title: Comprehensive Analysis of Transcriptome Sequencing Data in the Lung Tissues of COPD Subjects.
abstract: Background and Objectives. Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by airflow limitation. Although airway inflammation and oxidative stress are known to be important in the pathogenesis of COPD, the mechanism underlying airflow obstruction is not fully understood. Gene expression profiling of lung tissue was performed to define the molecular pathways that are dysregulated in COPD. Methods. RNA was isolated from lung tissues obtained from 98 subjects with COPD and 91 control subjects with normal spirometry. The RNA samples were processed with RNA-seq using the HiSeq 2000 system. Genes expressed differentially between the two groups were identified using Student's t-test. Results. After filtering for genes with zero counts and noncoding genes, 16,676 genes were evaluated. A total of 2312 genes were differentially expressed between the lung tissues of COPD and control subjects (false discovery rate corrected q < 0.01). The expression of genes related to oxidative phosphorylation and protein catabolism was reduced and genes related to chromatin modification were dysregulated in lung tissues of COPD subjects. Conclusions. Oxidative phosphorylation, protein degradation, and chromatin modification were the most dysregulated pathways in the lung tissues of COPD subjects. These findings may have clinical and mechanistic implications in COPD.
authors.affiliation: Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon 200-722, Republic of Korea.
authors.forename: Woo Jin
authors.identifier: 0000-0003-2927-370X
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Seoul National University Biomedical Informatics and Systems Biomedical Informatics Research Center, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Pulmonary and Critical Care Medicine, and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Pulmonary and Critical Care Medicine, and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Sang-Do
authors.initials: SD
authors.lastname: Lee
authors.affiliation: Seoul National University Biomedical Informatics and Systems Biomedical Informatics Research Center, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Ju Han
authors.identifier: 0000-0003-1522-9038
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pulmonary and Critical Care Medicine, and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors.forename: Yeon-Mok
authors.initials: YM
authors.lastname: Oh
references.citation: Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14895-900
references.pmid: 15469929
references.citation: Genome Med. 2012 Aug 31;4(8):67
references.pmid: 22937864
references.citation: Mol Cell Biol. 2009 Nov;29(22):6074-85
references.pmid: 19703992
references.citation: Respir Med. 2012 Jul;106(7):954-61
references.pmid: 22521224
references.citation: N Engl J Med. 2009 Jun 4;360(23):2445-54
references.pmid: 19494220
references.citation: Nat Methods. 2008 Jul;5(7):621-8
references.pmid: 18516045
references.citation: Am J Respir Cell Mol Biol. 2009 Mar;40(3):359-67
references.pmid: 18849563
references.citation: Nat Rev Genet. 2011 Sep 16;12(10):715-29
references.pmid: 21921927
references.citation: Bioinformatics. 2009 May 1;25(9):1105-11
references.pmid: 19289445
references.citation: Nat Rev Genet. 2011 Feb;12(2):87-98
references.pmid: 21191423
references.citation: Nat Biotechnol. 2010 May;28(5):511-5
references.pmid: 20436464
references.citation: Am J Respir Cell Mol Biol. 2004 Dec;31(6):601-10
references.pmid: 15374838
references.citation: PLoS Comput Biol. 2012;8(12):e1002858
references.pmid: 23300429
references.citation: Genome Res. 2012 Oct;22(10):2008-17
references.pmid: 22722343
references.citation: Am J Respir Crit Care Med. 2009 Dec 15;180(12):1196-207
references.pmid: 19797762
references.citation: Am J Respir Crit Care Med. 2011 May 15;183(10):1295-301
references.pmid: 21596832
references.citation: Am J Respir Crit Care Med. 2013 May 1;187(9):933-42
references.pmid: 23471465
references.citation: Am J Respir Crit Care Med. 2008 Feb 15;177(4):402-11
references.pmid: 17975202
references.citation: N Engl J Med. 2005 May 12;352(19):1967-76
references.pmid: 15888697
references.citation: Eur Respir J. 2005 Aug;26(2):319-38
references.pmid: 16055882
references.citation: Cancer Prev Res (Phila). 2011 Jun;4(6):803-17
references.pmid: 21636547
references.citation: Am J Physiol Lung Cell Mol Physiol. 2011 Jul;301(1):L110-6
references.pmid: 21460121
references.citation: Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65
references.pmid: 22878278
references.citation: Int J Hyg Environ Health. 2011 Mar;214(2):138-44
references.pmid: 21095158
references.citation: J Biol Chem. 2011 Oct 28;286(43):37067-76
references.pmid: 21903582
references.citation: Science. 2006 Sep 29;313(5795):1929-35
references.pmid: 17008526
references.citation: Eur J Hum Genet. 2013 Feb;21(2):134-42
references.pmid: 22739340
references.citation: Transcription. 2011 Nov-Dec;2(6):244-53
references.pmid: 22223048
references.citation: Nat Protoc. 2012 Mar 01;7(3):562-78
references.pmid: 22383036
references.citation: Respir Res. 2009 Sep 02;10:81
references.pmid: 19723343
references.citation: Proc Am Thorac Soc. 2008 Dec 1;5(8):834-41
references.pmid: 19017738
references.citation: Eur Respir J. 2012 Nov;40(5):1260-8
references.pmid: 22441749
references.citation: Am J Respir Cell Mol Biol. 2012 Nov;47(5):698-708
references.pmid: 22842494
references.citation: Nucleic Acids Res. 2012 Apr;40(8):e61
references.pmid: 22266656
references.citation: Am J Respir Cell Mol Biol. 2004 Dec;31(6):595-600
references.pmid: 15284076
references.citation: BMC Genomics. 2012 Feb 29;13:82
references.pmid: 22375630