Project description:Little is known about the lung microbiome dynamics and host-microbiome interactions in relation to chronic obstructive pulmonary disease (COPD) exacerbations and in patient subgroups based on smoking status and disease severity. Here we performed a 16S ribosomal RNA survey on sputum microbiome from 16 healthy and 43 COPD subjects. For COPD subjects, a longitudinal sampling was performed from stable state to exacerbations, at two and six weeks post-exacerbations and at six months from first stable visit. Host sputum transcriptome were characterized for a subset of COPD patient samples.
Project description:This repository contains human sample derived microbiome full-length 16S rRNA sequencing data for sputum samples in COPD patients. The project goal is to understand the association of the lung microbiome with accelerated lung function decline in COPD patients.
Project description:Chronic obstructive pulmonary disease (COPD) is a known risk factor for developing lung cancer suggesting that the COPD stroma contains factors supporting tumorigenesis. Since cancer initiation is complex we used a multi-omic approach to identify gene expression patterns that distinguish COPD stroma in patients with or without lung cancer. Our overall objective is the identification of gene expression pathways and levels of regulation in lung stroma of patients with COPD that harbor lung cancer. We obtained lung tissue from patients with COPD and lung cancer (tumor and adjacent non-malignant tissue) and those with COPD without lung cancer for proteomic and mRNA (cytoplasmic and polyribosomal) profiling. We used the joint and individual variation explained (JIVE) method to integrate and analysis across the three datasets. JIVE identified eight latent patterns that robustly distinguished and separated the three groups of tissue samples. Predictive variables that associated with the tumor, compared to adjacent stroma, were mainly represented in the transcriptomic data, whereas, predictive variables associated with adjacent tissue compared to controls was represented at the translatomic level. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed extracellular matrix (ECM) and PI3K-Akt signaling pathways as important signals in the pre-malignant stroma. COPD stroma adjacent to lung cancer is unique and differs from non-malignant COPD tissue and is distinguished by the extracellular matrix and PI3K-Akt signaling pathways.
Project description:Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer, suggesting that COPD stroma favors cancer initiation. Therefore, we used proteomics and polysome-profiling to identify gene expression programs that distinguish stroma of patients harboring lung cancer from those that do not, with varied COPD severities. This profiling unveiled distinct COPD-dependent cancer-associated gene expression programs predominantly manifesting as alterations in mRNA translation. Mechanistically, such programs are downstream of the mammalian target of rapamycin pathway in mild COPD and pathological extracellular matrix in more severe COPD; and both programs parallel activation of distinct pro-cancer fibroblast-derived secretomes. Therefore, depending upon COPD severity, the lung stroma can exist in two states favoring cancer initiation, which likely result in distinct disease entities.
Project description:Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Considering this, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, we found three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls.
Project description:Identifying protein biomarkers for chronic obstructive pulmonary disease (COPD) has been challenging. Most previous studies have utilized individual proteins or pre-selected protein panels measured in blood samples. To identify COPD protein biomarkers by applying comprehensive mass spectrometry proteomics in lung tissue samples. We utilized mass spectrometry proteomic approaches to identify protein biomarkers from 152 lung tissue samples representing COPD cases and controls.