ONTOLOGY SOURCE REFERENCE
Term Source Name	OBI	NCBITAXON	EFO	BTO	CHMO	CHEBI	NCIT	UO	N/A
Term Source File	http://data.bioontology.org/ontologies/OBI	http://data.bioontology.org/ontologies/NCBITAXON	http://data.bioontology.org/ontologies/EFO	http://data.bioontology.org/ontologies/BTO	http://data.bioontology.org/ontologies/CHMO	http://data.bioontology.org/ontologies/CHEBI	http://data.bioontology.org/ontologies/NCIT	http://data.bioontology.org/ontologies/UO	http://purl.obolibrary.org/obo/ncit.owl
Term Source Version	22	2	132	26	16	93	40	43	18.10e
Term Source Description	Ontology for Biomedical Investigations	National Center for Biotechnology Information (NCBI) Organismal Classification	Experimental Factor Ontology	BRENDA Tissue and Enzyme Source Ontology	Chemical Methods Ontology	Chemical Entities of Biological Interest Ontology	National Cancer Institute Thesaurus	Units of Measurement Ontology	NCI Thesaurus OBO Edition
INVESTIGATION
Investigation Identifier	MTBLS174
Investigation Title	Investigation
Investigation Description	
Investigation Submission Date	
Investigation Public Release Date	
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Comment[Last Opened With Configuration]	
INVESTIGATION PUBLICATIONS
Investigation PubMed ID
Investigation Publication DOI
Investigation Publication Author List
Investigation Publication Title
Investigation Publication Status
Investigation Publication Status Term Accession Number
Investigation Publication Status Term Source REF
INVESTIGATION CONTACTS
Investigation Person Last Name
Investigation Person First Name
Investigation Person Mid Initials
Investigation Person Email
Investigation Person Phone
Investigation Person Fax
Investigation Person Address
Investigation Person Affiliation
Investigation Person Roles
Investigation Person Roles Term Accession Number
Investigation Person Roles Term Source REF
STUDY
Study Identifier	MTBLS174
Study Title	Multi-omic profiles of human nonalcoholic fatty liver disease tissue highlight heterogenic phenotypes
Study Description	Non-alcoholic fatty liver disease (NAFLD) is a consequence of sedentary life style and high fat diets with an estimated prevalence of about 30% in western countries. It is associated with insulin resistance, obesity, glucose intolerance and drug toxicity. Additionally, polymorphisms in, e.g. APOC3, PNPLA3, NCAN and PPP1R3B, correlate with NAFLD. Several studies have already investigated later stages of the disease. This study characterizes and stratifies distinct grades of the early steatosis stages of the disease with the aim of identifying mechanisms underlying the etiology of the disease. We analyzed liver biopsies and serum samples from patients with distinct grades of steatosis (also pre-disease states) employing transcriptomics, serum biomarkers, metabolomics, and proteomics. We unveiled distinct transcriptome, proteome and metabolome profiles in patients with high-grade and low-grade steatosis. In line with previously reported causes of steatosis and insulin resistance our observed expression differences in the levels of cytokines, in the IGF-axis, in fat metabolism and branched chain amino acids provide a comprehensive image of the deregulated biological system underlying the disease.
Study Submission Date	2015-06-15
Study Public Release Date	2015-12-07
Study File Name	s_HNA_FLD.txt
STUDY DESIGN DESCRIPTORS
Study Design Type	untargeted metabolites	Steatosis	metabolic syndrome	Human Study Subject	Serum global profiling	nuclear magnetic resonance spectroscopy
Study Design Type Term Accession Number		http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl				
Study Design Type Term Source REF		NCIT	EFO	NCIT		CHMO
STUDY PUBLICATIONS
Study PubMed ID	26646939
Study Publication DOI	10.1038/sdata.2015.68
Study Publication Author List	Wruck Wasco, Kashofer Karl, Rehman Samrina, Daskalaki Andriani, Berg Daniela, Gralka Ewa, Jozefczuk Justyna, Drews Katharina, Pandey Vikash, Regenbrecht Christian, Wierling Christoph, Turano Paola, Korf Ulrike, Zatloukal Kurt, Lehrach Hans, Westerhoff Hans V., Adjaye James
Study Publication Title	Multi-omic profiles of human non-alcoholic fatty liver disease tissue highlight heterogenic phenotypes
Study Publication Status	Published
Study Publication Status Term Accession Number	http://www.ebi.ac.uk/efo/EFO_0001796
Study Publication Status Term Source REF	EFO
STUDY FACTORS
Study Factor Name	Metabolic syndrome	Steatosis 	Gender	BMI	Age
Study Factor Type	metabolic syndrome	fatty liver	Gender	body mass index	age
Study Factor Type Term Accession Number	http://www.ebi.ac.uk/efo/EFO_0000195	http://www.ebi.ac.uk/efo/EFO_0003934	http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl		
Study Factor Type Term Source REF	EFO	EFO	NCIT	EFO	EFO
STUDY ASSAYS
Study Assay File Name	a_hna_fld_metabolite_profiling_NMR_spectroscopy.txt
Study Assay Measurement Type	metabolite profiling
Study Assay Measurement Type Term Accession Number	http://purl.obolibrary.org/obo/OBI_0000366
Study Assay Measurement Type Term Source REF	OBI
Study Assay Technology Type	NMR spectroscopy
Study Assay Technology Type Term Accession Number	http://purl.obolibrary.org/obo/OBI_0000623
Study Assay Technology Type Term Source REF	OBI
Study Assay Technology Platform	Bruker
STUDY PROTOCOLS
Study Protocol Name	Sample collection	Extraction	NMR sample	NMR spectroscopy	NMR assay	Data transformation	Metabolite identification
Study Protocol Type	Sample collection	Extraction	NMR sample	NMR spectroscopy	NMR assay	Data transformation	Metabolite identification
Study Protocol Type Term Accession Number							
Study Protocol Type Term Source REF							
Study Protocol Description	Serum samples were collected from 18 patients with morbid obesity who admitted into hospital for treatment by bariatric surgery (gastric banding, gastric bypass, sleeve gastrectomy). All patients were recruited in the Multidisciplinary Obesity Research (MORE) project at the Medical University of Graz, Austria or at the Interdisciplinary Adipositas Center at the Kantonsspital St. Gallen, Switzerland. 	Not applicable.	"Frozen samples were thawed at room temperature and shaken before use. A total 300 μL of a sodium phosphate buffer (70 mM Na2HPO4; 20% (v/v) D2O; 6.15 mM NaN3; 6.64 mM TMSP; pH 7.4) was added to 300 µl of each sample. A total of 450 µl of this mixture was transferred into a 4.25 mm NMR tubes (Bruker BioSpin) for analysis."	The spectra of human serum samples were acquired on a Bruker spectrometer operating at 14.1 T (600.13 MHz proton Larmor frequency) equipped with a CPTPI cryoprobe, and an automatic tuning-matching unit and an automatic sample changer and temperature 313.4 K.	A 1D CPMG pulse sequence was used to analyze the serum samples. For each sample 64 transients were collected.	For each spectrum, the region between 5.0 and 4.5 ppm, which contains the residual water signal, was removed from the subsequent analysis. Taking into account the fact that plasma samples were collected using two different anti-coagulant treated tubes (citrate or EDTA), in further analysis regions with signals that belong to citrate and EDTA complexes were removed. In total five singlets and two multiplets were eliminated.  CPMG 1D spectrum in the range between 0.2 and 10.0 ppm was segmented into 0.02-ppm chemical shift buckets, and the corresponding spectral areas were integrated using AMIX software (Version 3.8.4; Bruker BioSpin) giving a total of 466 variables. Bucketing is a means to reduce the number of total variables and to compensate for small shifts in the signals.  The spectra were normalized by probabilistic quotient method.	All resonances of interest were manually checked, and signals were assigned on template one-dimensional NMR profiles by using matching routines of AMIX 7.3.2 (Bruker BioSpin) in combination with the BBIOREFCODE Version 2-0-0 reference database and published literature when available. Additional confirmation were done using data provided in our lab –data base containing spectra of standard  pure compounds. To assess which metabolites (i.e. NMR peaks) were significantly different between different sets a univariate paired Wilcoxon test was used. A P-value ≤ 0.05 was considered statistically significant.
Study Protocol URI							
Study Protocol Version							
Study Protocol Parameters Name		Extraction Method	NMR tube type;Temperature;Sample pH;Solvent	Magnetic field strength;Number of transients;Pulse sequence name;NMR Probe;Instrument			
Study Protocol Parameters Name Term Accession Number			;;;	;;;;			
Study Protocol Parameters Name Term Source REF			;;;	;;;;			
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STUDY CONTACTS
Study Person Last Name	Gralka	Turano	Wruck	Kashofer	Rehman	Daskalaki	Berg	Jozefczuk	Drews	Pandey	Regenbrecht	Wierling	Korf	Zatloukal	Lehrach	Westerhoff	Adjaye
Study Person First Name	Ewa	Paola	Wasco	Karl	Samrina	Andriani	Daniela	Justyna	Katharina	Vikash	Christian	Christoph	Ulrike	Kurt	Hans	Hans V	James
Study Person Mid Initials																	
Study Person Email	gralka@cerm.unifi.it	turano@cerm.unifi.it															
Study Person Phone																	
Study Person Fax																	
Study Person Address	CERM, Via Sacconi 6 , sesto Fiorentino	CERM, Via Sacconi 6 , Sesto Fiorentino															
Study Person Affiliation	University of Florence	University of Florence	Medical Faculty, Institute for Stem Cell Research and Regenerative Medicine, Heinrich Heine University, 40225 Düsseldorf, Germany.	Institute of Pathology, Medical University of Graz, Graz 8036, Austria.	The Manchester Centre for Integrative Systems Biology, Manchester Institute of Biotechnology, University of Manchester, Manchester M1 7DN, UK.	Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63, Berlin 14195, Germany.	Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.	Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63, Berlin 14195, Germany.	Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63, Berlin 14195, Germany.	Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63, Berlin 14195, Germany.	Institute for Pathology &Comprehensive Cancer Center, Cancer Stem Cell Group, Charité-Universitätsmedizin, 10117 Berlin, Germany.	Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63, Berlin 14195, Germany.	Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.	Institute of Pathology, Medical University of Graz, Graz 8036, Austria.	Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63, Berlin 14195, Germany.	Synthetic Systems Biology, Swammerdam Institute for Life Sciences, University of Amsterdam, 1018 WS Amsterdam, The Netherlands.	Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63, Berlin 14195, Germany.
Study Person Roles	principal investigator role	principal investigator role	Author	Author	Author	Author	Author	Author	Author	Author	Author	Author	Author	Author	Author	Author	Author
Study Person Roles Term Accession Number			http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781	http://purl.obolibrary.org/obo/NCIT_C42781
Study Person Roles Term Source REF																	
