Phenotype characterisation using integrated gene transcript, protein and metabolite profiling

Matej Oresic, Clary B. Clish, Eugene J. Davidov, Elwin Verheij, Jack Vogels, Louis M. Havekes, Eric Neumann, Aram Adourian, Stephen Naylor, Jan van der Greef, Thomas Plasterer (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

55 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)205 - 217
Number of pages13
JournalApplied Bioinformatics
Volume3
Issue number4
DOIs
Publication statusPublished - 2004
MoE publication typeA1 Journal article-refereed

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Phenotype
Atherosclerosis
Proteins
Apolipoprotein E3
Biological Phenomena
Metabolomics
Tandem Mass Spectrometry
Genomics
Lipid Metabolism
Liquid Chromatography
Proteomics
Transgenic Mice
Disease Progression
Maintenance
Inflammation
Genes

Cite this

Oresic, M., Clish, C. B., Davidov, E. J., Verheij, E., Vogels, J., Havekes, L. M., ... Plasterer, T. (2004). Phenotype characterisation using integrated gene transcript, protein and metabolite profiling. Applied Bioinformatics, 3(4), 205 - 217. https://doi.org/10.2165/00822942-200403040-00002
Oresic, Matej ; Clish, Clary B. ; Davidov, Eugene J. ; Verheij, Elwin ; Vogels, Jack ; Havekes, Louis M. ; Neumann, Eric ; Adourian, Aram ; Naylor, Stephen ; van der Greef, Jan ; Plasterer, Thomas. / Phenotype characterisation using integrated gene transcript, protein and metabolite profiling. In: Applied Bioinformatics. 2004 ; Vol. 3, No. 4. pp. 205 - 217.
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Oresic, M, Clish, CB, Davidov, EJ, Verheij, E, Vogels, J, Havekes, LM, Neumann, E, Adourian, A, Naylor, S, van der Greef, J & Plasterer, T 2004, 'Phenotype characterisation using integrated gene transcript, protein and metabolite profiling', Applied Bioinformatics, vol. 3, no. 4, pp. 205 - 217. https://doi.org/10.2165/00822942-200403040-00002

Phenotype characterisation using integrated gene transcript, protein and metabolite profiling. / Oresic, Matej; Clish, Clary B.; Davidov, Eugene J.; Verheij, Elwin; Vogels, Jack; Havekes, Louis M.; Neumann, Eric; Adourian, Aram; Naylor, Stephen; van der Greef, Jan; Plasterer, Thomas (Corresponding Author).

In: Applied Bioinformatics, Vol. 3, No. 4, 2004, p. 205 - 217.

Research output: Contribution to journalArticleScientificpeer-review

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AU - Oresic, Matej

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AU - Havekes, Louis M.

AU - Neumann, Eric

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AU - Plasterer, Thomas

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DO - 10.2165/00822942-200403040-00002

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