Exploring the function of genetic variants in the non-coding genomic regions: approaches for identifying human regulatory variants affecting gene expression
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TLDR
In this article, the authors systematically review an array of methods currently used to map RVs as well as the computational approaches in annotating and interpreting their regulatory effects, with emphasis on regulatory single-nucleotide polymorphism.Abstract:
Understanding the genetic basis of human traits/diseases and the underlying mechanisms of how these traits/diseases are affected by genetic variations is critical for public health. Current genome-wide functional genomics data uncovered a large number of functional elements in the noncoding regions of human genome, providing new opportunities to study regulatory variants (RVs). RVs play important roles in transcription factor bindings, chromatin states and epigenetic modifications. Here, we systematically review an array of methods currently used to map RVs as well as the computational approaches in annotating and interpreting their regulatory effects, with emphasis on regulatory single-nucleotide polymorphism. We also briefly introduce experimental methods to validate these functional RVs.read more
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GWASdb v2: an update database for human genetic variants identified by genome-wide association studies
Mulin Jun Li,Zipeng Liu,Panwen Wang,Maria Pik Wong,Matthew R. Nelson,Jean Pierre A. Kocher,Meredith Yeager,Pak C. Sham,Stephen J. Chanock,Zhengyuan Xia,Junwen Wang +10 more
TL;DR: The GWASdb v2 as discussed by the authors provides comprehensive data curation and knowledge integration for GWAS TASs, which provides comprehensive function annotation for each TAS by incorporating gene-based information, ENCODE ChIP-seq assays, eQTL, population haplotype, functional prediction across multiple biological domains, evolutionary signals and disease-related annotation.
Journal ArticleDOI
Identification of altered cis-regulatory elements in human disease.
TL;DR: The current state of computational tools and resources for identifying the genomic regulatory components (cis-regulatory regions and TF binding sites, TFBSs) controlling gene transcriptional regulation are presented and how such approaches can be used to interpret the potential disease causality of point mutations and small insertions or deletions are reviewed.
Journal ArticleDOI
GWAS4D: multidimensional analysis of context-specific regulatory variant for human complex diseases and traits.
Dandan Huang,Xianfu Yi,Shijie Zhang,Zhanye Zheng,Panwen Wang,Chenghao Xuan,Pak C. Sham,Junwen Wang,Junwen Wang,Mulin Jun Li +9 more
TL;DR: Using a GWAS fine-mapped set for 161 coronary artery disease risk loci, it is demonstrated that GWAS4D is able to efficiently prioritize disease-causal regulatory variants.
Journal ArticleDOI
QTLbase: an integrative resource for quantitative trait loci across multiple human molecular phenotypes.
Zhanye Zheng,Dandan Huang,Jianhua Wang,Ke Zhao,Yao Zhou,Zhenyang Guo,Sinan Zhai,Hang Xu,Hui Cui,Hongcheng Yao,Zhao Wang,Xianfu Yi,Shijie Zhang,Pak C. Sham,Mulin Jun Li +14 more
TL;DR: QTLbase provides a one-stop shop for QTL retrieval and comparison across multiple tissues and multiple layers of molecular complexity, and will greatly help researchers interrogate the biological mechanism of causal variants and guide the direction of functional validation.
Journal ArticleDOI
Disease-associated variants in different categories of disease located in distinct regulatory elements
Meng Ma,Meng Ma,Ying Ru,Ling-Shiang Chuang,Nai Yun Hsu,Lisong Shi,Jörg Hakenberg,Wei-Yi Cheng,Andrew V. Uzilov,Wei Ding,Benjamin S. Glicksberg,Rong Chen +11 more
TL;DR: Disease-associated variants in different disease categories are preferentially located in particular regulatory elements, and regulatory regions are located within over 50% coding exon regions.
References
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