Table 1 Summary of main findings for various omics approaches applied to the study of pulmonary diseases
From: Using omics approaches to understand pulmonary diseases
Disease | Main findings |
|---|---|
Genomics | |
Genome-wide/Exome-wide microarray | |
Asthma | Prominent asthma-associated loci are 17q21 locus (including ORMDL3, GSDMB), IL33, IL1RL1, TSLP [32] Rare, potentially functional variants within GRASP, GSDMB, and MTHFR are associated differently with asthma in subjects of Latino and African ancestry [56] Severe asthma-associated loci are CDHR3, GSDMB, IL33 and IL1RL1 [43] |
IgE levels | FCER1A and HLA-DQB1 are associated with IgE levels, the latter in asthma patients only [47] |
Asthma drug response | SPATS2L is associated with bronchodilator response in asthma patients [54] GLCCI1 is associated with lung function in patients treated with inhaled glucocorticoids [55] |
COPD | Robust COPD-associated loci are FAM13A, CHRNA3/CHRNA5/IREB2, HHIP [33] Rare, potentially functional variants in MOCS3, IFIT3 and SERPINA12 are associated with COPD and airflow limitation [58] |
COPD endotype | BICD1 is associated with emphysema [44] |
Lung function | FAM13A, HHIP, HTR4 are associated with both lung function (i.e. FEV1 and FEV1/FVC ratio) and COPD [48] |
IPF | |
PAH | CBLN2 is associated with PAH in patients without BMPR2 mutations [65] |
Whole exome sequencing | |
COPD | Increased number of rare, non-silent mutations in DNAH8, ALCAM, RARS, and GBF1 are present in severe, early-onset COPD [57] |
PAH | High penetrance missense variants in KCNK3 and TOPBP1 found in familial PAH and idiopathic PAH [67, 68] |
Transcriptomics | |
Gene expression microarray | |
Asthma | Bitter taste receptors have increased expression in severe asthma [86] Distinct epithelial gene expression signature involving in interferon response found in severe childhood asthma [87] Transcriptional activation of circulating CD8+ T cells but not CD4+ T cells present in severe asthma [88] |
Asthma endotype | Severe asthma subgroups defined based on transcriptomic and clinical characteristics [92,93,94] |
Asthma drug response | KLF15 is a glucocorticoid responsive gene in ASM cells [101] |
COPD | Distinct PBMC gene expression representing immune, inflammatory response and sphingolipid metabolism pathways, and including ASAH1, involved in COPD and emphysema [97] Sputum gene expression changes, including IL18R1, are associated with COPD severity [98] Increased gene expression of neutrophil proteases found in COPD patients with respiratory distress [99] |
ARDS | Blood neutrophil-related genes and pre-elafin are potential biomarkers in early sepsis-induced ARDS [106] and in acute stage of ARDS [107], respectively Neutrophil gene expression changes in ARDS similar to those in sepsis and burns [108] |
IPF | CCNA2 and alpha-defensin genes are upregulated in lung tissue of IPF patients with acute exacerbations [109] PBMC CD28, ICOS, LCK, and ITK are predictors of poor outcomes (transplantation, death) in IPF [110] |
PAH | Expression changes in BMP2 and BMPR2 are associated with PAH, even in tissues from patients without BMPR2 mutations [114] |
RNA-Seq | |
Asthma | Differential expression of SLC26A4, POSTN, and BCL2 observed in endobronchial biopsies from asthma patients [89] |
Asthma drug response | CRISPLD2 is a glucocorticoid responsive gene in ASM cells [103] Glucocorticoid-induced genes in ASM from asthma donors include FAM129A and SYNPO2 [104] Cytokine gene expression is modulated by vitamin D treatment in ASM [105] |
IPF | Splicing changes in lung tissue COL6A3 and POSTN are associated with IPF [111] |
Epigenomics | |
Methylation microarray | |
Asthma | Hypomethylation of IL13, RUNX3 and TIGIT observed in PBMCs of patients with persistent atopic asthma [136] SMAD3 methylation at birth is associated with asthma in children of mothers with asthma [140] |
IgE levels | AFPM1, ACOT7, and MND1 methylation are associated with total serum IgE levels in Hispanic children [141] Serum IgE levels are associated with low methylated loci within/near genes encoding known eosinophil products (e.g., IL5RA, IL1RL1, GATA1) [142] |
COPD | Methylation of C10orf11, a known COPD-associated gene identified via GWAS, observed in lung of smokers who develop COPD [134] EPAS1 identified as a key regulator of COPD by combining lung methylation and gene expression data [145] |
IPF | Methylation changes observed in CDKN2B, CAR10 and MGMT in fibroblasts from IPF patients [150] Hypermethylation of CASZ1, and subsequent gene expression changes, are observed in lung of IPF patients [153] |
ChIP-Seq | |
Asthma | H3K4me2-marked enhancers in T cells are enriched for asthma-associated SNPs and Th2 cell type [154] |
Asthma drug response | Glucocorticoid receptor and p65 cooperatively regulate anti-inflammatory gene expression in airway epithelial cells [130] |
Proteomics | |
Asthma | Plasma protein levels of CCL5, HPGDS, NPSR are associated with childhood asthma [162] |
COPD | CTSD, DPYSL2, TGM2, and TPP1 are potential COPD biomarkers; TGM2 in induced sputum and plasma is not associated with smoking but is associated with COPD severity [165] |
ARDS | Pathways including inflammation and epithelial injury are associated with ARDS but ARDS-specific biomarkers have not yet been identified [167] |
IPF | Levels of apolipoprotein A1, hemoglobin α, hemoglobin β [168], pulmonary fibrosis mediators and eosinophil- and neutrophil-derived proteins [169] differ in IPF patients vs. controls |
PAH | TCTP is a mediator of endothelial prosurvival and growth signaling in PAH [173] |
Metabolomics | |
Asthma | Pathways relating to hypoxia response, oxidative stress, immunity, inflammation, lipid metabolism and the tricarboxylic acid cycle were identified as significant in at least two of 21 asthma metabolomics studies. [180] |
COPD | Sphingolipids are highly expressed in sputum of smokers with COPD than smokers without COPD [191] |
ARDS | Octane, acetaldehyde and 3-methylheptane in exhaled breath discriminate ARDS patients from other intensive care unit patients [194] |
ARDS endotype | A subgroup of ARDS patients with 235 overexpressed metabolites in pulmonary edema fluid had higher mortality rate [197] |
IPF | Distinct changes observed in IPF lung tissues vs. controls include increased lactic acid [198], and changes in adenosine triphosphate degradation, glycolysis, glutathione biosynthesis, and ornithine aminotransferase pathways [199] |
PAH | Decreased arginine and increased nitric oxide was found in PAH lung tissues vs. healthy controls [200] |
Integrative Omics | |
Asthma | Asthma susceptibility loci are lung eQTLs, including a 17q21 locus associated with GSDMA mRNA expression levels. Network analyses of eQTLs and GWAS results identified SOCS3 pathway as a key driver of asthma [209] |
COPD | eQTLs near previously reported COPD GWAS loci (FAM13A, CHRNA3/5, HHIP) help identify potential functional loci [210] COPD blood pQTLs for surfactant protein D, vitamin D binding protein, and TNFRSF10C are associated with COPD phenotypes; association between eQTLs and pQTLs was low [211] |
Single Cell RNA-Seq | |
IPF | Coexpression of different cell-specific markers in IPF cells demonstrating “Indeterminate” states of differentiation in IPF [224] |