Bisulfite Bolt: A Bisulfite Sequencing Analysis Platform

Background: Bisulfite sequencing is commonly used to measure DNA methylation. Processing bisulfite sequencing data is often challenging owing 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 (BSBoIt), a fast and scalable bisulfite sequencing analysis platform. BSBoIt performs a pre-alignment sequencing read assessment step to improve efficiency when handling asymmetrical bisulfite sequencing libraries. Findings: We evaluated BSBoIt against simulated and real bisulfite sequencing libraries. We found that BSBoIt provides accurate and fast bisulfite sequencing alignments and methylation calls. We also compared BSBoIt to several existing bisulfite alignment tools and found BSBoIt outperforms Bismark, BSSeeker2, BISCUIT, and BWA-Meth based on alignment accuracy and methylation calling accuracy. Conclusion: BSBoIt offers streamlined processing of bisulfite sequencing data through an integrated toolset that offers support for simulation, alignment, methylation calling, and data aggregation. BSBoIt is implemented as a Python package and command line utility for flexibility when building informatics pipelines. BSBoIt is available at https://github.com/NuttyLogic/BSBolt under an MIT license.