SUMMARY: We present the cpPredictor webserver that implements a novel template-based method for prediction of secondary structure of RNA. The method outperforms available prediction methods as it uses RNA structures of related molecules, either predicted or experimentally identified, as structural templates. The server aims at three major tasks: i) prediction of RNA secondary structures that are difficult to predict by available methods, ii) characterization of uncharacterized RNAs as compatible or incompatible with a chosen template structure and iii) an identification of the most relevant structure among different candidate structures of a single RNA ambiguously predicted by available methods. The web server is accompanied with a comprehensive documentation. AVAILABILITY AND IMPLEMENTATION: The web server is freely available at http://cppredictor.elixir-czech.cz/. The source code of the cpPredictor algorithm is freely available from the webserver under the Apache License, Version 2.0.
BACKGROUND: Visualization of RNA secondary structures is a complex task, and, especially in the case of large RNA structures where the expected layout is largely habitual, the existing visualization tools often fail to produce suitable visualizations. This led us to the idea to use existing layouts as templates for the visualization of new RNAs similarly to how templates are used in homology-based structure prediction. RESULTS: This article introduces Traveler, a software tool enabling visualization of a target RNA secondary structure using an existing layout of a sufficiently similar RNA structure as a template. Traveler is based on an algorithm which converts the target and template structures into corresponding tree representations and utilizes tree edit distance coupled with layout modification operations to transform the template layout into the target one. Traveler thus accepts a pair of secondary structures and a template layout and outputs a layout for the target structure. CONCLUSIONS: Traveler is a command-line open source tool able to quickly generate layouts for even the largest RNA structures in the presence of a sufficiently similar layout. It is available at http://github.com/davidhoksza/traveler .
- MeSH
- Algorithms MeSH
- Nucleic Acid Conformation MeSH
- RNA chemistry MeSH
- Software * MeSH
- Publication type
- Journal Article MeSH
Non-coding RNAs (ncRNA) are essential for all life, and their functions often depend on their secondary (2D) and tertiary structure. Despite the abundance of software for the visualisation of ncRNAs, few automatically generate consistent and recognisable 2D layouts, which makes it challenging for users to construct, compare and analyse structures. Here, we present R2DT, a method for predicting and visualising a wide range of RNA structures in standardised layouts. R2DT is based on a library of 3,647 templates representing the majority of known structured RNAs. R2DT has been applied to ncRNA sequences from the RNAcentral database and produced >13 million diagrams, creating the world's largest RNA 2D structure dataset. The software is amenable to community expansion, and is freely available at https://github.com/rnacentral/R2DT and a web server is found at https://rnacentral.org/r2dt .
- MeSH
- Databases, Nucleic Acid MeSH
- Nucleic Acid Conformation MeSH
- RNA, Untranslated chemistry MeSH
- Reproducibility of Results MeSH
- RNA chemistry MeSH
- Sequence Analysis, RNA MeSH
- Software MeSH
- Computational Biology methods MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Intramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
The protein sequences found in nature represent a tiny fraction of the potential sequences that could be constructed from the 20-amino-acid alphabet. To help define the properties that shaped proteins to stand out from the space of possible alternatives, we conducted a systematic computational and experimental exploration of random (unevolved) sequences in comparison with biological proteins. In our study, combinations of secondary structure, disorder, and aggregation predictions are accompanied by experimental characterization of selected proteins. We found that the overall secondary structure and physicochemical properties of random and biological sequences are very similar. Moreover, random sequences can be well-tolerated by living cells. Contrary to early hypotheses about the toxicity of random and disordered proteins, we found that random sequences with high disorder have low aggregation propensity (unlike random sequences with high structural content) and were particularly well-tolerated. This direct structure content/aggregation propensity dependence differentiates random and biological proteins. Our study indicates that while random sequences can be both structured and disordered, the properties of the latter make them better suited as progenitors (in both in vivo and in vitro settings) for further evolution of complex, soluble, three-dimensional scaffolds that can perform specific biochemical tasks.
- MeSH
- Circular Dichroism MeSH
- Databases, Protein MeSH
- Datasets as Topic MeSH
- Models, Molecular * MeSH
- Nuclear Magnetic Resonance, Biomolecular MeSH
- Peptide Library * MeSH
- Protein Aggregates MeSH
- Recombinant Proteins chemistry isolation & purification toxicity MeSH
- Solubility MeSH
- Protein Folding MeSH
- Protein Structure, Secondary * MeSH
- Amino Acid Sequence MeSH
- Computational Biology MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Cyphellophora and Phialophora (Chaetothyriales, Pezizomycota) comprise species known from skin infections of humans and animals and from a variety of environmental sources. These fungi were studied based on the comparison of cultural and morphological features and phylogenetic analyses of five nuclear loci, i.e., internal transcribed spacer rDNA operon (ITS), large and small subunit nuclear ribosomal DNA (nuc28S rDNA, nuc18S rDNA), β-tubulin, DNA replication licensing factor (mcm7) and second largest subunit of RNA polymerase II (rpb2). Phylogenetic results were supported by comparative analysis of ITS1 and ITS2 secondary structure of representatives of the Chaetothyriales and the identification of substitutions among the taxa analyzed. Base pairs with non-conserved, co-evolving nucleotides that maintain base pairing in the RNA transcript and unique evolutionary motifs in the ITS2 that characterize whole clades or individual taxa were mapped on predicted secondary structure models. Morphological characteristics, structural data and phylogenetic analyses of three datasets, i.e., ITS, ITS-β-tubulin and 28S-18S-rpb2-mcm7, define a robust clade containing eight species of Cyphellophora (including the type) and six species of Phialophora. These taxa are now accommodated in the Cyphellophoraceae, a novel evolutionary lineage within the Chaetothyriales. Cyphellophora is emended and expanded to encompass species with both septate and nonseptate conidia formed on discrete, intercalary, terminal or lateral phialides. Six new combinations in Cyphellophora are proposed and a dichotomous key to species accepted in the genus is provided. Cyphellophora eugeniae and C. hylomeconis, which grouped in the Chaetothyriaceae, represent another novel lineage and are introduced as the type species of separate genera.
- MeSH
- Ascomycota genetics MeSH
- Phylogeny * MeSH
- Genetic Loci genetics MeSH
- Genes, Fungal genetics MeSH
- Nucleic Acid Conformation * MeSH
- Consensus Sequence MeSH
- DNA, Ribosomal Spacer chemistry genetics MeSH
- Evolution, Molecular * MeSH
- Molecular Sequence Data MeSH
- Nucleotide Motifs genetics MeSH
- RNA, Ribosomal chemistry genetics MeSH
- Base Sequence MeSH
- Spores, Fungal cytology MeSH
- Tubulin genetics MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
Secondary data structure of RNA molecules provides insights into the identity and function of RNAs. With RNAs readily sequenced, the question of their structural characterization is increasingly important. However, RNA structure is difficult to acquire. Its experimental identification is extremely technically demanding, while computational prediction is not accurate enough, especially for large structures of long sequences. We address this difficult situation with rPredictorDB, a predictive database of RNA secondary structures that aims to form a middle ground between experimentally identified structures in PDB and predicted consensus secondary structures in Rfam. The database contains individual secondary structures predicted using a tool for template-based prediction of RNA secondary structure for the homologs of the RNA families with at least one homolog with experimentally solved structure. Experimentally identified structures are used as the structural templates and thus the prediction has higher reliability than de novo predictions in Rfam. The sequences are downloaded from public resources. So far rPredictorDB covers 7365 RNAs with their secondary structures. Plots of the secondary structures use the Traveler package for readable display of RNAs with long sequences and complex structures, such as ribosomal RNAs. The RNAs in the output of rPredictorDB are extensively annotated and can be viewed, browsed, searched and downloaded according to taxonomic, sequence and structure data. Additionally, structure of user-provided sequences can be predicted using the templates stored in rPredictorDB.
Higher order RNA structures can mask splicing signals, loop out exons, or constitute riboswitches all of which contributes to the complexity of splicing regulation. We identified a G to A substitution between branch point (BP) and 3' splice site (3'ss) of Saccharomyces cerevisiae COF1 intron, which dramatically impaired its splicing. RNA structure prediction and in-line probing showed that this mutation disrupted a stem in the BP-3'ss region. Analyses of various COF1 intron modifications revealed that the secondary structure brought about the reduction of BP to 3'ss distance and masked potential 3'ss. We demonstrated the same structural requisite for the splicing of UBC13 intron. Moreover, RNAfold predicted stable structures for almost all distant BP introns in S. cerevisiae and for selected examples in several other Saccharomycotina species. The employment of intramolecular structure to localize 3'ss for the second splicing step suggests the existence of pre-mRNA structure-based mechanism of 3'ss recognition.
- MeSH
- Ascomycota genetics MeSH
- RNA, Fungal chemistry MeSH
- Introns MeSH
- Cofilin 1 genetics MeSH
- Nucleic Acid Conformation MeSH
- RNA Splice Sites MeSH
- Molecular Sequence Data MeSH
- Saccharomyces cerevisiae Proteins genetics MeSH
- Saccharomyces cerevisiae genetics MeSH
- Base Sequence MeSH
- RNA Splicing MeSH
- Temperature MeSH
- Ubiquitin-Conjugating Enzymes genetics MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Úvod: Peritonitida patří mezi život ohrožující stavy zatížené vysokou mortalitou a morbiditou. Prognóza závisí na faktorech spojených s pacientem, charakterem onemocnění, použitými diagnostickými a terapeutickými metodami. Cílem práce bylo retrospektivně analyzovat soubor pacientů se sekundární peritonitidou, z tohoto souboru porovnat skupiny pacientů bez sterkorální peritonitidy a se sterkorální peritonitidou, stanovit hodnotu indexu prognostického systému MPI a zjistit, nakolik se shoduje s našimi výsledky. Metoda: Za období dvou let (2012–2013) byla analyzována data 124 pacientů operovaných s nálezem sekundární peritonitidy. Soubor byl rozdělen podle typu peritonitidy na skupinu A s jinou než sterkorální a skupinu B se sterkorální peritonitidou. Tyto skupiny byly dále porovnávány. Predikce mortality byla ověřena pomocí Mannheim Peritonitis Index (MPI). Výsledky: V celém souboru 124 operovaných pacientů bylo celkem 70 mužů a 54 žen. Průměrný věk pacientů byl 63 let, průměrná délka hospitalizace 18 dní, během hospitalizace zemřelo 18 pacientů (15 %). Průměrná hodnota MPI skóre byla 19, což odpovídá predikci mortality 18 %. Ve skupině A 68 pacientů bez sterkorální peritonitidy byl průměrný věk 59 let, průměrná délka hospitalizace 12 dní. Z této skupiny zemřeli během hospitalizace 2 pacienti (3 %). Průměrná hodnota MPI skóre byla 9, což odpovídá predikci mortality 9 %. Ve skupině B 56 pacientů se sterkorální peritonitidou byl průměrný věk 67 let, průměrná délka hospitalizace 25 dní. Z této skupiny během hospitalizace zemřelo 16 pacientů (29 %). Průměrná hodnota MPI skóre byla 29, což odpovídá predikci mortality 31 % pro tuto skupinu pacientů. Závěr: Z porovnání obou skupin vyplývá, že u skupiny bez sterkorální peritonitidy je podstatně nižší mortalita, menší počet komplikací a kratší délka hospitalizace než u skupiny se sterkorální peritonitidou. K predikci mortality u peritonitidy lze použít základních klinických dat, stejně jako sofistikovaných skórovacích systémů. V naší studii se osvědčil jednoduchý skórovací systém Mannheim Peritonitis Index.
Introduction: Peritonitis is a life-threatening disease with high mortality and morbidity. The prognosis depends on patient factors, the nature of the disease, and on diagnostic and therapeutic methods. The goal of our study was to perform a retrospective analysis of a group of patients with secondary peritonitis and to compare patients with non-stercoral peritonitis and those with stercoral peritonitis, and finally, to determine the prognostic value of the MPI prognostic index. Methods: We analysed 124 patients who had undergone surgery for secondary peritonitis during the years 2012–2013. We divided the patients into two groups. Group A comprised patients with non-stercoral peritonitis and group B consisted of patients with stercoral peritonitis. We compared the two groups and predicted the peritonitis outcome using the Mannheim Peritonitis Index (MPI). Results: The complete sample of 124 patients consisted of 70 men and 54 women. The average age of the patients was 63 years and the average length of hospitalization was 18 days. In total, 18 patients (15%) died during their hospitalization. The average MPI score was 19, which correlates to an 18% mortality rate prediction. In group A, which consisted of 68 patients with non-stercoral peritonitis, the average age was 59 years and the average length of hospitalization was 12 days. Two patients (3%) from this group died during hospitalization. The average MPI score was 9, which correlates to a 9% mortality rate prediction. In group B, which consisted of 56 patients with stercoral peritonitis, the average age was 67 years and the average length of hospitalization was 25 days. 16 patients (29%) from this group died during hospitalization. The average MPI score was 29, which correlates to a 31% mortality rate prediction. Conclusions: The outcome of our comparison between the two groups is that group A with non-stercoral peritonitis had a significantly lower mortality, lower number of complications and a shorter length of hospitalization. Both basic clinical data and sophisticated scoring systems can be used for mortality prediction in peritonitis. The Mannheim Peritonitis Index, a simple scoring system, proved to be useful in our study.
- MeSH
- Surgical Procedures, Operative utilization MeSH
- Hospitalization MeSH
- Middle Aged MeSH
- Humans MeSH
- Peritonitis * etiology surgery mortality therapy MeSH
- Postoperative Complications MeSH
- Prognosis MeSH
- Risk Factors MeSH
- Aged MeSH
- Statistics as Topic MeSH
- Outcome and Process Assessment, Health Care MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
