Integrative Omics Approach Identifies Interleukin-16 as a Biomarker of Emphysema

Bowler, Russell P.; Bahr, Timothy M.; Hughes, Grant; Lutz, Sharon M.; Kim, Yu-Il; Coldren, Christopher D.; Reisdorph, Nichole; Kechris, Katerina

doi:10.1089/omi.2013.0038

Cited by 30 publications

(22 citation statements)

References 48 publications

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“…Alternatively, the network associated with percent emphysema had features such as growth hormone receptor, adipokines, amino acids, and lipids, suggesting that growth and metabolism may play a more important role in the pathogenesis of COPD. The individual correlations of the network features and network correlations were all in the correlation range of previously cited work [19][20][21].…”

Section: Discussionmentioning

confidence: 72%

Identifying Protein–metabolite Networks Associated with COPD Phenotypes

et al. 2020

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Chronic obstructive pulmonary disease (COPD) is a disease in which airflow obstruction in the lung makes it difficult for patients to breathe. Although COPD occurs predominantly in smokers, there are still deficits in our understanding of the additional risk factors in smokers. To gain a deeper understanding of the COPD molecular signatures, we used Sparse Multiple Canonical Correlation Network (SmCCNet), a recently developed tool that uses sparse multiple canonical correlation analysis, to integrate proteomic and metabolomic data from the blood of 1008 participants of the COPDGene study to identify novel protein–metabolite networks associated with lung function and emphysema. Our aim was to integrate -omic data through SmCCNet to build interpretable networks that could assist in the discovery of novel biomarkers that may have been overlooked in alternative biomarker discovery methods. We found a protein–metabolite network consisting of 13 proteins and 7 metabolites which had a −0.34 correlation (p-value = 2.5 × 10−28) to lung function. We also found a network of 13 proteins and 10 metabolites that had a −0.27 correlation (p-value = 2.6 × 10−17) to percent emphysema. Protein–metabolite networks can provide additional information on the progression of COPD that complements single biomarker or single -omic analyses.

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Section: Discussionmentioning

confidence: 72%

Identifying Protein–metabolite Networks Associated with COPD Phenotypes

et al. 2020

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“…To date, efforts to molecularly characterize COPD, or identify biomarkers of COPD predisposition and progression, have largely focused on genome-wide association studies (GWAS) (5)(6)(7)(8), transcriptome profiling of parenchymal lung tissues (9)(10)(11)(12)(13), or large and small airways (14)(15)(16)(17), and, recently, studies that integrate genotype (GWAS) and gene expression data for the purpose of identifying expression quantitative trait loci (18)(19)(20)(21). GWAS have revealed a significant interindividual genetic variance underlying lung function and response to major COPD risk factors.…”

Section: Clinical Relevancementioning

confidence: 99%

DNA Methylation Is Globally Disrupted and Associated with Expression Changes in Chronic Obstructive Pulmonary Disease Small Airways

Vucic

Chari

Thu

et al. 2014

Am J Respir Cell Mol Biol

126

110

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DNA methylation is an epigenetic modification that is highly disrupted in response to cigarette smoke and involved in a wide spectrum of malignant and nonmalignant diseases, but surprisingly not previously assessed in small airways of patients with chronic obstructive pulmonary disease (COPD). Small airways are the primary sites of airflow obstruction in COPD. We sought to determine whether DNA methylation patterns are disrupted in small airway epithelia of patients with COPD, and evaluate whether changes in gene expression are associated with these disruptions. Genome-wide methylation and gene expression analysis were performed on small airway epithelial DNA and RNA obtained from the same patient during bronchoscopy, using Illumina's Infinium HM27 and Affymetrix's Genechip Human Gene 1.0 ST arrays. To control for known effects of cigarette smoking on DNA methylation, methylation and gene expression profiles were compared between former smokers with and without COPD matched for age, pack-years, and years of smoking cessation. Our results indicate that aberrant DNA methylation is (1) a genome-wide phenomenon in small airways of patients with COPD, and (2) associated with altered expression of genes and pathways important to COPD, such as the NF-E2-related factor 2 oxidative response pathway. DNA methylation is likely an important mechanism contributing to modulation of genes important to COPD pathology. Because these methylation events may underlie disease-specific gene expression changes, their characterization is a critical first step toward the development of epigenetic markers and an opportunity for developing novel epigenetic therapeutic interventions for COPD.

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“…[95] In COPDGene study subjects, they measured IL-16 plasma protein levels and IL-16 gene expression in peripheral blood leukocytes. eQTL analysis found a SNP associated with IL-16 mRNA levels.…”

Section: Integration Of Genomic and Biomarker Data In Copdmentioning

confidence: 99%

Integrative genomics of chronic obstructive pulmonary disease

Hobbs

Hersh

2014

Biochemical and Biophysical Research Communications

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Chronic obstructive pulmonary disease (COPD) is a complex disease with both environmental and genetic determinants, the most important of which is cigarette smoking. There is marked heterogeneity in the development of COPD among persons with similar cigarette smoking histories, which is likely partially explained by genetic variation. Genomic approaches such as genomewide association studies and gene expression studies have been used to discover genes and molecular pathways involved in COPD pathogenesis; however, these “first generation” omics studies have limitations. Integrative genomic studies are emerging which can combine genomic datasets to further examine the molecular underpinnings of COPD. Future research in COPD genetics will likely use network-based approaches to integrate multiple genomic data types in order to model the complex molecular interactions involved in COPD pathogenesis. This article reviews the genomic research to date and offers a vision for the future of integrative genomic research in COPD.

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Integrative Omics Approach Identifies Interleukin-16 as a Biomarker of Emphysema

Cited by 30 publications

References 48 publications

Identifying Protein–metabolite Networks Associated with COPD Phenotypes

Identifying Protein–metabolite Networks Associated with COPD Phenotypes

DNA Methylation Is Globally Disrupted and Associated with Expression Changes in Chronic Obstructive Pulmonary Disease Small Airways

Integrative genomics of chronic obstructive pulmonary disease

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