Yanga Byun

PseudoViewer3: generating planar drawings of large-scale RNA structures with pseudoknots.

MOTIVATION Pseudoknots in RNA structures make visualization of RNA structures difficult. Even if a pseudoknot itself is represented without a crossing, visualization of the entire RNA structure with a pseudoknot often results in a drawing with crossings between the pseudoknot and other structural elements, and requires additional intervention by the user to ensure that the structure graph is overlap-free. Many programs such as web services prefer to obtain an overlap-free graph in one-shot rather than get a graph with overlaps to be edited. There are few programs for visualizing RNA pseudoknots, and PseudoViewer has been the almost only program that automatically draws RNA secondary structures with pseudoknots. The previous version of PseudoViewer visualizes all the known types of RNA pseudoknots as planar drawings, but visualizes some hypothetical pseudoknots as non-planar drawings. RESULTS We developed a new version of PseudoViewer for efficiently visualizing large RNA structures with any types of pseudoknots, both known and hypothetical, as planar drawings in one-shot. It is about 10 times faster than the previous algorithm, and produces a more compact and aesthetic structure drawing. PseudoViewer3 supports both web services and web applications. AVAILABILITY The new version of PseudoViewer, PseudoViewer3, is available at (http://pseudoviewer.inha.ac.kr).

PseudoViewer: web application and web service for visualizing RNA pseudoknots and secondary structures

Visualizing RNA secondary structures and pseudoknot structures is essential to bioinformatics systems that deal with RNA structures. However, many bioinformatics systems use heterogeneous data structures and incompatible software components, so integration of software components (including a visualization component) into a system can be hindered by incompatibilities between the components of the system. This paper presents an XML web service and web application program for visualizing RNA secondary structures with pseudoknots. Experimental results show that the PseudoViewer web service and web application are useful for resolving many problems with incompatible software components as well as for visualizing large-scale RNA secondary structures with pseudoknots of any type. The web service and web application are available at .

PSEUDOVIEWER2: Visualization of RNA pseudoknots of any type.

Visualizing RNA pseudoknot structures is computationally more difficult than depicting RNA secondary structures, because a drawing of a pseudoknot structure is a graph (and possibly a nonplanar graph) with inner cycles within the pseudoknot, and possibly outer cycles formed between the pseudoknot and other structural elements. We previously developed PSEUDOVIEWER for visualizing H-type pseudoknots. PSEUDOVIEWER2 improves on the first version in many ways: (i) PSEUDOVIEWER2 is more general because it can visualize a pseudoknot of any type, including H-type pseudoknots, as a planar graph; (ii) PSEUDOVIEWER2 computes a drawing of RNA structures much more efficiently and is an order of magnitude faster in actual running time; and (iii) PSEUDOVIEWER2 is a web-based application program. Experimental results demonstrate that PSEUDOVIEWER2 generates an aesthetically pleasing drawing of pseudoknots of any type and that the new representation offered by PSEUDOVIEWER2 ensures uniform and clear drawings, with no edge crossing, for all types of pseudoknots. The PSEUDOVIEWER2 algorithm is the first developed for the automatic drawing of RNA secondary structures, including pseudoknots of any type. PSEUDOVIEWER2 is accessible at http://wilab.inha.ac.kr/pseudoviewer2/.

Database note: FSDB: A frameshift signal database

Abstract Programmed frameshifting is a recoding event in which a ribosome shifts reading frame by one or more nucleotides at a specific mRNA signal between overlapping genes. Programmed frameshifting is involved in the expression of many genes in a wide range of organisms, especially in viruses and bacteria. The mechanism of programmed frameshifting is not fully understood despite many studies, and there are few databases available for detailed information on programmed frameshifting. We have developed a database called FSDB (Frameshift Signal Database), which is a comprehensive compilation of experimentally known or computationally predicted data about programmed ribosomal frameshifting. FSDB provides a graphical view of frameshift signals and the genes using programmed frameshifting for their expression. It also allows the user himself/herself to find programmed frameshift sites in genomic sequences using a program called FSFinder (http://wilab.inha.ac.kr/fsfinder2). We believe FSDB will be a valuable resource for scientists studying programmed ribosomal frameshifting. FSDB is freely accessible at http://wilab.inha.ac.kr/fsdb/.

Predicting RNA-Binding Sites in Proteins Using the Interaction Propensity of Amino Acid Triplets

In protein-RNA interactions, amino acids often exhibit different preferences for its RNA partners with different neighbor amino acids. Hence, the interaction propensity of an amino acid can be better assessed by considering neighbors of the amino acid than examining the amino acid alone. In this study, we computed the interaction propensity of three consecutive amino acids (called amino acid triplet or triple amino acids) from the rigorous analysis of the recent structure data of protein-RNA complexes. We used the interaction propensity to predict RNA-binding sites in protein sequences with a support vector machine (SVM) classifier, and observed that the interaction propensities of amino acid triplets are more effective than other biochemical properties of amino acids for predicting RNA-binding sites in proteins. Experimental results with non-redundant 134 protein sequences showed that the SVM classifier achieved a sensitivity of 77% and specificity of 76% and that the three-residue interaction propensity resulted in a better performance than single- or five-residue interaction propensities. Comparison of the SVM classifier with RNABindR and BindN demonstrated that it outperforms the other two methods in the net prediction and correlation coefficient. Our SVM classifier can also be used to predict protein-binding nucleotides in RNA sequences.

Three-dimensional visualization of protein interaction networks

Protein interaction networks provide us with contextual information within which protein function can be interpreted and will assist many biomedical studies. We have developed a new force-directed layout algorithm for visualizing protein interactions in three-dimensional space. Our algorithm divides nodes into three groups based on their interacting properties: bi-connected sub-graph in the center, terminal nodes at the outermost region, and the rest in between them. Experimental results show that our algorithm efficiently generates a clear and aesthetically pleasing drawing of large-scale protein interaction networks and that it is an order of magnitude faster than other force-directed layouts.

Computational Identification of -1 Frameshift Signals

Ribosomal frameshifts in the -1 direction are used frequently by RNA viruses to synthesize a single fusion protein from two or more overlapping open reading frames. The slippery heptamer sequence XXX YYY Z is the best recognized of the signals that promote -1 frameshifting. We have developed an algorithm that predicts plausible -1 frameshift signals in long DNA sequences. Our algorithm is implemented in a working program called FSFinder (Frameshift Signal Finder). We tested FSFinder on 72 genomic sequences from a number of organisms and found that FSFinder predicts -1 frameshift signals efficiently and with greater sensitivity and selectivity than existing approaches. Sensitivity is improved by considering all potentially relevant components of frameshift signals, and selectivity is increased by focusing on overlapping regions of open reading frames and by prioritizing candidate frameshift signals. FSFinder is useful for analyzing -1 frameshift signals as well as discovering unknown genes.

Visualization of protein-protein interaction networks using force-directed layout

Protein interactions, when visualized as an undirected graph, often yield a nonplanar, disconnected graph with nodes of wide range of degrees. Many graph-drawing programs are of limited use in visualizing protein interactions, either because they are too slow, or because they produce a cluttered drawing with many edge crossings or a static drawing that is not easy to modify to reflect changes in data. We have developed a new force-directed layout algorithm for drawing protein interactions in three-dimensional space. Our algorithm divides nodes into three groups based on their interacting properties: biconnected subgraph in the center, terminal nodes at the outermost region, and the rest in between them. Experimental results show that our algorithm efficiently generates a clear and aesthetically pleasing drawing of large-scale protein interaction networks and that it is much faster than other force-directed layouts.

An efficient algorithm for planar drawing of RNA structures with pseudoknots of any type

An RNA pseudoknot is a tertiary structural element in which bases of a loop pair with complementary bases are outside the loop. A drawing of RNA secondary structures is a tree, but a drawing of RNA pseudoknots is a graph that has an inner cycle within a pseudoknot and possibly outer cycles formed between the pseudoknot and other structural elements. Visualizing a large-scale RNA structure with pseudoknots as a planar drawing is challenging because a planar drawing of an RNA structure requires both pseudoknots and an entire structure enclosing the pseudoknots to be embedded into a plane without overlapping or crossing. This paper presents an efficient heuristic algorithm for visualizing a pseudoknotted RNA structure as a planar drawing. The algorithm consists of several parts for finding crossing stems and page mapping the stems, for the layout of stem-loops and pseudoknots, and for overlap detection between structural elements and resolving it. Unlike previous algorithms, our algorithm generates a planar drawing for a large RNA structure with pseudoknots of any type and provides a bracket view of the structure. It generates a compact and aesthetic structure graph for a large pseudoknotted RNA structure in O([Formula: see text]) time, where n is the number of stems of the RNA structure.

Web service for finding ribosomal frameshifts

Recent advances in biomedical research have generated a huge amount of data and software to deal with the data. Many biomedical systems use heterogeneous data structures and incompatible software components, so integration of software components into a system can be hindered by incompatibilities between the components of the system. This paper presents an XML web service and web application program for predicting ribosomal frameshifts from genomic sequences. Experimental results show that the web service of the program is useful for resolving many problems with incompatible software components as well as for predicting frameshifts of diverse types. The web service is available at http://wilab.inha.ac.kr/fsfinder2.