ONTOLOGY SOURCE REFERENCE										
Term Source Name	NEWT	EFO	UO	CHEBI	BTO	OBI	PATO			
Term Source File	NEWT UniProt Taxonomy Database	ArrayExpress Experimental Factor Ontology	Unit Ontology	Chemical Entities of Biological Interest	BRENDA tissue / enzyme source	Ontology for Biomedical Investigations	Phenotypic qualities (properties)			
Term Source Version	v 1.26	v 1.26	v 1.26	v 1.26	v 1.26	39317	v 1.26			
Term Source Description	NEWT UniProt Taxonomy Database	ArrayExpress Experimental Factor Ontology	Unit Ontology	Chemical Entities of Biological Interest	BRENDA tissue / enzyme source	Ontology for Biomedical Investigations	Phenotypic qualities (properties)			
INVESTIGATION										
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STUDY										
Study Identifier	BII-S-6									
Study Title	The Influence of Pharmacogenetics on Fatty Liver Disease in the Wistar and Kyoto Rats:  A Combined Transcriptomic and Metabonomic									
Study Submission Date	12/10/2004									
Study Public Release Date	10/03/2009									
Study Description	"Although fatty liver disease is caused by a number of toxicological insults and the metabolic syndrome, the exact mechanisms by which many of these pathophysiological stimulii induce fatty liver are unknown. The rapid and profound steatosis caused by orotic acid, resulting from an impairment in the production of ApoB, has been investigated in the Wistar strain rat using a combined transcriptomic and metabonomic/metabolomic approach. Analysis of liver tissue from rats exposed to orotic acid for 1, 3, and 14 days was performed by DNA microarrays and high resolution 1H NMR spectroscopy based metabonomics of both tissue extracts and intact tissue (n = 3). Data were analyzed using a combination of ANOVA and principal components analysis, used as a data reduction tool to visualize the most perturbed transcripts and metabolites. Orotic acid produced a profound 8-fold increase in total lipids, and in particular increases in resonances associated with polyunsaturated fats (CHCH and CH2CHCH groups). This was accompanied by increases in the concentrations of trimethylamine-oxide (TMAO), betaine, choline, and phosphocholine, as well as a relative decrease in glucose and glycogen. At the transcriptional level, perturbations were detected in both oxidative stress and osmoregulation/pH homeostasis. However, this contrasts with a previous transcriptomic/metabolic study of fatty liver disease in a combined data set of Wistar (out-bred) and Kyoto (in-bred) strains of rats, with only 4 transcripts being found to be in common between the two analyses. This emphasizes the need to understand how strain background interacts with a given toxic lesion or genetic modification.

Keywords: metabolomics, metabolic profiling, pattern recognition, nonalcoholic steatohepatisis"									
Study File Name	s_BII-S-6.txt									
STUDY DESIGN DESCRIPTORS										
Study Design Type	time series design									
Study Design Type Term Accession Number	500020									
Study Design Type Term Source REF	OBI									
STUDY PUBLICATIONS										
Study PubMed ID	17203948									
Study Publication DOI	DOI: 10.1021/pr0601640									
Study Publication Author list	"Griffin JL, Scott J, Nicholson JK."									
Study Publication Title	The influence of pharmacogenetics on fatty liver disease in the wistar and kyoto rats: a combined transcriptomic and metabonomic study.									
Study Publication Status										
Study Publication Status Term Accession Number										
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STUDY FACTORS										
Study Factor Name	compound	time	strain							
Study Factor Type	compound	time	strain							
Study Factor Type Term Accession Number	368									
Study Factor Type Term Source REF	EFO									
STUDY ASSAYS										
Study Assay Measurement Type	metabolite profiling	transcription profiling								
Study Assay Measurement Type Term Accession Number	366	424								
Study Assay Measurement Type Term Source REF	OBI	OBI								
Study Assay Technology Type	NMR spectroscopy	DNA microarray								
Study Assay Technology Type Term Accession Number		400148								
Study Assay Technology Type Term Source REF	OBI	OBI								
Study Assay Technology Platform	Varian	Affymetrix GeneChip								
Study Assay File Name	a_griffin-assay-Mx.txt	a_griffin-assay-Tx.txt								
STUDY PROTOCOLS										
Study Protocol Name	P-BMAP-1	P-BMAP-2	P-BMAP-3	P-BMAP-4	P-BMAP-5	P-BMAP-6	P-BMAP-7	P-BMAP-8	P-BMAP-9	P-BMAP-10
Study Protocol Type	animal care	nucleic acid extraction	labeling	nucleic acid hybridization	data acquisition	normalization data transformation	sample preparation for assay	data acquisition	data acquisition	data acquisition
Study Protocol Type Term Accession Number		 OBI_0666667 	 OBI_0600038 	 OBI_0302903 		 OBI_0200169 	73			
Study Protocol Type Term Source REF		OBI	OBI	OBI		OBI	OBI			
Study Protocol Description	"All animal procedures conformed to Home Office, UK, guidelines for animal welfare. Male Wistar rats (n = 3 for each time point; control animals fed control diet for the same time period; Charles River UK Ltd.) were fed either standard laboratory chow, or chow supplemented with 1 % orotic acid (Sigma Aldrich, UK) ad libitum. 5-6 Rats were killed by cervical dislocation at days 0, 1, 3 and 14, and the left lateral lobe of the liver excised. Tissues were snap frozen and stored at -80 C."	"Total RNA was extracted by RNA Isolation Kit (Stratagene) from the livers of Wistar rats at day 0 (n = 3), day 1 and 3 (n = 2), and day 14 (n = 3)."	Biotinylated cRNA was prepared following the guidelines described by Affymetrix.	Biotinylated cRNA probes was hybridized following the guidelines described by Affymetrix.	GeneChips were scanning following the guidelines described by Affymetrix using Affymetrix Scanner.	CEL were normalized using Affymetrix MAS 5.0 application	Extracts were prepared (n = 3 for each time point) using an acetonitrile/water extraction procedure as previously described and reconstituted in D2O containing 4 mM trisilylpropionic acid (TSP)	"Solvent suppressed spectra were acquired for tissue extracts on a 5 mm inverse geometry 1H/broadband probe into 32 k data points, averaged over 128 acquisitions."	"Intact tissue (10 mg) was examined using a high-resolution magic angle spinning (MAS) probe. Spectra were acquired at a spinning speed of 5000 Hz, and solvent suppressed spectra were averaged over 256 acquisitions."	
Study Protocol URI										
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Study Protocol Parameters Name	diet;diet availability;sacrifice method;compound;dose							probe; number of acquisition;frequency;magnetic field strength	probe; number of acquisition;frequency;magnetic field strength;spinning frequency	
Study Protocol Parameters Name Term Accession Number										
Study Protocol Parameters Name Term Source REF										
Study Protocol Components Name								Bruker AVANCE;XWINNMR	Bruker AVANCE;XWINNMR	
Study Protocol Components Type								instrument;software	instrument;software	
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STUDY CONTACTS										
Study Person Last Name	Griffin	Jeremy								
Study Person First Name	Julian	Nicholson								
Study Person Mid Initials		K								
Study Person Email										
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Study Person Address	University of Cambridge	Imperial College London								
Study Person Affiliation	Department of Molecular Biology	Biomedical Sciences								
Study Person Roles	submitter;investigator	investigator								
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