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促进公开可用的ChIP-Seq数据用于整合研究的分析。

Facilitating Analysis of Publicly Available ChIP-Seq Data for Integrative Studies.

作者信息

Diwadkar Avantika R, Kan Mengyuan, Himes Blanca E

机构信息

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, US.

出版信息

AMIA Annu Symp Proc. 2020 Mar 4;2019:371-379. eCollection 2019.

PMID:32308830
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7153109/
Abstract

ChIP-Seq, a technique that allows for quantification of DNA sequences bound by transcription factors or histones, has been widely used to characterize genome-wide DNA-protein binding at baseline and induced by specific exposures. Integrating results of multiple ChIP-Seq datasets is a convenient approach to identify robust DNA- protein binding sites and determine their cell-type specificity. We developed brocade, a computational pipeline for reproducible analysis of publicly available ChIP-Seq data that creates R markdown reports containing information on datasets downloaded, quality control metrics, and differential binding results. Glucocorticoids are commonly used anti-inflammatory drugs with tissue-specific effects that are not fully understood. We demonstrate the utility of brocade via the analysis of five ChIP-Seq datasets involving glucocorticoid receptor (GR), a transcription factor that mediates glucocorticoid response, to identify cell type-specific and shared GR binding sites across the five cell types. Our results show that brocade facilitates analysis of individual ChIP-Seq datasets and comparative studies involving multiple datasets.

摘要

染色质免疫沉淀测序(ChIP-Seq)是一种能够对与转录因子或组蛋白结合的DNA序列进行定量分析的技术,已被广泛用于在基线状态以及特定暴露诱导下对全基因组DNA-蛋白质结合情况进行表征。整合多个ChIP-Seq数据集的结果是识别稳定的DNA-蛋白质结合位点并确定其细胞类型特异性的便捷方法。我们开发了Brocade,这是一个用于对公开可用的ChIP-Seq数据进行可重复分析的计算流程,它会生成包含有关下载的数据集信息、质量控制指标和差异结合结果的R markdown报告。糖皮质激素是常用的抗炎药物,其组织特异性作用尚未完全明确。我们通过分析五个涉及糖皮质激素受体(GR)的ChIP-Seq数据集(GR是一种介导糖皮质激素反应的转录因子)来证明Brocade的实用性,以识别五种细胞类型中细胞类型特异性和共享的GR结合位点。我们的结果表明,Brocade有助于对单个ChIP-Seq数据集进行分析以及涉及多个数据集的比较研究。

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本文引用的文献

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Integration of Transcriptomic Data Identifies Global and Cell-Specific Asthma-Related Gene Expression Signatures.转录组数据整合识别出全局和细胞特异性哮喘相关基因表达特征。
AMIA Annu Symp Proc. 2018 Dec 5;2018:1338-1347. eCollection 2018.
2
Airway Smooth Muscle-Specific Transcriptomic Signatures of Glucocorticoid Exposure.糖皮质激素暴露的气道平滑肌特异性转录组特征。
Am J Respir Cell Mol Biol. 2019 Jul;61(1):110-120. doi: 10.1165/rcmb.2018-0385OC.
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Disease-Specific Integration of Omics Data to Guide Functional Validation of Genetic Associations.疾病特异性组学数据整合以指导基因关联的功能验证
AMIA Annu Symp Proc. 2018 Apr 16;2017:1589-1596. eCollection 2017.
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Glucocorticoid Receptor ChIP-Seq Identifies PLCD1 as a KLF15 Target that Represses Airway Smooth Muscle Hypertrophy.糖皮质激素受体染色质免疫沉淀测序确定PLCD1为抑制气道平滑肌肥大的KLF15靶点。
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Cistrome-based Cooperation between Airway Epithelial Glucocorticoid Receptor and NF-κB Orchestrates Anti-inflammatory Effects.气道上皮糖皮质激素受体与核因子κB基于顺式作用元件的协同作用调控抗炎效应。
J Biol Chem. 2016 Jun 10;291(24):12673-12687. doi: 10.1074/jbc.M116.721217. Epub 2016 Apr 13.
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The Gene Expression Omnibus Database.基因表达综合数据库
Methods Mol Biol. 2016;1418:93-110. doi: 10.1007/978-1-4939-3578-9_5.
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Functionally distinct patterns of nucleosome remodeling at enhancers in glucocorticoid-treated acute lymphoblastic leukemia.糖皮质激素治疗的急性淋巴细胞白血病中增强子处核小体重塑的功能不同模式。
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Computational methodology for ChIP-seq analysis.用于ChIP-seq分析的计算方法。
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