Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Respiratory Research
Published in: Respiratory Research 1/2017

Open Access 01-12-2017 | Review

Using omics approaches to understand pulmonary diseases

Authors: Mengyuan Kan, Maya Shumyatcher, Blanca E. Himes

Published in: Respiratory Research | Issue 1/2017

Login to get access

Abstract

Omics approaches are high-throughput unbiased technologies that provide snapshots of various aspects of biological systems and include: 1) genomics, the measure of DNA variation; 2) transcriptomics, the measure of RNA expression; 3) epigenomics, the measure of DNA alterations not involving sequence variation that influence RNA expression; 4) proteomics, the measure of protein expression or its chemical modifications; and 5) metabolomics, the measure of metabolite levels. Our understanding of pulmonary diseases has increased as a result of applying these omics approaches to characterize patients, uncover mechanisms underlying drug responsiveness, and identify effects of environmental exposures and interventions. As more tissue- and cell-specific omics data is analyzed and integrated for diverse patients under various conditions, there will be increased identification of key mechanisms that underlie pulmonary biological processes, disease endotypes, and novel therapeutics that are efficacious in select individuals. We provide a synopsis of how omics approaches have advanced our understanding of asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), and pulmonary arterial hypertension (PAH), and we highlight ongoing work that will facilitate pulmonary disease precision medicine.
Literature
1.
Duggan DJ, Bittner M, Chen Y, Meltzer P, Trent JM. Expression profiling using cDNA microarrays. Nat Genet. 1999;21:10–4.PubMedCrossRef
2.
3.
Altelaar AF, Munoz J, Heck AJ. Next-generation proteomics: towards an integrative view of proteome dynamics. Nat Rev Genet. 2013;14:35–48.PubMedCrossRef
4.
5.
6.
Plenge RM, Scolnick EM, Altshuler D. Validating therapeutic targets through human genetics. Nat Rev Drug Discov. 2013;12:581–94.PubMedCrossRef
7.
Collins DC, Sundar R, Lim JS, Yap TA. Towards precision medicine in the clinic: from biomarker discovery to novel therapeutics. Trends Pharmacol Sci. 2017;38:25–40.PubMedCrossRef
8.
9.
10.
11.
Ritchie MD, Holzinger ER, Li R, Pendergrass SA, Kim D. Methods of integrating data to uncover genotype-phenotype interactions. Nat Rev Genet. 2015;16:85–97.PubMedCrossRef
12.
Brookes AJ, Robinson PN. Human genotype-phenotype databases: aims, challenges and opportunities. Nat Rev Genet. 2015;16:702–15.PubMedCrossRef
13.
Akinbami L, Moorman J, Bailey C, Zahran H, King M, Johnson C, Liu X. Trends in asthma prevalence, health care use, and mortality in the United States, 2001–2010. In: NCHS data brief, no 94. Hyattsville, MD: National Center for Health Statistics; 2012.
14.
Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC. Chronic obstructive pulmonary disease surveillance--United States, 1971-2000. MMWR Surveill Summ. 2002;51:1–16.
15.
Stapleton RD, Wang BM, Hudson LD, Rubenfeld GD, Caldwell ES, Steinberg KP. Causes and timing of death in patients with ARDS. Chest. 2005;128:525–32.PubMedCrossRef
16.
Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188:733–48.PubMedCrossRef
17.
Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46:903–75.PubMedCrossRef
18.
Berg JS, Amendola LM, Eng C, Van Allen E, Gray SW, Wagle N, Rehm HL, DeChene ET, Dulik MC, Hisama FM, et al. Processes and preliminary outputs for identification of actionable genes as incidental findings in genomic sequence data in the clinical sequencing exploratory research consortium. Genet Med. 2013;15:860–7.PubMedPubMedCentralCrossRef
19.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24.PubMedPubMedCentralCrossRef
20.
The International HapMap Consortium. The international HapMap project. Nature. 2003;426:789–96.CrossRef
21.
22.
Goodwin S, McPherson JD, McCombie WR. Coming of age: ten years of next-generation sequencing technologies. Nat Rev Genet. 2016;17:333–51.PubMedCrossRef
23.
Hinds DA, McMahon G, Kiefer AK, Do CB, Eriksson N, Evans DM, St Pourcain B, Ring SM, Mountain JL, Francke U, et al. A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. Nat Genet. 2013;45:907–11.PubMedPubMedCentralCrossRef
24.
Manolio TA. Genomewide association studies and assessment of the risk of disease. N Engl J Med. 2010;363:166–76.PubMedCrossRef
25.
Spencer CC, Su Z, Donnelly P, Marchini J. Designing genome-wide association studies: sample size, power, imputation, and the choice of genotyping chip. PLoS Genet. 2009;5:e1000477.PubMedPubMedCentralCrossRef
26.
27.
Manolio TA. Bringing genome-wide association findings into clinical use. Nat Rev Genet. 2013;14:549–58.PubMedCrossRef
28.
Eicher JD, Landowski C, Stackhouse B, Sloan A, Chen W, Jensen N, Lien JP, Leslie R, Johnson AD. GRASP v2.0: an update on the genome-wide repository of associations between SNPs and phenotypes. Nucleic Acids Res. 2015;43:D799–804.PubMedCrossRef
29.
Mailman MD, Feolo M, Jin Y, Kimura M, Tryka K, Bagoutdinov R, Hao L, Kiang A, Paschall J, Phan L, et al. The NCBI dbGaP database of genotypes and phenotypes. Nat Genet. 2007;39:1181–6.PubMedPubMedCentralCrossRef
30.
Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, Downey P, Elliott P, Green J, Landray M, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12:e1001779.PubMedPubMedCentralCrossRef
31.
Auer PL, Reiner AP, Wang G, Kang HM, Abecasis GR, Altshuler D, Bamshad MJ, Nickerson DA, Tracy RP, Rich SS, et al. Guidelines for large-scale sequence-based complex trait association studies: lessons learned from the NHLBI exome sequencing project. Am J Hum Genet. 2016;99:791–801.PubMedPubMedCentralCrossRef
32.
33.
Hardin M, Silverman E. Chronic obstructive pulmonary disease genetics: a review of the past and a look into the future. Chronic Obstruct Pulm Dis: Journal of the COPD Foundation. 2014;1:33–46.CrossRef
34.
Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, von Mutius E, Farrall M, Lathrop M, Cookson WO. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med. 2010;363:1211–21.PubMedPubMedCentralCrossRef
35.
Torgerson DG, Ampleford EJ, Chiu GY, Gauderman WJ, Gignoux CR, Graves PE, Himes BE, Levin AM, Mathias RA, Hancock DB, et al. Meta-analysis of genome-wide association studies of asthma in ethnically diverse north American populations. Nat Genet. 2011;43:887–92.PubMedPubMedCentralCrossRef
36.
Cho MH, Boutaoui N, Klanderman BJ, Sylvia JS, Ziniti JP, Hersh CP, DeMeo DL, Hunninghake GM, Litonjua AA, Sparrow D, et al. Variants in FAM13A are associated with chronic obstructive pulmonary disease. Nat Genet. 2010;42:200–2.PubMedPubMedCentralCrossRef
37.
Cho MH, McDonald ML, Zhou X, Mattheisen M, Castaldi PJ, Hersh CP, Demeo DL, Sylvia JS, Ziniti J, Laird NM, et al. Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis. Lancet Respir Med. 2014;2:214–25.PubMedPubMedCentralCrossRef
38.
Ono JG, Worgall TS, Worgall S. 17q21 locus and ORMDL3: an increased risk for childhood asthma. Pediatr Res. 2014;75:165–70.PubMedCrossRef
39.
Miller M, Rosenthal P, Beppu A, Mueller JL, Hoffman HM, Tam AB, Doherty TA, MD MG, Pena CA, Suzukawa M, et al. ORMDL3 transgenic mice have increased airway remodeling and airway responsiveness characteristic of asthma. J Immunol. 2014;192:3475–87.PubMedPubMedCentralCrossRef
40.
Miller M, Tam AB, Cho JY, Doherty TA, Pham A, Khorram N, Rosenthal P, Mueller JL, Hoffman HM, Suzukawa M, et al. ORMDL3 is an inducible lung epithelial gene regulating metalloproteases, chemokines, OAS, and ATF6. Proc Natl Acad Sci. 2012;109:16648–53.PubMedPubMedCentralCrossRef
41.
Lao T, Jiang Z, Yun J, Qiu W, Guo F, Huang C, Mancini JD, Gupta K, Laucho-Contreras ME, Naing ZZ, et al. Hhip haploinsufficiency sensitizes mice to age-related emphysema. Proc Natl Acad Sci U S A. 2016;113:E4681–7.PubMedPubMedCentralCrossRef
42.
Kaur-Knudsen D, Nordestgaard BG, Bojesen SE. CHRNA3 genotype, nicotine dependence, lung function and disease in the general population. Eur Respir J. 2012;40:1538–44.PubMedCrossRef
43.
Bonnelykke K, Sleiman P, Nielsen K, Kreiner-Moller E, Mercader JM, Belgrave D, den Dekker HT, Husby A, Sevelsted A, Faura-Tellez G, et al. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. Nat Genet. 2014;46:51–5.PubMedCrossRef
44.
Kong X, Cho MH, Anderson W, Coxson HO, Muller N, Washko G, Hoffman EA, Bakke P, Gulsvik A, Lomas DA, et al. Genome-wide association study identifies BICD1 as a susceptibility gene for emphysema. Am J Respir Crit Care Med. 2011;183:43–9.PubMedCrossRef
45.
Levin AM, Mathias RA, Huang L, Roth LA, Daley D, Myers RA, Himes BE, Romieu I, Yang M, Eng C, et al. A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations. J Allergy Clin Immunol. 2013;131:1176–84.PubMedCrossRef
46.
Granada M, Wilk JB, Tuzova M, Strachan DP, Weidinger S, Albrecht E, Gieger C, Heinrich J, Himes BE, Hunninghake GM, et al. A genome-wide association study of plasma total IgE concentrations in the Framingham heart study. J Allergy Clin Immunol. 2012;129:840–5. e821PubMedCrossRef
47.
Potaczek DP, Kabesch M. Current concepts of IgE regulation and impact of genetic determinants. Clin Exp Allergy. 2012;42:852–71.PubMedCrossRef
48.
Kheirallah AK, Miller S, Hall IP, Sayers I. Translating lung function genome-wide association study (GWAS) findings: new insights for lung biology. Adv Genet. 2016;93:57–145.PubMed
49.
50.
Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187:347–65.PubMedCrossRef
51.
Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS, Committee GS. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO global initiative for chronic obstructive lung disease (GOLD) workshop summary. Am J Respir Crit Care Med. 2001;163:1256–76.PubMedCrossRef
52.
Quax RA, Manenschijn L, Koper JW, Hazes JM, Lamberts SW, van Rossum EF, Feelders RA. Glucocorticoid sensitivity in health and disease. Nat Rev Endocrinol. 2013;9:670–86.PubMedCrossRef
53.
McGeachie MJ, Stahl EA, Himes BE, Pendergrass SA, Lima JJ, Irvin CG, Peters SP, Ritchie MD, Plenge RM, Tantisira KG. Polygenic heritability estimates in pharmacogenetics: focus on asthma and related phenotypes. Pharmacogenet Genomics. 2013;23:324–8.PubMedPubMedCentralCrossRef
54.
Himes BE, Jiang X, Hu R, Wu AC, Lasky-Su JA, Klanderman BJ, Ziniti J, Senter-Sylvia J, Lima JJ, Irvin CG, et al. Genome-wide association analysis in asthma subjects identifies SPATS2L as a novel bronchodilator response gene. PLoS Genet. 2012;8:e1002824.PubMedPubMedCentralCrossRef
55.
Tantisira KG, Lasky-Su J, Harada M, Murphy A, Litonjua AA, Himes BE, Lange C, Lazarus R, Sylvia J, Klanderman B, et al. Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma. N Engl J Med. 2011;365:1173–83.PubMedPubMedCentralCrossRef
56.
Igartua C, Myers RA, Mathias RA, Pino-Yanes M, Eng C, Graves PE, Levin AM, Del-Rio-Navarro BE, Jackson DJ, Livne OE, et al. Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma. Nat Commun. 2015;6:5965.PubMedPubMedCentralCrossRef
57.
Qiao D, Lange C, Beaty TH, Crapo JD, Barnes KC, Bamshad M, Hersh CP, Morrow J, Pinto-Plata VM, Marchetti N, et al. Exome sequencing analysis in severe, early-onset chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2016;193:1353–63.PubMedPubMedCentralCrossRef
58.
Jackson VE, Ntalla I, Sayers I, Morris R, Whincup P, Casas JP, Amuzu A, Choi M, Dale C, Kumari M, et al. Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12. Thorax. 2016;71:501–9.PubMedPubMedCentralCrossRef
59.
Wurfel MM, Christie JD, Holden TD, O'Keefe GE, Calfee CS, Matthay MA, Hakonarson H, Jarvik GP, Crosslin DR, Lin X, et al. Genome-Wide Association Study Of Acute Lung Injury Risk Loci In The Ispaar Consortium [abstract]. Am J Respir Crit Care Med. 2011;183:A5536.
60.
Wurfel MM, Christie JD, Calfee CS, Matthay MA, Barneet I, Meyer NJ, O'Mahony DD, O'Keefe GE, Hakonarson H, Jarvik GP, et al. Validation Of Genome-Wide Association Study Of Acute Respiratory Distress Syndrome Risk Loci In The Ispaar Consortium [abstract]. Am J Respir Crit Care Med. 2014;189:A6716.
61.
Mushiroda T, Wattanapokayakit S, Takahashi A, Nukiwa T, Kudoh S, Ogura T, Taniguchi H, Kubo M, Kamatani N, Nakamura Y. A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis. J Med Genet. 2008;45:654–6.PubMedCrossRef
62.
Noth I, Zhang Y, Ma SF, Flores C, Barber M, Huang Y, Broderick SM, Wade MS, Hysi P, Scuirba J, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Lancet Respir Med. 2013;1:309–17.PubMedPubMedCentralCrossRef
63.
Fingerlin TE, Murphy E, Zhang W, Peljto AL, Brown KK, Steele MP, Loyd JE, Cosgrove GP, Lynch D, Groshong S, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet. 2013;45:613–20.PubMedPubMedCentralCrossRef
64.
Machado RD, Southgate L, Eichstaedt CA, Aldred MA, Austin ED, Best DH, Chung WK, Benjamin N, Elliott CG, Eyries M, et al. Pulmonary arterial hypertension: a current perspective on established and emerging molecular genetic defects. Hum Mutat. 2015;36:1113–27.PubMedPubMedCentralCrossRef
65.
Germain M, Eyries M, Montani D, Poirier O, Girerd B, Dorfmuller P, Coulet F, Nadaud S, Maugenre S, Guignabert C, et al. Genome-wide association analysis identifies a susceptibility locus for pulmonary arterial hypertension. Nat Genet. 2013;45:518–21.PubMedPubMedCentralCrossRef
66.
Cogan JD, Kropski JA, Zhao M, Mitchell DB, Rives L, Markin C, Garnett ET, Montgomery KH, Mason WR, McKean DF, et al. Rare variants in RTEL1 are associated with familial interstitial pneumonia. Am J Respir Crit Care Med. 2015;191:646–55.PubMedPubMedCentralCrossRef
67.
de Jesus Perez VA, Yuan K, Lyuksyutova MA, Dewey F, Orcholski ME, Shuffle EM, Mathur M, Yancy L Jr, Rojas V, Li CG, et al. Whole-exome sequencing reveals TopBP1 as a novel gene in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2014;189:1260–72.PubMedPubMedCentralCrossRef
68.
Ma L, Roman-Campos D, Austin ED, Eyries M, Sampson KS, Soubrier F, Germain M, Tregouet DA, Borczuk A, Rosenzweig EB, et al. A novel channelopathy in pulmonary arterial hypertension. N Engl J Med. 2013;369:351–61.PubMedPubMedCentralCrossRef
69.
Stuart BD, Choi J, Zaidi S, Xing C, Holohan B, Chen R, Choi M, Dharwadkar P, Torres F, Girod CE, et al. Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening. Nat Genet. 2015;47:512–7.PubMedPubMedCentralCrossRef
70.
71.
72.
GTEx Consortium. Human genomics. The genotype-tissue expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science. 2015;348:648–60.
73.
Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18:716–25.PubMedCrossRef
74.
Allison DB, Cui X, Page GP, Sabripour M. Microarray data analysis: from disarray to consolidation and consensus. Nat Rev Genet. 2006;7:55–65.PubMedCrossRef
75.
Barrett T, Suzek TO, Troup DB, Wilhite SE, Ngau WC, Ledoux P, Rudnev D, Lash AE, Fujibuchi W, Edgar R. NCBI GEO: mining millions of expression profiles--database and tools. Nucleic Acids Res. 2005;33:D562–6.PubMedCrossRef
76.
Ioannidis JP, Khoury MJ. Improving validation practices in “omics” research. Science. 2011;334:1230–2.PubMedCrossRef
77.
78.
Marioni JC, Mason CE, Mane SM, Stephens M, Gilad Y. RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res. 2008;18:1509–17.PubMedPubMedCentralCrossRef
79.
Consortium SM-I. A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the sequencing quality control consortium. Nat Biotechnol. 2014;32:903–14.CrossRef
80.
Teng M, Love MI, Davis CA, Djebali S, Dobin A, Graveley BR, Li S, Mason CE, Olson S, Pervouchine D, et al. A benchmark for RNA-seq quantification pipelines. Genome Biol. 2016;17:74.PubMedPubMedCentralCrossRef
81.
Leinonen R, Sugawara H, Shumway M. International nucleotide sequence database C: the sequence read archive. Nucleic Acids Res. 2011;39:D19–21.PubMedCrossRef
82.
Berube JC, Bosse Y. Future clinical implications emerging from recent genome-wide expression studies in asthma. Expert Rev Clin Immunol. 2014;10:985–1004.PubMedCrossRef
83.
Bunyavanich S, Schadt EE. Systems biology of asthma and allergic diseases: a multiscale approach. J Allergy Clin Immunol. 2015;135:31–42.PubMedCrossRef
84.
Ghosh N, Dutta M, Singh B, Banerjee R, Bhattacharyya P, Chaudhury K. Transcriptomics, proteomics and metabolomics driven biomarker discovery in COPD: an update. Expert Rev Mol Diagn. 2016;16:897–913.PubMedCrossRef
85.
Lefaudeux D, De Meulder B, Loza MJ, Peffer N, Rowe A, Baribaud F, Bansal AT, Lutter R, Sousa AR, Corfield J, et al. U-BIOPRED clinical adult asthma clusters linked to a subset of sputum -omics. J Allergy Clin Immunol. 2016;139(6):1797–1807.PubMedCrossRef
86.
Orsmark-Pietras C, James A, Konradsen JR, Nordlund B, Soderhall C, Pulkkinen V, Pedroletti C, Daham K, Kupczyk M, Dahlen B, et al. Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics. Eur Respir J. 2013;42:65–78.PubMedCrossRef
87.
Giovannini-Chami L, Marcet B, Moreilhon C, Chevalier B, Illie MI, Lebrigand K, Robbe-Sermesant K, Bourrier T, Michiels JF, Mari B, et al. Distinct epithelial gene expression phenotypes in childhood respiratory allergy. Eur Respir J. 2012;39:1197–205.PubMedCrossRef
88.
Tsitsiou E, Williams AE, Moschos SA, Patel K, Rossios C, Jiang X, Adams OD, Macedo P, Booton R, Gibeon D, et al. Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma. J Allergy Clin Immunol. 2012;129:95–103.PubMedCrossRef
89.
Yick CY, Zwinderman AH, Kunst PW, Grunberg K, Mauad T, Dijkhuis A, Bel EH, Baas F, Lutter R, Sterk PJ. Transcriptome sequencing (RNA-Seq) of human endobronchial biopsies: asthma versus controls. Eur Respir J. 2013;42:662–70.PubMedCrossRef
90.
Modena BD, Tedrow JR, Milosevic J, Bleecker ER, Meyers DA, Wu W, Bar-Joseph Z, Erzurum SC, Gaston BM, Busse WW, et al. Gene expression in relation to exhaled nitric oxide identifies novel asthma phenotypes with unique biomolecular pathways. Am J Respir Crit Care Med. 2014;190:1363–72.PubMedPubMedCentralCrossRef
91.
Rossios C, Pavlidis S, Hoda U, Kuo CH, Wiegman C, Russell K, Sun K, Loza MJ, Baribaud F, Durham AL, et al. Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma. J Allergy Clin Immunol. 2017 May 18. pii: S0091-6749(17)30764-9.
92.
Bigler J, Boedigheimer M, Schofield JPR, Skipp PJ, Corfield J, Rowe A, Sousa AR, Timour M, Twehues L, Hu X, et al. A severe asthma disease signature from gene expression profiling of peripheral blood from U-BIOPRED cohorts. Am J Respir Crit Care Med. 2017;195:1311–20.PubMedCrossRef
93.
Lefaudeux D, De Meulder B, Loza MJ, Peffer N, Rowe A, Baribaud F, Bansal AT, Lutter R, Sousa AR, Corfield J, et al. U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics. J Allergy Clin Immunol. 2017;139:1797–807.PubMedCrossRef
94.
Modena BD, Bleecker ER, Busse WW, Erzurum SC, Gaston BM, Jarjour NN, Meyers DA, Milosevic J, Tedrow JR, Wu W, et al. Gene expression correlated with severe asthma characteristics reveals heterogeneous mechanisms of severe disease. Am J Respir Crit Care Med. 2017;195:1449–63.PubMedCrossRef
95.
Hackett NR, Butler MW, Shaykhiev R, Salit J, Omberg L, Rodriguez-Flores JL, Mezey JG, Strulovici-Barel Y, Wang G, Didon L, Crystal RG. RNA-Seq quantification of the human small airway epithelium transcriptome. BMC Genomics. 2012;13:82.PubMedPubMedCentralCrossRef
96.
Beane J, Sebastiani P, Liu G, Brody JS, Lenburg ME, Spira A. Reversible and permanent effects of tobacco smoke exposure on airway epithelial gene expression. Genome Biol. 2007;8:R201.PubMedPubMedCentralCrossRef
97.
Bahr TM, Hughes GJ, Armstrong M, Reisdorph R, Coldren CD, Edwards MG, Schnell C, Kedl R, LaFlamme DJ, Reisdorph N, et al. Peripheral blood mononuclear cell gene expression in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2013;49:316–23.PubMedPubMedCentralCrossRef
98.
Singh D, Fox SM, Tal-Singer R, Plumb J, Bates S, Broad P, Riley JH, Celli B, Investigators E. Induced sputum genes associated with spirometric and radiological disease severity in COPD ex-smokers. Thorax. 2011;66:489–95.PubMedCrossRef
99.
Almansa R, Socias L, Sanchez-Garcia M, Martin-Loeches I, del Olmo M, Andaluz-Ojeda D, Bobillo F, Rico L, Herrero A, Roig V, et al. Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes. BMC Res Notes. 2012;5:401.PubMedPubMedCentralCrossRef
100.
Kusko RL, Brothers JF 2nd, Tedrow J, Pandit K, Huleihel L, Perdomo C, Liu G, Juan-Guardela B, Kass D, Zhang S, et al. Integrated genomics reveals convergent Transcriptomic networks underlying chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2016;194:948–60.PubMedCrossRef
101.
Masuno K, Haldar SM, Jeyaraj D, Mailloux CM, Huang X, Panettieri RA Jr, Jain MK, Gerber AN. Expression profiling identifies Klf15 as a glucocorticoid target that regulates airway hyperresponsiveness. Am J Respir Cell Mol Biol. 2011;45:642–9.PubMedPubMedCentralCrossRef
102.
Misior AM, Deshpande DA, Loza MJ, Pascual RM, Hipp JD, Penn RB. Glucocorticoid- and protein kinase A-dependent transcriptome regulation in airway smooth muscle. Am J Respir Cell Mol Biol. 2009;41:24–39.PubMedCrossRef
103.
Himes BE, Jiang X, Wagner P, Hu R, Wang Q, Klanderman B, Whitaker RM, Duan Q, Lasky-Su J, Nikolos C, et al. RNA-Seq transcriptome profiling identifies CRISPLD2 as a glucocorticoid responsive gene that modulates cytokine function in airway smooth muscle cells. PLoS One. 2014;9:e99625.PubMedPubMedCentralCrossRef
104.
Yick CY, Zwinderman AH, Kunst PW, Grunberg K, Mauad T, Fluiter K, Bel EH, Lutter R, Baas F, Sterk PJ. Glucocorticoid-induced changes in gene expression of airway smooth muscle in patients with asthma. Am J Respir Crit Care Med. 2013;187:1076–84.PubMedCrossRef
105.
Himes BE, Koziol-White C, Johnson M, Nikolos C, Jester W, Klanderman B, Litonjua AA, Tantisira KG, Truskowski K, MacDonald K, et al. Vitamin D modulates expression of the airway smooth muscle Transcriptome in fatal asthma. PLoS One. 2015;10:e0134057.PubMedPubMedCentralCrossRef
106.
Kangelaris KN, Prakash A, Liu KD, Aouizerat B, Woodruff PG, Erle DJ, Rogers A, Seeley EJ, Chu J, Liu T, et al. Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS. Am J Physiol Lung Cell Mol Physiol. 2015;308:L1102–13.PubMedPubMedCentralCrossRef
107.
Wang Z, Beach D, Su L, Zhai R, Christiani DC. A genome-wide expression analysis in blood identifies pre-elafin as a biomarker in ARDS. Am J Respir Cell Mol Biol. 2008;38:724–32.PubMedPubMedCentralCrossRef
108.
Juss J, Herre J, Begg M, Bradley G, Lennon M, Amour A, House D, Hessel EM, Summers C, Condliffe AM, Chilvers ER. Genome-wide transcription profiling in neutrophils in acute respiratory distress syndrome. Lancet. 2015;385(Suppl 1):S55.PubMedCrossRef
109.
Konishi K, Gibson KF, Lindell KO, Richards TJ, Zhang Y, Dhir R, Bisceglia M, Gilbert S, Yousem SA, Song JW, et al. Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2009;180:167–75.PubMedPubMedCentralCrossRef
110.
Herazo-Maya JD, Noth I, Duncan SR, Kim S, Ma SF, Tseng GC, Feingold E, Juan-Guardela BM, Richards TJ, Lussier Y, et al. Peripheral blood mononuclear cell gene expression profiles predict poor outcome in idiopathic pulmonary fibrosis. Sci Transl Med. 2013;5:205ra136.PubMedPubMedCentralCrossRef
111.
Nance T, Smith KS, Anaya V, Richardson R, Ho L, Pala M, Mostafavi S, Battle A, Feghali-Bostwick C, Rosen G, Montgomery SB. Transcriptome analysis reveals differential splicing events in IPF lung tissue. PLoS One. 2014;9:e92111.PubMedPubMedCentralCrossRef
112.
Yang IV, Coldren CD, Leach SM, Seibold MA, Murphy E, Lin J, Rosen R, Neidermyer AJ, McKean DF, Groshong SD, et al. Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis. Thorax. 2013;68:1114–21.PubMedCrossRef
113.
Yang IV, Luna LG, Cotter J, Talbert J, Leach SM, Kidd R, Turner J, Kummer N, Kervitsky D, Brown KK, et al. The peripheral blood transcriptome identifies the presence and extent of disease in idiopathic pulmonary fibrosis. PLoS One. 2012;7:e37708.PubMedPubMedCentralCrossRef
114.
115.
Rajkumar R, Konishi K, Richards TJ, Ishizawar DC, Wiechert AC, Kaminski N, Ahmad F. Genomewide RNA expression profiling in lung identifies distinct signatures in idiopathic pulmonary arterial hypertension and secondary pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2010;298:H1235–48.PubMedPubMedCentralCrossRef
116.
Geraci MW, Moore M, Gesell T, Yeager ME, Alger L, Golpon H, Gao B, Loyd JE, Tuder RM, Voelkel NF. Gene expression patterns in the lungs of patients with primary pulmonary hypertension: a gene microarray analysis. Circ Res. 2001;88:555–62.PubMedCrossRef
117.
Roadmap Epigenomics C, Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, et al. Integrative analysis of 111 reference human epigenomes. Nature. 2015;518:317–30.CrossRef
118.
Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13:484–92.PubMedCrossRef
119.
Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462:315–22.PubMedPubMedCentralCrossRef
120.
Weber M, Davies JJ, Wittig D, Oakeley EJ, Haase M, Lam WL, Schubeler D. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet. 2005;37:853–62.PubMedCrossRef
121.
Zhou VW, Goren A, Bernstein BE. Charting histone modifications and the functional organization of mammalian genomes. Nat Rev Genet. 2011;12:7–18.PubMedCrossRef
122.
123.
Liu T, Ortiz JA, Taing L, Meyer CA, Lee B, Zhang Y, Shin H, Wong SS, Ma J, Lei Y, et al. Cistrome: an integrative platform for transcriptional regulation studies. Genome Biol. 2011;12:R83.PubMedPubMedCentralCrossRef
124.
125.
Pidsley R, Zotenko E, Peters TJ, Lawrence MG, Risbridger GP, Molloy P, Van Djik S, Muhlhausler B, Stirzaker C, Clark SJ. Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biol. 2016;17:208.PubMedPubMedCentralCrossRef
126.
127.
Barrett T, Troup DB, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, et al. NCBI GEO: archive for functional genomics data sets--10 years on. Nucleic Acids Res. 2011;39:D1005–10.PubMedCrossRef
128.
ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74.CrossRef
129.
Landt SG, Marinov GK, Kundaje A, Kheradpour P, Pauli F, Batzoglou S, Bernstein BE, Bickel P, Brown JB, Cayting P, et al. ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia. Genome Res. 2012;22:1813–31.PubMedPubMedCentralCrossRef
130.
Kadiyala V, Sasse SK, Altonsy MO, Berman R, Chu HW, Phang TL, Gerber AN. Cistrome-based cooperation between airway epithelial Glucocorticoid receptor and NF-kappaB orchestrates anti-inflammatory effects. J Biol Chem. 2016;291:12673–87.PubMedPubMedCentralCrossRef
131.
Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods. 2013;10:1213–8.PubMedPubMedCentralCrossRef
132.
Speir ML, Zweig AS, Rosenbloom KR, Raney BJ, Paten B, Nejad P, Lee BT, Learned K, Karolchik D, Hinrichs AS, et al. The UCSC genome browser database: 2016 update. Nucleic Acids Res. 2016;44:D717–25.PubMedCrossRef
133.
Kim YJ, Park SW, Kim TH, Park JS, Cheong HS, Shin HD, Park CS. Genome-wide methylation profiling of the bronchial mucosa of asthmatics: relationship to atopy. BMC Med Genet. 2013;14:39.PubMedPubMedCentralCrossRef
134.
Morrow JD, Cho MH, Hersh CP, Pinto-Plata V, Celli B, Marchetti N, Criner G, Bueno R, Washko G, Glass K, et al. DNA methylation profiling in human lung tissue identifies genes associated with COPD. Epigenetics. 2016:1–10. [Epub ahead of print]
135.
Vucic EA, Chari R, Thu KL, Wilson IM, Cotton AM, Kennett JY, Zhang M, Lonergan KM, Steiling K, Brown CJ, et al. DNA methylation is globally disrupted and associated with expression changes in chronic obstructive pulmonary disease small airways. Am J Respir Cell Mol Biol. 2014;50:912–22.PubMedPubMedCentralCrossRef
136.
Yang IV, Pedersen BS, Liu A, O'Connor GT, Teach SJ, Kattan M, Misiak RT, Gruchalla R, Steinbach SF, Szefler SJ, et al. DNA methylation and childhood asthma in the inner city. J Allergy Clin Immunol. 2015;136:69–80.PubMedPubMedCentralCrossRef
137.
Ji H, Biagini Myers JM, Brandt EB, Brokamp C, Ryan PH, Khurana Hershey GK. Air pollution, epigenetics, and asthma. Allergy Asthma Clin Immunol. 2016;12:51.PubMedPubMedCentralCrossRef
138.
Gref A, Kebede Merid S, Gruzieva O, Ballereau S, Becker A, Bellander T, Bergstrom A, Bosse Y, Bottai M, Chan-Yeung M, et al. Genome-wide interaction analysis of air pollution exposure and childhood asthma with functional follow-up. Am J Respir Crit Care Med. 2017;195(10):1373–83.PubMedCrossRef
139.
Joubert BR, Felix JF, Yousefi P, Bakulski KM, Just AC, Breton C, Reese SE, Markunas CA, Richmond RC, Xu CJ, et al. DNA Methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis. Am J Hum Genet. 2016;98:680–96.PubMedPubMedCentralCrossRef
140.
DeVries A, Wlasiuk G, Miller SJ, Bosco A, Stern DA, Lohman IC, Rothers J, Jones AC, Nicodemus-Johnson J, Vasquez MM, et al. Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers. J Allergy Clin Immunol. 2016. pii:S0091-6749(16)32459-9.
141.
Chen W, Wang T, Pino-Yanes M, Forno E, Liang L, Yan Q, Hu D, Weeks DE, Baccarelli A, Acosta-Perez E, et al. An epigenome-wide association study of total serum IgE in Hispanic children. J Allergy Clin Immunol. 2017. pii: S0091-6749(16)32546-5.
142.
Liang L, Willis-Owen SA, Laprise C, Wong KC, Davies GA, Hudson TJ, Binia A, Hopkin JM, Yang IV, Grundberg E, et al. An epigenome-wide association study of total serum immunoglobulin E concentration. Nature. 2015;520:670–4.PubMedPubMedCentralCrossRef
143.
Qiu W, Baccarelli A, Carey VJ, Boutaoui N, Bacherman H, Klanderman B, Rennard S, Agusti A, Anderson W, Lomas DA, DeMeo DL. Variable DNA methylation is associated with chronic obstructive pulmonary disease and lung function. Am J Respir Crit Care Med. 2012;185:373–81.PubMedPubMedCentralCrossRef
144.
Wan ES, Qiu W, Baccarelli A, Carey VJ, Bacherman H, Rennard SI, Agusti A, Anderson WH, Lomas DA, DeMeo DL. Systemic steroid exposure is associated with differential methylation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186:1248–55.PubMedPubMedCentralCrossRef
145.
Yoo S, Takikawa S, Geraghty P, Argmann C, Campbell J, Lin L, Huang T, Tu Z, Foronjy RF, Spira A, et al. Integrative analysis of DNA methylation and gene expression data identifies EPAS1 as a key regulator of COPD. PLoS Genet. 2015;11:e1004898.PubMedPubMedCentralCrossRef
146.
Breitling LP, Yang R, Korn B, Burwinkel B, Brenner H. Tobacco-smoking-related differential DNA methylation: 27K discovery and replication. Am J Hum Genet. 2011;88:450–7.PubMedPubMedCentralCrossRef
147.
Wan ES, Qiu W, Carey VJ, Morrow J, Bacherman H, Foreman MG, Hokanson JE, Bowler RP, Crapo JD, DeMeo DL. Smoking-associated site-specific differential Methylation in Buccal mucosa in the COPDGene study. Am J Respir Cell Mol Biol. 2015;53:246–54.PubMedPubMedCentralCrossRef
148.
Tessema M, Yingling CM, Picchi MA, Wu G, Liu Y, Weissfeld JL, Siegfried JM, Tesfaigzi Y, Belinsky SA. Epigenetic repression of CCDC37 and MAP1B links chronic obstructive pulmonary disease to lung cancer. J Thorac Oncol. 2015;10:1181–8.PubMedPubMedCentralCrossRef
149.
Szilagyi KL, Liu C, Zhang X, Wang T, Fortman JD, Zhang W, Garcia JG. Epigenetic contribution of the myosin light chain kinase gene to the risk for acute respiratory distress syndrome. Transl Res. 2017;180:12–21.PubMedCrossRef
150.
Huang SK, Scruggs AM, McEachin RC, White ES, Peters-Golden M. Lung fibroblasts from patients with idiopathic pulmonary fibrosis exhibit genome-wide differences in DNA methylation compared to fibroblasts from nonfibrotic lung. PLoS One. 2014;9:e107055.PubMedPubMedCentralCrossRef
151.
Rabinovich EI, Kapetanaki MG, Steinfeld I, Gibson KF, Pandit KV, Yu G, Yakhini Z, Kaminski N. Global methylation patterns in idiopathic pulmonary fibrosis. PLoS One. 2012;7:e33770.PubMedPubMedCentralCrossRef
152.
Sanders YY, Ambalavanan N, Halloran B, Zhang X, Liu H, Crossman DK, Bray M, Zhang K, Thannickal VJ, Hagood JS. Altered DNA methylation profile in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2012;186:525–35.PubMedPubMedCentralCrossRef
153.
Yang IV, Pedersen BS, Rabinovich E, Hennessy CE, Davidson EJ, Murphy E, Guardela BJ, Tedrow JR, Zhang Y, Singh MK, et al. Relationship of DNA methylation and gene expression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2014;190:1263–72.PubMedPubMedCentralCrossRef
154.
Seumois G, Chavez L, Gerasimova A, Lienhard M, Omran N, Kalinke L, Vedanayagam M, Ganesan AP, Chawla A, Djukanovic R, et al. Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility. Nat Immunol. 2014;15:777–88.PubMedPubMedCentralCrossRef
155.
Yu X, Schneiderhan-Marra N, Joos TO. Protein microarrays for personalized medicine. Clin Chem. 2010;56:376–87.PubMedCrossRef
156.
Terracciano R, Pelaia G, Preiano M, Savino R. Asthma and COPD proteomics: current approaches and future directions. Proteomics Clin Appl. 2015;9:203–20.PubMedCrossRef
157.
Vizcaino JA, Csordas A, Del-Toro N, Dianes JA, Griss J, Lavidas I, Mayer G, Perez-Riverol Y, Reisinger F, Ternent T, et al. 2016 update of the PRIDE database and its related tools. Nucleic Acids Res. 2016;44:11033.PubMedPubMedCentralCrossRef
158.
Wilhelm M, Schlegl J, Hahne H, Gholami AM, Lieberenz M, Savitski MM, Ziegler E, Butzmann L, Gessulat S, Marx H, et al. Mass-spectrometry-based draft of the human proteome. Nature. 2014;509:582–7.PubMedCrossRef
159.
Young NL, PA DM, Plazas-Mayorca MD, Baliban RC, Floudas CA, Garcia BA. High throughput characterization of combinatorial histone codes. Mol Cell Proteomics. 2009;8:2266–84.PubMedPubMedCentralCrossRef
160.
Molden RC, Garcia BA. Middle-down and top-down mass spectrometric analysis of co-occurring Histone modifications. Curr Protoc Protein Sci. 2014;77:23.7.1–28.CrossRef
161.
van den Biggelaar M, Hernandez-Fernaud JR, van den Eshof BL, Neilson LJ, Meijer AB, Mertens K, Zanivan S. Quantitative phosphoproteomics unveils temporal dynamics of thrombin signaling in human endothelial cells. Blood. 2014;123:e22–36.PubMedPubMedCentralCrossRef
162.
Hamsten C, Haggmark A, Grundstrom J, Mikus M, Lindskog C, Konradsen JR, Eklund A, Pershagen G, Wickman M, Grunewald J, et al. Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma. Allergy. 2016;71:1357–61.PubMedCrossRef
163.
Gharib SA, Nguyen EV, Lai Y, Plampin JD, Goodlett DR, Hallstrand TS. Induced sputum proteome in healthy subjects and asthmatic patients. J Allergy Clin Immunol. 2011;128:1176–84. e1176PubMedPubMedCentralCrossRef
164.
Gray RD, MacGregor G, Noble D, Imrie M, Dewar M, Boyd AC, Innes JA, Porteous DJ, Greening AP. Sputum proteomics in inflammatory and suppurative respiratory diseases. Am J Respir Crit Care Med. 2008;178:444–52.PubMedPubMedCentralCrossRef
165.
Ohlmeier S, Nieminen P, Gao J, Kanerva T, Ronty M, Toljamo T, Bergmann U, Mazur W, Pulkkinen V. Lung tissue proteomics identifies elevated transglutaminase 2 levels in stable chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol. 2016;310:L1155–65.PubMedCrossRef
166.
Barnes PJ. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2013;131:636–45.PubMedCrossRef
167.
Levitt JE, Rogers AJ. Proteomic study of acute respiratory distress syndrome: current knowledge and implications for drug development. Expert Rev Proteomics. 2016;13:457–69.PubMedCrossRef
168.
Priyadharshini VS, Teran LM. Personalized medicine in respiratory disease: role of proteomics. Adv Protein Chem Struct Biol. 2016;102:115–46.PubMedCrossRef
169.
Foster MW, Morrison LD, Todd JL, Snyder LD, Thompson JW, Soderblom EJ, Plonk K, Weinhold KJ, Townsend R, Minnich A, Moseley MA. Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis. J Proteome Res. 2015;14:1238–49.PubMedCrossRef
170.
Abdul-Salam VB, Wharton J, Cupitt J, Berryman M, Edwards RJ, Wilkins MR. Proteomic analysis of lung tissues from patients with pulmonary arterial hypertension. Circulation. 2010;122:2058–67.PubMedCrossRef
171.
Terrier B, Tamby MC, Camoin L, Guilpain P, Broussard C, Bussone G, Yaici A, Hotellier F, Simonneau G, Guillevin L, et al. Identification of target antigens of antifibroblast antibodies in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2008;177:1128–34.PubMedCrossRef
172.
Abdul-Salam VB, Paul GA, Ali JO, Gibbs SR, Rahman D, Taylor GW, Wilkins MR, Edwards RJ. Identification of plasma protein biomarkers associated with idiopathic pulmonary arterial hypertension. Proteomics. 2006;6:2286–94.PubMedCrossRef
173.
Lavoie JR, Ormiston ML, Perez-Iratxeta C, Courtman DW, Jiang B, Ferrer E, Caruso P, Southwood M, Foster WS, Morrell NW, Stewart DJ. Proteomic analysis implicates translationally controlled tumor protein as a novel mediator of occlusive vascular remodeling in pulmonary arterial hypertension. Circulation. 2014;129:2125–35.PubMedCrossRef
174.
Meyrick BO, Friedman DB, Billheimer DD, Cogan JD, Prince MA, Phillips JA 3rd, Loyd JE. Proteomics of transformed lymphocytes from a family with familial pulmonary arterial hypertension. Am J Respir Crit Care Med. 2008;177:99–107.PubMedCrossRef
175.
Johnson CH, Ivanisevic J, Siuzdak G. Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol. 2016;17:451–9.PubMedCrossRef
176.
Markley JL, Bruschweiler R, Edison AS, Eghbalnia HR, Powers R, Raftery D, Wishart DS. The future of NMR-based metabolomics. Curr Opin Biotechnol. 2017;43:34–40.PubMedCrossRef
177.
Junot C, Fenaille F, Colsch B, Becher F. High resolution mass spectrometry based techniques at the crossroads of metabolic pathways. Mass Spectrom Rev. 2014;33:471–500.PubMedCrossRef
178.
Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Aziat F, Dong E, et al. HMDB 3.0--the human Metabolome database in 2013. Nucleic Acids Res. 2013;41:D801–7.PubMedCrossRef
179.
Nobakht MGBF, Aliannejad R, Rezaei-Tavirani M, Taheri S, Oskouie AA. The metabolomics of airway diseases, including COPD, asthma and cystic fibrosis. Biomarkers. 2015;20:5–16.CrossRef
180.
Kelly RS, Dahlin A, McGeachie MJ, Qiu W, Sordillo J, Wan ES, Wu AC, Lasky-Su J. Asthma Metabolomics and the potential for integrative Omics in research and the clinic. Chest. 2017;151:262–77.PubMedCrossRef
181.
Carraro S, Giordano G, Reniero F, Carpi D, Stocchero M, Sterk PJ, Baraldi E. Asthma severity in childhood and metabolomic profiling of breath condensate. Allergy. 2013;68:110–7.PubMedCrossRef
182.
Fitzpatrick AM, Park Y, Brown LA, Jones DP. Children with severe asthma have unique oxidative stress-associated metabolomic profiles. J Allergy Clin Immunol, 2014. 133:258–61. e251-258
183.
Saude EJ, Skappak CD, Regush S, Cook K, Ben-Zvi A, Becker A, Moqbel R, Sykes BD, Rowe BH, Adamko DJ. Metabolomic profiling of asthma: diagnostic utility of urine nuclear magnetic resonance spectroscopy. J Allergy Clin Immunol. 2011;127:757–64. e751-756PubMedCrossRef
184.
185.
Ibrahim B, Marsden P, Smith JA, Custovic A, Nilsson M, Fowler SJ. Breath metabolomic profiling by nuclear magnetic resonance spectroscopy in asthma. Allergy. 2013;68:1050–6.PubMedCrossRef
186.
Carraro S, Rezzi S, Reniero F, Heberger K, Giordano G, Zanconato S, Guillou C, Baraldi E. Metabolomics applied to exhaled breath condensate in childhood asthma. Am J Respir Crit Care Med. 2007;175:986–90.PubMedCrossRef
187.
Dallinga JW, Robroeks CM, van Berkel JJ, Moonen EJ, Godschalk RW, Jobsis Q, Dompeling E, Wouters EF, van Schooten FJ. Volatile organic compounds in exhaled breath as a diagnostic tool for asthma in children. Clin Exp Allergy. 2010;40:68–76.PubMed
188.
Chen Q, Deeb RS, Ma Y, Staudt MR, Crystal RG, Gross SS. Serum metabolite biomarkers discriminate healthy smokers from COPD smokers. PLoS One. 2015;10:e0143937.PubMedPubMedCentralCrossRef
189.
Paige M, Burdick MD, Kim S, Xu J, Lee JK, Shim YM. Pilot analysis of the plasma metabolite profiles associated with emphysematous chronic obstructive pulmonary disease phenotype. Biochem Biophys Res Commun. 2011;413:588–93.PubMedPubMedCentralCrossRef
190.
Ubhi BK, Riley JH, Shaw PA, Lomas DA, Tal-Singer R, MacNee W, Griffin JL, Connor SC. Metabolic profiling detects biomarkers of protein degradation in COPD patients. Eur Respir J. 2012;40:345–55.PubMedCrossRef
191.
Telenga ED, Hoffmann RF, Ruben TK, Hoonhorst SJ, Willemse BW, van Oosterhout AJ, Heijink IH, van den Berge M, Jorge L, Sandra P, et al. Untargeted lipidomic analysis in chronic obstructive pulmonary disease. Uncovering sphingolipids. Am J Respir Crit Care Med. 2014;190:155–64.PubMedCrossRef
192.
Bowler RP, Jacobson S, Cruickshank C, Hughes GJ, Siska C, Ory DS, Petrache I, Schaffer JE, Reisdorph N, Kechris K. Plasma sphingolipids associated with chronic obstructive pulmonary disease phenotypes. Am J Respir Crit Care Med. 2015;191:275–84.PubMedPubMedCentralCrossRef
193.
Adamko DJ, Nair P, Mayers I, Tsuyuki RT, Regush S, Rowe BH. Metabolomic profiling of asthma and chronic obstructive pulmonary disease: a pilot study differentiating diseases. J Allergy Clin Immunol. 2015;136:571–80. e573PubMedCrossRef
194.
Bos LD, Weda H, Wang Y, Knobel HH, Nijsen TM, Vink TJ, Zwinderman AH, Sterk PJ, Schultz MJ. Exhaled breath metabolomics as a noninvasive diagnostic tool for acute respiratory distress syndrome. Eur Respir J. 2014;44:188–97.PubMedCrossRef
195.
Evans CR, Karnovsky A, Kovach MA, Standiford TJ, Burant CF, Stringer KA. Untargeted LC-MS metabolomics of bronchoalveolar lavage fluid differentiates acute respiratory distress syndrome from health. J Proteome Res. 2014;13:640–9.PubMedCrossRef
196.
Stringer KA, Serkova NJ, Karnovsky A, Guire K, Paine R 3rd, Standiford TJ. Metabolic consequences of sepsis-induced acute lung injury revealed by plasma (1)H-nuclear magnetic resonance quantitative metabolomics and computational analysis. Am J Physiol Lung Cell Mol Physiol. 2011;300:L4–L11.PubMedCrossRef
197.
Rogers AJ, Contrepois K, Wu M, Zheng M, Peltz G, Ware LB, Matthay MA: Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset. Am J Physiol Lung Cell Mol Physiol 2017:ajplung 00438 02016.
198.
Kottmann RM, Kulkarni AA, Smolnycki KA, Lyda E, Dahanayake T, Salibi R, Honnons S, Jones C, Isern NG, Hu JZ, et al. Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-beta. Am J Respir Crit Care Med. 2012;186:740–51.PubMedPubMedCentralCrossRef
199.
Kang YP, Lee SB, Lee JM, Kim HM, Hong JY, Lee WJ, Choi CW, Shin HK, Kim DJ, Koh ES, et al. Metabolic profiling regarding pathogenesis of idiopathic pulmonary fibrosis. J Proteome Res. 2016;15:1717–24.PubMedCrossRef
200.
Zhao YD, Chu L, Lin K, Granton E, Yin L, Peng J, Hsin M, Wu L, Yu A, Waddell T, et al. A biochemical approach to understand the pathogenesis of advanced pulmonary arterial hypertension: Metabolomic profiles of Arginine, Sphingosine-1-phosphate, and Heme of human lung. PLoS One. 2015;10:e0134958.PubMedPubMedCentralCrossRef
201.
Vaske CJ, Benz SC, Sanborn JZ, Earl D, Szeto C, Zhu J, Haussler D, Stuart JM. Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM. Bioinformatics. 2010;26:i237–45.PubMedPubMedCentralCrossRef
202.
GTEx Consortium. The genotype-tissue expression (GTEx) project. Nat Genet. 2013;45:580–5.
203.
Wu L, Candille SI, Choi Y, Xie D, Jiang L, Li-Pook-Than J, Tang H, Snyder M. Variation and genetic control of protein abundance in humans. Nature. 2013;499:79–82.PubMedPubMedCentralCrossRef
204.
Smith AK, Kilaru V, Kocak M, Almli LM, Mercer KB, Ressler KJ, Tylavsky FA, Conneely KN. Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type. BMC Genomics. 2014;15:145.PubMedPubMedCentralCrossRef
205.
206.
Holzinger ER, Ritchie MD. Integrating heterogeneous high-throughput data for meta-dimensional pharmacogenomics and disease-related studies. Pharmacogenomics. 2012;13:213–22.PubMedPubMedCentralCrossRef
207.
Bosse Y. Genome-wide expression quantitative trait loci analysis in asthma. Curr Opin Allergy Clin Immunol. 2013;13:487–94.PubMedCrossRef
208.
209.
Hao K, Bosse Y, Nickle DC, Pare PD, Postma DS, Laviolette M, Sandford A, Hackett TL, Daley D, Hogg JC, et al. Lung eQTLs to help reveal the molecular underpinnings of asthma. PLoS Genet. 2012;8:e1003029.PubMedPubMedCentralCrossRef
210.
Castaldi PJ, Cho MH, Zhou X, Qiu W, McGeachie M, Celli B, Bakke P, Gulsvik A, Lomas DA, Crapo JD, et al. Genetic control of gene expression at novel and established chronic obstructive pulmonary disease loci. Hum Mol Genet. 2015;24:1200–10.PubMedCrossRef
211.
Sun W, Kechris K, Jacobson S, Drummond MB, Hawkins GA, Yang J, Chen TH, Quibrera PM, Anderson W, Barr RG, et al. Common genetic polymorphisms influence blood biomarker measurements in COPD. PLoS Genet. 2016;12:e1006011.PubMedPubMedCentralCrossRef
212.
Wu K, Gamazon ER, Im HK, Geeleher P, White SR, Solway J, Clemmer GL, Weiss ST, Tantisira KG, Cox NJ, et al. Genome-wide interrogation of longitudinal FEV1 in children with asthma. Am J Respir Crit Care Med. 2014;190:619–27.PubMedPubMedCentralCrossRef
213.
Gustafsson M, Nestor CE, Zhang H, Barabasi AL, Baranzini S, Brunak S, Chung KF, Federoff HJ, Gavin AC, Meehan RR, et al. Modules, networks and systems medicine for understanding disease and aiding diagnosis. Genome Med. 2014;6:82.PubMedPubMedCentralCrossRef
214.
Diez D, Agusti A, Wheelock CE. Network analysis in the investigation of chronic respiratory diseases. From basics to application. Am J Respir Crit Care Med. 2014;190:981–8.PubMedCrossRef
215.
Chang Y, Glass K, Liu YY, Silverman EK, Crapo JD, Tal-Singer R, Bowler R, Dy J, Cho M, Castaldi P. COPD subtypes identified by network-based clustering of blood gene expression. Genomics. 2016;107:51–8.PubMedPubMedCentralCrossRef
216.
Obeidat M, Nie Y, Chen V, Shannon CP, Andiappan AK, Lee B, Rotzschke O, Castaldi PJ, Hersh CP, Fishbane N, et al. Network-based analysis reveals novel gene signatures in peripheral blood of patients with chronic obstructive pulmonary disease. Respir Res. 2017;18:72.PubMedPubMedCentralCrossRef
217.
218.
Islam S, Kjallquist U, Moliner A, Zajac P, Fan JB, Lonnerberg P, Linnarsson S. Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq. Genome Res. 2011;21:1160–7.PubMedPubMedCentralCrossRef
219.
Wills QF, Livak KJ, Tipping AJ, Enver T, Goldson AJ, Sexton DW, Holmes C. Single-cell gene expression analysis reveals genetic associations masked in whole-tissue experiments. Nat Biotechnol. 2013;31:748–52.PubMedCrossRef
220.
Gawad C, Koh W, Quake SR. Single-cell genome sequencing: current state of the science. Nat Rev Genet. 2016;17:175–88.PubMedCrossRef
221.
222.
Treutlein B, Brownfield DG, Wu AR, Neff NF, Mantalas GL, Espinoza FH, Desai TJ, Krasnow MA, Quake SR. Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq. Nature. 2014;509:371–5.PubMedPubMedCentralCrossRef
223.
Yu Y, Tsang JC, Wang C, Clare S, Wang J, Chen X, Brandt C, Kane L, Campos LS, Lu L, et al. Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway. Nature. 2016;539:102–6.PubMedCrossRef
224.
Xu Y, Mizuno T, Sridharan A, Du Y, Guo M, Tang J, Wikenheiser-Brokamp KA, Perl AT, Funari VA, Gokey JJ, et al. Single-cell RNA sequencing identifies diverse roles of epithelial cells in idiopathic pulmonary fibrosis. JCI Insight. 2016;1:e90558.PubMedPubMedCentralCrossRef
Metadata
Title
Using omics approaches to understand pulmonary diseases
Authors
Mengyuan Kan
Maya Shumyatcher
Blanca E. Himes
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2017
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-017-0631-9

Other articles of this Issue 1/2017

Respiratory Research 1/2017 Go to the issue

Research

Sex-specific lung functional changes in adult mice exposed only to second-hand smoke in utero

Research

Involvements of p38 MAPK and oxidative stress in the ozone-induced enhancement of AHR and pulmonary inflammation in an allergic asthma model

Research

Determining the presence of asthma-related molecules and salivary contamination in exhaled breath condensate

Research

Interaction of CD14 haplotypes and soluble CD14 on pulmonary function in agricultural workers

Research

Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD

Research

Exposure to ambient particulate matter alters the microbial composition and induces immune changes in rat lung
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits