Department of Genetics, The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Department of Pediatrics, University of Minnesota, 2450 Riverside Avenue, Minneapolis, MN, 55454, USA.
BMC Bioinformatics. 2018 Feb 5;19(1):31. doi: 10.1186/s12859-018-2037-1.
Identification of differentially methylated regions (DMRs) is the initial step towards the study of DNA methylation-mediated gene regulation. Previous approaches to call DMRs suffer from false prediction, use extreme resources, and/or require library installation and input conversion.
We developed a new approach called Defiant to identify DMRs. Employing Weighted Welch Expansion (WWE), Defiant showed superior performance to other predictors in the series of benchmarking tests on artificial and real data. Defiant was subsequently used to investigate DNA methylation changes in iron-deficient rat hippocampus. Defiant identified DMRs close to genes associated with neuronal development and plasticity, which were not identified by its competitor. Importantly, Defiant runs between 5 to 479 times faster than currently available software packages. Also, Defiant accepts 10 different input formats widely used for DNA methylation data.
Defiant effectively identifies DMRs for whole-genome bisulfite sequencing (WGBS), reduced-representation bisulfite sequencing (RRBS), Tet-assisted bisulfite sequencing (TAB-seq), and HpaII tiny fragment enrichment by ligation-mediated PCR-tag (HELP) assays.
差异甲基化区域（DMR）的鉴定是研究 DNA 甲基化介导的基因调控的初始步骤。先前鉴定 DMR 的方法存在假阳性预测、需要极端资源、以及需要库安装和输入转换等问题。
我们开发了一种称为 Defiant 的新方法来鉴定 DMR。Defiant 采用加权 Welch 扩展（WWE），在对人工和真实数据的一系列基准测试中，其性能优于其他预测器。随后，我们使用 Defiant 研究缺铁大鼠海马体中的 DNA 甲基化变化。Defiant 鉴定到了与神经元发育和可塑性相关的基因附近的 DMR，而其竞争对手则没有鉴定到这些 DMR。重要的是，Defiant 的运行速度比当前可用的软件包快 5 到 479 倍。此外，Defiant 可以接受广泛用于 DNA 甲基化数据的 10 种不同输入格式。
Defiant 可以有效地识别全基因组亚硫酸氢盐测序（WGBS）、简化代表性亚硫酸氢盐测序（RRBS）、Tet 辅助亚硫酸氢盐测序（TAB-seq）和 HpaII 微小片段富集连接介导的 PCR 标记（HELP）检测的 DMR。
