Boston Early-Onset COPD Study
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ABSTRACT:
PROVIDER: PRJNA326857 | ENA |
REPOSITORIES: ENA
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Project description:NHLBI TOPMed: Boston Early-Onset COPD Study
| PRJNA288739 | ENA
Project description:<p>Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States and the only leading cause of death that is steadily increasing in frequency. This project collected a set of extended pedigrees ascertained through subjects with severe, early-onset COPD. This study has enrolled subjects with severe COPD (forced expiratory volume in one second (FEV1) < 40% predicted) at an early age (< 53 years) without alpha-1 antitrypsin deficiency (a known Mendelian risk factor for COPD). Extended pedigrees are enrolled, primarily in New England, although some more geographically distant subjects have been included. This study has been used for epidemiological studies, familial aggregation analysis, linkage analysis, and candidate gene association analysis. Approximately 80 of the severe, early-onset COPD probands will undergo whole genome sequencing in this project with sequencing data available through dbGaP.</p> <p> <ul> <li>This third study release makes available VCF files derived from sequence aligned to genome build 38, in addition to those aligned to build 37 and available through study version 1. The samples in the b38 vs b37 VCF may also differ.</li> </ul> </p>
| phs000946 | dbGaP
Project description:Early Onset Malignancies Initiative
| PRJNA597501 | ENA
Project description:Early Onset Malignancies Initiative
| PRJNA597502 | ENA
Project description:Methods: This study analyzed lung tissue sequencing data from early-stage COPD patients (GSE47460) and smoke-exposed mice. We employed Weighted Gene Co-Expression Network Analysis (WGCNA) and machine learning to identify potential pathogenic genes. Further analyses included single-cell sequencing from mice and COPD patients to identify gene expression in specific cell subgroups. Cell-chat and pseudo-temporal analyses were conducted, with findings validated in smoke-exposed mice. Additionally, Mendelian randomization (MR) was utilized to verify the relationship between candidate genes and lung function/COPD. Lastly, functional validation was performed in vitro in cell cultures. Results: "Machine learning analysis of 30 differentially expressed genes pinpointed 8 key genes, with CLEC5A identified as a potential pathogenic factor in early COPD. Bioinformatics suggested CLEC5A's role in macrophage-mediated inflammation in COPD. Two-sample Mendelian randomization linked CLEC5A SNPs with FEV1, FEV1/FVC, and emphysema/chronic bronchitis. In vitro, CLEC5A knockdown reduced inflammatory markers in macrophages. Conclusion: Our study identifies CLEC5A as a pivotal gene in early-stage COPD, contributing to its pathogenesis through pro-inflammatory mechanisms. This discovery offers insights for early diagnosis and treatment strategies in COPD, highlighting CLEC5A as a target for further research.
2024-07-21 | GSE255319 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is one of the most prevalent lung diseases, and involves persistent airflow limitation and incorporates both emphysema and chronic bronchitis. Cigarette smoking has been identified as the main risk factor for disease development and progression. In a basic model of COPD, the disease is initiated when the physiologic response mechanisms to cigarette smoke exposure are overwhelmed; for example, because of long-term exposure effects or other aging-related changes. In this parallel-group case-controlled clinical study we asked to what extent the different transitions in a chronic-exposure-to-disease model are reflected in the proteome and cellular transcriptome of induced sputum samples from the lung. For this, we selected 60 age- and gender-matched individuals for each of four study groups: current healthy smokers, current-smoker COPD patients, former smokers, and never smokers (a total of 240 individuals). Induced sputum was collected, the cell-free supernatant was analyzed by quantitative proteomics (isobaric-tag based), and the cellular mRNA fraction was analyzed by microarray-based expression profiling. The sputum proteome of current smokers (healthy or COPD patients) clearly reflected the common physiological responses to smoke exposure, including alterations in mucin/trefoil proteins (e.g., MUC5AC and TFF1/3up-regulation), peptidase regulators (e.g., TIMP1 up-regulation), and a prominent xenobiotic/oxidative stress response (e.g., NQO1 and ALDH3A1 up-regulation). The latter response also was observed in the sputum transcriptome, which additionally demonstrated an immune-related polarization change (toward a M2 signature). The (long-term) former smoker group showed nearly complete reversal of the observable biological effects. Thirteen differentially abundant proteins between the COPD and healthy smoker groups were identified. These abundant proteins included previously reported COPD-associated proteins (e.g., TIMP1 (up-regulation) and APOA1 (down-regulation)) and novel proteins such as C6orf58 and BPIFB1 (LPLUNC1) (both up-regulated in the COPD group compared with the healthy smokers). In summary, our study demonstrates that sputum proteomics/transcriptomics can capture the complex and reversible physiological response to cigarette smoke exposure, which appears to be only slightly modulated in early-stage COPD patients. The study has been registered on ClinicalTrials.gov with identifier NCT01780298.
2016-10-21 | MSV000080275 | MassIVE
Project description:Epigenome-wide study of widespread hypomethylated loci associated with early-onset preeclampsia
| PRJNA516910 | ENA
Project description:Upregulation of Expression of the Ubiquitin Carboxyl Terminal Hydrolase L1 Gene in Human Airway Epithelium of Cigarette Smokers The microarray data deposited here is from 39 HG-U133 Plus 2.0 GeneChips, from 12 normal non-smokers, 12 phenotypic normal smokers, 9 Early COPD and 6 COPD individuals, all small airways, all small airway. A subset of these samples have been already submitted under GEO Accession Number GSE 4498. These are: 12 non-smokers samples (GSM101095-GSM101106) and 10 smoker samples (GSM101107-GSM101116). These 22 samples that are also in GSE4498 were described in Harvey, B-G; Heguy, A.; Leopold, P.L.; Carolan, B.; Ferris, B. and Crystal R.G. Modification of Gene Expression of the Small Airway Epithelium in Response to Cigarette Smoking. J. Mol. Med (in press). These data are part of a study aimed at understanding how cigarette smoking modifies neuroendocrine cells, in which microarray analysis with TaqMan confirmation was used to assess airway epithelial samples obtained by fiberoptic bronchoscopy from 81 individuals (normal nonsmokers, normal smokers, smokers with early COPD and smokers with established COPD). Of 11 genes considered to be neuroendocrine cell-specific, only ubiquitin C-terminal hydrolase L1(UCHL1), a member of the ubiquitin proteasome pathway, was consistently upregulated in smokers compared to nonsmokers. Up-regulation of UCHL1 at the protein level was observed with immunohistochemistry of bronchial biopsies of smokers compared to nonsmokers. Interestingly, however, while UCHL1 expression was present only in neuroendocrine cells of the airway epithelium in nonsmokers, UCHL1 expression was also expressed in ciliated epithelial cells in smokers, an intriguing observation in light of recent observations that ciliated cells can are capable of transdifferentiating to other airway epithelium. In the context that UCHL1 is involved in the degradation of unwanted, misfolded or damaged proteins within the cell and is overexpressed in >50% of lung cancers, its overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy. Keywords: non-smokers vs phenotypic normal smokers, smokers with early COPD, and smokers with COPD
2006-11-21 | GSE5058 | GEO