IEEE/ACM Trans Comput Biol Bioinform. 2022 May-Jun;19(3):1640-1650. doi: 10.1109/TCBB.2021.3049366. Epub 2022 Jun 3.
Recent studies have shown that in-depth studies on epi-transcriptomic patterns of N6-methyladenosine (mA) may help understand its complex functions and co-regulatory mechanisms. Since most biclustering algorithms are developed in scenarios of gene expression analysis, which does not share the same characteristics with mA methylation profile, we propose a weighted Plaid biclustering model (FBCwPlaid) based on the Lagrange multiplier method to discover the potential functional patterns. Each pattern is achieved by minimizing approximation error between FBCwPlaid predicted value and real data. To address the issue that site expression level determines methylation level confidence, it uses RNA expression levels of each site as weights to make lower expressed sites less confident. FBCwPlaid also allows overlapping biclusters, indicating some sites may participate in multiple biological functions. FBCwPlaid was then applied on MeRIP-Seq data of 69,446 methylation sites under 32 experimental conditions, each of which represented a stimulus to a particular cell line or environment. Finally, three patterns were discovered, and further pathway analysis and enzyme specificity test showed that sites involved in each pattern are highly relevant to mA methyltransferases. Further detailed analyses showed that some patterns are condition-specific, indicating that some specific sites' methylation profiles may occur in specific cell lines or conditions.
最近的研究表明，深入研究 N6-甲基腺苷（m6A）的外转录组模式可能有助于理解其复杂的功能和共同调控机制。由于大多数双聚类算法都是在基因表达分析的场景中开发的，而这些场景与 m6A 甲基化图谱没有相同的特征，因此我们提出了一种基于拉格朗日乘子法的加权格子双聚类模型（FBCwPlaid），以发现潜在的功能模式。每个模式都是通过最小化 FBCwPlaid 预测值与真实数据之间的逼近误差来实现的。为了解决位点表达水平决定甲基化水平置信度的问题，它使用每个位点的 RNA 表达水平作为权重，使表达水平较低的位点的置信度降低。FBCwPlaid 还允许重叠的双聚类，这表明一些位点可能参与多个生物学功能。然后，将 FBCwPlaid 应用于 32 种实验条件下 69446 个甲基化位点的 MeRIP-Seq 数据中，每种条件都代表对特定细胞系或环境的一种刺激。最后，发现了三个模式，进一步的通路分析和酶特异性测试表明，每个模式中涉及的位点与 m6A 甲基转移酶高度相关。进一步的详细分析表明，一些模式是条件特异性的，这表明一些特定位点的甲基化图谱可能只发生在特定的细胞系或条件下。
