Structural Alignment of RNAs Using Profile-csHMMs and Its Application to RNA Homology Search: Overview and New Results

Systematic research on noncoding RNAs (ncRNAs) has revealed that many ncRNAs are actively involved in various biological networks. Therefore, in order to fully understand the mechanisms of these networks, it is crucial to understand the roles of ncRNAs. Unfortunately, the annotation of ncRNA genes that give rise to functional RNA molecules has begun only recently, and it is far from being complete. Considering the huge amount of genome sequence data, we need efficient computational methods for finding ncRNA genes. One effective way of finding ncRNA genes is to look for regions that are similar to known ncRNA genes. As many ncRNAs have well-conserved secondary structures, we need statistical models that can represent such structures for this purpose. In this paper, we propose a new method for representing RNA sequence profiles and finding structural alignment of RNAs based on profile context-sensitive hidden Markov models (profile-csHMMs). Unlike existing models, the proposed approach can handle any kind of RNA secondary structures, including pseudoknots. We show that profile-csHMMs can provide an effective framework for the computational analysis of RNAs and the identification of ncRNA genes

Fast search of sequences with complex symbol correlations using profile context-sensitive HMMS and pre-screening filters

Recently, profile context-sensitive HMMs (profile-csHMMs) have been proposed which are very effective in modeling the common patterns and motifs in related symbol sequences. Profile-csHMMs are capable of representing long-range correlations between distant symbols, even when these correlations are entangled in a complicated manner. This makes profile-csHMMs an useful tool in computational biology, especially in modeling noncoding RNAs (ncRNAs) and finding new ncRNA genes. However, a profile-csHMM based search is quite slow, hence not practical for searching a large database. In this paper, we propose a practical scheme for making the search speed significantly faster without any degradation in the prediction accuracy. The proposed method utilizes a pre-screening filter based on a profile-HMM, which filters out most sequences that will not be predicted as a match by the original profile-csHMM. Experimental results show that the proposed approach can make the search speed eighty times faster

Fast Structural Alignment of RNAs by Optimizing the Adjoining Order of Profile-csHMMs

Abstract—Recently, a novel RNA structural alignment method has been proposed based on profile-csHMMs. In principle, the profile-csHMM based approach can handle any kind of RNA secondary structures including pseudoknots, and it has been shown that the proposed approach can find highly accurate RNA alignments. In order to find the optimal alignment, the method employs the SCA algorithm that can be used for finding the optimal state sequence of profile-csHMMs. The computational complexity of the SCA algorithm is not fixed, and it depends on the so-called adjoining order that describes how we can trace-back the optimal state sequence in a given profile-csHMM. Therefore, for fast RNA structural alignments, it is important to find the adjoining order that has the minimum computational cost. In this paper, we propose an efficient algorithm that can systematically find the optimal adjoining order that minimizes the computational cost for finding the RNA alignments. Numerical experiments show that employing the proposed algorithm can make the alignment speed up to 3.6 times faster, without any degradation in the quality of the RNA alignments. Index Terms—Profile-csHMM, pseudoknot, RNA homology search, RNA structural alignment, SCA algorithm. I