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108
VARNA: interactive drawing and editing of the RNA secondary structure. Bioinformatics 25: 1974–1975
- Journal of General Microbiology
, 2009
"... Description: VARNA is a tool for the automated drawing, visualization and annotation of the secondary structure of RNA, designed as a companion software for web servers and databases. Features: VARNA implements four drawing algorithms, supports input/output using the classic formats dbn, ct, bpseq a ..."
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Cited by 70 (1 self)
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Description: VARNA is a tool for the automated drawing, visualization and annotation of the secondary structure of RNA, designed as a companion software for web servers and databases. Features: VARNA implements four drawing algorithms, supports input/output using the classic formats dbn, ct, bpseq and RNAML and exports the drawing as five picture formats, either pixel-based (JPEG, PNG) or vector-based (SVG, EPS and XFIG). It also allows manual modification and structural annotation of the resulting drawing using either an interactive point and click approach, within a web server or through command-line arguments. Availability: VARNA is a free software, released under the terms of the GPLv3.0 license and available at
Thermodynamics of RNA-RNA Binding
, 2005
"... Background: Reliable predictions of RNA-RNA binding energies is crucial e.g. for the understanding on RNAi, microRNA-mRNA binding, and antisense interactions. The thermodynamics of such RNA-RNA interactions can be understood as the sum of two energy contributions: (1) the energy necessary to “open ” ..."
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Cited by 63 (13 self)
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Background: Reliable predictions of RNA-RNA binding energies is crucial e.g. for the understanding on RNAi, microRNA-mRNA binding, and antisense interactions. The thermodynamics of such RNA-RNA interactions can be understood as the sum of two energy contributions: (1) the energy necessary to “open ” the binding site, and (2) the energy gained from hybridization. Methods: 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. Results: 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 energies of siRNAs to their respective mRNA target.
Boltzmann probability of RNA structural neighbors and riboswitch detection
- Bioinformatics
, 2007
"... Abstract Given an RNA nucleotide sequence s, let S0 be any secondary structure s. S0 could be the minimum free energy structure of s, it could be the secondary structure obtained by analysis of the X-ray structure or by comparative sequence analysis, or it could be an arbitrary intermediate structu ..."
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Cited by 15 (6 self)
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Abstract Given an RNA nucleotide sequence s, let S0 be any secondary structure s. S0 could be the minimum free energy structure of s, it could be the secondary structure obtained by analysis of the X-ray structure or by comparative sequence analysis, or it could be an arbitrary intermediate structure. Another secondary structure S of s is called a δ-neighbor of S0 if S and S0 differ by exactly δ base pairs. Here we describe a new software package, RNAbor, to compute the number N δ , the Boltzmann partition function Z δ and the minimum free energy structure MFE δ over the collection of all δ-neighbors of S0. This computation is done simultaneously for all δ ≤ m, in run time O(mn 3 ) and memory O(mn 2 ). Our novel algorithms depend on a new manner of partitioning up the space of secondary structures, nested multiple recursions and dynamic programming. Computations are done with the Turner nearest neighbor energy parameters, known for its success in ab initio secondary structure prediction. We apply RNAbor to automatic detection of possible RNA conformational switches, and compare RNAbor to existent switch detection methods. Public access to our software, RNAbor (RNA neighbor), is provided by a web server available at
Computational methods in noncoding RNA research
- J. MATH. BIOL. (2008) 56:15–49
, 2008
"... Non protein-coding RNAs (ncRNAs) are a research hotspot in bioinfor-matics. Recent discoveries have revealed new ncRNA ... families performing a variety of roles, from gene expression regulation to catalytic activities. It is also believed that other families are still to be unveiled. Computational ..."
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Cited by 14 (1 self)
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Non protein-coding RNAs (ncRNAs) are a research hotspot in bioinfor-matics. Recent discoveries have revealed new ncRNA ... families performing a variety of roles, from gene expression regulation to catalytic activities. It is also believed that other families are still to be unveiled. Computational methods developed for protein coding genes often fail when searching for ncRNAs. Noncoding RNAs functionality is often heavily dependent on their secondary structure, which makes gene discovery very different from protein coding RNA genes. This motivated the development of specific methods for ncRNA research. This article reviews the main approaches used to identify ncRNAs and predict secondary structure.
Functional microRNA targets in protein coding sequences
- Bioinformatics
, 2012
"... Motivation: Experimental evidence has accumulated showing that microRNA (miRNA) binding sites within protein coding sequences (CDSs) are functional in controlling gene expression. Results: Here we report a computational analysis of such miRNA target sites, based on features extracted from existing m ..."
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Cited by 14 (2 self)
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Motivation: Experimental evidence has accumulated showing that microRNA (miRNA) binding sites within protein coding sequences (CDSs) are functional in controlling gene expression. Results: Here we report a computational analysis of such miRNA target sites, based on features extracted from existing mammalian high throughput immunoprecipitation and sequencing data. The analysis is performed independently for the CDS and the 3’ Untranslated Regions (3’UTRs) and reveals different sets of features and models for the two regions. The two models are combined into a novel computational model for miRNA target genes, DIANA-microT-CDS, which achieves higher sensitivity compared to other popular programs and the model that uses only the 3’UTR target sites. Further analysis indicates that genes with shorter 3’UTRs are preferentially targeted in the CDS, suggesting that evolutionary selection might favor additional sites on the CDS in cases where there is restricted space on the 3'UTR. Availability: The results of DIANA-microT-CDS are available at www.microrna.gr/microT-CDS. Contact:
Predicting RNA secondary structures with pseudoknots by mcmc sampling
- J. Math. Biol
, 2008
"... The most probable secondary structure of an RNA molecule, given the nucleotide sequence, can be computed efficiently if a stochastic context-free grammar (SCFG) is used as the prior distribution of the secondary structure. The structures of some RNA molecules contain so-called pseudoknots. Allowing ..."
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Cited by 13 (2 self)
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The most probable secondary structure of an RNA molecule, given the nucleotide sequence, can be computed efficiently if a stochastic context-free grammar (SCFG) is used as the prior distribution of the secondary structure. The structures of some RNA molecules contain so-called pseudoknots. Allowing all possible configurations of pseudoknots is not compatible with context-free grammar models and makes the search for an optimal secondary structure NP-complete. We suggest a probabilistic model for RNA secondary structures with pseudoknots and present a Markov-chain Monte-Carlo Method for sampling RNA structures according to their posterior distribution for a given sequence. We favor Bayesian sampling over optimization methods in this context, because it makes the uncertainty of RNA structure predictions assessable. We demonstrate the benefit of our method in examples with tmRNA and also with simulated data. McQFold, an implementation of our method, is freely available from
Advances in RNA structure prediction from sequence: new tools for generating hypotheses about viral RNA structure–function relationships
- J. VIROL
, 2009
"... Advances in sequencing technology have made abundant RNA sequence information available, but the challenge of how to interpret these data remains. The RNA sequence contains many layers of information. RNA sequences code for proteins and small RNAs, such as microRNAs or transacting small interfering ..."
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Cited by 11 (0 self)
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Advances in sequencing technology have made abundant RNA sequence information available, but the challenge of how to interpret these data remains. The RNA sequence contains many layers of information. RNA sequences code for proteins and small RNAs, such as microRNAs or transacting small interfering RNAs (siRNAs). RNA encodes information about both structure and function. Viral RNA structures, such as riboswitches, internal ribosome entry sites (75), and panhandles (71), regulate the stages of the viral life cycle, including replication (100), transcription (99), splicing (40, 48), aminoacylation (31, 55), translation (12, 75, 98), and encapsidation (27, 60, 71, 84). Because viral RNAs are structurally dynamic, current prediction methods focusing on a single minimum freeenergy structure may not always identify functionally relevant structures without additional experimental restraints. Because
Rational design and rapid screening of antisense oligonucleotides for prokaryotic gene modulation
- Nucleic Acids Res
, 2006
"... Antisense oligodeoxynucleotides (oligos) are widely used for functional studies of both prokaryotic and eukaryotic genes. However, the identification of effective target sites is a major issue in antisense applications. Here, we study a number of thermo-dynamic and structural parameters that may aff ..."
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Cited by 11 (2 self)
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Antisense oligodeoxynucleotides (oligos) are widely used for functional studies of both prokaryotic and eukaryotic genes. However, the identification of effective target sites is a major issue in antisense applications. Here, we study a number of thermo-dynamic and structural parameters that may affect the potency of antisense inhibition. We develop a cell-free assay for rapid oligo screening. This assay is used for measuring the expression of Escherichia coli lacZ, the antisense target for experimental testing and validation. Based on a training set of 18 oligos, we found that structural accessibility predicted by local folding of the target mRNA is the most important predictor for antisense activity. This finding was further confirmed by a direct validation study. In this study, a set of 10 oligos was designed to target accessible sites, and another set of 10 oligos was selected to target inaccessible sites. Seven of the 10 oligos for accessible sites were found to be effective (.50 % inhibition), but none of the oligos for inaccessible sites was effective. The difference in the antisense activity between the two sets of oligos was statistically significant. We also found that the predictability of antisense activity by target accessibility was greatly improved for oligos targeted to the regions upstream of the end of the active domain for b-galactosidase, the protein encoded by lacZ. The combination of the structure-based antisense design and extension of the lacZ assay to include gene fusions will be applicable to high-throughput gene functional screening, and to the identification of new drug targets in pathogenic microbes. Design tools are available through the Sfold Web server at
Emerging Role of MicroRNAs in Cardiovascular Biology
"... Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which p ..."
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Cited by 10 (0 self)
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Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at:
Efficient RNAi-based gene family knockdown via set cover optimization
- Artif. Intell. Med
, 2005
"... RNA interference (RNAi) is a recently discovered genetic immune system with widespread therapeutic and genomic applications. In this paper, we address the problem of selecting an efficient set of initiator molecules (siRNAs) for RNAi-based gene family knockdown experiments. Our goal is to select a m ..."
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Cited by 9 (0 self)
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RNA interference (RNAi) is a recently discovered genetic immune system with widespread therapeutic and genomic applications. In this paper, we address the problem of selecting an efficient set of initiator molecules (siRNAs) for RNAi-based gene family knockdown experiments. Our goal is to select a minimal set of siRNAs that (a) cover a targeted gene family or a specified subset of it, (b) do not cover any untargeted genes, and (c) are individually highly effective at inducing knockdown. We show that the problem of minimizing the number of siRNAs required to knock down a family of genes is NP-Hard via a reduction to the set cover problem. We also give a formal statement of a generalization of the basic problem that incorporates additional biological constraints and optimality criteria. We modify the classical branch-and-bound algorithm to include some of these biological criteria. We find that, in many typical cases, these constraints reduce the search space enough that we are able to compute exact minimal siRNA covers within reasonable time. For larger cases, we propose a probabilistic greedy algorithm for finding minimal siRNA covers efficiently. Our computational results on real biological data show that the probabilistic greedy algorithm produces siRNA covers as good as the branch-andbound algorithm in most cases. Both algorithms return minimal siRNA covers with high predicted probability that the selected siRNAs will be effective at inducing knockdown. We also examine the role of “off-target ” interactions – the constraint of avoiding covering untargeted genes can, in some cases, substantially increase the complexity of the resulting solution. Overall, however, we find that in many common cases, our approach significantly reduces the number of siRNAs required in gene family knockdown experiments, as compared to knocking down genes independently.
