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

Abstract

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 bi-directional 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/.

Two algorithmic problems in analyzing genetic and epigenetic variations

“…Experimental results with respect to either problem demonstrate the high capability of the corresponding approach that we developed. The materials of these two chapters are based on our previously published papers [64] and [65].…”

“…We further extended TAMeBS to estimate cytosine methylation distributions from the aligned BS reads. Our work can be found in [65] and the software can be freely downloaded at http://sourceforge.net/ projects/tamebs/.…”