Adaptable probabilistic mapping of short reads using position specific scoring matrices.
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).


CONCLUSIONS
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.
Peter
P
Kerpedjiev
Jes
J
Frellsen
Stinus
S
Lindgreen
Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark. krogh@binf.ku.dk.
Anders
A
Krogh
D000818:Animals; D004330:Drosophila; D019143:Evolution, Molecular; D016678:Genome; D006801:Humans; D056510:Position-Specific Scoring Matrices; D011336:Probability; D017422:Sequence Analysis, DNA; D012984:Software