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

Computational identification and analysis of noncoding RNAs - Unearthing the buried treasures in the genome

The central dogma of molecular biology states that the genetic information flows from DNA to RNA to protein. This dogma has exerted a substantial influence on our understanding of the genetic activities in the cells. Under this influence, the prevailing assumption until the recent past was that genes are basically repositories for protein coding information, and proteins are responsible for most of the important biological functions in all cells. In the meanwhile, the importance of RNAs has remained rather obscure, and RNA was mainly viewed as a passive intermediary that bridges the gap between DNA and protein. Except for classic examples such as tRNAs (transfer RNAs) and rRNAs (ribosomal RNAs), functional noncoding RNAs were considered to be rare. However, this view has experienced a dramatic change during the last decade, as systematic screening of various genomes identified myriads of noncoding RNAs (ncRNAs), which are RNA molecules that function without being translated into proteins [11], [40]. It has been realized that many ncRNAs play important roles in various biological processes. As RNAs can interact with other RNAs and DNAs in a sequence-specific manner, they are especially useful in tasks that require highly specific nucleotide recognition [11]. Good examples are the miRNAs (microRNAs) that regulate gene expression by targeting mRNAs (messenger RNAs) [4], [20], and the siRNAs (small interfering RNAs) that take part in the RNAi (RNA interference) pathways for gene silencing [29], [30]. Recent developments show that ncRNAs are extensively involved in many gene regulatory mechanisms [14], [17]. The roles of ncRNAs known to this day are truly diverse. These include transcription and translation control, chromosome replication, RNA processing and modification, and protein degradation and translocation [40], just to name a few. These days, it is even claimed that ncRNAs dominate the genomic output of the higher organisms such as mammals, and it is being suggested that the greater portion of their genome (which does not encode proteins) is dedicated to the control and regulation of cell development [27]. As more and more evidence piles up, greater attention is paid to ncRNAs, which have been neglected for a long time. Researchers began to realize that the vast majority of the genome that was regarded as “junk,” mainly because it was not well understood, may indeed hold the key for the best kept secrets in life, such as the mechanism of alternative splicing, the control of epigenetic variations and so forth [27]. The complete range and extent of the role of ncRNAs are not so obvious at this point, but it is certain that a comprehensive understanding of cellular processes is not possible without understanding the functions of ncRNAs [47]

Learning cover context-free grammars from structural data

We consider the problem of learning an unknown context-free grammar when the only knowledge available and of interest to the learner is about its structural descriptions with depth at most $\ell.$ The goal is to learn a cover context-free grammar (CCFG) with respect to $\ell$, that is, a CFG whose structural descriptions with depth at most $\ell$ agree with those of the unknown CFG. We propose an algorithm, called $LA^\ell$, that efficiently learns a CCFG using two types of queries: structural equivalence and structural membership. We show that $LA^\ell$ runs in time polynomial in the number of states of a minimal deterministic finite cover tree automaton (DCTA) with respect to $\ell$. This number is often much smaller than the number of states of a minimum deterministic finite tree automaton for the structural descriptions of the unknown grammar

A survey of normal form covers for context-free grammars

An overview is given of cover results for normal forms of context-free grammars. The emphasis in this paper is on the possibility of constructing ɛ-free grammars, non-left-recursive grammars and grammars in Greibach normal form. Among others it is proved that any ɛ-free context-free grammar can be right covered with a context-free grammar in Greibach normal form. All the cover results concerning the ɛ-free grammars, the non-left-recursive grammars and the grammars in Greibach normal form are listed, with respect to several types of covers, in a cover-table

Implicit learning of recursive context-free grammars

Context-free grammars are fundamental for the description of linguistic syntax. However, most artificial grammar learning experiments have explored learning of simpler finite-state grammars, while studies exploring context-free grammars have not assessed awareness and implicitness. This paper explores the implicit learning of context-free grammars employing features of hierarchical organization, recursive embedding and long-distance dependencies. The grammars also featured the distinction between left- and right-branching structures, as well as between centre- and tail-embedding, both distinctions found in natural languages. People acquired unconscious knowledge of relations between grammatical classes even for dependencies over long distances, in ways that went beyond learning simpler relations (e.g. n-grams) between individual words. The structural distinctions drawn from linguistics also proved important as performance was greater for tail-embedding than centre-embedding structures. The results suggest the plausibility of implicit learning of complex context-free structures, which model some features of natural languages. They support the relevance of artificial grammar learning for probing mechanisms of language learning and challenge existing theories and computational models of implicit learning

Automatic parsing of sports videos with grammars

Motivated by the analogies between languages and sports videos, we introduce a novel approach for video parsing with grammars. It utilizes compiler techniques for integrating both semantic annotation and syntactic analysis to generate a semantic index of events and a table of content for a given sports video. The video sequence is first segmented and annotated by event detection with domain knowledge. A grammar-based parser is then used to identify the structure of the video content. Meanwhile, facilities for error handling are introduced which are particularly useful when the results of automatic parsing need to be adjusted. As a case study, we have developed a system for video parsing in the particular domain of TV diving programs. Experimental results indicate the proposed approach is effectiv

Structure preserving transformations on non-left-recursive grammars

We will be concerned with grammar covers, The first part of this paper presents a general framework for covers. The second part introduces a transformation from nonleft-recursive grammars to grammars in Greibach normal form. An investigation of the structure preserving properties of this transformation, which serves also as an illustration of our framework for covers, is presented