Accurately measuring epigenetic marks such as 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) at the single-nucleotide level, requires combining data from DNA processing methods including traditional (BS), oxidative (oxBS) or Tet-Assisted (TAB) bisulfite conversion. We introduce the R package MLML2R, which provides maximum likelihood estimates (MLE) of 5-mC and 5-hmC proportions. While all other available R packages provide 5-mC and 5-hmC MLEs only for the oxBS+BS combination, MLML2R also provides MLE for TAB combinations. For combinations of any two of the methods, we derived the pool-adjacent-violators algorithm (PAVA) exact constrained MLE in analytical form. For the three methods combination, we implemented both the iterative method by Qu et al. [Qu, J., M. Zhou, Q. Song, E. E. Hong and A. D. Smith (2013): "Mlml: consistent simultaneous estimates of dna methylation and hydroxymethylation," Bioinformatics, 29, 2645-2646.], and also a novel non iterative approximation using Lagrange multipliers. The newly proposed non iterative solutions greatly decrease computational time, common bottlenecks when processing high-throughput data. The MLML2R package is flexible as it takes as input both, preprocessed intensities from Infinium Methylation arrays and counts from Next Generation Sequencing technologies. The MLML2R package is freely available at https://CRAN.R-project.org/package=MLML2R.

中文翻译：

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MLML2R：一个R包，用于最大可能性地估计DNA甲基化和羟甲基化比例。

在单核苷酸水平上准确测量表观遗传标记，例如5-甲基胞嘧啶（5-mC）和5-羟甲基胞嘧啶（5-hmC），需要结合来自DNA处理方法的数据，包括传统的（BS），氧化的（oxBS）或Tet-辅助（TAB）亚硫酸氢盐转化。我们介绍了R包MLML2R，它提供了5mC和5hmC比例的最大似然估计（MLE）。虽然所有其他可用的R封装仅为oxBS + BS组合提供5-mC和5-hmC MLE，但MLML2R还为TAB组合提供MLE。对于任何两种方法的组合，我们以分析形式导出了池相邻违反者算法（PAVA）精确约束的MLE。对于这三种方法的组合，我们实现了Qu等人的两种迭代方法。[Qu，J.，M. Zhou，Q. Song，EE Hong和AD Smith（2013）：“ 处理高通量数据时常见的瓶颈。MLML2R软件包非常灵活，因为它既可以输入来自Infinium甲基化阵列的预处理强度，也可以接收来自下一代测序技术的计数。MLML2R软件包可从https://CRAN.R-project.org/package=MLML2R免费获得。处理高通量数据时常见的瓶颈。MLML2R软件包非常灵活，因为它既可以输入来自Infinium甲基化阵列的预处理强度，也可以接收来自下一代测序技术的计数。MLML2R软件包可从https://CRAN.R-project.org/package=MLML2R免费获得。