Mapping short DNA sequencing reads and calling variants using mapping quality scores.
New sequencing technologies promise a new era in the use of DNA sequence. However, some of these technologies produce very short reads, typically of a few tens of base pairs, and to use these reads effectively requires new algorithms and software. In particular, there is a major issue in efficiently aligning short reads to a reference genome and handling ambiguity or lack of accuracy in this alignment. Here we introduce the concept of mapping quality, a measure of the confidence that a read actually comes from the position it is aligned to by the mapping algorithm. We describe the software MAQ that can build assemblies by mapping shotgun short reads to a reference genome, using quality scores to derive genotype calls of the consensus sequence of a diploid genome, e.g., from a human sample. MAQ makes full use of mate-pair information and estimates the error probability of each read alignment. Error probabilities are also derived for the final genotype calls, using a Bayesian statistical model that incorporates the mapping qualities, error probabilities from the raw sequence quality scores, sampling of the two haplotypes, and an empirical model for correlated errors at a site. Both read mapping and genotype calling are evaluated on simulated data and real data. MAQ is accurate, efficient, versatile, and user-friendly. It is freely available at http://maq.sourceforge.net.
Li
Heng
H
The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom.
Ruan
Jue
J
Durbin
Richard
R
D000465:Algorithms; D001499:Bayes Theorem; D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D003198:Computer Simulation; D004247:DNA / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics; D004171:Diploidy; D016680:Genome, Bacterial; D015894:Genome, Human; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012482:Salmonella paratyphi A / Q000235:genetics; D016415:Sequence Alignment / Q000706:statistics & numerical data; D017422:Sequence Analysis, DNA / Q000706:statistics & numerical data; D012984:Software
D004269:DNA, Bacterial; D004247:DNA