Similar Datasets
Project description:The endpoint of this study was to prospectively validate the prognostic significance of fecal Akk in advanced NSCLC patients treated with first or second line ICI. We performed RNA sequencing to compare transcriptomic profiles of the different groups.
2021-08-20 | GSE182328 | GEO
Project description:Background & Aims: The contribution of genetics to the pathogenesis of inflammatory bowel disease (IBD) has been established by twin studies, targeted sequencing and genome-wide association studies (GWASs). This has yielded a plethora of risk loci with an aim to identify causal variants. Research on the genetic components of IBD has mainly focused on protein coding genes, thereby omitting other functional elements in the human genome i.e. the regulatory regions. Methods: Using acetylated histone 3 lysine 27 (H3K27ac) chromatin immunoprecipitation and sequencing (ChIP-seq), we identified tens of thousands of potential regulatory regions that are active in intestinal epithelium and immune cells, the main cell types involved in IBD. We correlated these regions with susceptibility loci for IBD. Results: We show that 45 out of 163 single nucleotide polymorphisms (SNPs) associated with IBD co-localize with active regulatory elements. In addition, another 47 IBD associated SNPs co-localize with active regulatory element via other SNP in strong linkage disequilibrium. Altogether 92 out of 163 IBD-associated SNPs can be connected with distinct regulatory element. This is 2.5 to 3.5 times more frequent than expected from random sampling. The genomic variation in these SNPs often creates or disrupts known binding motifs - thereby possibly affecting the binding affinity of transcriptional regulators and altering the expression of regulated genes. Conclusions: We show that in addition to protein coding genes, non-coding DNA regulatory regions, active in immune cells and in intestinal epithelium, are involved in IBD. H3K27ac ChIP-seq (ab4729, Abcam) profile of 7 intestinal epithelial samples
2013-12-06 | E-GEOD-51425 | biostudies-arrayexpress
Project description:The early detection of tissue and organ damage associated with autoimmune diseases (AID) has been identified as key to improve long-term survival, but non-invasive biomarkers are lacking. Elevated cell-free DNA (cfDNA) levels have been observed in AID and inflammatory bowel disease (IBD), prompting interest to use cfDNA as a potential non-invasive diagnostic and prognostic biomarker. Despite these known disease-related changes in concentration, it remains impossible to identify AID and IBD patients through cfDNA analysis alone. By using unsupervised clustering on large sets of shallow whole-genome sequencing (sWGS) cfDNA data, we uncover AID- and IBD-specific genome-wide patterns in plasma cfDNA in both the obstetric and general AID and IBD populations. Supervised learning of the genome-wide patterns allows AID prediction with 50% sensitivity at 95% specificity. Importantly, the method can identify pregnant women with AID during routine non-invasive prenatal screening. Since AID pregnancies have an increased risk of severe complications, early recognition or detection of new onset AID can redirect pregnancy management and limit potential adverse events. This method opens up new avenues for screening, diagnosis and monitoring of AID and IBD.
2022-09-14 | E-MTAB-11607 | biostudies-arrayexpress
Project description:A computational platform, the Boolean network explorer (BoNE), has recently been developed to infuse AI-enhanced precision into drug discovery; it enables querying and navigating invariant Boolean Implication Networks of disease maps for prioritizing high-value targets. Here we used BoNE to query an Inflammatory Bowel Disease (IBD)-map and prioritize two nuclear receptors, PPARa/g. Balanced agonism of PPARa/g was predicted to impact macrophage processes, ameliorate colitis in network-prioritized animal models, ‘reset’ the gene expression network from disease to health, and achieve a favorable therapeutic index that tracked other FDA-approved targets. Predictions were validated using a balanced and potent PPARa/g-dual agonist (PAR5359) in two pre-clinical murine models, i.e., Citrobacter rodentium-induced infectious colitis and DSS-induced colitis. Mechanistically, we show that such balanced dual agonism promotes bacterial clearance more efficiently than individual agonists both in vivo and in vitro; PPARa is required and its agonism is sufficient to induce the pro-inflammatory cytokines and cellular ROS, which are essential for bacterial clearance and immunity, whereas PPARg-agonism blunts these responses, delays microbial clearance and induces the anti-inflammatory cytokine, IL10. Balanced agonism achieved controlled inflammation while protecting the gut barrier and ‘reversal’ of the transcriptomic network. Furthermore, dual agonism effectively reversed the defective bacterial clearance observed in PBMCs derived from IBD patients. These findings not only deliver a macrophage modulator for use as barrier-protective therapy in IBD, but also highlight the potential of BoNE to accelerate and enhance the precision of drug discovery.
2022-02-03 | GSE171057 | GEO