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从甲基化到活性:一个通过个体肿瘤DNA甲基化组揭示启动子活性图谱的深度学习框架指南。

A Guide to MethylationToActivity: A Deep Learning Framework That Reveals Promoter Activity Landscapes from DNA Methylomes in Individual Tumors.

作者信息

Dieseldorff Jones Karissa, Putnam Daniel, Williams Justin, Chen Xiang

机构信息

Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

出版信息

Methods Mol Biol. 2023;2624:73-85. doi: 10.1007/978-1-0716-2962-8_6.

DOI:10.1007/978-1-0716-2962-8_6
PMID:36723810
Abstract

Genome-wide DNA methylomes have contributed greatly to tumor detection and subclassification. However, interpreting the biological impact of the DNA methylome at the individual gene level remains a challenge. MethylationToActivity (M2A) is a pipeline that uses convolutional neural networks to infer H3K4me3 and H3K27ac enrichment from DNA methylomes and thus infer promoter activity. It was shown to be highly accurate and robust in revealing promoter activity landscapes in various pediatric and adult cancers. The following will present a user-friendly guide through the model pipeline.

摘要

全基因组DNA甲基化组对肿瘤检测和亚分类有很大贡献。然而,在单个基因水平上解释DNA甲基化组的生物学影响仍然是一项挑战。甲基化到活性(M2A)是一种利用卷积神经网络从DNA甲基化组推断H3K4me3和H3K27ac富集从而推断启动子活性的流程。在揭示各种儿科和成人癌症的启动子活性图谱方面,它被证明具有高度准确性和稳健性。以下将提供一个通过该模型流程的用户友好指南。

相似文献

1
A Guide to MethylationToActivity: A Deep Learning Framework That Reveals Promoter Activity Landscapes from DNA Methylomes in Individual Tumors.从甲基化到活性:一个通过个体肿瘤DNA甲基化组揭示启动子活性图谱的深度学习框架指南。
Methods Mol Biol. 2023;2624:73-85. doi: 10.1007/978-1-0716-2962-8_6.
2
MethylationToActivity: a deep-learning framework that reveals promoter activity landscapes from DNA methylomes in individual tumors.甲基化到活性:一个深度学习框架,能够从单个肿瘤的 DNA 甲基组中揭示启动子活性图谱。
Genome Biol. 2021 Jan 19;22(1):24. doi: 10.1186/s13059-020-02220-y.
3
A reference methylome database and analysis pipeline to facilitate integrative and comparative epigenomics.一个有助于整合和比较表观基因组学的参考甲基化组数据库及分析流程。
PLoS One. 2013 Dec 6;8(12):e81148. doi: 10.1371/journal.pone.0081148. eCollection 2013.
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Impact of mutations in DNA methylation modification genes on genome-wide methylation landscapes and downstream gene activations in pan-cancer.泛癌中 DNA 甲基化修饰基因突变对全基因组甲基化景观和下游基因激活的影响。
BMC Med Genomics. 2020 Feb 24;13(Suppl 3):27. doi: 10.1186/s12920-020-0659-4.
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Investigating crosstalk between H3K27 acetylation and H3K4 trimethylation in CRISPR/dCas-based epigenome editing and gene activation.研究基于 CRISPR/dCas 的表观基因组编辑和基因激活中 H3K27 乙酰化与 H3K4 三甲基化之间的串扰。
Sci Rep. 2021 Aug 5;11(1):15912. doi: 10.1038/s41598-021-95398-5.
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The cell-free DNA methylome captures distinctions between localized and metastatic prostate tumors.无细胞游离 DNA 甲基组捕获局部性和转移性前列腺肿瘤之间的差异。
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Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma.实体瘤中的比较甲基化组分析揭示了鼻咽癌6号染色体短臂上的异常甲基化。
Cancer Med. 2015 Jul;4(7):1079-90. doi: 10.1002/cam4.451. Epub 2015 Apr 29.

本文引用的文献

1
MethylationToActivity: a deep-learning framework that reveals promoter activity landscapes from DNA methylomes in individual tumors.甲基化到活性:一个深度学习框架,能够从单个肿瘤的 DNA 甲基组中揭示启动子活性图谱。
Genome Biol. 2021 Jan 19;22(1):24. doi: 10.1186/s13059-020-02220-y.
2
A Pan-cancer Transcriptome Analysis Reveals Pervasive Regulation through Alternative Promoters.泛癌症转录组分析揭示了通过选择性启动子的普遍调控。
Cell. 2019 Sep 5;178(6):1465-1477.e17. doi: 10.1016/j.cell.2019.08.018.
3
Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours.
泛癌症基因组和转录组分析 1699 例儿童白血病和实体瘤。
Nature. 2018 Mar 15;555(7696):371-376. doi: 10.1038/nature25795. Epub 2018 Feb 28.
4
The landscape of genomic alterations across childhood cancers.儿童癌症中基因组改变的全景。
Nature. 2018 Mar 15;555(7696):321-327. doi: 10.1038/nature25480. Epub 2018 Feb 28.
5
Epigenetic regulation of gene expression in cancer: techniques, resources and analysis.癌症中基因表达的表观遗传调控:技术、资源与分析。
Brief Funct Genomics. 2018 Jan 1;17(1):49-63. doi: 10.1093/bfgp/elx018.
6
Integrated Analysis of Whole-Genome ChIP-Seq and RNA-Seq Data of Primary Head and Neck Tumor Samples Associates HPV Integration Sites with Open Chromatin Marks.原发性头颈肿瘤样本的全基因组ChIP-Seq和RNA-Seq数据的综合分析将人乳头瘤病毒(HPV)整合位点与开放染色质标记联系起来。
Cancer Res. 2017 Dec 1;77(23):6538-6550. doi: 10.1158/0008-5472.CAN-17-0833. Epub 2017 Sep 25.
7
Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma.表观基因组启动子改变扩增胃腺癌基因异构体和免疫原性多样性。
Cancer Discov. 2017 Jun;7(6):630-651. doi: 10.1158/2159-8290.CD-16-1022. Epub 2017 Mar 20.
8
The Utilization of Formalin Fixed-Paraffin-Embedded Specimens in High Throughput Genomic Studies.福尔马林固定石蜡包埋标本在高通量基因组研究中的应用
Int J Genomics. 2017;2017:1926304. doi: 10.1155/2017/1926304. Epub 2017 Jan 26.
9
DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma.DNA甲基化异质性定义了尤因肉瘤的疾病谱。
Nat Med. 2017 Mar;23(3):386-395. doi: 10.1038/nm.4273. Epub 2017 Jan 30.
10
DeepChrome: deep-learning for predicting gene expression from histone modifications.深度铬:用于从组蛋白修饰预测基因表达的深度学习
Bioinformatics. 2016 Sep 1;32(17):i639-i648. doi: 10.1093/bioinformatics/btw427.