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Integrative biological analysis of the APOE*3-leiden transgenic mouse

Clish, Clary B. (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Davidov, Eugene (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Oresic, Matej, 1967- (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
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Plasterer, Thomas N. (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Lavine, Gary (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Londo, Tom (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Meys, Michael (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Snell, Philip (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Stochaj, Wayne (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Adourian, Aram (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Zhang, Xiang (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Morel, Nicole (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Neumann, Eric (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Verheij, Elwin (author)
TNO Pharma, Zeist, Netherlands
Vogels, Jack T. W. E. (author)
TNO Pharma, Zeist, Netherlands
Havekes, Louis M. (author)
TNO Prevention and Health, Gaubius Laboratorium, Leiden, Netherlands; Departments of Cardiology and Internal Medicine and Leiden Center for Cardiovascular Research, Leiden University Medical Center, Leiden, Netherlands
Afeyan, Noubar (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
Regnier, Fred (author)
Department of Chemistry, Purdue University, Lafayette, Indiana, USA
van der Greef, Jan (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA; TNO Pharma, Zeist, Netherlands; Division of Analytical Biosciences, Leiden/Amsterdam Centre for Drug Research, Leiden University, Leiden, Netherlands
Naylor, Stephen (author)
Beyond Genomics, Inc., Waltham, Massachusetts, USA
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Beyond Genomics, Inc, Waltham, Massachusetts, USA TNO Pharma, Zeist, Netherlands (creator_code:org_t)
Mary Ann Liebert, 2004
2004
English.
In: Omics. - : Mary Ann Liebert. - 1536-2310 .- 1557-8100. ; 8:1, s. 3-13
Related links:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Integrative (or systems biology) is a new approach to analyzing biological entities as integrated systems of genetic, genomic, protein, metabolite, cellular, and pathway events that are in flux and interdependent. Here, we demonstrate the application of intregrative biological analysis to a mammalian disease model, the apolipoprotein E3-Leiden (APO*E3) transgenic mouse. Mice selected for the study were fed a normal chow diet and sacrificed at 9 weeks of age-conditions under which they develop only mild type I and II atherosclerotic lesions. Hepatic mRNA expression analysis showed a 25% decrease in APO A1 and a 43% increase in liver fatty acid binding protein expression between transgenic and wild type control mice, while there was no change in PPAR-alpha expression. On-line high performance liquid chromatography-mass spectrometry quantitative profiling of tryptic digests of soluble liver proteins and liver lipids, coupled with principle component analysis, enabled rapid identification of early protein and metabolite markers of disease pathology. These included a 44% increase in L-FABP in transgenic animals compared to controls, as well as an increase in triglycerides and select bioactive lysophosphatidylcholine species. A correlation analysis of identified genes, proteins, and lipids was used to construct an interaction network. Taken together, these results indicate that integrative biology is a powerful tool for rapid identification of early markers and key components of pathophysiologic processes, and constitute the first application of this approach to a mammalian system.

Subject headings

NATURVETENSKAP  -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)

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