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This article is part of the supplement: Selected articles from the Second Annual Translational Bioinformatics Conference (TBC 2012)

Open Access Research

Key genes for modulating information flow play a temporal role as breast tumor coexpression networks are dynamically rewired by letrozole

Nadia M Penrod1 and Jason H Moore23*

Author Affiliations

1 Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth College, HB7937 One Medical Center Dr., Lebanon, NH 03766, USA

2 Department of Genetics, Geisel School of Medicine at Dartmouth College, HB7937 One Medical Center Dr., Lebanon, NH 03766, USA

3 Institute for Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth College, HB7937 One Medical Center Dr., Lebanon, NH 03766, USA

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BMC Medical Genomics 2013, 6(Suppl 2):S2  doi:10.1186/1755-8794-6-S2-S2

Published: 7 May 2013

Abstract

Background

Genes do not act in isolation but instead as part of complex regulatory networks. To understand how breast tumors adapt to the presence of the drug letrozole, at the molecular level, it is necessary to consider how the expression levels of genes in these networks change relative to one another.

Methods

Using transcriptomic data generated from sequential tumor biopsy samples, taken at diagnosis, following 10-14 days and following 90 days of letrozole treatment, and a pairwise partial correlation statistic, we build temporal gene coexpression networks. We characterize the structure of each network and identify genes that hold prominent positions for maintaining network integrity and controlling information-flow.

Results

Letrozole treatment leads to extensive rewiring of the breast tumor coexpression network. Approximately 20% of gene-gene relationships are conserved over time in the presence of letrozole while 80% of relationships are condition dependent. The positions of influence within the networks are transiently held with few genes stably maintaining high centrality scores across the three time points.

Conclusions

Genes integral for maintaining network integrity and controlling information flow are dynamically changing as the breast tumor coexpression network adapts to perturbation by the drug letrozole.