ArticleNucleic acids research2021
Leveraging three-dimensional chromatin architecture for effective reconstruction of enhancer-target gene regulatory interactions.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- iEnhancer-Flow: Integrating Transformer-Based Sequence Learning with DNA Shape Insights for Robust Enhancer Prediction.Interdisciplinary sciences, computational life sciences · 2026Article
- Decoding 3D chromatin architecture reveals distinct enhancer classes underlying hierarchical gene regulation in prostate cancer.Genome biology · 2026Article
- CRM-TI: an enhanced pipeline for computationally assigning the target genes of cis-regulatory modules by considering comprehensive long-range regulation mechanisms.BioData mining · 2026Article
- An upstream enhancer and MEF2 transcription factors fine-tune the regulation of the Bdnf gene in cortical and hippocampal neurons.The Journal of biological chemistry · 2024Article
- Leveraging Tissue-Specific Enhancer-Target Gene Regulatory Networks Identifies Enhancer Somatic Mutations That Functionally Impact Lung Cancer.Cancer research · 2024Article
- IVEA: an integrative variational Bayesian inference method for predicting enhancer-gene regulatory interactions.Bioinformatics advances · 2024Article
- Harnessing PROTAC technology to combat stress hormone receptor activation.Nature communications · 2023Article
- Landscape and perturbation of enhancer-driven core transcription regulatory circuits in cancer.Molecular therapy. Nucleic acids · 2023Article
- Integrating Long-Range Regulatory Interactions to Predict Gene Expression Using Graph Convolutional Networks.Journal of computational biology : a journal of computational molecular cell biology · 2022Article
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Authors and funding
6 authors.
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Abstract
A growing amount of evidence in literature suggests that germline sequence variants and somatic mutations in non-coding distal regulatory elements may be crucial for defining disease risk and prognostic stratification of patients, in genetic disorders as well as in cancer. Their functional interpretation is challenging because genome-wide enhancer-target gene (ETG) pairing is an open problem in genomics. The solutions proposed so far do not account for the hierarchy of structural domains which define chromatin three-dimensional (3D) architecture. Here we introduce a change of perspective based on the definition of multi-scale structural chromatin domains, integrated in a statistical framework to define ETG pairs. In this work (i) we develop a computational and statistical framework to reconstruct a comprehensive map of ETG pairs leveraging functional genomics data; (ii) we demonstrate that the incorporation of chromatin 3D architecture information improves ETG pairing accuracy and (iii) we use multiple experimental datasets to extensively benchmark our method against previous solutions for the genome-wide reconstruction of ETG pairs. This solution will facilitate the annotation and interpretation of sequence variants in distal non-coding regulatory elements. We expect this to be especially helpful in clinically oriented applications of whole genome sequencing in cancer and undiagnosed genetic diseases research.
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