Automated Modeling of RNA 3D Structure
This chapter gives an overview over the current methods for automated modeling of RNA structures, with emphasis on template-based methods. The currently used approaches to RNA modeling are presented with a side view on the protein world, where many similar ideas have been used. Two main programs for automated template-based modeling are presented: ModeRNA assembling structures from fragments and MacroMoleculeBuilder performing a simulation to satisfy spatial restraints. Both approaches have in common that they require an alignment of the target sequence to a known RNA structure that is used as a modeling template. As a way...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
The Art of Editing RNA Structural Alignments
Manual editing of RNA structural alignments may be considered more art than science, since it still requires an expert biologist to take multiple levels of information into account and be slightly creative when constructing high-quality alignments. Even though the task is rather tedious, it is rewarded by great insight into the evolution of structure and function of your favorite RNA molecule. In this chapter I will review the methods and considerations that go into constructing RNA structural alignments at the secondary and tertiary structure level; introduce software, databases, and algorithms that have proven useful in ...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
Phylogeny and Evolution of RNA Structure
Darwin’s conviction that all living beings on Earth are related and the graph of relatedness is tree-shaped has been essentially confirmed by phylogenetic reconstruction first from morphology and later from data obtained by molecular sequencing. Limitations of the phylogenetic tree concept were recognized as more and more sequence information became available. The other path-breaking idea of Darwin, natural selection of fitter variants in populations, is cast into simple mathematical form and extended to mutation-selection dynamics. In this form the theory is directly applicable to RNA evolution in vitro and to virus...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
De Novo Discovery of Structured ncRNA Motifs in Genomic Sequences
De novo discovery of “motifs” capturing the commonalities among related noncoding
ncRNA
structured RNAs is among the most difficult problems in computational biology. This chapter outlines the challenges presented by this problem, together with some approaches towards solving them, with an emphasis on an approach based on the CMfinder
CMfinder
program as a case study. Applications to genomic screens for novel de novo structured ncRNA
ncRNA
s, including structured RNA elements in untranslated portions of protein-coding ge...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
RNA Structural Alignments, Part II: Non-Sankoff Approaches for Structural Alignments
In structural alignments of RNA sequences, the computational cost of Sankoff algorithm, which simultaneously optimizes the score of the common secondary structure and the score of the alignment, is too high for long sequences (O(L
6) time for two sequences of length L). In this chapter, we introduce the methods that predict the structures and the alignment separately to avoid the heavy computations in Sankoff algorithm. In those methods, neither of those two prediction processes is independent, but each of them utilizes the information of the other process. The first process typically includes prediction of b...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
RNA Structural Alignments, Part I: Sankoff-Based Approaches for Structural Alignments
Simultaneous alignment and secondary structure prediction of RNA sequences is often referred to as “RNA structural alignment.” A class of the methods for structural alignment is based on the principles proposed by Sankoff more than 25 years ago. The Sankoff algorithm simultaneously folds and aligns two or more sequences. The advantage of this algorithm over those that separate the folding and alignment steps is that it makes better predictions. The disadvantage is that it is slower and requires more computer memory to run. The amount of computational resources needed to run the Sankoff algorithm is so high that...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
Introduction to RNA Secondary Structure Comparison
Many methods have been proposed for RNA secondary structure comparison, and new ones are still being developed. In this chapter, we first consider structure representations and discuss their suitability for structure comparison. Then, we take a look at the more commonly used methods, restricting ourselves to structures without pseudo-knots. For comparing structures of the same sequence, we study base pair distances. For structures of different sequences (and of different length), we study variants of the tree edit model. We name some of the available tools and give pointers to the literature. We end with a short review on ...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
Abstract Shape Analysis of RNA
Abstract shape analysis
abstract shape analysis
is a method to learn more about the complete Boltzmann ensemble of the secondary structures of a single RNA molecule. Abstract shapes classify competing secondary structures into classes that are defined by their arrangement of helices. It allows us to compute, in addition to the structure of minimal free energy, a set of structures that represents relevant and interesting structural alternatives. Furthermore, it allows to compute probabilities of all structures within a shape class. This allows to ensure that our representative subset covers t...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
Class-Specific Prediction of ncRNAs
Many RNA families, i.e., groups of homologous RNA genes, belong to RNA classes, such as tRNAs, snoRNAs, or microRNAs, that are characterized by common sequence motifs and/or common secondary structure features. The detection of new members of RNA classes, as well as the comprehensive annotation of genomes with members of RNA classes is a challenging task that goes beyond simple homology search. Computational methods addressing this problem typically use a three-tiered approach: In the first step an efficient and sensitive filter is employed. In the second step the candidate set is narrowed down using computationally expens...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
Concepts and Introduction to RNA Bioinformatics
RNA bioinformatics and computational RNA biology have emerged from implementing methods for predicting the secondary structure of single sequences. The field has evolved to exploit multiple sequences to take evolutionary information into account, such as compensating (and structure preserving) base changes. These methods have been developed further and applied for computational screens of genomic sequence. Furthermore, a number of additional directions have emerged. These include methods to search for RNA 3D structure, RNA–RNA interactions, and design of interfering RNAs (RNAi) as well as methods for interactions bet...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
Computational Prediction of MicroRNA Genes
The computational identification of novel microRNA (miRNA) genes is a challenging task in bioinformatics. Massive amounts of data describing unknown functional RNA transcripts have to be analyzed for putative miRNA candidates with automated computational pipelines. Beyond those miRNAs that meet the classical definition, high-throughput sequencing techniques have revealed additional miRNA-like molecules that are derived by alternative biogenesis pathways. Exhaustive bioinformatics analyses on such data involve statistical issues as well as precise sequence and structure inspection not only of the functional mature part but ...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
MicroRNA Target Finding by Comparative Genomics
MicroRNAs (miRNAs) have been implicated in virtually every metazoan biological process, exerting a widespread impact on gene expression. MicroRNA repression is conferred by relatively short “seed match” sequences, although the degree of repression varies widely for individual target sites. The factors controlling whether, and to what extent, a target site is repressed are not fully understood. As an alternative to target prediction based on sequence alone, comparative genomics has emerged as an invaluable tool for identifying miRNA targets that are conserved by natural selection, and hence likely effective and ...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
Annotating Functional RNAs in Genomes Using Infernal
Many different types of functional non-coding RNAs participate in a wide range of important cellular functions but the large majority of these RNAs are not routinely annotated in published genomes. Several programs have been developed for identifying RNAs, including specific tools tailored to a particular RNA family as well as more general ones designed to work for any family. Many of these tools utilize covariance models (CMs), statistical models of the conserved sequence, and structure of an RNA family. In this chapter, as an illustrative example, the Infernal software package and CMs from the Rfam database are used to i...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
SCFGs in RNA Secondary Structure Prediction RNA secondary structure prediction : A Hands-on Approach
Stochastic context-free grammars (SCFGs) were first established in the context of natural language modelling, and only later found their applications in RNA secondary structure prediction. In this chapter, we discuss the basic SCFG algorithms (CYK and inside–outside algorithms) in an application-centered manner and use the pfold grammar as a case study to show how the algorithms can be adapted to a grammar in a nonstandard form. We extend our discussion to the use of grammars with additional information (such as evolutionary information) to improve the quality of predictions. Finally, we provide a brief survey of pro...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
Energy-Based RNA Consensus Secondary Structure Prediction in Multiple Sequence Alignments
Many biologically important RNA structures are conserved in evolution leading to characteristic mutational patterns. RNAalifold is a widely used program to predict consensus secondary structures in multiple alignments by combining evolutionary information with traditional energy-based RNA folding algorithms. Here we describe the theory and applications of the RNAalifold algorithm. Consensus secondary structure prediction not only leads to significantly more accurate structure models, but it also allows to study structural conservation of functional RNAs. (Source: Springer protocols feed by Bioinformatics)
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news
