2019 ◽  
Vol 20 (S18) ◽  
Author(s):  
Qing Zhan ◽  
Nan Wang ◽  
Shuilin Jin ◽  
Renjie Tan ◽  
Qinghua Jiang ◽  
...  

Abstract Background During procedures for conducting multiple sequence alignment, that is so essential to use the substitution score of pairwise alignment. To compute adaptive scores for alignment, researchers usually use Hidden Markov Model or probabilistic consistency methods such as partition function. Recent studies show that optimizing the parameters for hidden Markov model, as well as integrating hidden Markov model with partition function can raise the accuracy of alignment. The combination of partition function and optimized HMM, which could further improve the alignment’s accuracy, however, was ignored by these researches. Results A novel algorithm for MSA called ProbPFP is presented in this paper. It intergrate optimized HMM by particle swarm with partition function. The algorithm of PSO was applied to optimize HMM’s parameters. After that, the posterior probability obtained by the HMM was combined with the one obtained by partition function, and thus to calculate an integrated substitution score for alignment. In order to evaluate the effectiveness of ProbPFP, we compared it with 13 outstanding or classic MSA methods. The results demonstrate that the alignments obtained by ProbPFP got the maximum mean TC scores and mean SP scores on these two benchmark datasets: SABmark and OXBench, and it got the second highest mean TC scores and mean SP scores on the benchmark dataset BAliBASE. ProbPFP is also compared with 4 other outstanding methods, by reconstructing the phylogenetic trees for six protein families extracted from the database TreeFam, based on the alignments obtained by these 5 methods. The result indicates that the reference trees are closer to the phylogenetic trees reconstructed from the alignments obtained by ProbPFP than the other methods. Conclusions We propose a new multiple sequence alignment method combining optimized HMM and partition function in this paper. The performance validates this method could make a great improvement of the alignment’s accuracy.


Author(s):  
M. Vidyasagar

This chapter considers some applications of Markov processes and hidden Markov processes to computational biology. It introduces three important problems, namely: sequence alignment, the gene-finding problem, and protein classification. After providing an overview of some relevant aspects of biology, the chapter examines the problem of optimal gapped alignment between two sequences. This is a way to detect similarity between two sequences over a common alphabet, such as the four-symbol alphabet of nucleotides, or the 20-symbol alphabet of amino acids. The chapter proceeds by discussing some widely used algorithms for finding genes from DNA sequences (genomes), including the GLIMMER algorithm and the GENSCAN algorithm. Finally, it describes a special type of hidden Markov model termed profile hidden Markov model, which is commonly used to classify proteins into a small number of groups.


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