OdPhoFict
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB97685 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Phorbas cf. fictitius (HMA microbiome), genomic and transcriptomic data
| PRJEB97684 | ENA
Project description:Phorbas fictitius (HMA microbiome) sponge metagenome assembly, odPhoFict1.metagenome
| PRJEB98001 | ENA
Project description:This study aimed to compare – at a multi-omics level, inflammation, protease abundance and activity, microbiome, and proteome in sputum samples from patients with cystic fibrosis (CF, n=38) or chronic obstructive pulmonary disease (COPD, n=18) and healthy controls (n=10) to identify shared and unique pathways between these respiratory conditions. Sputum analysis revealed elevated inflammatory cell counts in both CF and COPD patients, with neutrophils being the dominant cell type. Key inflammatory markers, including IL-1β, TNF-α, TGF-β1, IL-8, and LTB4, were increased in both disease groups, with the highest levels observed in CF. Conversely, COPD patients exhibited higher levels of IL-5, IL-6, and IL-10. Microbiome analysis showed distinct clusters for each group, with CF patients often characterized by a preponderance of Pseudomonas. Hierarchical clustering unveiled robust interdependencies between microbiome parameters and inflammation, a richer and more diverse microbiome was associated with a healthier microbial community. This study uncovered significant disparities in inflammation, microbiome composition, and proteome profiles among CF, COPD, and healthy control cohorts. Neutrophilic inflammation and protease activity emerged as common factors in both diseases highlighting proteases as good targets for both indications, while distinct microbial signatures were identified. These findings offer valuable insights into the underlying mechanisms of CF and COPD and may inform future clinical strategies.
2025-09-08 | PXD048388 | Pride
Project description:Rationale: We recently demonstrated that the triple combination CFTR modulator therapy elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves lung ventilation and airway mucus plugging determined by multiple-breath washout and magnetic resonance imaging in CF patients with at least one F508del allele. However, effects of ELX/TEZ/IVA on viscoelastic properties of airway mucus, chronic airway infection and inflammation have not been studied. Objectives: To examine the effects of ELX/TEZ/IVA on airway mucus rheology, microbiome and inflammation in CF patients with one or two F508del alleles aged 12 years and older. Methods: In this prospective observational study, we determined sputum rheology, microbiome, inflammation markers and proteome before and 1, 3 and 12 months after initiation of ELX/TEZ/IVA. Measurements and Main Results: CF patients with at least one F508del allele and healthy controls were enrolled in this study. ELX/TEZ/IVA improved the elastic and viscous modulus of CF sputum. Further, ELX/TEZ/IVA improved the microbiome α-diversity and decreased the relative abundance of Pseudomonas aeruginosa (P<0.05) in CF sputum. ELX/TEZ/IVA also reduced IL-8 and free NE activity, and shifted the CF sputum proteome towards healthy. Conclusions: Our data demonstrate that ELX/TEZ/IVA improves sputum viscoelastic properties, chronic airway infection and inflammation in CF patients with at least one F508del allele, however, without reaching levels close to healthy.
2023-06-22 | PXD041844 | Pride
Project description:Hypomethylating agents (HMAs) are frontline therapies effective at altering the natural course of Myelodysplastic Neoplasms (MDS). However, acquired resistance and treatment failure are hallmarks of HMA therapy. Developing effective and rational HMA-focused combinatorial therapies is challenging as the underlying mechanisms driving HMA efficacy are complex. To address this clinical need, we performed a genome-wide CRISPR-Cas9 screen in a human MDS-derived cell line, MDS-L, and characterized TOPORS as a highly ranked target that synergizes with HMAs to reduce leukemic burden and improve survival in xenograft models. We demonstrated that the depletion of TOPORS mediates sensitivity to HMAs by predisposing leukemic blasts to an impaired DNA damage response (DDR) accompanied by an accumulation of SUMOylated DNMT1 in HMA-treated TOPORS-depleted cells. Importantly, the combination of HMAs with targeting of TOPORS did not functionally impair healthy hematopoiesis. While inhibitors of TOPORS are currently unavailable, we show that inhibition of SUMOylation (upstream of TOPORS functions) with TAK-981 partially phenocopies HMA-sensitivity and DDR impairment. Overall, our data suggest that the combination of HMAs with the inhibition of SUMOylation demonstrates a favourable therapeutic index and represents a rational framework towards the treatment of High-Risk MDS (HR-MDS) or Acute Myeloid Leukemia (AML).
2024-07-25 | PXD050539 | Pride