Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases.
Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases.
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DOI：
10.1038/nmeth.3799
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发表时间：
2016-04
期刊：
影响因子：
48
通讯作者：
Bergmann S
中科院分区：
文献类型：
--
作者：
Marbach D;Lamparter D;Quon G;Kellis M;Kutalik Z;Bergmann S
绘制受到遗传变异干扰的分子回路仍然是一个巨大的挑战，这些遗传变异是复杂性状和疾病的基础。我们为人类提供了394种细胞类型和组织特异性基因调控网络的综合资源，每个网络都指定了转录因子、增强子、启动子和基因之间的全基因组连接性。与37个全基因组关联研究（GWAS）的整合表明，疾病相关的遗传变异-包括未达到全基因组意义的变异-通常会干扰对疾病相关细胞类型或组织高度特异性的调控模块。我们的资源为系统分析数百种人类细胞类型和组织的调控程序打开了大门。
Mapping the molecular circuits that are perturbed by genetic variants underlying complex traits and diseases remains a great challenge. We present a comprehensive resource of 394 cell type and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity between transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) shows that disease-associated genetic variants — including variants that do not reach genome-wide significance — often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissues.