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caBIONet--A .NET wrapper to access and process genomic data stored at the National Cancer Institute's Center for Bioinformatics databases.

MOTIVATION: The National Cancer Institute's Center for Bioinformatics (NCICB) has developed a Java based data management and information system called caCORE. One component of this software suite is the object oriented API (caBIO) used to access the rich biological datasets collected at the NCI. This API can access the data using native Java classes, SOAP requests or HTTP calls. Non-Java based clients wanting to use this API have to use the SOAP or HTTP interfaces with the data being returned from the NCI servers as an XML data stream. Although the XML can be read and manipulated using DOM or SAX parsers, one loses the convenience and usability of an object oriented programming paradigm. caBIONet is a set of .NET wrapper classes (managers, genes, chromosomes, sequences, etc.) capable of serializing the XML data stream into local .NET objects. The software is able to search NCICB databases and provide local objects representing the data that can be manipulated and used by other .NET programs. The software was written in C# and compiled as a .NET DLL.

Chromosome Mapping↗

Friend, an integrated analytical front-end application for bioinformatics.

UNLABELLED: Friend is a bioinformatics application designed for simultaneous analysis and visualization of multiple structures and sequences of proteins and/or DNA/RNA. The application provides basic functionalities, such as structure visualization, with different rendering and coloring, sequence alignment and simple phylogeny analysis, along with a number of extended features to perform more complex analyses of sequence structure relationships, including structural alignment of proteins, investigation of specific interaction motifs, studies of protein-protein and protein-DNA interactions and protein super-families. It is also useful for functional annotation of proteins, protein modeling and protein folding studies. Friend provides three levels of usage: (1) an extensive GUI for a scientist with no programming experience, (2) a command line interface for scripting for a scientist with some programming experience and (3) the ability to extend Friend with user written libraries for an experienced programmer. The application is linked and communicates with local and remote sequence and structure databases. AVAILABILITY: http://mozart.bio.neu.edu/friend.

Computational Biology↗

Bioinformatic analysis of exon repetition, exon scrambling and trans-splicing in humans.

MOTIVATION: Using bioinformatic approaches we aimed to characterize poorly understood abnormalities in splicing known as exon scrambling, exon repetition and trans-splicing. RESULTS: We developed a software package that allows large-scale comparison of all human expressed sequence tags (EST) sequences to the entire set of human gene sequences. Among 5,992,495 EST sequences, 401 cases of exon repetition and 416 cases of exon scrambling were found. The vast majority of identified ESTs contain fragments rather than full-length repeated or scrambled exons. Their structures suggest that the scrambled or repeated exon fragments may have arisen in the process of cDNA cloning and not from splicing abnormalities. Nevertheless, we found 11 cases of full-length exon repetition showing that this phenomenon is real yet very rare. In searching for examples of trans-splicing, we looked only at reproducible events where at least two independent ESTs represent the same putative trans-splicing event. We found 15 ESTs representing five types of putative trans-splicing. However, all 15 cases were derived from human malignant tissues and could have resulted from genomic rearrangements. Our results provide support for a very rare but physiological occurrence of exon repetition, but suggest that apparent exon scrambling and trans-splicing result, respectively, from in vitro artifact and gene-level abnormalities. AVAILABILITY: Exon-Intron Database (EID) is available at http://www.meduohio.edu/bioinfo/eid. Programs are available at http://www.meduohio.edu/bioinfo/software.html. The Laboratory website is available at http://www.meduohio.edu/medicine/fedorov SUPPLEMENTARY INFORMATION: Supplementary file is available at http://www.meduohio.edu/bioinfo/software.html.

Algorithms↗

Functional bioinformatics for Arabidopsis thaliana.

MOTIVATION: The genome of Arabidopsis thaliana, which has the best understood plant genome, still has approximately one-third of its genes with no functional annotation at all from either MIPS or TAIR. We have applied our Data Mining Prediction (DMP) method to the problem of predicting the functional classes of these protein sequences. This method is based on using a hybrid machine-learning/data-mining method to identify patterns in the bioinformatic data about sequences that are predictive of function. We use data about sequence, predicted secondary structure, predicted structural domain, InterPro patterns, sequence similarity profile and expressions data. RESULTS: We predicted the functional class of a high percentage of the Arabidopsis genes with currently unknown function. These predictions are interpretable and have good test accuracies. We describe in detail seven of the rules produced.

Algorithms↗

Structural bioinformatics of DNA: a web-based tool for the analysis of molecular dynamics results and structure prediction.

UNLABELLED: We report here the release of a web-based tool (MDDNA) to study and model the fine structural details of DNA on the basis of data extracted from a set of molecular dynamics (MD) trajectories of DNA sequences involving all the unique tetranucleotides. The dynamic web interface can be employed to analyze the first neighbor sequence context effects on the 10 unique dinucleotide steps of DNA. Functionality is included to build all atom models of any user-defined sequence based on the MD results. The backend of this interface is a relational database storing the conformational details of DNA obtained in 39 different MD simulation trajectories comprising all the 136 unique tetranucleotide steps. Examples of the use of this data to predict DNA structures are included. AVAILABILITY: http://humphry.chem.wesleyan.edu:8080/MDDNA. SUPPLEMENTARY INFORMATION: Supplementary data including color figures are available at Bioinformatics online.

Base Sequence↗

A bioinformatics analysis of protein tyrosine phosphatases in humans.

Protein tyrosine phosphatases (PTPs) cooperate with protein tyrosine kinases to regulate signal transduction pathways. Genome-wide surveys cataloging protein tyrosine phosphatases in humans have recently been carried out. Here, we present a bioinformatics analysis of protein tyrosine phosphatases in the human genome to examine their domain architecture, alternative splicing and pseudogenes. We present evidence that alternative transcripts exist for 25 out of 35 PTPs analyzed. These alternative transcripts include novel exons; skipped exons as well as cryptic donor/acceptor splice sites. We discovered a novel isoform of PTPN18 based on analysis of expressed sequence tags (ESTs). The deletion of 4 exons in the catalytic domain of the novel isoform may alter the enzymatic activity toward its substrates. We were able to experimentally validate 2 of our novel isoform predictions through RT-PCR. Finally, a user-friendly web-based resource that consolidates the gene and protein annotations for all human protein tyrosine phosphatases has been developed and is freely available at http://ptpr.ibioinformatics.org.

Alternative Splicing↗

Genetic and bioinformatic analysis of 41C and the 2R heterochromatin of Drosophila melanogaster: a window on the heterochromatin-euchromatin junction.

Genomic sequences provide powerful new tools in genetic analysis, making it possible to combine classical genetics with genomics to characterize the genes in a particular chromosome region. These approaches have been applied successfully to the euchromatin, but analysis of the heterochromatin has lagged somewhat behind. We describe a combined genetic and bioinformatics approach to the base of the right arm of the Drosophila melanogaster second chromosome, at the boundary between pericentric heterochromatin and euchromatin. We used resources provided by the genome project to derive a physical map of the region, examine gene density, and estimate the number of potential genes. We also carried out a large-scale genetic screen for lethal mutations in the region. We identified new alleles of the known essential genes and also identified mutations in 21 novel loci. Fourteen complementation groups map proximal to the assembled sequence. We used PCR to map the endpoints of several deficiencies and used the same set of deficiencies to order the essential genes, correlating the genetic and physical map. This allowed us to assign two of the complementation groups to particular "computed/curated genes" (CGs), one of which is Nipped-A, which our evidence suggests encodes Drosophila Tra1/TRRAP.

Animals↗

Bioinformatics as a critical prerequisite to transcriptome and proteome studies.

Large-scale genomic studies rely strongly on annotations available in databases to design experimental supports such as arrays or to explain results in term of biological meaning. Most of this information originates from bioinformatic predictions. Their accuracy as well as their relevance to existing biological data are critical in avoiding the misinterpretation of experimental results.

Computational Biology↗

Bioinformatic analysis of the genomes of the cyanobacteria Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942 for the presence of peroxiredoxins and their transcript regulation under stress.

The genomes of the cyanobacteria Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942 encode five and six open reading frames (ORFs), respectively, with similarity to peroxide-detoxifying peroxiredoxins (Prx). In addition to one highly conserved gene each for 2-Cys Prx and 1-Cys Prx, the Synechocystis sp. PCC 6803 genome contains one TypeII Prx and two PrxQ-like ORFs, while Synechococcus elongatus PCC 7942 has four PrxQ-like ORFs. The transcript regulation of all these bioinformatically identified genes was analysed under selected stress conditions, i.e. light limitation and light stress, hydrogen peroxide, methylviologen, salinity, as well as nitrogen- and iron-deficiency. The results on specific time- and stress-dependent regulation of transcript amounts suggest conserved as well as variable functions of these putative Prx-s in antioxidant defence. The results are discussed in the context of evolution and physiological function, particularly in relation to photosynthesis.

Amino Acid Sequence↗

The European Bioinformatics Institute (EBI) databases.

This paper describes the databases and services of the European Bioinformatics Institute (EBI). In collaboration with DDBJ and GenBank/NCBI, the EBI maintains and distributes the EMBL Nucleotide Sequence Database, Europe's primary nucleotide sequence data resource. The EBI also maintains and distributes the SWISS-PROT Protein Sequence Database, in collaboration with Amos Bairoch of the University of Geneva. Over thirty additional specialist molecular biology databases, as well as software and documentation of interest to molecular biologists, are also available. The EBI network services include database searching, entry retrieval, and sequence similarity searching facilities.

Amino Acid Sequence↗

The European Bioinformatics Institute (EBI) databases.

The European Bioinformatics Institute (EBI) maintains and distributes the EMBL Nucleotide Sequence database, Europe's primary nucleotide sequence data resource. The EBI also maintains and distributes the SWISS-PROT Protein Sequence database, in collaboration with Amos Bairoch of the University of Geneva. Over fifty additional specialist molecular biology databases, as well as software and documentation of interest to molecular biologists are available. The EBI network services include database searching and sequence similarity searching facilities.

Amino Acid Sequence↗

UK CropNet: a collection of databases and bioinformatics resources for crop plant genomics.

The UK Crop Plant Bioinformatics Network (UK CropNet) was established in 1996 in order to harness the extensive work in genome mapping in crop plants in the UK. Since this date we have published five databases from our central UK CropNet WWW site (http://synteny.nott.ac.uk/) with a further three to follow shortly. Our resource facilitates the identification and manipulation of agronomically important genes by laying a foundation for comparative analysis among crop plants and model species. In addition, we have developed a number of software tools that facilitate the visualisation and analysis of our data. Many of our tools are made freely available for use with both crop plant data and with data from other species.

Crops, Agricultural↗

GénoPlante-Info (GPI): a collection of databases and bioinformatics resources for plant genomics.

Génoplante is a partnership program between public French institutes (INRA, CIRAD, IRD and CNRS) and private companies (Biogemma, Bayer CropScience and Bioplante) that aims at developing genome analysis programs for crop species (corn, wheat, rapeseed, sunflower and pea) and model plants (Arabidopsis and rice). The outputs of these programs form a wealth of information (genomic sequence, transcriptome, proteome, allelic variability, mapping and synteny, and mutation data) and tools (databases, interfaces, analysis software), that are being integrated and made public at the public bioinformatics resource centre of Génoplante: GénoPlante-Info (GPI). This continuous flood of data and tools is regularly updated and will grow continuously during the coming two years. Access to the GPI databases and tools is available at http://genoplante-info.infobiogen.fr/.

Alleles↗

The European Bioinformatics Institute's data resources.

As the amount of biological data grows, so does the need for biologists to store and access this information in central repositories in a free and unambiguous manner. The European Bioinformatics Institute (EBI) hosts six core databases, which store information on DNA sequences (EMBL-Bank), protein sequences (SWISS-PROT and TrEMBL), protein structure (MSD), whole genomes (Ensembl) and gene expression (ArrayExpress). But just as a cell would be useless if it couldn't transcribe DNA or translate RNA, our resources would be compromised if each existed in isolation. We have therefore developed a range of tools that not only facilitate the deposition and retrieval of biological information, but also allow users to carry out searches that reflect the interconnectedness of biological information. The EBI's databases and tools are all available on our website at www.ebi.ac.uk.

Animals↗

WU-Blast2 server at the European Bioinformatics Institute.

Since 1995, the WU-BLAST programs (http://blast.wustl.edu) have provided a fast, flexible and reliable method for similarity searching of biological sequence databases. The software is in use at many locales and web sites. The European Bioinformatics Institute's WU-Blast2 (http://www.ebi.ac.uk/blast2/) server has been providing free access to these search services since 1997 and today supports many features that both enhance the usability and expand on the scope of the software.

Computational Biology↗

RNA-related tools on the Bielefeld Bioinformatics Server.

We present four tools for the analysis of RNA secondary structure. They provide animated visualization of multiple structures, prediction of potential conformational switching, structure comparison (including local structure alignment) and prediction of structures potentially containing a certain kind of pseudoknots. All are available via the Bielefeld University Bioinformatics Server (http://bibiserv.techfak.uni-bielefeld.de).

Base Sequence↗

The web server of IBM's Bioinformatics and Pattern Discovery group.

We herein present and discuss the services and content which are available on the web server of IBM's Bioinformatics and Pattern Discovery group. The server is operational around the clock and provides access to a variety of methods that have been published by the group's members and collaborators. The available tools correspond to applications ranging from the discovery of patterns in streams of events and the computation of multiple sequence alignments, to the discovery of genes in nucleic acid sequences and the interactive annotation of amino acid sequences. Additionally, annotations for more than 70 archaeal, bacterial, eukaryotic and viral genomes are available on-line and can be searched interactively. The tools and code bundles can be accessed beginning at http://cbcsrv.watson.ibm.com/Tspd.html whereas the genomics annotations are available at http://cbcsrv.watson.ibm.com/Annotations/.

Computational Biology↗

E-MSD: an integrated data resource for bioinformatics.

The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the Protein Data Bank (PDB) and to work towards the integration of various bioinformatics data resources. We have implemented a simple form-based interface that allows users to query the MSD directly. The MSD 'atlas pages' show all of the information in the MSD for a particular PDB entry. The group has designed new search interfaces aimed at specific areas of interest, such as the environment of ligands and the secondary structures of proteins. We have also implemented a novel search interface that begins to integrate separate MSD search services in a single graphical tool. We have worked closely with collaborators to build a new visualization tool that can present both structure and sequence data in a unified interface, and this data viewer is now used throughout the MSD services for the visualization and presentation of search results. Examples showcasing the functionality and power of these tools are available from tutorial webpages (http://www. ebi.ac.uk/msd-srv/docs/roadshow_tutorial/).

Algorithms↗