Meta-Align: A Novel HMM-based Algorithm for Pairwise Alignment of Error-Prone Sequencing Reads

Background Insertion and deletion sequencing errors are relatively common in next-generation sequencing data and produce long stretches of mistranslated sequence. These frameshifting errors can cause very serious damages to downstream data analysis of reads. However, it is possible to obtain more precise alignment of DNA sequences by taking into account both coding frame and sequencing errors estimated by quality scores.

Results Here we designed and proposed a novel hidden Markov model (HMM)-based pairwise alignment algorithm, Meta-Align, that aligns DNA sequences in the protein space, incorporating quality scores from the DNA sequences and allowing frameshifts caused by insertions and deletions. Our model is based on both an HMM transducer of a pair HMM and profile HMMs for all possible amino acid pairs. A Viterbi algorithm over our model produces the optimal alignment of a pair of metagenomic reads taking into account all possible translating frames and gap penalties in both the protein space and the DNA space. To reduce the sheer number of states of this model, we also derived and implemented a computationally feasible model, leveraging the degeneracy of the genetic code. In a benchmark test on a diverse set of simulated reads based on BAliBASE we show that Meta-Align outperforms TBLASTX which compares the six-frame translations of a nucleotide query sequence against the six-frame translations of a nucleotide sequence database using the BLAST algorithm. We also demonstrate the effects of incorporating quality scores on Meta-Align.

Conclusions Meta-Align will be particularly effective when applied to error-prone DNA sequences. The package of our software can be downloaded at https://github.com/shravan-repos/Metaalign.