1560940
Sfold web server for statistical folding and rational design of nucleic acids
The Sfold web server provides user-friendly access to Sfold, a recently developed nucleic acid folding software package, via the World Wide Web (WWW). The software is based on a new statistical sampling paradigm for the prediction of RNA secondary structure. One of the main objectives of this software is to offer computational tools for the rational design of RNA-targeting nucleic acids, which include small interfering RNAs (siRNAs), antisense oligonucleotides and trans-cleaving ribozymes for gene knock-down studies. The methodology for siRNA design is based on a combination of RNA target accessibility prediction, siRNA duplex thermodynamic properties and empirical design rules. Our approach to target accessibility evaluation is an original extension of the underlying RNA folding algorithm to account for the likely existence of a population of structures for the target mRNA. In addition to the application modules Sirna, Soligo and Sribo for siRNAs, antisense oligos and ribozymes, respectively, the module Srna offers comprehensive features for statistical representation of sampled structures. Detailed output in both graphical and text formats is available for all modules. The Sfold server is available at http://sfold.wadsworth.org and http://www.bioinfo.rpi.edu/applications/sfold.
2800614
A Bayesian Statistical Algorithm for RNA Secondary Structure Prediction
A Bayesian approach for predicting RNA secondary structure that addresses the following three open issues is described: (1) the need for a representation of the full ensemble of probable structures; (2) the need to specify a fixed set of energy parameters; (3) the desire to make statistical inferences on all variables in the problem. It has recently been shown that Bayesian inference can be employed to relax or eliminate the need to specify the parameters of bioinformatics recursive algorithms and to give a statistical representation of the full ensemble of probable solutions with the incorporation of uncertainty in parameter values. In this paper, we make an initial exploration of these potential advantages of the Bayesian approach. We present a Bayesian algorithm that is based on stacking energy rules but relaxes the need to specify the parameters. The algorithm returns the exact posterior distribution of the number of destabilizing loops, stacking energy matrices, and secondary structures. The algorithm generates statistically representative structures from the full ensemble of probable secondary structures in exact proportion to the posterior probabilities. Once the forward recursions for the algorithm are completed, the backward recursive sampling executes in O(n) time, providing a very efficient approach for generating representative structures. We demonstrate the utility of the Bayesian approach with several tRNA sequences. The potential of the approach for predicting RNA secondary structures and presenting alternative structures is illustrated with applications to the Escherichia coli tRNA(Ala) sequence and the Xenopus laevis oocyte 5S rRNA sequence.
17272225
Structure clustering features on the Sfold Web server
UNLABELLED
The energy landscape of RNA secondary structures is often complex, and the Boltzmann-weighted ensemble usually contains distinct clusters. Furthermore, the minimum free energy structure often lies outside of the cluster containing the structure determined by comparative sequence analysis. We have developed procedures to characterize and visualize the Boltzmann-weighted ensemble, and have made them available on the Sfold Web server. The new features on the Web server include clustering statistics, ensemble and cluster centroids, multi-dimensional scaling display and energy landscape representation of the Boltzmann-weighted ensemble.


AVAILABILITY
http://sfold.wadsworth.org; http://www.bioinfo.rpi.edu/applications/sfold


CONTACT
chanc@wadsworth.org.
18722688
Towards Efficient Reasoning for Description Logics with Inverse Roles
This paper presents a first proposal for improving the efficiency of modern description logic (DL) reasoners that are known to be less efficient for DLs with inverse roles. The current loss of performance is usually caused by the missing applicability of well-known optimization techniques such as caching the satisfiability status of modal successors. In order to improve this situation we propose a first version of a modified tableau algorithm for ALCI that can be considered as a basis for integrating sound caching techniques into modern reasoners supporting DLs with inverse roles.
1075390
Automatic Learning of Parallel Dependency Treelet Pairs
Induction of synchronous grammars from empirical data has long been an unsolved problem; despite generative synchronous grammars theoretically suit the machine translation task very well. This fact is mainly due to pervasive structural divergences between languages. This paper presents a statistical approach that learns dependency structure mappings from parallel corpora. The new algorithm automatically learns parallel dependency treelet pairs from loosely matched non-isomorphic dependency trees while keeping computational complexity polynomial in the length of the sentences. A set of heuristics is introduced and specifically optimized for parallel treelet learning purposes using Minimum Error Rate training.