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探索具有 eQTL 网络的组织中的调控。

Exploring regulation in tissues with eQTL networks.

机构信息

Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115.

Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115.

出版信息

Proc Natl Acad Sci U S A. 2017 Sep 12;114(37):E7841-E7850. doi: 10.1073/pnas.1707375114. Epub 2017 Aug 29.


DOI:10.1073/pnas.1707375114
PMID:28851834
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5604022/
Abstract

Characterizing the collective regulatory impact of genetic variants on complex phenotypes is a major challenge in developing a genotype to phenotype map. Using expression quantitative trait locus (eQTL) analyses, we constructed bipartite networks in which edges represent significant associations between genetic variants and gene expression levels and found that the network structure informs regulatory function. We show, in 13 tissues, that these eQTL networks are organized into dense, highly modular communities grouping genes often involved in coherent biological processes. We find communities representing shared processes across tissues, as well as communities associated with tissue-specific processes that coalesce around variants in tissue-specific active chromatin regions. Node centrality is also highly informative, with the global and community hubs differing in regulatory potential and likelihood of being disease associated.

摘要

描述遗传变异对复杂表型的集体调控影响是开发基因型到表型图谱的主要挑战。我们使用表达数量性状基因座(eQTL)分析构建了二部网络,其中边缘表示遗传变异与基因表达水平之间的显著关联,并且发现网络结构提供了调控功能的信息。我们在 13 种组织中表明,这些 eQTL 网络被组织成密集的、高度模块化的社区,这些社区将经常涉及协调生物过程的基因分组。我们发现代表跨组织共享过程的社区,以及与组织特异性过程相关的社区,这些社区围绕组织特异性活性染色质区域中的变体凝聚。节点中心性也具有高度的信息量,全局和社区枢纽在调节潜力和与疾病相关的可能性方面存在差异。

相似文献

[1]
Exploring regulation in tissues with eQTL networks.

Proc Natl Acad Sci U S A. 2017-8-29

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
The Importance of Regulatory Network Structure for Complex Trait Heritability and Evolution.

Mol Biol Evol. 2025-7-30

[2]
BLOBFISH: Bipartite Limited Subnetworks from Multiple Observations using Breadth-First Search with Constrained Hops.

bioRxiv. 2025-3-13

[3]
Interpretable AI for inference of causal molecular relationships from omics data.

Sci Adv. 2025-2-14

[4]
Novel putative causal mutations associated with fat traits in Nellore cattle uncovered by eQTLs located in open chromatin regions.

Sci Rep. 2024-5-2

[5]
Cis-eQTLs in seven duck tissues identify novel candidate genes for growth and carcass traits.

BMC Genomics. 2024-4-30

[6]
Epigenome-augmented eQTL-hotspots reveal genome-wide transcriptional programs in 36 human tissues.

Brief Bioinform. 2024-3-27

[7]
The Importance of Regulatory Network Structure for Complex Trait Heritability and Evolution.

bioRxiv. 2024-9-9

[8]
Single-cell dissection of aggression in honeybee colonies.

Nat Ecol Evol. 2023-8

[9]
The genetic architecture of behavioral canalization.

Trends Genet. 2023-8

[10]
Connectivity in eQTL networks dictates reproducibility and genomic properties.

Cell Rep Methods. 2022-5-23

本文引用的文献

[1]
Large-Scale trans-eQTLs Affect Hundreds of Transcripts and Mediate Patterns of Transcriptional Co-regulation.

Am J Hum Genet. 2017-4-6

[2]
Bipartite Community Structure of eQTLs.

PLoS Comput Biol. 2016-9-12

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Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases.

Science. 2016-8-19

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Making sense of GWAS: using epigenomics and genome engineering to understand the functional relevance of SNPs in non-coding regions of the human genome.

Epigenetics Chromatin. 2015-12-30

[5]
Dissecting the genetics of the human transcriptome identifies novel trait-related trans-eQTLs and corroborates the regulatory relevance of non-protein coding loci†.

Hum Mol Genet. 2015-8-15

[6]
Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans.

Science. 2015-5-8

[7]
Integrative analysis of 111 reference human epigenomes.

Nature. 2015-2-19

[8]
Genomic variation. Impact of regulatory variation from RNA to protein.

Science. 2015-2-6

[9]
limma powers differential expression analyses for RNA-sequencing and microarray studies.

Nucleic Acids Res. 2015-4-20

[10]
Cross-tissue and tissue-specific eQTLs: partitioning the heritability of a complex trait.

Am J Hum Genet. 2014-11-6

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