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

An Introduction to RNA Databases
We present an introduction to RNA databases. The history and technology behind RNA databases are briefly discussed. We examine differing methods of data collection and curation and discuss their impact on both the scope and accuracy of the resulting databases. Finally, we demonstrate these principles through detailed examination of four leading RNA databases: Noncode, miRBase, Rfam, and SILVA. (Source: Springer protocols feed by Bioinformatics)
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news

Introduction to Stochastic Context Free Grammars
Stochastic context free grammars are a formalism which plays a prominent role in RNA secondary structure analysis. This chapter provides the theoretical background on stochastic context free grammars. We recall the general definitions and study the basic properties, virtues, and shortcomings of stochastic context free grammars. We then introduce two ways in which they are used in RNA secondary structure analysis, secondary structure prediction and RNA family modeling. This prepares for the discussion of applications of stochastic context free grammars in the chapters on Rfam (6), Pfold (8), and Infernal (9). (Source: Sprin...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news

Energy-Directed RNA Structure Prediction
In this chapter we present the classic dynamic programming algorithms for RNA structure prediction by energy minimization, as well as variations of this approach that allow to compute suboptimal foldings, or even the partition function over all possible secondary structures. The latter are essential in order to deal with the inaccuracy of minimum free energy (MFE) structure prediction, and can be used, for example, to derive reliability measures that assign a confidence value to all or part of a predicted structure. In addition, we discuss recently proposed alternatives to the MFE criterion such as the use of maximum expec...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news

The Determination of RNA Folding Nearest Neighbor Parameters
The stability of RNA secondary structure can be predicted using a set of nearest neighbor parameters. These parameters are widely used by algorithms that predict secondary structure. This contribution introduces the UV optical melting experiments that are used to determine the folding stability of short RNA strands. It explains how the nearest neighbor parameters are chosen and how the values are fit to the data. A sample nearest neighbor calculation is provided. The contribution concludes with new methods that use the database of sequences with known structures to determine parameter values. (Source: Springer protocols fe...
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The Principles of RNA Structure Architecture
Being informational, enzymatic, as well as a nanoscale molecular machine, ribonucleic acid (RNA) permeates all areas of biology and has been exploited in biotechnology as drug and sensor. Here we describe the composition and fundamental properties of RNA and how the single-stranded RNA chains fold and shape certain motifs that are repeatedly observed in different structures. Small and large molecular mass RNA binders are being touched upon, as is the technology for selecting RNA molecules in vitro that bind almost any kind of natural or artificial target. Recognizing the versatility of RNA is expected to foster the develop...
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RNA–Protein Interactions: An Overview
RNA binding proteins (RBPs) are key players in the regulation of gene expression. In this chapter we discuss the main protein–RNA recognition modes used by RBPs in order to regulate multiple steps of RNA processing. We discuss traditional and state-of-the-art technologies that can be used to study RNAs bound by individual RBPs, or vice versa, for both in vitro and in vivo methodologies. To help highlight the biological significance of RBP mediated regulation, online resources on experimentally verified protein–RNA interactions are briefly presented. Finally, we present the major tools to computationally infer R...
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Bioinformatics of siRNA Design
RNA interference mediated by small interfering RNAs is a powerful tool for investigation of gene functions and is increasingly used as a therapeutic agent. However, not all siRNAs are equally potent, and although simple rules for the selection of good siRNAs were proposed early on, siRNAs are still plagued with widely fluctuating efficiency. Recently, new design tools incorporating both the structural features of the targeted RNAs and the sequence features of the siRNAs substantially improved the efficacy of siRNAs. In this chapter we will present a review of sequence and structure-based algorithms behind them. (Source: Sp...
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

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

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 RNA–RNA Interactions
We describe different tools and approaches for RNA–RNA interaction prediction. Recognition of ncRNA targets is predominantly governed by two principles, namely the stability of the duplex between the two interacting RNAs and the internal structure of both mRNA and ncRNA. Thus, approaches can be distinguished into different major categories depending on how they consider inter- and intramolecular structure. The first class completely neglects the internal structure and measures only the stability of the duplex. The second class of approaches abstracts from specific intramolecular structures and uses an ensemble-based ...
Source: Springer protocols feed by Bioinformatics - December 4, 2013 Category: Bioinformatics Source Type: news

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...
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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