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The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition. We identify 4765 independent primary and 616 secondary cis-expression quantitative trait loci (cis-eQTLs) in the synovium and find that the eQTLs with multiple independent signals have stronger effects and heritability than single independent eQTLs. Integration of genome-wide association studies (GWASs) and eQTLs identifies 84 arthritis related genes, revealing 38 novel genes which have not been reported by previous studies using eQTL data from the GTEx project or immune cells. We further develop a method called eQTac to identify variants that could affect gene expression by affecting chromatin accessibility and identify 1517 regions with potential regulatory function of chromatin accessibility. Altogether, our study provides a comprehensive synovium multi-omics resource for arthritic diseases and gains new insights into the regulation of gene expression.
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http://dx.doi.org/10.1038/s41467-024-45652-x | DOI Listing |
Hum Cell
September 2025
Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Age-related eye diseases (AREDs) are the leading cause of visual impairment in the elderly, affecting the structure of the anterior and posterior segments of the eye, significantly reducing the quality of life of patients, and even leading to irreversible blindness. Typical AREDs include age-related cataract (ARC), dry eye disease (DED), age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), the global prevalence of which continues to rise, becoming a serious public health concern. SIRT1 is an NAD + dependent deacetylase, which plays an important physiological regulatory role in ocular tissues, mainly affecting gene expression and various cellular processes by regulating the acetylation status of substrate proteins.
View Article and Find Full Text PDFJ Chem Inf Model
September 2025
Key Laboratory of Micro-nano Sensing and IoT of Wenzhou, Wenzhou Institute of Hangzhou Dianzi University, Wenzhou 325038, China.
Transcription factors (TFs) are essential proteins that regulate gene expression by specifically binding to transcription factor binding sites (TFBSs) within DNA sequences. Their ability to precisely control the transcription process is crucial for understanding gene regulatory networks, uncovering disease mechanisms, and designing synthetic biology tools. Accurate TFBS prediction, therefore, holds significant importance in advancing these areas of research.
View Article and Find Full Text PDFInflamm Bowel Dis
September 2025
Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom.
Background: Intestinal cells receive incoming signals from neighboring cells and microbial communities. Upstream signaling pathways transduce these signals to reach transcription factors (TFs) that regulate gene expression. In inflammatory bowel disease (IBD), most single nucleotide polymorphisms (SNPs) are in non-coding genomic regions containing TF binding sites.
View Article and Find Full Text PDFPest Manag Sci
September 2025
School of Life Sciences, Genetic Engineering Research Center, Chongqing University, Chongqing, China.
Background: Entomopathogenic fungi show great potential as biological control agents for managing insect pests. However, host defenses have limited the effectiveness of these fungi in practice. Utilizing genetic engineering-based technology could be a promising strategy to enhance the killing efficiency of these fungi against insect pests.
View Article and Find Full Text PDFUrol J
September 2025
Affiliated Hospital of Nantong University, Emergency Department, Nantong, 226000, Jiangsu, China.
Purpose: Urosepsis, a condition caused by a urinary tract infection spreading to the bloodstream, has a complex epigenetic behavior in its cellular and molecular pathophysiology. The objective of this study was to identify relevant genes and signaling pathways in adult urosepsis through a bioinformatic analysis of differentially expressed genes (DEGs).
Materials And Methods: In this in-silico study, the GSE69528 dataset, containing 138 total RNA blood samples from patients with sepsis and uninfected controls, was obtained from the Gene Expression Omnibus (GEO) database.