Title
Phenotype characterisation using integrated gene transcript, protein and metabolite profiling
Author
Orešič, M.
Clish, C.B.
Davidov, E.J.
Verheij, E.
Vogels, J.
Havekes, L.M.
Neumann, E.
Adourian, A.
Naylor, S.
van der Greef, J.
Plasterer, T.
TNO Preventie en Gezondheid
Publication year
2004
Abstract
Multifactorial diseases present a significant challenge for functional genomics. Owing to their multiple compartmental effects and complex biomolecular activities, such diseases cannot be adequately characterised by changes in single components, nor can pathophysiological changes be understood by observing gene transcripts alone. Instead, a pattern of subtle changes is observed in multifactorial diseases across multiple tissues and organs with complex associations between corresponding gene, protein and metabolite levels. This article presents methods for exploratory and integrative analysis of pathophysiological changes at the biomolecular level. In particular, novel approaches are introduced for the following challenges: (i) data processing and analysis methods for proteomic and metabolomic data obtained by electrospray ionisation (ESI) liquid chromatography-tandem mass spectrometry (LC/MS); (ii) association analysis of integrated gene, protein and metabolite patterns that are most descriptive of pathophysiological changes; and (iii) interpretation of results obtained from association analyses in the context of known biological processes. These novel approaches are illustrated with the apolipoprotein E3-Leiden transgenic mouse model, a commonly used model of atherosclerosis. We seek to gain insight into the early responses of disease onset and progression by determining and identifying - well in advance of pathogenic manifestations of disease - the sets of gene transcripts, proteins and metabolites, along with their putative relationships in the transgenic model and associated wild-type cohort. Our results corroborate previous findings and extend predictions for three processes in atherosclerosis: aberrant lipid metabolism, inflammation, and tissue development and maintenance. © 2004 Adis Data Information BV. All rights reserved.
Subject
Biology
Analytical research
Biomedical research
Apolipoprotein E3
Protein
Animal experiment
Animal tissue
Atherosclerosis
Cohort analysis
Controlled study
Disease course
Electrospray
Genetic transcription
Information processing
Liquid chromatography
Male
Mass spectrometry
Metabolite
Metabolomics
Mouse
Nonhuman
Nucleotide sequence
Onset age
Pathophysiology
Proteomics
Transgenic mouse
Wild type
Algorithms
Animals
Cells, Cultured
Computer Simulation
Gene Expression Regulation
Liver
Mass Spectrometry
Mice
Models, Biological
Peptide Mapping
Phenotype
Proteome
Signal Transduction
Systems Integration
Transcription Factors
Mus musculus
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DOI
https://doi.org/10.2165/00822942-200403040-00002
TNO identifier
238100
ISSN
1175-5636
Source
Applied Bioinformatics, 3 (4), 205-217
Document type
article