Similar Datasets
Project description:Sepsis, sequela of bloodstream infections and dysregulated host responses, is a leading cause of death globally. Neutrophils tightly regulate responses to pathogens to prevent organ damage. Profiling early host epigenetic responses in neutrophils may aid in disease recognition. We performed assay for transposase-accessible chromatin (ATAC)-seq of human neutrophils challenged with six toll-like receptor ligands and two organisms; and RNA-seq after Escherichia coli exposure for 1 and 4 h along with ATAC-seq. ATAC-seq of neutrophils facilitates detection of pathogen DNA. In addition, despite similarities in genomic distribution of differential chromatin changes across challenges, only a fraction overlaps between the challenges. Ligands depict shared signatures, but majority are unique in position, function, and challenge. Epigenomic changes are plastic, only ∼120 are shared by Ecoli challenges over time, resulting in varied differential genes and associated processes. We identify three classes of gene regulation, chromatin access changes in the promoter; changes in the promoter and distal enhancers; and controlling expression through changes solely in distal enhancers. These and transcription factor footprinting reveal timely and challenge specific mechanisms of transcriptional regulation in neutrophils.
| S-EPMC8321655 | biostudies-literature
Project description:ATAC-seq and RNA-seq of primary human neutrophils challenged with multiple pathogen mimicking ligands and whole organisms.
2020-06-30 | GSE153521 | GEO
Project description:ATAC-seq and RNA-seq of primary human neutrophils challenged with multiple pathogen mimicking ligands and whole organisms.
2020-06-30 | GSE153520 | GEO
Project description:Integrative profiling of early host chromatin accessibility responses in human neutrophils with sensitive pathogen detection
| PRJNA642890 | ENA
Project description:Integrative profiling of early host chromatin accessibility responses in human neutrophils with sensitive pathogen detection [RNA-seq]
| PRJNA642891 | ENA
Project description:BackgroundEnhancers play a fundamental role in orchestrating cell state and development. Although several methods have been developed to identify enhancers, linking them to their target genes is still an open problem. Several theories have been proposed on the functional mechanisms of enhancers, which triggered the development of various methods to infer promoter-enhancer interactions (PEIs). The advancement of high-throughput techniques describing the three-dimensional organization of the chromatin, paved the way to pinpoint long-range PEIs. Here we investigated whether including PEIs in computational models for the prediction of gene expression improves performance and interpretability.ResultsWe have extended our [Formula: see text] framework to include DNA contacts deduced from chromatin conformation capture experiments and compared various methods to determine PEIs using predictive modelling of gene expression from chromatin accessibility data and predicted transcription factor (TF) motif data. We designed a novel machine learning approach that allows the prioritization of TFs binding to distal loop and promoter regions with respect to their importance for gene expression regulation. Our analysis revealed a set of core TFs that are part of enhancer-promoter loops involving YY1 in different cell lines.ConclusionWe present a novel approach that can be used to prioritize TFs involved in distal and promoter-proximal regulatory events by integrating chromatin accessibility, conformation, and gene expression data. We show that the integration of chromatin conformation data can improve gene expression prediction and aids model interpretability.
| S-EPMC7003490 | biostudies-literature
Project description:The advent of single-cell chromatin accessibility profiling has accelerated the ability to map gene regulatory landscapes but has outpaced the development of scalable software to rapidly extract biological meaning from these data. Here we present a software suite for single-cell analysis of regulatory chromatin in R (ArchR; https://www.archrproject.com/ ) that enables fast and comprehensive analysis of single-cell chromatin accessibility data. ArchR provides an intuitive, user-focused interface for complex single-cell analyses, including doublet removal, single-cell clustering and cell type identification, unified peak set generation, cellular trajectory identification, DNA element-to-gene linkage, transcription factor footprinting, mRNA expression level prediction from chromatin accessibility and multi-omic integration with single-cell RNA sequencing (scRNA-seq). Enabling the analysis of over 1.2 million single cells within 8 h on a standard Unix laptop, ArchR is a comprehensive software suite for end-to-end analysis of single-cell chromatin accessibility that will accelerate the understanding of gene regulation at the resolution of individual cells.
| S-EPMC8012210 | biostudies-literature
Project description:Recent advances in single-cell assay for transposase accessible chromatin using sequencing (scATAC-seq) and its coassays have transformed the field of single-cell epigenomics and transcriptomics. However, the low detection efficiency of current methods has limited our understanding of the true complexity of chromatin accessibility and its relationship with gene expression in single cells. Here, we report a high-sensitivity scATAC-seq method, termed multiplexed end-tagging amplification of transposase accessible chromatin (METATAC), which detects a large number of accessible sites per cell and is compatible with automation. Our high detectability and statistical framework allowed precise linking of enhancers to promoters without merging single cells. We systematically investigated allele-specific accessibility in the mouse cerebral cortex, revealing allele-specific accessibility of promotors of certain imprinted genes but biallelic accessibility of their enhancers. Finally, we combined METATAC with our high-sensitivity single-cell RNA sequencing (scRNA-seq) method, multiple annealing and looping based amplification cycles for digital transcriptomics (MALBAC-DT), to develop a joint ATAC-RNA assay, termed METATAC and MALBAC-DT coassay by sequencing (M2C-seq). M2C-seq achieved significant improvements for both ATAC and RNA compared with previous methods, with consistent performance across cell lines and early mouse embryos.
| S-EPMC9546615 | biostudies-literature
Project description:Neutrophils, the most abundant leukocyte population in humans, constantly patrol the body for foreign cells, including pathogens and cancer cells. Once neutrophils are activated, they engage distinct metabolic pathways to fulfill their specialized antipathogen functions. In this review, we examine current research on the metabolism of neutrophil differentiation and antipathogen responses. We also discuss how tumor-associated neutrophils (TANs) can be educated by cytokines and by the nutrient-restrictive milieu of the tumor microenvironment (TME) to suppress antitumor immunity, promote cancer progression, and contribute to biological heterogeneity among tumors. Last, we discuss the clinical implications of circulating neutrophils and infiltrating TANs and consider how targeting TAN metabolism may synergize with cancer immunotherapy.
| S-EPMC9270875 | biostudies-literature
Project description:Pathogens face a hostile and often novel environment when infecting a new host, and adaptation is likely to be an important determinant of the success in colonization and establishment. We hypothesized that resistant hosts will impose stronger selection on pathogens than susceptible hosts, which should accelerate pathogen evolution through selection biased toward effector genes. To test this hypothesis, we conducted an experimental evolution study on Xanthomonas citri subsp. citri (Xcc) in a susceptible plant species and a resistant plant species. We performed 55 rounds of repeated reinoculation of Xcc through susceptible host grapefruit (isolates G1, G2, G3) and resistant host kumquat (isolates K1, K2, K3). Consequently, only K1 and K3 isolates lost their ability to elicit a hypersensitive response (HR) in kumquat. Illumina sequencing of the parental and descendant strains P, G1, G2, G3, K1, K2 and K3 revealed that fixed mutations were biased toward type three secretion system effectors in isolates K1 and K3. Parallel evolution was observed in the K1 and K3 strains, suggesting that the mutations result from selection rather than by random drift. Our results support our hypothesis and suggest that repeated infection of resistant hosts by pathogens should be prevented to avoid selecting for adaptive pathogens.
| S-EPMC3930326 | biostudies-literature