PMID- 25582225 OWN - NLM STAT- MEDLINE DCOM- 20160129 LR - 20181113 IS - 1755-8794 (Electronic) IS - 1755-8794 (Linking) VI - 8 DP - 2015 Jan 13 TI - Identifying a gene expression signature of frequent COPD exacerbations in peripheral blood using network methods. PG - 1 LID - 10.1186/s12920-014-0072-y [doi] LID - 1 AB - BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors. Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility. Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations. METHODS: Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) study. Linear regression, weighted gene co-expression network analysis (WGCNA), and pathway analysis were used to identify signatures and network sub-modules associated with the number of exacerbations within the previous year; other COPD-related phenotypes were also investigated. RESULTS: Individual genes were not found to be significantly associated with the number of exacerbations. However using network methods, a statistically significant gene module was identified, along with other modules showing moderate association. A diverse signature was observed across these modules using pathway analysis, marked by differences in B cell and NK cell activity, as well as cellular markers of viral infection. Within two modules, gene set enrichment analysis recapitulated the molecular signatures of two gene expression experiments; one involving sputum from asthma exacerbations and another involving viral lung infections. The plasma biomarker myeloperoxidase (MPO) was associated with the number of recent exacerbations. CONCLUSION: A distinct signature of COPD exacerbations may be observed in peripheral blood months following the acute illness. While not predictive in this cross-sectional analysis, these results will be useful in uncovering the molecular pathogenesis of COPD exacerbations. FAU - Morrow, Jarrett D AU - Morrow JD AD - Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA, 02115, USA. jarrett.morrow@channing.harvard.edu. FAU - Qiu, Weiliang AU - Qiu W AD - Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA, 02115, USA. weiliang.qiu@channing.harvard.edu. FAU - Chhabra, Divya AU - Chhabra D AD - Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA, 02115, USA. redic@channing.harvard.edu. AD - Division of Biomedical Informatics, University of California, San Diego, CA, USA. redic@channing.harvard.edu. FAU - Rennard, Stephen I AU - Rennard SI AD - University of Nebraska Medical Center, Omaha, NE, USA. srennard@unmc.edu. FAU - Belloni, Paula AU - Belloni P AD - Genentech, Member of the Roche Group, South San Francisco, CA, USA. belloni.paula@gene.com. FAU - Belousov, Anton AU - Belousov A AD - Roche Innovation Center, Penzberg, Germany. anton.belousov@roche.com. FAU - Pillai, Sreekumar G AU - Pillai SG AD - Hoffman La Roche, Nutley, NJ, USA. pillaisreekumar@yahoo.com. AD - Current address: Eli Lilly and Company, Indianapolis, IN, USA. pillaisreekumar@yahoo.com. FAU - Hersh, Craig P AU - Hersh CP AD - Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA, 02115, USA. craig.hersh@channing.harvard.edu. LA - eng GR - R01 HL094635/HL/NHLBI NIH HHS/United States GR - R01 NR013377/NR/NINR NIH HHS/United States GR - R01HL094635/HL/NHLBI NIH HHS/United States GR - P01 HL105339/HL/NHLBI NIH HHS/United States GR - R01NR013377/NR/NINR NIH HHS/United States GR - R01HL111759/HL/NHLBI NIH HHS/United States GR - P01HL105339/HL/NHLBI NIH HHS/United States GR - R01 HL111759/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150113 PL - England TA - BMC Med Genomics JT - BMC medical genomics JID - 101319628 RN - 0 (Biomarkers) SB - IM MH - Aged MH - Algorithms MH - Biomarkers/blood MH - Computational Biology/*methods MH - Cross-Sectional Studies MH - Emphysema/blood MH - Female MH - *Gene Expression Profiling MH - *Genetic Predisposition to Disease MH - Humans MH - Linear Models MH - Male MH - Middle Aged MH - Phenotype MH - Pulmonary Disease, Chronic Obstructive/blood/*genetics MH - Sequence Analysis, RNA MH - Severity of Illness Index MH - Transcriptome PMC - PMC4302028 EDAT- 2015/01/15 06:00 MHDA- 2016/01/30 06:00 PMCR- 2015/01/13 CRDT- 2015/01/14 06:00 PHST- 2014/07/03 00:00 [received] PHST- 2014/12/12 00:00 [accepted] PHST- 2015/01/14 06:00 [entrez] PHST- 2015/01/15 06:00 [pubmed] PHST- 2016/01/30 06:00 [medline] PHST- 2015/01/13 00:00 [pmc-release] AID - s12920-014-0072-y [pii] AID - 72 [pii] AID - 10.1186/s12920-014-0072-y [doi] PST - epublish SO - BMC Med Genomics. 2015 Jan 13;8:1. doi: 10.1186/s12920-014-0072-y.