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611
SnoReport: Computational identification of snoRNAs with unknown targets
, 2007
"... Summary: Unlike tRNAs and microRNAs, both classes of snoRNAs, which direct two distinct types of chemical modifications of uracil residues, have proved to be surprisingly difficult to find in genomic sequences. Most computational approaches so far have explicitly used the fact that snoRNAs predomina ..."
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Cited by 50 (16 self)
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Summary: Unlike tRNAs and microRNAs, both classes of snoRNAs, which direct two distinct types of chemical modifications of uracil residues, have proved to be surprisingly difficult to find in genomic sequences. Most computational approaches so far have explicitly used the fact that snoRNAs predominantly target ribosomal RNAs and spliceosomal RNAs. The target is specified by a short stretch of sequence complementarity between the snoRNA and its target. This sequence complementarity to known targets crucially contributes to sensitivity and specificity of snoRNA gene finding algorithms. The discovery of “orphan” snoRNAs, which either have no known target, or which target ordinary protein-coding mRNAs, however, begs the question whether this class of “housekeeping” non-coding RNAs is much more wide-spread and might have a diverse set of regulatory functions. In order to approach this question, we present here a combination
Comparative Genomics of Foot-and-Mouth Disease Virus†
, 2004
"... Here we present complete genome sequences, including a comparative analysis, of 103 isolates of foot-andmouth disease virus (FMDV) representing all seven serotypes and including the first complete sequences of the SAT1 and SAT3 genomes. The data reveal novel highly conserved genomic regions, indicat ..."
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Cited by 49 (4 self)
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Here we present complete genome sequences, including a comparative analysis, of 103 isolates of foot-andmouth disease virus (FMDV) representing all seven serotypes and including the first complete sequences of the SAT1 and SAT3 genomes. The data reveal novel highly conserved genomic regions, indicating functional constraints for variability as well as novel viral genomic motifs with likely biological relevance. Previously undescribed invariant motifs were identified in the 5 � and 3 � untranslated regions (UTR), as was tolerance for insertions/deletions in the 5 � UTR. Fifty-eight percent of the amino acids encoded by FMDV isolates are invariant, suggesting that these residues are critical for virus biology. Novel, conserved sequence motifs with likely functional significance were identified within proteins L pro, 1B, 1D, and 3C. An analysis of the complete FMDV genomes indicated phylogenetic incongruities between different genomic regions which were suggestive of interserotypic recombination. Additionally, a novel SAT virus lineage containing nonstructural proteinencoding regions distinct from other SAT and Euroasiatic lineages was identified. Insights into viral RNA sequence conservation and variability and genetic diversity in nature will likely impact our understanding of FMDV infections, host range, and transmission. Foot-and-mouth disease (FMD) is an acute, systemic disease of domestic and wild cloven-hooved animal species and is
Predicting a set of minimal free energy RNA secondary structures common to two sequences
- Bioinformatics
, 2005
"... Function derives from structure; therefore there is need of methods for predicting functional RNA structures. Results: The Dynalign algorithm, which predicts the lowest free energy secondary structure common to two unaligned RNA sequences, is extended to the prediction of a set of low energy structu ..."
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Cited by 45 (6 self)
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Function derives from structure; therefore there is need of methods for predicting functional RNA structures. Results: The Dynalign algorithm, which predicts the lowest free energy secondary structure common to two unaligned RNA sequences, is extended to the prediction of a set of low energy structures. Dot plots can be drawn to show all base pairs in structures within an energy increment. Dynalign predicts more well-defined structures than structure prediction using a single sequence; in 5S rRNA sequences, the average number of base pairs in structures with energy within 20 % of the lowest energy structure is 317 using Dynalign, but 569 using a single sequence. Structure prediction with Dynalign can also be constrained according to experiment or comparative analysis. The accuracy, measured as sensitivity and positive predictive value, of Dynalign is greater than predictions with a single sequence. Availability: Dynalign can be downloaded at
The expansion of the metazoan microRNA repertoire
- The Students of Bioinformatics Computer Labs 2004 and 2005
, 2006
"... MicroRNAs have been identified as crucial regulators in both animals and plants. Here we report on a comprehensive comparative study of all known miRNA families in animals. We expand the MicroRNA Registry 6.0 by more than 1000 new homologs of miRNA precursors whose expression has been verified in at ..."
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Cited by 45 (3 self)
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MicroRNAs have been identified as crucial regulators in both animals and plants. Here we report on a comprehensive comparative study of all known miRNA families in animals. We expand the MicroRNA Registry 6.0 by more than 1000 new homologs of miRNA precursors whose expression has been verified in at least one species. Using this uniform data basis we analyze their evolutionary history in terms of individual gene phylogenies and in terms of preservation of genomic nearness across species. This allows us to reliably identify microRNA clusters that are derived from a common transcript. We identify three episodes of microRNA innovation that correspond to major developmental innovations: A class of about 20 miRNAs is common to protostomes and deuterostomes and might be related to the advent of bilaterians. A second large wave of innovations maps to the branch leading to the vertebrates. The third significant outburst of miRNA innovation coincides with placental (eutherian) mammals. In addition, we observe the expected expansion of the microRNA inventory due to genome duplications in early vertebrates and in an ancestral teleost. The non-local duplications in the vertebrate ancestor are predated by local (tandem) duplications leading to the formation of about a dozend ancient microRNA clusters.
Paradigms for computational nucleic acid design
- Nucleic Acids Res
"... The design of DNA and RNA sequences is critical for many endeavors, from DNA nanotechnology, to PCR-based applications, to DNA hybridization arrays. Results in the literature rely on a wide variety of design criteria adapted to the particular requirements of each application. Using an extensively-st ..."
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Cited by 44 (5 self)
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The design of DNA and RNA sequences is critical for many endeavors, from DNA nanotechnology, to PCR-based applications, to DNA hybridization arrays. Results in the literature rely on a wide variety of design criteria adapted to the particular requirements of each application. Using an extensively-studied thermodynamic model, we perform a detailed study of several criteria for designing sequences intended to adopt a target secondary structure. We conclude that superior design methods should explicitly implement both a positive design paradigm (optimize affinity for the target structure) and a negative design paradigm (optimize specificity for the target structure). The commonly used approaches of sequence symmetry minimization and minimum free energy satisfaction primarily implement negative design and can be strengthened by introducing a positive design component. Surprisingly, our findings hold for a wide range of secondary structures and are robust to modest perturbation of the thermodynamic parameters used for evaluating sequence quality, suggesting the feasibility and ongoing utility of a unified approach to nucleic acid design as parameter sets are further refined. Finally, we observe that designing for thermodynamic stability does not determine folding kinetics, emphasizing the opportunity for extending design criteria to target kinetic features of the energy landscape.
Correlation of mRNA expression and protein abundance affected by multiple sequence features related to translational efficiency in Desulfovibrio vulgaris: a quantitative analysis. Genetics
"... ABSTRACT The modest correlation between mRNA expression and protein abundance in large-scale data sets is explained in part by experimental challenges, such as technological limitations, and in part by fundamental biological factors in the transcription and translation processes. Among various fact ..."
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Cited by 36 (4 self)
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ABSTRACT The modest correlation between mRNA expression and protein abundance in large-scale data sets is explained in part by experimental challenges, such as technological limitations, and in part by fundamental biological factors in the transcription and translation processes. Among various factors affecting the mRNA-protein correlation, the roles of biological factors related to translation are poorly understood. In this study, using experimental mRNA expression and protein abundance data collected from Desulfovibrio vulgaris by DNA microarray and liquid chromatography coupled with tandem mass spectrometry (LC-MS/ MS) proteomic analysis, we quantitatively examined the effects of several translational-efficiency-related sequence features on mRNA-protein correlation. Three classes of sequence features were investigated according to different translational stages: (i) initiation, Shine-Dalgarno sequences, start codon identity, and start codon context; (ii) elongation, codon usage and amino acid usage; and (iii) termination, stop codon identity and stop codon context. Surprisingly, although it is widely accepted that translation initiation is the rate-limiting step for translation, our results showed that the mRNA-protein correlation was affected the most by the features at elongation stages, i.e., codon usage and amino acid composition (5.3-15.7% and 5.8-11.9% of the total variation of mRNA-protein correlation, respectively), followed by stop codon context and the Shine-Dalgarno sequence (3.7-5.1% and 1.9-3.8%, respectively). Taken together, all sequence features contributed to 15.2-26.2% of the total variation of mRNA-protein correlation. This study provides the first comprehensive quantitative analysis of the mRNA-protein correlation in bacterial D. vulgaris and adds new insights into the relative importance of various sequence features in prokaryotic protein translation.
P (2004) Efficient computation of RNA folding dynamics
- J Phys A: Math Gen
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MicroInspector: a web tool for detection of miRNA binding sites in an RNA sequence
- Nucleic Acids Res
, 2005
"... Regulationofpost-transcriptionalgeneexpressionby microRNAs (miRNA)hasso farbeenvalidated foronly a few mRNA targets. Based on the large number of miRNA genes and the possibility that one miRNA might influence gene expression of several targets simultaneously, the quantity of ribo-regulated genes is ..."
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Cited by 34 (0 self)
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Regulationofpost-transcriptionalgeneexpressionby microRNAs (miRNA)hasso farbeenvalidated foronly a few mRNA targets. Based on the large number of miRNA genes and the possibility that one miRNA might influence gene expression of several targets simultaneously, the quantity of ribo-regulated genes is expected to be much higher. Here, we describe the web tool MicroInspector that will analyse a user-defined RNA sequence, which is typically an mRNA or a part of an mRNA, for the occurrence of binding sites for known and registeredmiRNAs. The program allows variation of temperature, the setting of energy values as well as the selection of different miRNA databases to identifymiRNA-bindingsitesof different strength.MicroInspector could spot the correct sites for miRNA-interaction in known target mRNAs. Using other mRNAs, for which such an interaction has not yet been described, we discovered frequently poten-tial miRNA binding sites of similar quality, which can now be analysed experimentally. TheMicroInspector program is easy to use and does not require specific computer skills. The service can be accessed via the MicroInspector web server at
Evolutionary conservation of sequence and secondary structures in CRISPR repeats
- Genome Biol
, 2007
"... The electronic version of this article is the complete one and can be ..."
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Cited by 33 (0 self)
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The electronic version of this article is the complete one and can be
