NDLI: The use of network analyses for elucidating mechanisms in cardiovascular disease

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Molecular BioSystems Vol -5

Molecular BioSystems Vol -4

Molecular BioSystems Vol -3

Molecular BioSystems Vol -2

The use of network analyses for elucidating mechanisms in cardiovascular disease

Content Provider	Royal Society of Chemistry (RSC)
Author	Diez, Diego Hansson, Göran K. Paulsson-Berne, Gabrielle Hedin, Ulf Gabrielsen, Anders Wheelock, Craig E. Wheelock, Åsa M. Goto, Susumu Haeggström, Jesper Z.
Copyright Year	2010
Abstract	Systems biology offers the potential to provide new insights into our understanding of the pathogenesis of complex diseases such as atherosclerosis. It seeks to comprehend the system properties of the non-linear interactions of the multiple biomolecular components that characterize a living organism. An important component of this research approach is identifying the biological networks that connect the differing elements of a system and in the process describe the characteristics that define a shift in equilibrium from a healthy to a diseased state. The utility of this method becomes clear when applied to multifactorial diseases with complex etiologies such as inflammatory-related diseases, herein exemplified by cardiovascular disease. In this study, the application of network theory to systems biology is described in detail and an example is provided using data from a clinical biobank database of carotid endarterectomies from the Karolinska University Hospital (Biobank of Karolinska Endarterectomies, BiKE). Data from 47 microarrays were examined using a combination of Bioconductor modules and the Cytoscape resource with several associated plugins to analyze the transcriptomics data and create a combined gene association and correlation network of atherosclerosis. The methodology and workflow are described in detail, with a total of 43 genes found to be differentially expressed on a gender-specific basis, of which 15 were not directly linked to the sex chromosomes. In particular, the APOC1 gene was 2.1-fold down-regulated in plaques in women relative to men and was selected for further analysis based upon a purported role in cardiovascular disease. The resulting network was identified as a scale-free network that contained specific sub-networks related to immune function and lipid biosynthesis. These sub-networks link atherosclerotic-related genes to other genes that may not have previously known roles in disease etiology and only evidence small alterations, which are challenging to find by statistical and comparison-based methods. A number of Gene Ontology (GO), BioCarta and KEGG pathways involved in the atherosclerotic process were identified in the constructed sub-network, with 19 GO pathways related to APOC1 of which ‘phospholipid efflux’ evidenced the strongest association. The utility and functionality of network analysis and the different Cytoscape plugins employed are discussed. Lastly, the applications of these methods to cardiovascular disease are discussed with focus on the current limitations and future visions of this emerging field.
Starting Page	289
Ending Page	304
Page Count	16
File Format	HTM / HTML PDF
ISSN	1742206X
Volume Number	6
Issue Number	2
Journal	Molecular BioSystems
DOI	10.1039/b912078e
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Cytoscape Bioconductor Scale-free network Phospholipid Cardiovascular disease Karolinska University Hospital Common carotid artery Lipid Gene ontology Network theory Gene Systems biology Biobank Atherosclerosis KEGG BioCarta Biobank of Karolinska Endarterectomies
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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Supplementary information: (2008).

Systems biology approaches and pathway tools for investigating cardiovascular disease

Carotid Atherosclerosis is Correlated with Extent and Severity of Coronary Artery Disease Evaluated by Myocardial Perfusion Scintigraphy

Intimal Medial Thickening of Common Carotid Artery as Indicator of Coronary Artery Disease

Lipoprotein(a) and Cardiovascular Outcomes after Revascularization of Carotid and Lower Limbs Arteries

Characterization of systemic metabolic phenotypes associated with subclinical atherosclerosis

Association between coronary artery atherosclerosis and the intima-media thickness of the common carotid artery measured on ultrasonography.

Symptomatic Carotid Artery Stenosis: Surgery, Stenting, or Medical Therapy?

Carotid artery atherosclerosis evaluation research based on vascular wall magnetic resonance imaging.

The use of network analyses for elucidating mechanisms in cardiovascular disease

Similar Documents

Supplementary information: (2008).

Systems biology approaches and pathway tools for investigating cardiovascular disease

Carotid Atherosclerosis is Correlated with Extent and Severity of Coronary Artery Disease Evaluated by Myocardial Perfusion Scintigraphy

Intimal Medial Thickening of Common Carotid Artery as Indicator of Coronary Artery Disease

Lipoprotein(a) and Cardiovascular Outcomes after Revascularization of Carotid and Lower Limbs Arteries

Characterization of systemic metabolic phenotypes associated with subclinical atherosclerosis

Association between coronary artery atherosclerosis and the intima-media thickness of the common carotid artery measured on ultrasonography.

Symptomatic Carotid Artery Stenosis: Surgery, Stenting, or Medical Therapy?

Carotid artery atherosclerosis evaluation research based on vascular wall magnetic resonance imaging.

The use of network analyses for elucidating mechanisms in cardiovascular disease