Motivation: Identifying regions of the genome that demonstrate significant differences in DNA methylation between groups of samples is an important problem in computational epigenetics. Available methods assume that methylation occurs in a statistically independent manner at individual cytosine-phosphate-guanine (CpG) sites or perform analysis using empirically estimated joint probability distributions of methylation patterns at no more than 4 contiguous CpG sites. These approaches can lead to poor detection performance and loss of reliability and reproducibility due to reduced specificity and sensitivity in the presence of insufficient data. Results: To accommodate data obtained with different bisulfite sequencing technologies, such as RRBS, ERRBS, and WGBS, and improve statistical power, we developed CpelTdm.jl, a Julia package for targeted differential analysis of DNA methylation stochasticity between groups of unmatched or matched samples. This package performs rigorous statistical analysis of methylation patterns within regions of the genome specified by the user that takes into account correlations in methylation and results in robust detection of genomic regions exhibiting statistically significant differences in methylation stochasticity. CpelTdm.jl does not only detect mean methylation differences, as it is commonly done by previous methods, but also differences in methylation entropy and, more generally, between probability distributions of methylation. Availability and Implementation: This Julia package is supported for Windows, macOS, and Linux, and can be freely downloaded from GitHub: https://github.com/jordiabante/CpelTdm.jl .

中文翻译：

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CpelTdm.jl：用于差异DNA甲基化分析的Julia软件包

动机：鉴定证明样本组之间DNA甲基化差异显着的基因组区域是计算表观遗传学中的重要问题。可用的方法假定甲基化在每个胞嘧啶-磷酸-鸟嘌呤（CpG）位点以统计学上独立的方式发生，或使用经验估计的甲基化模式在不超过4个连续的CpG位点的联合概率分布进行分析。由于在数据不足的情况下特异性和灵敏度降低，这些方法可能导致检测性能差，可靠性和可重复性下降。结果：为了容纳通过不同的亚硫酸氢盐测序技术（例如RRBS，ERRBS和WGBS）获得的数据，并提高统计能力，我们开发了CpelTdm.jl，Julia软件包，用于对不匹配或匹配的样本之间的DNA甲基化随机性进行有针对性的差异分析。该软件包对用户指定的基因组区域内的甲基化模式进行了严格的统计分析，其中考虑了甲基化的相关性，从而可以可靠地检测出在甲基化随机性方面具有统计学显着性差异的基因组区域。CpelTdm.jl不仅可以检测到平均甲基化差异（如以前的方法通常所做的那样），而且还可以检测甲基化熵的差异，以及更普遍地检测甲基化概率分布之间的差异。可用性和实施​​：此Julia软件包受Windows，macOS和Linux支持，可以从GitHub免费下载：https://github.com/jordiabante/CpelTdm.jl。