@article{bf570fa7d53545169075511ed30ec02c,
title = "Sexually-dimorphic targeting of functionally-related genes in COPD",
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.",
author = "Kimberly Glass and John Quackenbush and Silverman, {Edwin K.} and Bartolome Celli and Rennard, {Stephen I.} and Yuan, {Guo Cheng} and DeMeo, {Dawn L.}",
note = "Funding Information: Dr. Silverman reports grants from NIH, grants and other support from COPD Foundation, grants and personal fees from GlaxoSmithKline, personal fees from Merck and travel support from Novartis. Dr. Celli reports research activities for GlaxoSmithKline, Almirall, Novartis, Rorrest and Aeris and consultant activities for GlaxoSmithKline, Boehringer Ingelheim, Dey, Altana, Almirall, Pfizer and Rox. Dr. Rennard reports relationships (board membership/consultancy/lectures/ research funding) since 2011 with AARC, American Board of Internal Medicine, Able Associates, Align2 Acton, Almirall, APT, AstraZeneca, American Thoracic Society, Beilenson, Boehringer Ingelheim, Chiesi, CIPLA, Clarus Acuity, CME Incite, COPDFoundation, Cory Paeth, CSA, CSL Behring, CTS Carmel, Dailchi Sankyo, Decision Resources, Dunn Group, Easton Associates, Elevation Pharma, FirstWord, Forest, GLG Research, Gilead, Globe Life Sciences, GlaxoSmithKline, Guidepoint, Health Advance, HealthStar, HSC Medical Education, Johnson and Johnson, Leerink Swan, LEK, McKinsey, Medical Knowledge, Medimmune, Merck, Navigant, Novartis, Nycomed, Osterman, Pearl, PeerVoice, Penn Technology, Pennside, Pfizer, Prescott, Pro Ed Communications, PriMed, Pulmatrix, Quadrant, Regeneron, Saatchi and Saatchi, Sankyo, Schering, Schlesinger Associates, Shaw Science, Strategic North, Summer Street Research, Synapse, Takeda, Telecon SC, and ThinkEquity. Drs. Glass, DeMeo, Yuan and Quackenbush declare no conflicts of interest. Funding Information: This project has been supported by R01 HL089438, R01 HL111759-01A1, R01 HL111759-02S1 and P01 HL105339. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ECLIPSE clinical Investigators — Bulgaria: Y. Ivanov, Pleven; K. Kostov, Sofia. Canada: J. Bourbeau, Montreal; M. Fitzgerald, Vancouver, BC; P. Hernandez, Halifax, NS; K. Killian, Hamilton, ON; R. Levy, Vancouver, BC; F. Maltais, Montreal; D. O{\textquoteright}Donnell, Kingston, ON. Czech Republic: J. Krepelka, Prague. Denmark: J. Vestbo, Hvidovre. The Netherlands: E. Wouters, Horn-Maastricht. New Zealand: D. Quinn, Wellington. Norway: P. Bakke, Bergen. Slovenia: M. Kosnik, Golnik. Spain: A. Agusti, J. Sauleda, P. de Mallorca. Ukraine: Y. Feschenko, V. Gavrisyuk, L. Yashina, Kiev; N. Monogarova, Donetsk. United Kingdom: P. Calverley, Liverpool; D. Lomas, Cambridge; W. MacNee, Edinburgh; D. Singh, Manchester; J. Wedzicha, London. United States: A. Anzueto, San Antonio, TX; S. Braman, Providence, RI; R. Casaburi, Torrance CA; B. Celli, Boston; G. Giessel, Richmond, VA; M. Gotfried, Phoenix, AZ; G. Greenwald, Rancho Mirage, CA; N. Hanania, Houston; D. Mahler, Lebanon, NH; B. Make, Denver; S. Rennard, Omaha, NE; C. Rochester, New Haven, CT; P. Scanlon, Rochester, MN; D. Schuller, Omaha, NE; F. Sciurba, Pittsburgh; A. Sharafkhaneh, Houston; T. Siler, St. Charles, MO; E. Silverman, Boston; A. Wanner, Miami; R. Wise, Baltimore; R. ZuWallack, Hartford, CT. Steering Committee: H. Coxson (Canada), C. Crim (GlaxoSmithKline, USA), L. Edwards (GlaxoSmithKline, USA), D. Lomas (UK), W. MacNee (UK), E. Silverman (USA), R. Tal Singer (Co-chair, GlaxoSmithKline, USA), J. Vestbo (Co-chair, Denmark), J. Yates (GlaxoSmithKline, USA). Scientific Committee: A. Agusti (Spain), P. Calverley (UK), B. Celli (USA), C. Crim (GlaxoSmithKline, USA), B. Miller (GlaxoSmithKline, USA), W. MacNee (Chair, UK), S. Rennard (USA), R. Tal-Singer (GlaxoSmithKline, USA), E. Wouters (The Netherlands), J. Yates (GlaxoSmithKline, USA).",
year = "2014",
doi = "10.1186/s12918-014-0118-y",
language = "English (US)",
volume = "8",
pages = "118",
journal = "BMC systems biology",
issn = "1752-0509",
publisher = "BioMed Central Ltd.",
}