Fast and memory efficient approach for mapping NGS reads to a reference genome

摘要

New generation sequencing machines: Illumina and Solexa can generate millions of short reads from a given genome sequence on a single run. Alignment of these reads to a reference genome is a core step in Next-generation sequencing data analysis such as genetic variation and genome resequencing etc. Therefore there is a need of a new approach, efficient with respect to memory as well as time to align these enormous reads with the reference genome. Existing techniques such as MAQ, Bowtie, BWA, BWBBLE, Subread, Kart, and Minimap2 require huge memory for whole reference genome indexing and reads alignment. Gapped alignment versions of these techniques are also 20-40% slower than their respective normal versions. In this paper, an efficient approach: WIT for reference genome indexing and reads alignment using Burrows- Wheeler Transform (BWT) and Wavelet Tree (WT) is proposed. Both exact and approximate alignments are possible by it. Experimental work shows that the proposed approach WIT performs the best in case of protein sequence indexing. For indexing, the reference genome space required by WIT is 0.6 N (N is the size of reference genome) whereas existing techniques BWA, Subread, Kart, and Minimap2 require space in between 1.25 N to 5 N. Experimentally, it is also observed that even using such small index size alignment time of proposed approach is comparable in comparison to BWA, Subread, Kart, and Minimap2. Other alignment parameters accuracy and confidentiality are also experimentally shown to be better than Minimap2. The source code of the proposed approach WIT is available at http://www.algorithm-skg.com/wit/home.html.