Multi-tissue coexpression networks reveal unexpected subnetworks associated with disease

Obesity is a particularly complex disease that at least partially involves genetic and environmental perturbations to gene-networks connecting the hypothalamus and several metabolic tissues, resulting in an energy imbalance at the systems level. To provide an inter-tissue view of obesity with respec...

Full description

Saved in:

Bibliographic Details
Published in:	Genome biology Vol. 10; no. 5; p. R55
Main Authors:	Dobrin, Radu, Zhu, Jun, Molony, Cliona, Argman, Carmen, Parrish, Mark L, Carlson, Sonia, Allan, Mark F, Pomp, Daniel, Schadt, Eric E
Format:	Journal Article
Language:	English
Published:	England BioMed Central 22-05-2009
Subjects:	Adipose Tissue - metabolism Animals Gene Regulatory Networks Humans Liver - metabolism Mice Obesity - genetics Obesity - physiopathology
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Obesity is a particularly complex disease that at least partially involves genetic and environmental perturbations to gene-networks connecting the hypothalamus and several metabolic tissues, resulting in an energy imbalance at the systems level. To provide an inter-tissue view of obesity with respect to molecular states that are associated with physiological states, we developed a framework for constructing tissue-to-tissue coexpression networks between genes in the hypothalamus, liver or adipose tissue. These networks have a scale-free architecture and are strikingly independent of gene-gene coexpression networks that are constructed from more standard analyses of single tissues. This is the first systematic effort to study inter-tissue relationships and highlights genes in the hypothalamus that act as information relays in the control of peripheral tissues in obese mice. The subnetworks identified as specific to tissue-to-tissue interactions are enriched in genes that have obesity-relevant biological functions such as circadian rhythm, energy balance, stress response, or immune response. Tissue-to-tissue networks enable the identification of disease-specific genes that respond to changes induced by different tissues and they also provide unique details regarding candidate genes for obesity that are identified in genome-wide association studies. Identifying such genes from single tissue analyses would be difficult or impossible.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1474-760X 1465-6906 1474-760X 1465-6914
DOI:	10.1186/gb-2009-10-5-r55