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HBCR_DMR:一种基于贝塔-二项式贝叶斯分层模型和排序方法组合的混合方法,用于检测亚硫酸氢盐测序数据中的差异甲基化区域。

HBCR_DMR: A Hybrid Method Based on Beta-Binomial Bayesian Hierarchical Model and Combination of Ranking Method to Detect Differential Methylation Regions in Bisulfite Sequencing Data.

作者信息

Yassi Maryam, Shams Davodly Ehsan, Hajebi Khaniki Saeedeh, Kerachian Mohammad Amin

机构信息

Cancer Genetics Research Unit, Reza Radiotherapy and Oncology Center, Mashhad 9184156815, Iran.

Department of Mathematics and Statistics, University of Otago, Dunedin 9054, New Zealand.

出版信息

J Pers Med. 2024 Mar 29;14(4):361. doi: 10.3390/jpm14040361.

DOI:10.3390/jpm14040361
PMID:38672987
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11051304/
Abstract

DNA methylation is a key epigenetic modification involved in gene regulation, contributing to both physiological and pathological conditions. For a more profound comprehension, it is essential to conduct a precise comparison of DNA methylation patterns between sample groups that represent distinct statuses. Analysis of differentially methylated regions (DMRs) using computational approaches can help uncover the precise relationships between these phenomena. This paper describes a hybrid model that combines the beta-binomial Bayesian hierarchical model with a combination of ranking methods known as HBCR_DMR. During the initial phase, we model the actual methylation proportions of the CpG sites (CpGs) within the replicates. This modeling is achieved through beta-binomial distribution, with parameters set by a group mean and a dispersion parameter. During the second stage, we establish the selection of distinguishing CpG sites based on their methylation status, employing multiple ranking techniques. Finally, we combine the ranking lists of differentially methylated CpG sites through a voting system. Our analyses, encompassing simulations and real data, reveal outstanding performance metrics, including a sensitivity of 0.72, specificity of 0.89, and an F1 score of 0.76, yielding an overall accuracy of 0.82 and an AUC of 0.94. These findings underscore HBCR_DMR's robust capacity to distinguish methylated regions, confirming its utility as a valuable tool for DNA methylation analysis.

摘要

DNA甲基化是一种参与基因调控的关键表观遗传修饰,在生理和病理状况中均发挥作用。为了更深入地理解,有必要对代表不同状态的样本组之间的DNA甲基化模式进行精确比较。使用计算方法分析差异甲基化区域(DMR)有助于揭示这些现象之间的精确关系。本文描述了一种混合模型,该模型将贝塔二项式贝叶斯分层模型与一种称为HBCR_DMR的排序方法组合相结合。在初始阶段,我们对重复样本中CpG位点(CpGs)的实际甲基化比例进行建模。这种建模是通过贝塔二项式分布实现的,其参数由组均值和离散参数设置。在第二阶段,我们根据CpG位点的甲基化状态,采用多种排序技术来确定有区别的CpG位点。最后,我们通过投票系统将差异甲基化CpG位点的排序列表进行合并。我们涵盖模拟和真实数据的分析揭示了出色的性能指标,包括灵敏度为0.72、特异性为0.89、F1分数为0.76,总体准确率为0.82,曲线下面积(AUC)为0.94。这些发现强调了HBCR_DMR区分甲基化区域的强大能力,证实了其作为DNA甲基化分析的宝贵工具的实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19de/11051304/ce975f548056/jpm-14-00361-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19de/11051304/bc4d48b3a6e8/jpm-14-00361-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19de/11051304/9f71071320e5/jpm-14-00361-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19de/11051304/33be6ff5fe4c/jpm-14-00361-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19de/11051304/31739b34650f/jpm-14-00361-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19de/11051304/ce975f548056/jpm-14-00361-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19de/11051304/bc4d48b3a6e8/jpm-14-00361-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19de/11051304/9f71071320e5/jpm-14-00361-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19de/11051304/33be6ff5fe4c/jpm-14-00361-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19de/11051304/31739b34650f/jpm-14-00361-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19de/11051304/ce975f548056/jpm-14-00361-g005.jpg

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本文引用的文献

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Crosstalk between DNA methylation and gene expression in colorectal cancer, a potential plasma biomarker for tracing this tumor.结直肠癌中 DNA 甲基化与基因表达的相互作用,一种追踪这种肿瘤的潜在血浆生物标志物。
Sci Rep. 2020 Feb 18;10(1):2813. doi: 10.1038/s41598-020-59690-0.
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HOME: a histogram based machine learning approach for effective identification of differentially methylated regions.
HOME:一种基于直方图的机器学习方法,可有效识别差异甲基化区域。
BMC Bioinformatics. 2019 May 16;20(1):253. doi: 10.1186/s12859-019-2845-y.
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BiSpark: a Spark-based highly scalable aligner for bisulfite sequencing data.BiSpark:一种基于 Spark 的高度可扩展的亚硫酸氢盐测序数据比对工具。
BMC Bioinformatics. 2018 Dec 10;19(1):472. doi: 10.1186/s12859-018-2498-2.
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A hidden markov model for identifying differentially methylated sites in bisulfite sequencing data.一种用于识别亚硫酸氢盐测序数据中差异甲基化位点的隐马尔可夫模型。
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