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Auflistung nach Autor:in "Hofacker, Ivo L."

1 - 7 von 7
  • Konferenzbeitrag
    2D projections of RNA folding landscapes
    (German conference on bioinformatics 2009, 2009) Lorenz, Rony; Flamm, Christoph; Hofacker, Ivo L.
    The analysis of RNA folding landscapes yields insights into the kinetic folding behavior not available from classical structure prediction methods. This is especially important for multi-stable RNAs whose function is related to structural changes, as in the case of riboswitches. However, exact methods such as barrier tree analysis scale exponentially with sequence length. Here we present an algorithm that computes a projection of the energy landscape into two dimensions, namely the distances to two reference structures. This yields an abstraction of the high-dimensional energy landscape that can be conveniently visualized, and can serve as the basis for estimating energy barriers and refolding pathways. With an asymptotic time complexity of O(n7) the algorithm is computationally demanding. However, by exploiting the sparsity of the dynamic programming matrices and parallelization for multi-core processors, our implementation is practical for sequences of up to 400 nt, which includes most RNAs of biological interest.
  • Konferenzbeitrag
    Comparative analysis of cyclic sequences: Viroids and other small circular RNAs
    (German Conference on Bioinformatics, 2006) Mosig, Axel; Hofacker, Ivo L.; Stadler, Peter F.
    The analysis of small circular sequences requires specialized tools. While the differences between linear and circular sequences can be neglected in the case of long molecules such as bacterial genomes since in practice all analysis is performed in sequence windows, this is not true for viroids and related sequences which are usually only a few hundred basepairs long. In this contribution we present basic algorithms and corresponding software for circular RNAs. In particular, we discuss the problem of pairwise and multiple cyclic sequence alignments with affine gap costs, and an extension of a recent approach to circular RNA folding to the computation of consensus structures.
  • Konferenzbeitrag
    Conserved RNA pseudoknots
    (German Conference on Bioinformatics 2004, GCB 2004, 2004) Thurner, Caroline; Hofacker, Ivo L.; Stadler, Peter F.
    Pseudoknots are essential for the functioning of many small RNA molecules. In addition, viral RNAs often exhibit pseudoknots that are required at various stages of the viral life-cycle. Techniques for detecting evolutionarily conserved, and hence most likely functional RNA pseudoknots, are therefore of interest. Here we present an extension of the alidot approach that extracts conserved secondary structures from a multiple sequence alignment and predicted secondary structures of the individual sequences. In contrast to purely phylogenetic methods, this approach yields good results already for small samples of 10 sequences or even less.
  • Konferenzbeitrag
    Memory efficient folding algorithms for circular RNA secondary structures
    (German Conference on Bioinformatics 2005 (GCB 2005), 2005) Hofacker, Ivo L.; Stadler, Peter F.
    A small class of RNA molecules, in particular the tiny genomes of viroids, are circular. Yet most structure prediction algorithms handle only linear RNAs. The most straightforward approach is to compute circular structures from "internal" and "external" substructures separated by a base pair. This is incompatible, however, with the memory-saving approach of the Vienna RNA Package which builds a linear RNA structure from shorter (internal) structures only. Here we describe how circular secondary structures can be obtained without additional memory requirements as a kind of "post-processing" of the linear structures.
  • Konferenzbeitrag
    RNALfoldz: efficient prediction of thermodynamically stable, local secondary structures
    (German Conference on Bioinformatics 2010, 2010) Gruber, Andreas R.; Bernhart, Stephan H.; Zhou, You; Hofacker, Ivo L.
    The search for local RNA secondary structures and the annotation of unusually stable folding regions in genomic sequences are two well motivated bioinformatic problems. In this contribution we introduce RNALfoldz an efficient solution two tackle both tasks. It is an extension of the RNALfold algorithm augmented by support vector regression for efficient calculation of a structure's thermodynamic stability. We demonstrate the applicability of this approach on the genome of E. coli and investigate a potential strategy to determine z-score cutoffs given a predefined false discovery rate.
  • Konferenzbeitrag
    RNAplex: a fast and flexible RNA-RNA interaction search tool
    (German conference on bioinformatics – GCB 2007, 2007) Tafer, Hakim; Hofacker, Ivo L.
    Regulatory RNAs often unfold their action via RNA-RNA interaction. Transcriptional gene silencing by means of siRNAs and miRNA as well as snoRNA directed RNA editing rely on this mechanism. ncRNA regulation in bacteria is mainly based upon RNA duplex formation. Finding putative target sites for newly discovered ncR-NAs is a lengthy task as tools for cofolding RNA molecules like RNAcofold and RNAup have a run time proportional to O((n + m)3) which makes them unpractical for whole genome search. We present a new program, RNAplex, especially designed to quickly find possible hybridization sites for a query RNA in large RNA databases. In contrast to earlier approaches, RNAplex uses a slightly different energy model which reduces the computational time by a factor 65 compared to RNAhybrid without loss of sensitivity.
  • Konferenzbeitrag
    Thermodynamics of RNA-RNA binding
    (German Conference on Bioinformatics 2005 (GCB 2005), 2005) Mückstein, Ulrike; Tafer, Hakim; Hackermüller, Jörg; Bernhart, Stephan H.; Stadler, Peter F.; Hofacker, Ivo L.
    We present an extension of the standard partition function approach to RNA secondary structures that computes the probabilities Pu[i, j] that a sequence interval [i, j] is unpaired. Comparison with experimental data shows that Pu[i, j] can be applied as a significant determinant of local target site accessibility for RNA interference (RNAi). Furthermore, these quantities can be used to rigorously determine binding free energies of short oligomers to large mRNA targets. The resource consumption is comparable to a single partition function computation for the large target molecule. We can show that RNAi efficiency correlates well with the binding probabilities of siRNAs to their respective mRNA target.