Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterized by enthesitis of the spine and sacroiliac joints. Genome-wide association studies (GWASs) have revealed more than 100 genetic associations whose functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls. We find that, while CD14+ monocytes and CD4+ and CD8+ T cells show disease-specific differences at the RNA level, epigenomic differences are only apparent upon multi-omics integration. The latter reveals enrichment at disease-associated loci in monocytes. We link putative functional SNPs to genes using high-resolution Capture-C at 10 loci, including PTGER4 and ETS1, and show how disease-specific functional genomic data can be integrated with GWASs to enhance therapeutic target discovery. This study combines epigenetic and transcriptional analysis with GWASs to identify disease-relevant cell types and gene regulation of likely pathogenic relevance and prioritize drug targets.
Pubmed ID: 37388915 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This unknown targets
View all literature mentionsThis monoclonal targets CD14
View all literature mentionsThis monoclonal targets CD8
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis polyclonal targets H3K4me1
View all literature mentionsThis polyclonal targets H3K4me3
View all literature mentionsThis polyclonal targets H3K27ac
View all literature mentionsThis monoclonal targets CD16
View all literature mentionsThis monoclonal targets CD14
View all literature mentionsThis monoclonal targets CD8
View all literature mentionsThis monoclonal targets CD14
View all literature mentionsBD LSRFortessa cell analyzer provides power, performance, and consistency and supports the expanding needs of multicolor flow cytometry assays.
View all literature mentionsBenchtop manager cell sorter for cell isolation in automated workflows. Sorts cells directly from whole blood or bone marrow without density gradient centrifugation or erythrocyte lysis.
View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsSoftware tool for comparing lists with Venn's diagrams.
View all literature mentionsSoftware R package to produce publication ready volcano plots with enhanced colouring and labeling. Used to visualise results of differential expression analyses.
View all literature mentionsOpen source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.
View all literature mentionsOpen source software tool to merge paired-end reads from next-generation sequencing experiments. Designed to merge pairs of reads when original DNA fragments are shorter than twice length of reads. Can improve genome assemblies and transcriptome assembly by merging RNA-seq data.
View all literature mentionsSoftware tool that removes adapter sequences from DNA sequencing reads.
View all literature mentionsQuality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.
View all literature mentionsSoftware R package for multivariate analysis which takes into account different types of data structure. Data can be organized in groups of variable, groups of individuals, or into hierarchy of variables.
View all literature mentionsSoftware tool for chromatin state discovery and characterization. Used for chromatin state discovery and genome annotation of non coding genome using epigenomic information across one or multiple cell types. Combines multiple genome wide epigenomic maps, and uses combinatorial and spatial mark patterns to infer complete annotation for each cell type. Provides automated enrichment analysis of resulting annotations.
View all literature mentionsSoftware package to retrieve nearest genes around peak, annotate genomic region of peak, implements statstical methods for estimate significance of overlap among ChIP peak data sets, and incorporate GEO database for user to compare own dataset with those deposited in database.Several visualization functions are implemented to summarize coverage of peak experiment, average profile and heatmap of peaks binding to TSS regions, genomic annotation, distance to TSS, and overlap of peaks or genes.
View all literature mentionsA read summarization program, which counts mapped reads for the genomic features such as genes and exons.
View all literature mentionsSoftware Python package for identifying transcript factor binding sites. Used to evaluate significance of enriched ChIP regions. Improves spatial resolution of binding sites through combining information of both sequencing tag position and orientation. Can be used for ChIP-Seq data alone, or with control sample with increase of specificity.
View all literature mentionsOriginal SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.
View all literature mentionsUltrafast and memory efficient tool for aligning sequencing reads to long reference sequences. Supports gapped, local, and paired end alignment modes. More suited to finding longer, gapped alignments in comparison with original Bowtie method.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsA powerful toolset for genome arithmetic allowing one to address common genomics tasks such as finding feature overlaps and computing coverage. Bedtools allows one to intersect, merge, count, complement, and shuffle genomic intervals from multiple files in widely-used genomic file formats such as BAM, BED, GFF/GTF, VCF. While each individual tool is designed to do a relatively simple task (e.g., intersect two interval files), quite sophisticated analyses can be conducted by combining multiple bedtools operations on the UNIX command line.
View all literature mentionsScript distributed with the HT-Seq Python framework for processing RNA-seq or DNA-seq data.
View all literature mentionsJava toolset for working with next generation sequencing data in the BAM format.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentions