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Bioinformatics. 2010 Aug 15;26(16):1958-64. doi: 10.1093/bioinformatics/btq338. Epub 2010 Jun 23.

MSAProbs: multiple sequence alignment based on pair hidden Markov models and partition function posterior probabilities.

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School of Computer Engineering, Nanyang Technological University, Singapore.



Multiple sequence alignment is of central importance to bioinformatics and computational biology. Although a large number of algorithms for computing a multiple sequence alignment have been designed, the efficient computation of highly accurate multiple alignments is still a challenge.


We present MSAProbs, a new and practical multiple alignment algorithm for protein sequences. The design of MSAProbs is based on a combination of pair hidden Markov models and partition functions to calculate posterior probabilities. Furthermore, two critical bioinformatics techniques, namely weighted probabilistic consistency transformation and weighted profile-profile alignment, are incorporated to improve alignment accuracy. Assessed using the popular benchmarks: BAliBASE, PREFAB, SABmark and OXBENCH, MSAProbs achieves statistically significant accuracy improvements over the existing top performing aligners, including ClustalW, MAFFT, MUSCLE, ProbCons and Probalign. Furthermore, MSAProbs is optimized for multi-core CPUs by employing a multi-threaded design, leading to a competitive execution time compared to other aligners.


The source code of MSAProbs, written in C++, is freely and publicly available from

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