74 research outputs found
Complete RNA inverse folding: computational design of functional hammerhead ribozymes
Nanotechnology and synthetic biology currently constitute one of the most
innovative, interdisciplinary fields of research, poised to radically transform
society in the 21st century. This paper concerns the synthetic design of
ribonucleic acid molecules, using our recent algorithm, RNAiFold, which can
determine all RNA sequences whose minimum free energy secondary structure is a
user-specified target structure. Using RNAiFold, we design ten cis-cleaving
hammerhead ribozymes, all of which are shown to be functional by a cleavage
assay. We additionally use RNAiFold to design a functional cis-cleaving
hammerhead as a modular unit of a synthetic larger RNA. Analysis of kinetics on
this small set of hammerheads suggests that cleavage rate of computationally
designed ribozymes may be correlated with positional entropy, ensemble defect,
structural flexibility/rigidity and related measures. Artificial ribozymes have
been designed in the past either manually or by SELEX (Systematic Evolution of
Ligands by Exponential Enrichment); however, this appears to be the first
purely computational design and experimental validation of novel functional
ribozymes. RNAiFold is available at
http://bioinformatics.bc.edu/clotelab/RNAiFold/.Comment: 17 pages, 2 tables, 7 figures, final version to appear in Nucleic
Acids Researc
Boosting video tracking performance by means of Tabu Search in Intelligent Visual Surveillance Systems
In this paper, we present a fast and efficient technique for the data association problem applied to visual tracking systems. Visual tracking process is formulated as a combinatorial hypotheses search with a heuristic evaluation function taking into account structural and specific information such as distance, shape, color, etc. We introduce a Tabu Search algorithm which performs a search on an indirect space. A novel problem formulation allows us to transform any solution into the real search space, which is needed for fitness calculation, in linear time. This new formulation and the use of auxiliary structures yields a fast transformation from a blob-to-track assignment space to the real shape and position of tracks space (while calculating fitness in an incremental fashion), which is key in order to produce efficient and fast results. Other previous approaches are based on statistical techniques or on evolutionary algorithms. These techniques are quite efficient and robust although they cannot converge as fast as our approach.This work was supported in part by Projects CICYT TIN2008-06742-C02-02/TSI, CICYT
TEC2008-06732-C02-02/TEC, CAM CONTEXTS (S2009/TIC-1485) and DPS2008-07029-C02-02.Publicad
Computing folding pathways between RNA secondary structures
Given an RNA sequence and two designated secondary structures A, B, we describe a new algorithm that computes a nearly optimal folding pathway from A to B. The algorithm, RNAtabupath, employs a tabu semi-greedy heuristic, known to be an effective search strategy in combinatorial optimization. Folding pathways, sometimes called routes or trajectories, are computed by RNAtabupath in a fraction of the time required by the barriers program of Vienna RNA Package. We benchmark RNAtabupath with other algorithms to compute low energy folding pathways between experimentally known structures of several conformational switches. The RNApathfinder web server, source code for algorithms to compute and analyze pathways and supplementary data are available at http://bioinformatics.bc.edu/clotelab/RNApathfinder
Energy parameters and novel algorithms for an extended nearest neighbor energy model of RNA.
We describe the first algorithm and software, RNAenn, to compute the partition function and minimum free energy secondary structure for RNA with respect to an extended nearest neighbor energy model. Our next-nearest-neighbor triplet energy model appears to lead to somewhat more cooperative folding than does the nearest neighbor energy model, as judged by melting curves computed with RNAenn and with two popular software implementations for the nearest-neighbor energy model. A web server is available at http://bioinformatics.bc.edu/clotelab/RNAenn/
RNAiFold 2.0: a web server and software to design custom and Rfam-based RNA molecules.
Several algorithms for RNA inverse folding have been used to design synthetic riboswitches, ribozymes and thermoswitches, whose activity has been experimentally validated. The RNAiFold software is unique among approaches for inverse folding in that (exhaustive) constraint programming is used instead of heuristic methods. For that reason, RNAiFold can generate all sequences that fold into the target structure or determine that there is no solution. RNAiFold 2.0 is a complete overhaul of RNAiFold 1.0, rewritten from the now defunct COMET language to C++. The new code properly extends the capabilities of its predecessor by providing a user-friendly pipeline to design synthetic constructs having the functionality of given Rfam families. In addition, the new software supports amino acid constraints, even for proteins translated in different reading frames from overlapping coding sequences; moreover, structure compatibility/incompatibility constraints have been expanded. With these features, RNAiFold 2.0 allows the user to design single RNA molecules as well as hybridization complexes of two RNA molecules.National Science Foundation [DBI-1262439]. Funding for open access charge: National Science Foundation./nConflict of interest statement. None declared
RNAiFold 2.0: a web server and software to design custom and Rfam-based RNA molecules.
Several algorithms for RNA inverse folding have been used to design synthetic riboswitches, ribozymes and thermoswitches, whose activity has been experimentally validated. The RNAiFold software is unique among approaches for inverse folding in that (exhaustive) constraint programming is used instead of heuristic methods. For that reason, RNAiFold can generate all sequences that fold into the target structure or determine that there is no solution. RNAiFold 2.0 is a complete overhaul of RNAiFold 1.0, rewritten from the now defunct COMET language to C++. The new code properly extends the capabilities of its predecessor by providing a user-friendly pipeline to design synthetic constructs having the functionality of given Rfam families. In addition, the new software supports amino acid constraints, even for proteins translated in different reading frames from overlapping coding sequences; moreover, structure compatibility/incompatibility constraints have been expanded. With these features, RNAiFold 2.0 allows the user to design single RNA molecules as well as hybridization complexes of two RNA molecules.National Science Foundation [DBI-1262439]. Funding for open access charge: National Science Foundation./nConflict of interest statement. None declared
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