The mechanistic details of most disease-causing mutations remain poorly explored within the context of regulatory networks. We present a high-resolution three-dimensional integrated regulatory network (iRegNet3D) in the form of a web tool, where we resolve the interfaces of all known transcription factor (TF)-TF, TF-DNA and chromatin-chromatin interactions for the analysis of both coding and non-coding disease-associated mutations to obtain mechanistic insights into their functional impact. Using iRegNet3D, we find that disease-associated mutations may perturb the regulatory network through diverse mechanisms including chromatin looping. iRegNet3D promises to be an indispensable tool in large-scale sequencing and disease association studies.
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http://dx.doi.org/10.1186/s13059-016-1138-2 | DOI Listing |
PLoS One
January 2025
Molecular Biophysics Unit, Indian Institute of Science, Bengaluru, Karnataka, India.
PLoS One
January 2025
Department of Reproductive Medicine, Guangzhou Women and Children's Medical center Liuzhou Hospital, Liuzhou, Guangxi, China.
Endometrial cancer (UCEC) is the most prevalent gynecological malignancy in high-income countries, and its incidence is rising globally. Although early-stage UCEC can be treated with surgery, advanced cases have a poor prognosis, highlighting the need for effective molecular biomarkers to improve diagnosis and prognosis. In this study, we analyzed mRNA and miRNA sequencing data from UCEC tissues and adjacent non-cancerous tissues from the TCGA database.
View Article and Find Full Text PDFPLoS One
January 2025
Biomedical Sciences Research Institute, Centre for Genomic Medicine, Ulster University, Coleraine, Northern Ireland, United Kingdom.
Pseudoexfoliation glaucoma is a severe form of secondary open angle glaucoma and is associated with activation of the TGF-β pathway by TGF-β1. MicroRNAs (miRNAs) are small non-coding RNA species that are involved in regulation of mRNA expression and translation. To investigate what glaucomatous changes occur in the trabecular meshwork and how these changes may be regulated by miRNAs, we performed a bioinformatics analysis resulting in a miRNA-mRNA interactome.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, United States of America.
Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated MLL1 recruitment and aberrant homeotic topologically associated domains (TADs) that enhanced chromatin accessibilities and activated homeotic/hematopoietic oncogenes.
View Article and Find Full Text PDFBrief Bioinform
November 2024
School of Artificial Intelligence, Jilin University, Qianjin Street 2699, 130010 Changchun, China.
Imaging-based spatial transcriptomics (iST), such as MERFISH, CosMx SMI, and Xenium, quantify gene expression level across cells in space, but more importantly, they directly reveal the subcellular distribution of RNA transcripts at the single-molecule resolution. The subcellular localization of RNA molecules plays a crucial role in the compartmentalization-dependent regulation of genes within individual cells. Understanding the intracellular spatial distribution of RNA for a particular cell type thus not only improves the characterization of cell identity but also is of paramount importance in elucidating unique subcellular regulatory mechanisms specific to the cell type.
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