This article is part of the supplement: Selected articles from the Twelfth Asia Pacific Bioinformatics Conference (APBC 2014): Genomics
Sequence alignment by passing messages
Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843-3128, USA
BMC Genomics 2014, 15(Suppl 1):S14 doi:10.1186/1471-2164-15-S1-S14Published: 24 January 2014
Sequence alignment has become an indispensable tool in modern molecular biology research, and probabilistic sequence alignment models have been shown to provide an effective framework for building accurate sequence alignment tools. One such example is the pair hidden Markov model (pair-HMM), which has been especially popular in comparative sequence analysis for several reasons, including their effectiveness in modeling and detecting sequence homology, model simplicity, and the existence of efficient algorithms for applying the model to sequence alignment problems. However, despite these advantages, pair-HMMs also have a number of practical limitations that may degrade their alignment performance or render them unsuitable for certain alignment tasks.
In this work, we propose a novel scheme for comparing and aligning biological sequences that can effectively address the shortcomings of the traditional pair-HMMs. The proposed scheme is based on a simple message-passing approach, where messages are exchanged between neighboring symbol pairs that may be potentially aligned in the optimal sequence alignment. The message-passing process yields probabilistic symbol alignment confidence scores, which may be used for predicting the optimal alignment that maximizes the expected number of correctly aligned symbol pairs.
Extensive performance evaluation on protein alignment benchmark datasets shows that the proposed message-passing scheme clearly outperforms the traditional pair-HMM-based approach, in terms of both alignment accuracy and computational efficiency. Furthermore, the proposed scheme is numerically robust and amenable to massive parallelization.