Supporting data for "BiSulfite Bolt: A BiSulfite Sequencing Analysis Platform"

Bisulfite sequencing is commonly employed to measure DNA methylation. Processing bisulfite sequencing data is often challenging due to the computational demands of mapping a low complexity, asymmetrical library and the lack of a unified processing toolset to produce an analysis ready methylation matrix from read alignments. To address these shortcomings, we have developed BiSulfite Bolt (BSBolt); a fast and scalable bisulfite sequencing analysis platform. BSBolt performs a pre-alignment sequencing read assessment step to improve efficiency when handling asymmetrical bisulfite sequencing libraries. We evaluated BSBolt against simulated and real bisulfite sequencing libraries. We found that BSBolt provides accurate and fast bisulfite sequencing alignments and methylation calls. We also compared BSBolt to several existing bisulfite alignment tools and found BSBolt outperforms Bismark, BSSeeker2, BISCUIT, and BWA-Meth based on alignment accuracy and methylation calling accuracy. BSBolt offers streamlined processing of bisulfite sequencing data through an integrated toolset that offers support for simulation, alignment, methylation calling, and data aggregation. BSBolt is implemented as a python package and command line utility for flexibility when building informatics pipelines. BSBolt is available at https://github.com/NuttyLogic/BSBolt under an MIT license.

亚硫酸氢盐测序（Bisulfite sequencing）是目前检测DNA甲基化的常用手段。然而，亚硫酸氢盐测序数据的分析处理往往颇具挑战：一方面，其文库具有低复杂度、不对称性的特征，序列比对所需的计算量极大；另一方面，目前缺乏统一的分析工具集，难以直接从测序读段比对结果生成可用于下游分析的甲基化矩阵。为解决上述痛点，本研究开发了亚硫酸氢盐测序分析平台BiSulfite Bolt（以下简称BSBolt），其具备快速、可扩展的分析能力。BSBolt通过在比对前加入测序读段评估步骤，有效提升了不对称亚硫酸氢盐测序文库的处理效率。本研究通过模拟及真实亚硫酸氢盐测序文库对BSBolt进行了性能评估，结果显示BSBolt可实现快速且准确的测序读段比对与甲基化位点识别。同时，本研究将BSBolt与多款现有亚硫酸氢盐比对工具进行对比，结果表明，在比对准确率与甲基化识别准确率两项指标上，BSBolt均优于Bismark、BSSeeker2、BISCUIT及BWA-Meth。BSBolt通过集成化工具链实现亚硫酸氢盐测序数据的一站式处理，支持模拟文库生成、序列比对、甲基化位点识别及数据汇总等全流程分析。BSBolt以Python包与命令行工具的形式实现，便于研究者灵活搭建生物信息学分析流程。BSBolt基于MIT开源协议发布，源代码可从https://github.com/NuttyLogic/BSBolt获取。