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Open Access Highly Accessed Research article

Adaptable probabilistic mapping of short reads using position specific scoring matrices

Peter Kerpedjiev12, Jes Frellsen13, Stinus Lindgreen14 and Anders Krogh15*

Author Affiliations

1 Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark

2 Institute for Theoretical Chemistry, University of Vienna, Währinger Straße 17, A-1090 Vienna, Austria

3 Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK

4 Biomolecular Interaction Centre, School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8020, New Zealand

5 Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350 Copenhagen K, Denmark

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BMC Bioinformatics 2014, 15:100  doi:10.1186/1471-2105-15-100

Published: 9 April 2014

Abstract

Background

Modern DNA sequencing methods produce vast amounts of data that often requires mapping to a reference genome. Most existing programs use the number of mismatches between the read and the genome as a measure of quality. This approach is without a statistical foundation and can for some data types result in many wrongly mapped reads. Here we present a probabilistic mapping method based on position-specific scoring matrices, which can take into account not only the quality scores of the reads but also user-specified models of evolution and data-specific biases.

Results

We show how evolution, data-specific biases, and sequencing errors are naturally dealt with probabilistically. Our method achieves better results than Bowtie and BWA on simulated and real ancient and PAR-CLIP reads, as well as on simulated reads from the AT rich organism P. falciparum, when modeling the biases of these data. For simulated Illumina reads, the method has consistently higher sensitivity for both single-end and paired-end data. We also show that our probabilistic approach can limit the problem of random matches from short reads of contamination and that it improves the mapping of real reads from one organism (D. melanogaster) to a related genome (D. simulans).

Conclusion

The presented work is an implementation of a novel approach to short read mapping where quality scores, prior mismatch probabilities and mapping qualities are handled in a statistically sound manner. The resulting implementation provides not only a tool for biologists working with low quality and/or biased sequencing data but also a demonstration of the feasibility of using a probability based alignment method on real and simulated data sets.

Keywords:
Short-read mapping; Sequence alignment; Next-generation sequencing; Ancient DNA; PAR-CLIP; Xeno mapping