title: iRegNet3D: three-dimensional integrated regulatory network for the genomic analysis of coding and non-coding disease mutations.
abstract: 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.
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, 14853, USA.|Weill Institute for Cell and Molecular Biology, Ithaca, NY, 14853, USA.
authors.forename: Siqi
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, 14853, USA.|Weill Institute for Cell and Molecular Biology, Ithaca, NY, 14853, USA.
authors.forename: Nathaniel D
authors.initials: ND
authors.lastname: Tippens
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, 14853, USA.|Weill Institute for Cell and Molecular Biology, Ithaca, NY, 14853, USA.
authors.forename: Yaoda
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Mort
authors.affiliation: Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Stenson
authors.affiliation: Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
authors.forename: David N
authors.initials: DN
authors.lastname: Cooper
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, 14853, USA. haiyuan.yu@cornell.edu.|Weill Institute for Cell and Molecular Biology, Ithaca, NY, 14853, USA. haiyuan.yu@cornell.edu.
authors.forename: Haiyuan
authors.initials: H
authors.lastname: Yu
mesh_terms: D001665:Binding Sites; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D004843:Epistasis, Genetic; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D023281:Genomics / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D059372:Nucleotide Motifs; D016366:Open Reading Frames; D021281:Quantitative Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D020506:Untranslated Regions
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D020506:Untranslated Regions; D004247:DNA
keywords: Chromatin interaction network; Disease-associated mutation; Inherited disease; Missense mutation; Non-coding mutation; TF-DNA interaction network; TF-TF interaction network; Transcriptional regulation; iRegNet3D