TAMeBS: A sensitive bisulfite-sequencing read mapping tool for DNA methylation analysis

Cytosine methylation plays an important role in many biological regulation processes. The current gold-standard method for analyzing cytosine methylation is based on sodium bisulfite treatment and high-throughput sequencing technologies. In this paper we introduce a new tool called TAMeBS for cytosine methylation analysis using bisulfite sequencing data. It aims to align long bisulfite-treated DNA reads onto a reference genome sequence with high mapping efficiency and estimate the methylation status of each cytosine very accurately. Our approach builds on recent advances in alignment techniques, including bidirectional FM-index, approximate seeds, and the likelihood-ratio scoring matrix which was designed particularly for aligning bisulfite-treated DNA reads. We compared TAMeBS with several popular bisulfite-treated read mapping tools on both simulation and real data. Experimental results showed that TAMeBS could detect many more uniquely best mapped reads than other tested tools while achieving a good balance between sensitivity and precision. The source code of TAMeBS is freely available at https://sourceforge.net/projects/tamebs/.