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A comparative guide to gene prediction tools for the bioinformatics amateur.

Several hundred programs using different algorithms have been designed to predict individual coding features within any genomic sequence, but none of these tools covers all aspects of a gene or is 100% accurate in its prediction. Automated simultaneous processing of the results from a number of these programs minimizes the chance of a false positive prediction and quickly generates integrated data. We report here on the analysis of two known genes in 5 and 25 kb segments of genomic sequence using four genome annotation packages, NIX, RUMMAGE, Genotator and EMBOSS. Gene predictions were confirmed using cDNA sequences and a comparison was made between the packages. This study showed a similarity in the ability of NIX, RUMMAGE and Genotator to predict well-characterised genes and basic structures, but poor exon prediction for a small, 3 exon gene. However, the BLAST subprograms of all three packages correctly identified the 3 exons. In addition, EST BLAST subprograms identified a previously undescribed, possible 5' untranslated exon for the smaller gene and a number of putative alternatively spliced exons in the larger gene. Overall, NIX was found to be the most user-friendly package, in terms of easy access to databases and the interactive graphical display of results.

Algorithms↗

Transporter associated with antigen processing preselection of peptides binding to the MHC: a bioinformatic evaluation.

TAP is responsible for the transit of peptides from the cytosol to the lumen of the endoplasmic reticulum. In an immunological context, this event is followed by the binding of peptides to MHC molecules before export to the cell surface and recognition by T cells. Because TAP transport precedes MHC binding, TAP preferences may make a significant contribution to epitope selection. To assess the impact of this preselection, we have developed a scoring function for TAP affinity prediction using the additive method, have used it to analyze and extend the TAP binding motif, and have evaluated how well this model acts as a preselection step in predicting MHC binding peptides. To distinguish between MHC alleles that are exclusively dependent on TAP and those exhibiting only a partial dependence on TAP, two sets of MHC binding peptides were examined: HLA-A*0201 was selected as a representative of partially TAP-dependent HLA alleles, and HLA-A*0301 represented fully TAP-dependent HLA alleles. TAP preselection has a greater impact on TAP-dependent alleles than on TAP-independent alleles. The reduction in the number of nonbinders varied from 10% (TAP-independent) to 33% (TAP-dependent), suggesting that TAP preselection is an important component in the successful in silico prediction of T cell epitopes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A bioinformatics approach to investigating developmental pathways in the kidney and other tissues.

Over the past few years, large amounts of data linking gene-expression (GE) patterns and other genetic data with the development of the mouse kidney have been published, and the next task will be to integrate these data with the molecular networks responsible for the emergence of the kidney phenotype. This paper discusses how a start to this task can be made by using the kidney database and its associated search tools, and shows how the data generated by such an approach can be used as a guide to future experimentation. Many of the events taking place as the kidney develops do, of course, also take place in other tissues and organisms and it will soon be possible to incorporate relevant information from these systems into analyses of kidney data as well as the new information from microarray technology. The key to success here will be the ability to access over the internet data from the textual and graphical databases for the mouse and other organisms now being established. In order to do this, informatic tools will be needed that will allow a user working with one database to query another. This paper also considers both the types of tools that will be necessary and the databases on which they will operate.

Animals↗

Environmental genome project develops a new bioinformatics tool

The NIEHS Environmental Genome Project is founded on the sound scientific concept that an individual's genetic makeup is a major factor in human disease resulting from exposure to environmental agents. The project is a long-term effort to characterize specific genetic variations, or polymorphisms, that contribute to either resistance or susceptibility to environmentally induced diseases.

Journal Article↗

[Genomics. Proteomics. Bioinformatics. What else?].

The biology of the past century was, undoubtedly, reductionist. Its general trend was expressed in the appearance and burst of scientific disciplines, such as biochemistry, biophysics, molecular biology, molecular genetics, virology, cell biology, and bioorganic chemistry. All these disciplines are united by an aspiration to explain the phenomena of life through the description of the properties of molecules, first of all, biopolymers, which constitute the living organisms. In current science, all these directions are often united under the general heading "physicochemical biology", while classical biological disciplines, such as zoology, botany, embryology, etc., are referred to as "general biology".

Animals↗

Integrating Application Programs for Bioinformatics Using a Web Browser.

We have constructed a general framework for integrating application programs with control through a local Web browser. This method is based on a simple inter-process message function from an external process to application programs. Commands to a target program are prepared in a script file, which is parsed by a message dispatcher program. When it is used as a helper application to a Web browser, these messages will be sent from the browser by clicking a hyper-link in a Web document. Our framework also supports pluggable extension-modules for application programs by means of dynamic linking. A prototype system is implemented on our molecular structure-viewer program, MOSBY. It successfully featured a function to load an extension-module required for the docking study of molecular fragments from a Web page. Our simple framework facilitates the concise configuration of Web softwares without complicated knowledge on network computation and security issues. It is also applicable for a wide range of network computations processing private data using a Web browser.

Journal Article↗

Mapping XML documents into databases: a Data-Driven Framework for bioinformatic data interchange.

The Data-Driven Framework (DDF) described here addresses two major problems for healthcare Electronic Data Interchange, data formats and software development costs. The use of a standard XML Document Type Definition (DTD) allows robust representation in any application area and leverages industry-standard tools and development directions. The DDF allows reduced software development and maintenance costs since all data-entry and database tools are generated from the DTD. The DTD can change and the tools can be regenerated. The case-study below uses the DDF for reporting cell assays to determine the roles of factors influencing cellular gene expression and regulation.

Computer Communication Networks↗

Graphically-enabled integration of bioinformatics tools allowing parallel execution.

Rapid analysis of large amounts of genomic data is of great biological as well as medical interest. This type of analysis will greatly benefit from the ability to rapidly assemble a set of related analysis programs and to exploit the power of parallel computing. TurboGenomics, which is a software package currently in its alpha-testing phase, allows integration of heterogeneous software components to be done graphically. In addition, the tool is capable of making the integrated components run in parallel. To demonstrate these abilities, we use the tool to develop a Web-based application that allows integrated access to a set of large-scale sequence data analysis programs used by a transposon-insertion based yeast genome project. We also contrast the differences in building such an application with and without using the TurboGenomics software.

Computational Biology↗

Bioinformatics.

Explore the source record for details and available documents.

Biotechnology↗

Bioinformatics, target discovery and the pharmaceutical/biotechnology industry.

With the first draft of the human genome now available a directed genome-wide mining strategy is being implemented by many pharmaceutical and biotechnology companies in order to identify novel members of the most therapeutically relevant target families. At the same time there is an increasing amount of annotation relevant to the human genome sequence entering into the public domain. The ability to identify protein families on a genome-wide scale can only be done at speed by using high-throughput computational approaches. This review describes many of the latest algorithmic developments in this field and shows how they can be best put to use for target identification and prioritization.

Algorithms↗