Multi-tissue coexpression networks reveal unexpected subnetworks associated with disease.

Abstract:

BACKGROUND: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. RESULTS: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. CONCLUSIONS: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.

journal_name

Genome Biol

journal_title

Genome biology

authors

Dobrin R,Zhu J,Molony C,Argman C,Parrish ML,Carlson S,Allan MF,Pomp D,Schadt EE

doi

10.1186/gb-2009-10-5-r55

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

R55

issue

5

eissn

1474-7596

issn

1474-760X

pii

gb-2009-10-5-r55

journal_volume

10

pub_type

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