Lung proteomic biomarkers associated with chronic obstructive pulmonary disease
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Lung
DISEASE(S): Chronic Obstructive Pulmonary Disease
SUBMITTER: 
Michael Hoopmann
LAB HEAD: Robert L. Mortiz
PROVIDER: PXD024124 | Pride | 2022-01-07
REPOSITORIES: Pride
Similar Datasets
Project description:Paleofeces are an important source of information to study the evolution of dietary habits and human health. The UNESCO World Heritage region of Hallstatt-Dachstein/Salzkammergut is one of Europe’s oldest cultural and industrial landscapes; its underground salt mines dating back at least to the 14th century BC are one of the few archaeological sites where paleofeces are well preserved. The high salt concentrations and the constant annual temperature at around 8°C inside the isolated Hallstatt mines have perfectly preserved organic archaeological artefacts (e.g. paleofeces, clothing, mining tools) that provide unique insights into the daily life of a progressive community in Hallstatt. Here we subjected human paleofeces dated from the Bronze Age to early Modern Times to an in-depth microscopic, metagenomic and proteomic analysis. This allowed us to reconstruct the diet of the former population and gain insights into their ancient gut microbiome composition. Our dietary survey identified bran and glumes of different cereals as one of the most prevalent plant fragments. This highly fibrous, carbohydrate-rich diet was supplemented with proteins from broad beans and occasionally with fruits, nuts, or animal food. Linked to these traditional dietary habits all ancient miners up to the early Modern times have gut microbiome structures akin to modern non-Westernized individuals which may indicate a shift in the gut community composition of modern Westernized populations due to quite recent dietary and lifestyle changes. When we extended our microbial survey to fungi present in the paleofeces, we observed in one of the Iron Age samples a high abundance of Penicillium roqueforti and Saccharomyces cerevisiae DNA. Genome-wide analysis indicates that both fungi were involved in food fermentation and provide the first molecular evidence for blue cheese and beer consumption during Iron Age Europe.
2021-11-02 | PXD027613 | Pride
Project description:Elucidating the molecular mechanisms underlying snake venom variability provides important clues for understanding how the biological functions of this powerful toxic arsenal evolve. We analyzed in detail individual transcripts and venom protein isoforms produced by five specimens of a venomous snake (Bothrops atrox) from two nearby but genetically distinct populations from the Brazilian Amazon rainforest which show functional similarities in venom properties. Individual variation was observed among the venoms of these specimens, but the overall abundance of each general toxin family was conserved both in transcript and in venom protein levels. However, when expression of independent paralogues was analyzed, remarkable differences were observed within and among each toxin group, both between individuals and between populations. Transcripts for functionally essential venom proteins (“core function” proteins) were highly expressed in all specimens and showed similar transcription/translation rates. In contrast, other paralogues (“adaptive” proteins) showed lower expression levels and the toxins they coded for varied among different individuals. These results provide support for the inferences that (a) expression and translational differences play a greater role in defining adaptive variation in venom phenotypes than does sequence variation in protein coding genes and (b) convergent adaptive venom phenotypes can be generated through different molecular mechanisms. Significance: Analysis of individual transcripts and venom protein isoforms produced by specimens of a venomous snake (Bothrops atrox), from the Brazilian Amazon rainforest, revealed that transcriptional and translational mechanisms contribute to venom phenotypic variation. Our finding of evidence for high expression of toxin proteins with conserved function supports the hypothesis that the venom phenotype consists of two kinds of proteins: conserved “core function” proteins that provide essential functional activities with broader relevance and less conserved “adaptive” proteins that vary in expression and may permit customization of protein function. These observations allowed us to suggest that genetic mechanisms controlling venom variability are not restricted to selection of gene copies or mutations in structural genes but also to selection of the mechanisms controlling gene expression, contributing to the plasticity of this important phenotype for venomous snakes.
2023-07-04 | PXD043541 | Pride
Project description:A standard proteolytic digest of a human protein mixture, prepared at 1.5-fold to 3-fold protein concentration changes, and diluted into a constant background of yeast proteins. Similar to other datasets used for ground truth in quantitative studies, with the exception of being more granular, and much larger in terms of replicates, to enable more rigorous and accurate testing of quantitative algorithms.
2018-09-24 | PXD006447 | Pride
Project description:Extracellular vesicles (EVs) are produced and released by both healthy and malignant cells and bear markers indicative of ongoing biological processes. In the present study we utilized high resolution flow cytometry to detect EVs in the plasma of patients with pancreatic ductal adenocarcinoma (PDAC) and in the supernatants of PDAC and healthy control (HC) pancreatic organoid cultures. Using ultrafiltration and size exclusion chromatography, PDAC and HC pancreatic organoid EVs were isolated for mass spectrometry analysis. Proteomic and functional analysis showed a striking distinction in that EV proteins profiled in pancreatic cancer organoids were involved in vesicular transport and tumorigenesis while EV proteins in healthy organoids were involved in cellular homeostasis. Thus, the most abundant proteins identified in either case represented non-overlapping cellular programs. Tumor-promoting candidates LAMA5, SCDB1 and TENA were consistently upregulated in PDAC EVs. Validation of specific markers for PDAC EVs versus healthy pancreatic EVs will provide the biomarkers and enhanced sensitivity necessary to monitor early disease or disease progression, with or without treatment. Moreover, disease-associated changes in EV protein profiles provide an opportunity to investigate alterations in cellular programming with disease progression.
2022-04-04 | PXD030325 | Pride
Project description:Chronic obstructive pulmonary disease (COPD) is combination of progressive lung diseases. The diagnosis of COPD is generally based on the pulmonary function testing, however, difficulties underlie in prognosis of potential or early stage of COPD patients due to the complexity and heterogeneity of the pathogenesis. Transcriptomic technology is expected as one of the solution to resolve such complexities; therefore, we obtained transcriptomic data by in vitro testing with exposures of human 3D cultured bronchial epithelial tissues (MucilAir) to known inducible factors for early events of COPD to identify the potential descriptive marker genes. Fifteen potential biomarker genes were identified by transcriptomic analysis, and 10 out of 15 genes, as well as their coding proteins, have not been previously reported as biomarkers for chronic inflammatory lung diseases. The expression levels of these 15 genes with machine learning classification well distinguished between COPD and non-COPD patients with remarkable accuracy, suggesting these identified genes are potential descriptive marker genes for COPD.
2020-01-22 | E-MTAB-7992 | biostudies-arrayexpress
Project description:Persisters, a dormant and multi-drug tolerant subpopulation that are able to resuscitate after antibiotic treatment, have recently received considerable attentions as the major risk of the relapse of various infectious diseases in clinics. However, due to their low abundance and inherent mutability, it is extremely difficult to study them by proteomics. Here, we developed a magnetic beads-based separation approach to enrich Escherichia coli persisters and then subject them to Filter-Aided Sample Perparation (FASP) followed by LC-MS/MS analysis. We applied spectral counting-based quantitative proteomics to study the proteomic changes of E. coli persisters under high concentration of ampicillin treatment.
2018-10-16 | PXD010590 | Pride
Project description:Several groups have shown that through evolution experiments, tolerance evolved rapidly under cyclic antibiotic treatment which then promote the emergence of resistance. In other words, intermittent antibiotic exposure will “train” the bacteria to become tolerant to the drug, and then boost the chances for them to become fully resistant. This evolutionary trajectory of evolving tolerance and resistance not only occurs in vitro, but also in clinical patients with MRSA blood infections. Despite the fact that repetitive antibiotic treatment will lead to tolerance and resistance development in bacterial populations, the difference on the evolutionary path between those treated with a single drug and drug combination remains unaddressed. In this study, we monitored the development of tolerance in MRSA by treating them with either daptomycin alone for 2 weeks (Scheme 1), or daptomycin combined with rifampin for two weeks (Scheme 2), in a cyclic manner. In addition, we also investigate another scenario where we treat MRSA cells with daptomycin alone for one week, and subsequently treat them with daptomycin and rifampin combination in the second week (Scheme 3). At the end of the evolution experiment, we observed that the population from Scheme 1 developed tolerance towards daptomycin, the population from Scheme 2 developed both tolerance and resistance towards daptomycin, while the population from Scheme 3 developed tolerance after a week of treatment, but then the tolerance phenotype diminished at the end of the second week due to the drug combination treatment. We subjected them to whole genome sequencing and identified single point mutations that are responsible for the observed phenotype. Through proteomics, we compared the proteome profile of the population evolved from scheme 1 (S1D14), scheme 2 (S2D14) and scheme 3 (S3D14), and we observed that these three populations employ distinct mechanisms to survive antibiotic treatment, suggesting that the treatment strategy for these populations should be tailored depending on the treatment conditions.
2021-07-27 | PXD021667 | Pride
Project description:The differential expression of circular RNAs (circRNAs) in individuals with very severe chronic obstructive pulmonary disease (COPD) and healthy individuals was screened using microarray technology. The related functions and mechanisms were analyzed using bioinformatic methods to explore the potential of target circRNAs as biomarkers of COPD and provide insights for future pathogenesis.
2022-12-30 | GSE221812 | GEO
Project description:Several groups have shown that through evolution experiments, tolerance and resistance evolved rapidly under cyclic antibiotic treatment. In other words, intermittent antibiotic exposure performed in a typical adaptive laboratory evolution (ALE) experiments will “train” the bacteria to become tolerant/resistant to the drug. Using this experimental strategy, we performed in vitro laboratory evolution in MRSA using daptomycin, and mine novel daptomycin tolerance and resistance mutants, which were isolated at specific time points during the evolution experiments. Three daptomycin-tolerant isolates with different tolerance level were generated from our laboratory evolution (TOL2 and TOL5 with a mild-tolerance phenotype, and TOL6 with a high-tolerance phenotype). They all bear mutations at different genes, and have no increase in MIC towards daptomycin. Besides, we also isolated three daptomycin-resistant isolates (RES1, RES2, RES3) that have a single point mutation in the same gene, mprF, but at different locations, leading to an increased MIC towards daptomycin. Through proteomics, we uncovered the differential adaptation strategies of these daptomycin tolerant and resistant MRSA strains, and how they respond differently to antibiotics compared to the ancestral wild-type.
2022-07-14 | PXD026741 | Pride
Project description:Several groups have shown that through evolution experiments, tolerance and resistance evolved rapidly under cyclic antibiotic treatment. In other words, intermittent antibiotic exposure performed in a typical adaptive laboratory evolution (ALE) experiments will “train” the bacteria to become tolerant/resistant to the drug. Although ALE has added new knowledge regarding the impact of varying treatment conditions on the evolution of tolerance/resistance, the role of some parameters such as population bottlenecks remains poorly understood. In this study, we employed ALE to investigate the evolution of methicillin-resistant S. aureus under repetitive daptomycin treatment using a modified protocol that incorporated population bottleneck following antibiotic exposure. We observed that although tolerance development is slower under bottlenecking conditions, the populations finally attained tolerance mutation in the yycH gene after twelve cycles of treatment. Extending the evolution experiment and changing the treatment scheme to a fast evolution protocol (treatment during exponential phase without bottlenecking) led to the emergence of daptomycin resistance (mutation in mprF gene). Through proteomics, we uncovered the differential adaptation strategies of these daptomycin tolerant and resistant MRSA strains, and how they respond differently to antibiotics compared to the ancestral wild-type.
2022-07-16 | PXD031078 | Pride