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Improving read mapping using additional prefix grams.

ABSTRACT: Next-generation sequencing (NGS) enables rapid production of billions of bases at a relatively low cost. Mapping reads from next-generation sequencers to a given reference genome is an important first step in many sequencing applications. Popular read mappers, such as Bowtie and BWA, are optimized to return top one or a few candidate locations of each read. However, identifying all mapping locations of each read, instead of just one or a few, is also important in some sequencing applications such as ChIP-seq for discovering binding sites in repeat regions, and RNA-seq for transcript abundance estimation.Here we present Hobbes2, a software package designed for fast and accurate alignment of NGS reads and specialized in identifying all mapping locations of each read. Hobbes2 efficiently identifies all mapping locations of reads using a novel technique that utilizes additional prefix q-grams to improve filtering. We extensively compare Hobbes2 with state-of-the-art read mappers, and show that Hobbes2 can be an order of magnitude faster than other read mappers while consuming less memory space and achieving similar accuracy.We propose Hobbes2 to improve the accuracy of read mapping, specialized in identifying all mapping locations of each read. Hobbes2 is implemented in C++, and the source code is freely available for download at http://hobbes.ics.uci.edu.

SUBMITTER: Kim J

PROVIDER: S-EPMC3927682 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Improving read mapping using additional prefix grams.

Kim Jongik J Li Chen C Xie Xiaohui X

BMC bioinformatics 20140205

<h4>Background</h4>Next-generation sequencing (NGS) enables rapid production of billions of bases at a relatively low cost. Mapping reads from next-generation sequencers to a given reference genome is an important first step in many sequencing applications. Popular read mappers, such as Bowtie and BWA, are optimized to return top one or a few candidate locations of each read. However, identifying all mapping locations of each read, instead of just one or a few, is also important in some sequenci ...[more]

PMID: 24499321

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Project description:BACKGROUND: Next-Generation Sequencing has revolutionized our approach to ancient DNA (aDNA) research, by providing complete genomic sequences of ancient individuals and extinct species. However, the recovery of genetic material from long-dead organisms is still complicated by a number of issues, including post-mortem DNA damage and high levels of environmental contamination. Together with error profiles specific to the type of sequencing platforms used, these specificities could limit our ability to map sequencing reads against modern reference genomes and therefore limit our ability to identify endogenous ancient reads, reducing the efficiency of shotgun sequencing aDNA. RESULTS: In this study, we compare different computational methods for improving the accuracy and sensitivity of aDNA sequence identification, based on shotgun sequencing reads recovered from Pleistocene horse extracts using Illumina GAIIx and Helicos Heliscope platforms. We show that the performance of the Burrows Wheeler Aligner (BWA), that has been developed for mapping of undamaged sequencing reads using platforms with low rates of indel-types of sequencing errors, can be employed at acceptable run-times by modifying default parameters in a platform-specific manner. We also examine if trimming likely damaged positions at read ends can increase the recovery of genuine aDNA fragments and if accurate identification of human contamination can be achieved using a strategy previously suggested based on best hit filtering. We show that combining our different mapping and filtering approaches can increase the number of high-quality endogenous hits recovered by up to 33%. CONCLUSIONS: We have shown that Illumina and Helicos sequences recovered from aDNA extracts could not be aligned to modern reference genomes with the same efficiency unless mapping parameters are optimized for the specific types of errors generated by these platforms and by post-mortem DNA damage. Our findings have important implications for future aDNA research, as we define mapping guidelines that improve our ability to identify genuine aDNA sequences, which in turn could improve the genotyping accuracy of ancient specimens. Our framework provides a significant improvement to the standard procedures used for characterizing ancient genomes, which is challenged by contamination and often low amounts of DNA material.

Dataset Information

Improving read mapping using additional prefix grams.

Publications

Improving read mapping using additional prefix grams.

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