CrossLink: visualization and exploration of sequence relationships between (micro) RNAs

CrossLink is a versatile tool for the exploration of relationships between RNA sequences. After a parametrization phase, CrossLink delegates the determination of sequence relationships to established tools (BLAST, Vmatch and RNAhybrid) and then constructs a network. Each node in this network represents a sequence and each link represents a match or a set of matches. Match attributes are reflected by graphical attributes of the links and corresponding alignments are displayed on a mouse-click. The distributions of match attributes such as E-value, match length and proportion of identical nucleotides are displayed as histograms. Sequence sets can be highlighted and visibility of designated matches can be suppressed by real-time adjustable thresholds for attribute combinations. Powerful network layout operations (such as spring-embedding algorithms) and navigation capabilities complete the exploration features of this tool. CrossLink can be especially useful in a microRNA context since Vmatch and RNAhybrid are suitable tools for determining the antisense and hybridization relationships, which are decisive for the interaction between microRNAs and their targets. CrossLink is available both online and as a standalone version at

Dendroscope: An interactive viewer for large phylogenetic trees

<p>Abstract</p> <p>Background</p> <p>Research in evolution requires software for visualizing and editing phylogenetic trees, for increasingly very large datasets, such as arise in expression analysis or metagenomics, for example. It would be desirable to have a program that provides these services in an effcient and user-friendly way, and that can be easily installed and run on all major operating systems. Although a large number of tree visualization tools are freely available, some as a part of more comprehensive analysis packages, all have drawbacks in one or more domains. They either lack some of the standard tree visualization techniques or basic graphics and editing features, or they are restricted to small trees containing only tens of thousands of taxa. Moreover, many programs are diffcult to install or are not available for all common operating systems.</p> <p>Results</p> <p>We have developed a new program, Dendroscope, for the interactive visualization and navigation of phylogenetic trees. The program provides all standard tree visualizations and is optimized to run interactively on trees containing hundreds of thousands of taxa. The program provides tree editing and graphics export capabilities. To support the inspection of large trees, Dendroscope offers a magnification tool. The software is written in Java 1.4 and installers are provided for Linux/Unix, MacOS X and Windows XP.</p> <p>Conclusion</p> <p>Dendroscope is a user-friendly program for visualizing and navigating phylogenetic trees, for both small and large datasets.</p

Vorhersage von MicroRNAs in Pflanzen

In allen Lebewesen wird der in Genen kodierte Bauplan von der Zellmaschinerie mit Hilfe von RNA in Proteine übersetzt. Erst Anfang dieses Jahrtausends wurde entdeckt, dass bei diesem Prozess in höheren Lebewesen wie Tieren und Pflanzen einer bislang unbekannten Klasse von RNA Molekülen eine entscheidende regulatorische Rolle zukommt. Gegenstand dieser Arbeit sind die sogenannten microRNA Gene, welche keine Proteine kodieren, sondern bereits auf RNA Ebene ihre Wirkung auf andere Transkripte entfalten. In diesem Rahmen wurden mehrere bioinformatischeWerkzeuge konzipiert. Eines davon erlaubt es, neue microRNA Gene durch den Vergleich zweier Pflanzengenome aufzuspüren. Dies wurde auf die Genome von Arabidopsis thaliana und Pappel, sowie von Reis und Hirse angewandt. Die resultierenden Gen-Kandidaten wurden dann in enger Zusammenarbeit von molekularbiologischen Kooperationspartnern in vitro und in vivo näher untersucht. Eine weitere, universell einsetzbare Software ermöglicht dem Benutzer die Visualisierung und interaktive Erforschung zweier beliebiger RNA Sequenzmengen und ist insbesondere nützlich bei der Anwendung auf microRNAs. Die Idee für eine andere Anwendung entstand durch die Verfügbarkeit der Ergebnisse einer neuen Sequenziertechnologie für die Signaturen kleiner RNAs. Diese dienten als Informationsquelle für eine Methode, um auf deren Basis neue microRNAs in Arabidopsis vorherzusagen, die dann auch erfolgreich von Kooperationspartnern biologisch verifiziert werden konnten. Ferner wurde ein simples Programm entwickelt, welches ausgehend von einer bekannten microRNA dessen Homologe in nahezu beliebigen Sequenzdaten mit hoher Sensitivität und Spezifizität detektieren kann. Dieses wurde genutzt, um ausgehend von den 286 beim Sanger Institut registrierten pflanzlichen microRNAs weitere 200 Homologe in verschiedenen Pflanzen zu identifizieren. Diese vergrösserte Datenbasis diente schliesslich als Ausgangsbasis für eine Überblicksarbeit über Konservierung und Divergenz von microRNAs in Pflanzen.The blueprint stored in the genes of each living creature is translated into proteins via RNA. But it was not until the beginning of this millennium that a class of small RNAs was discovered that performs crucial regulatory roles during this process in higher organisms such as animals and plants. The focus of this thesis are the so–called “microRNAs”--gene products which do not code for proteins but instead have a regulatory impact on other transcripts at the RNA level. In this context, several computational biology tools were designed and implemented. One of them permits the identification of new microRNA genes by comparing two plant genomes. It was applied to the genomes of Arabidopsis and poplar, as well as to rice and sorghum. The resulting gene candidates were then analyzed experimentally by a collaboration of molecular biologists. Another, universally applicable software allows the user to visualize and interactively explore two arbitrary RNA sequence sets and is especially useful in the context of microRNAs. The idea for a further application was spawned by the availability of the small RNA signatures resulting from a new sequencing technology. These signatures served as the basis on which we could predict new microRNAs--some of which could afterwards be validated by experimental collaboration. In addition, we developed a simple program that can--given a known microRNA--identify its homologs in almost arbitrary sequence data with high sensitivity and specificity. When this tool was supplied with the 286 microRNAs registered at the Sanger institute, an additional 200 homologs could be found across different plants. Eventually, this enlarged data set served as the basis for a survey article on conservation and divergence of microRNAs in plants

Evolution of Arabidopsis thaliana microRNAs from random sequences

One mechanism for the origin of new plant microRNAs (miRNAs) is from inverted duplications of transcribed genes. However, even though many young MIRNA genes have recently been identified in Arabidopsis thaliana, only a subset shows evidence for having evolved by this route. We propose that the hundreds of thousands of partially self-complementary foldback sequences found in a typical plant genome provide an alternative path for miRNA evolution. Our genome-wide analyses of young MIRNA genes suggest that some arose from DNA that either has self-complementarity by chance or that represents a highly eroded inverted duplication. These observations are compatible with the idea that, following capture of transcriptional regulatory sequences, random foldbacks can occasionally spawn new miRNAs. Subsequent stabilization through coevolution with initially fortuitous targets may lead to fixation of a small subset of these proto-miRNA genes. Published by Cold Spring Harbor Laboratory Press.</p