Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia, 97, Catania, 95123, Italy.
Department of Mathematics and Computer Science, University of Catania, Viale A. Doria, 6, Catania, 95125, Italy.
BMC Bioinformatics. 2019 Feb 4;19(Suppl 13):385. doi: 10.1186/s12859-018-2397-6.
DNA methylation is an epigenetic mechanism of genomic regulation involved in the maintenance of homeostatic balance. Dysregulation of DNA methylation status is one of the driver alterations occurring in neoplastic transformation and cancer progression. The identification of methylation hotspots associated to gene dysregulation may contribute to discover new prognostic and diagnostic biomarkers, as well as, new therapeutic targets.
We present EpiMethEx (Epigenetic Methylation and Expression), a R package to perform a large-scale integrated analysis by cyclic correlation analyses between methylation and gene expression data. For each gene, samples are segmented according to the expression levels to select genes that are differentially expressed. This stratification allows to identify CG methylation probesets modulated among gene-stratified samples. Subsequently, the methylation probesets are grouped by their relative position in gene sequence to identify wide genomic methylation events statically related to genetic modulation.
The beta-test study showed that the global methylation analysis was in agreement with scientific literature. In particular, this analysis revealed a negative association between promoter hypomethylation and overexpression in a wide number of genes. Less frequently, this overexpression was sustained by intragenic hypermethylation events.
DNA 甲基化是一种参与维持体内平衡的基因组调控的表观遗传机制。DNA 甲基化状态的失调是发生在肿瘤转化和癌症进展中的驱动改变之一。鉴定与基因调控失调相关的甲基化热点可能有助于发现新的预后和诊断生物标志物,以及新的治疗靶点。
我们提出了 EpiMethEx(表观遗传甲基化和表达),这是一个 R 包,可以通过对甲基化和基因表达数据进行循环相关分析来进行大规模的综合分析。对于每个基因,根据表达水平对样本进行分段,以选择差异表达的基因。这种分层允许识别在基因分层样本中被调节的 CG 甲基化探针。随后,根据它们在基因序列中的相对位置对甲基化探针进行分组,以识别与遗传调节静态相关的广泛基因组甲基化事件。
β测试研究表明,全局甲基化分析与科学文献一致。特别是,这项分析揭示了启动子低甲基化与大量基因过表达之间的负相关关系。较少情况下,这种过表达是由基因内高甲基化事件维持的。