosis:Normal Diagnosis:Steatosis Diagnosis:NASH Diagnosis:Normal Diagnosis:Normal Diagnosis:NASH Diagnosis:NASH Diagnosis:Normal Diagnosis:NASH Diagnosis:Normal Dolichol-17 1.51 3.70 0.60 1.44 1.53 0.78 1.91 2.02 2.39 0.39 1.44 1.71 0.52 1.83 1.37 1.42 NA 1.16 0.62 1.38 4.43 2.05 2.76 5.57 2.82 1.94 0.40 3.23 1.59 0.91 3.00 2.77 5.61 3.73 3.36 1.76 2.31 0.68 3.59 2.74 1.85 1.46 1.05 3.16 3.57 3.23 1.59 3.02 3.96 NA 0.65 1.23 2.67 2.58 3.47 2.43 4.37 1.14 1.36 1.96 1.79 1.80 3.02 2.40 1.75 1.91 NA 0.92 1.92 80.06 2.12 0.81 5.12 1.40 1.42 1.55 0.86 1.70 2.51 2.84 4.74 1.01 2.07 2.64 1.70 2.33 2.71 1.82 Dolichol-18 9.56 23.44 3.65 8.29 10.57 4.94 11.46 13.43 13.90 1.61 7.19 8.99 3.03 8.83 7.39 8.36 NA 5.02 2.13 6.52 26.43 11.90 16.44 30.52 14.81 9.36 2.61 15.44 8.52 5.71 17.27 15.21 30.56 22.83 19.69 7.83 12.12 3.00 23.39 15.76 10.57 6.54 5.69 19.01 20.66 19.42 9.69 19.28 24.73 NA 2.81 7.43 15.16 14.17 19.56 14.89 24.14 5.47 6.78 9.13 10.43 10.31 17.27 12.65 11.74 11.25 NA 3.54 10.82 96.91 11.65 3.32 13.26 4.78 6.39 6.82 3.47 8.68 12.20 12.04 24.21 3.55 8.18 11.93 7.90 12.18 13.00 7.73 Dolichol-19 17.82 46.36 9.04 18.06 20.43 11.27 22.37 26.72 34.03 2.88 18.66 18.66 5.49 17.49 15.75 12.25 NA 8.74 4.40 11.97 45.71 24.95 33.27 59.56 21.46 15.66 3.76 33.67 21.06 11.77 41.35 28.99 65.62 49.24 38.43 17.88 26.96 5.68 45.64 36.84 23.64 15.94 11.37 39.56 36.76 47.16 22.92 41.21 58.61 NA 6.47 15.41 36.21 32.76 34.91 29.27 52.19 10.89 16.23 20.58 22.51 20.26 36.11 31.55 24.00 23.02 NA 6.43 24.30 163.24 24.06 5.04 27.97 9.51 14.19 14.57 6.45 18.77 26.03 28.19 65.99 7.82 16.72 26.89 18.17 28.48 30.38 18.73 Dolichol-20 6.84 19.40 3.79 8.62 7.51 3.81 9.18 11.03 16.94 1.05 11.18 7.51 2.18 7.41 6.32 3.53 NA 3.60 1.75 4.99 17.91 11.36 12.93 23.41 6.67 7.22 1.36 18.56 10.07 4.68 17.70 10.50 31.46 18.95 13.68 7.65 12.26 2.70 16.57 16.14 10.47 10.50 5.24 19.01 11.24 23.13 11.46 15.67 25.90 NA 3.80 9.93 17.37 15.94 12.78 11.33 21.62 4.30 7.03 8.39 8.82 7.63 13.72 13.41 9.29 9.53 NA 2.64 10.18 70.74 9.78 1.86 12.47 3.76 5.90 7.00 2.58 8.38 10.41 12.16 36.31 5.23 7.53 11.40 8.95 12.99 14.00 10.46 CoQ-9 5.66 12.70 1.36 25.76 6.94 9.35 13.48 12.11 11.10 1.32 8.66 24.24 1.06 10.18 9.56 4.87 NA 5.36 5.00 22.33 34.14 29.49 26.55 41.57 14.64 8.20 4.02 14.65 5.01 7.26 15.01 10.36 19.61 8.13 30.83 10.70 12.41 2.76 16.87 18.01 20.66 7.59 3.13 28.42 47.49 16.37 8.71 11.21 15.72 13.28 2.92 20.48 7.00 11.21 19.76 11.30 20.48 5.13 3.74 6.41 6.42 10.80 13.34 7.95 16.10 6.46 NA 2.70 6.46 107.14 8.90 1.96 12.10 4.73 2.49 5.32 1.67 6.65 7.75 6.29 20.47 2.64 4.94 5.65 2.28 5.44 17.87 3.82 CoQ-10 337.11 801.59 96.38 1195.19 572.45 510.81 629.29 774.10 818.19 72.91 530.24 1504.46 74.29 698.99 607.31 217.08 NA 283.33 214.25 901.11 1700.00 1343.21 1634.62 2471.43 710.40 546.78 323.99 856.71 255.43 252.17 551.35 458.57 1098.60 516.21 1037.37 366.48 571.57 143.38 757.93 695.09 613.30 287.62 131.34 1179.85 2572.67 880.58 541.29 576.75 760.19 724.67 119.69 874.09 409.70 421.88 1294.13 579.23 874.09 185.91 218.57 273.71 365.41 314.46 965.03 404.60 632.17 363.05 NA 88.11 263.40 1492.28 366.27 79.37 309.90 190.16 123.42 270.94 70.32 345.54 392.47 365.36 1465.13 169.14 261.46 289.13 193.14 389.87 608.52 178.21 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Dolichol-17 Dolichol-18 Dolichol-19 Dolichol-20 CoQ-9 CoQ-10 METABOLITES_END #END