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BDBB:一种基于 Beta 分布的新型双聚类算法,用于揭示表观转录组分析数据中的局部共甲基化模式。

BDBB: A Novel Beta-Distribution-Based Biclustering Algorithm for Revealing Local Co-Methylation Patterns in Epi-Transcriptome Profiling Data.

出版信息

IEEE J Biomed Health Inform. 2022 Jun;26(6):2405-2416. doi: 10.1109/JBHI.2021.3068783. Epub 2022 Jun 3.

Abstract

N6-methyladenosine (mA) has been shown to play crucial roles in RNA metabolism, physiology, and pathological processes. However, the specific regulatory mechanisms of most methylation sites remain uncharted due to the complexity of life processes. Biological experimental methods are costly to solve this problem, and computational methods are relatively lacking. The discovery of local co-methylation patterns (LCPs) of mA epi-transcriptome data can benefit to solve the above problems. Based on this, we propose a novel biclustering algorithm based on the beta distribution (BDBB), which realizes the mining of LCPs of mA epi-transcriptome data. BDBB employs the Gibbs sampling method to complete parameter estimation. In the process of modeling, LCPs are recognized as sharp beta distributions compared to the background distribution. Simulation study showed BDBB can extract all the three actual LCPs implanted in the background data and the overlap conditions between them with considerable accuracy (almost close to 100%). On MeRIP-Seq data of 69,446 methylation sites under 32 experimental conditions from 10 human cell lines, BDBB unveiled two LCPs, and Gene Ontology (GO) enrichment analysis showed that they were enriched in histone modification and embryo development, etc. important biological processes respectively. The GOE_Score scoring indicated that the biclustering results of BDBB in the mA epi-transcriptome data are more biologically meaningful than the results of other biclustering algorithms.

摘要

N6-甲基腺苷(mA)已被证明在 RNA 代谢、生理和病理过程中发挥关键作用。然而,由于生命过程的复杂性,大多数甲基化位点的具体调控机制仍未被发现。生物实验方法解决这个问题成本高昂,而计算方法相对缺乏。发现 mA epi-transcriptome 数据的局部共甲基化模式(LCPs)可以有助于解决上述问题。基于此,我们提出了一种基于 beta 分布的新型双聚类算法(BDBB),实现了 mA epi-transcriptome 数据的 LCPs 挖掘。BDBB 使用 Gibbs 抽样方法完成参数估计。在建模过程中,LCPs 被识别为sharp beta 分布,与背景分布相比。模拟研究表明,BDBB 可以以相当高的准确性(几乎接近 100%)提取植入背景数据中的所有三个实际 LCP 及其重叠条件。在来自 10 个人类细胞系的 32 种实验条件下的 69446 个甲基化位点的 MeRIP-Seq 数据中,BDBB 揭示了两个 LCPs,GO 富集分析表明它们分别富集在组蛋白修饰和胚胎发育等重要生物学过程中。GOE_Score 评分表明,BDBB 在 mA epi-transcriptome 数据中的双聚类结果比其他双聚类算法的结果更具有生物学意义。

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