Document Type
Article
Journal Title
BMC Systems Biology
Publication Date
2014
Volume
8
Abstract
BACKGROUND: There is growing evidence that many diseases develop, progress, and respond to therapy differently in men and women. This variability may manifest as a result of sex-specific structures in gene regulatory networks that influence how those networks operate. However, there are few methods to identify and characterize differences in network structure, slowing progress in understanding mechanisms driving sexual dimorphism.
RESULTS: Here we apply an integrative network inference method, PANDA (Passing Attributes between Networks for Data Assimilation), to model sex-specific networks in blood and sputum samples from subjects with Chronic Obstructive Pulmonary Disease (COPD). We used a jack-knifing approach to build an ensemble of likely networks for each sex. By adapting statistical methods to compare these network ensembles, we were able to identify strong differential-targeting patterns associated with functionally-related sets of genes, including those involved in mitochondrial function and energy metabolism. Network analysis also identified several potential sex- and disease-specific transcriptional regulators of these pathways.
CONCLUSIONS: Network analysis yielded insight into potential mechanisms driving sexual dimorphism in COPD that were not evident from gene expression analysis alone. We believe our ensemble approach to network analysis provides a principled way to capture sex-specific regulatory relationships and could be applied to identify differences in gene regulatory patterns in a wide variety of diseases and contexts.
MeSH Headings
Female, Gene Regulatory Networks, Humans, Male, Models, Biological, Principal Component Analysis, Pulmonary Disease, Chronic Obstructive, Regulatory Elements, Transcriptional, Sex Characteristics, Software, Sputum
DOI Link
ISSN
1752-0509
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Glass, Kimberly; Quackenbush, John; Silverman, Edwin K.; Celli, Bartolome; Rennard, Stephen I.; Yuan, Guo-Cheng; and DeMeo, Dawn L., "Sexually-Dimorphic Targeting of Functionally-Related Genes in COPD" (2014). Journal Articles: Pulmonary & Critical Care Med. 72.
https://digitalcommons.unmc.edu/com_pulm_articles/72
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