Plotting haplotype-specific linkage disequilibrium patterns by extended haplotype homozygosity

Association studies may request more details of a specific haplotype. Haplotype-specific decay of linkage disequilibrium is such a crucial and versatile characteristic. It may be used, e.g. to search for signals of natural selection in a risk haplotype. Here, we present a web-based tool to explore the relationship between population frequency and extended linkage disequilibrium measured as haplotype homozygosity of observed haplotypes within a specified candidate region. AVAILABILITY: The web-tool is available at http://ihg.gsf.de/cgi-bin/mueller/webehh.pl     

BioParser

The widely used programs BLAST (in this article, 'BLAST' includes both the National Center for Biotechnology Information [NCBI] BLAST and the Washington University version WU BLAST) and FASTA for similarity searches in nucleotide and protein databases usually result in copious output. However, when large query sets are used, human inspection rapidly becomes impractical. BioParser is a Perl program for parsing BLAST and FASTA reports. Making extensive use of the BioPerl toolkit, the program filters, stores and returns components of these reports in either ASCII or HTML format. BioParser is also capable of automatically feeding a local MySQL database with the parsed information, allowing subsequent filtering of hits and/or alignments with specific attributes. For this reason, BioParser is a valuable tool for large-scale similarity analyses by improving the access to the information present in BLAST or FASTA reports, facilitating extraction of useful information of large sets of sequence alignments, and allowing for easy handling and processing of the data. AVAILABILITY: BioParser is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs 2.0 license terms (http://creativecommons.org/licenses/by-nc-nd/2.0/) and is available upon request. Additional information can be found at the BioParser website (http://www.dbbm.fiocruz.br/BioParser.html).     

Highly specific localization of promoter regions in large genomic sequences by PromoterInspector: a novel context analysis approach

We present a new algorithm called PromoterInspector to locate eukaryotic polymase II promoter regions in large genomic sequences with a high degree of specificity. PromoterInspector focuses on the genetic context of promoters, rather than their exact location. Application of PromoterInspector can serve as a crucial pre-processing step for other methods to locate exactly, or to analyze promoters.PromoterInspector does not depend on heuristics, because it is purely based on libraries of IUPAC words extracted from training sequences by an unsupervised learning approach. We compared PromoterInspector to in silico promoter prediction tools using the sequences from the review by J.W. Fickett. PromoterInspector compared favourably on Fickett's evaluation scheme. A true positive to false positive ratio of 2.3 was obtained, surpassing the best ratio of 0.6, reported for TSSG. The application of our method to several large genomic sequences of over 1.3 million base-pairs in total resulted in even more specific predictions. The coverage of annotated promoters was comparable to other in silico promoter prediction methods, while the true positive predictions increased by up to 100% of total matches.PromoterInspector scans 100 kb in less than one minute on a workstation, and thus is especially applicable for large genome analysis. The method is available at http://genomatix.gsf. de/cgi-bin/promoterinspector/promoterinspector.pl.     

Genomic BLAST: custom-defined virtual databases for complete and unfinished genomes

BLAST (Basic Local Alignment Search Tool) searches against DNA and protein sequence databases have become an indispensable tool for biomedical research. The proliferation of the genome sequencing projects is steadily increasing the fraction of genome-derived sequences in the public databases and their importance as a public resource. We report here the availability of Genomic BLAST, a novel graphical tool for simplifying BLAST searches against complete and unfinished genome sequences. This tool allows the user to compare the query sequence against a virtual database of DNA and/or protein sequences from a selected group of organisms with finished or unfinished genomes. The organisms for such a database can be selected using either a graphic taxonomy-based tree or an alphabetical list of organism-specific sequences. The first option is designed to help explore the evolutionary relationships among organisms within a certain taxonomy group when performing BLAST searches. The use of an alphabetical list allows the user to perform a more elaborate set of selections, assembling any given number of organism-specific databases from unfinished or complete genomes. This tool, available at the NCBI web site http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/genom_table_cgi, currently provides access to over 170 bacterial and archaeal genomes and over 40 eukaryotic genomes.     

BLAST2SRS,a web server for flexible retrieval of related protein sequences in the SWISS-PROT and SPTrEMBL databases

SRS (Sequence Retrieval System) is a widely used keyword search engine for querying biological databases. BLAST2 is the most widely used tool to query databases by sequence similarity search. These tools allow users to retrieve sequences by shared keyword or by shared similarity, with many public web servers available. However, with the increasingly large datasets available it is now quite common that a user is interested in some subset of homologous sequences but has no efficient way to restrict retrieval to that set. By allowing the user to control SRS from the BLAST output, BLAST2SRS (http://blast2srs.embl.de/) aims to meet this need. This server therefore combines the two ways to search sequence databases: similarity and keyword.     

Intersect: identification and visualization of overlaps in database search results

The determination of distant evolutionary relationships remains an important biological problem, and distant homologs often appear in statistically insignificant regions of sequence similarity searches. Intersect is a computer program designed to identify and visualize the overlaps between sets of sequences reported by multiple database searches. This capability extends the usefulness of database search results and aids researchers in identifying the individual sequences that best bridge sequence families and superfamilies. AVAILABILITY: The Intersect program is available from the Babbitt laboratory website at http://www.babbittlab.ucsf.edu/software/intersect     

SNAPper: gene order predicts gene function

SNAPper is a network service for predicting gene function based on the conservation of gene order. AVAILABILITY: The SNAPper server is available at http://pedant.gsf.de/snapper. SNAPper-based functional predictions will soon be offered as part of the PEDANT genome analysis server http://pedant.gsf.de.     

Peptide sequence tags for fast database search in mass-spectrometry

Filtration techniques in the form of rapid elimination of candidate sequences while retaining the true one are key ingredients of database searches in genomics. Although SEQUEST and Mascot perform a conceptually similar task to the tool BLAST, the key algorithmic idea of BLAST (filtration) was never implemented in these tools. As a result MS/MS protein identification tools are becoming too time-consuming for many applications including search for post-translationally modified peptides. Moreover, matching millions of spectra against all known proteins will soon make these tools too slow in the same way that "genome vs genome" comparisons instantly made BLAST too slow. We describe the development of filters for MS/MS database searches that dramatically reduce the running time and effectively remove the bottlenecks in searching the huge space of protein modifications. Our approach, based on a probability model for determining the accuracy of sequence tags, achieves superior results compared to GutenTag, a popular tag generation algorithm. Our tag generating algorithm along with our de novo sequencing algorithm PepNovo can be accessed via the URL http://peptide.ucsd.edu/.     

EUGENE'HOM: A generic similarity-based gene finder using multiple homologous sequences

EUGENE'HOM is a gene prediction software for eukaryotic organisms based on comparative analysis. EUGENE'HOM is able to take into account multiple homologous sequences from more or less closely related organisms. It integrates the results of TBLASTX analysis, splice site and start codon prediction and a robust coding/non-coding probabilistic model which allows EUGENE'HOM to handle sequences from a variety of organisms. The current target of EUGENE'HOM is plant sequences. The EUGENE'HOM web site is available at http://genopole.toulouse.inra.fr/bioinfo/eugene/EuGeneHom/cgi-bin/EuGeneHom.pl.     

GWFASTA: server for FASTA search in eukaryotic and microbial genomes

Similarity searches are a powerful method for solving important biological problems such as database scanning, evolutionary studies, gene prediction, and protein structure prediction. FASTA is a widely used sequence comparison tool for rapid database scanning. Here we describe the GWFASTA server that was developed to assist the FASTA user in similarity searches against partially and/or completely sequenced genomes. GWFASTA consists of more than 60 microbial genomes, eight eukaryote genomes, and proteomes of annotatedgenomes. Infact, it provides the maximum number of databases for similarity searching from a single platform. GWFASTA allows the submission of more than one sequence as a single query for a FASTA search. It also provides integrated post-processing of FASTA output, including compositional analysis of proteins, multiple sequences alignment, and phylogenetic analysis. Furthermore, it summarizes the search results organism-wise for prokaryotes and chromosome-wise for eukaryotes. Thus, the integration of different tools for sequence analyses makes GWFASTA a powerful toolfor biologists.     

ViroBLAST: a stand-alone BLAST web server for flexible queries of multiple databases and user's datasets

ViroBLAST is a stand-alone BLAST web interface for nucleotide and amino acid sequence similarity searches. It extends the utility of BLAST to query against multiple sequence databases and user sequence datasets, and provides a friendly output to easily parse and navigate BLAST results. ViroBLAST is readily useful for all research areas that require BLAST functions and is available online and as a downloadable archive for independent installation. Availability: http://indra.mullins.microbiol.washington.edu/blast/viroblast.php.     

Fast assignment of protein structures to sequences using the intermediate sequence library PDB-ISL

MOTIVATION: For large-scale structural assignment to sequences, as in computational structural genomics, a fast yet sensitive sequence search procedure is essential. A new approach using intermediate sequences was tested as a shortcut to iterative multiple sequence search methods such as PSI-BLAST. RESULTS: A library containing potential intermediate sequences for proteins of known structure (PDB-ISL) was constructed. The sequences in the library were collected from a large sequence database using the sequences of the domains of proteins of known structure as the query sequences and the program PSI-BLAST. Sequences of proteins of unknown structure can be matched to distantly related proteins of known structure by using pairwise sequence comparison methods to find homologues in PDB-ISL. Searches of PDB-ISL were calibrated, and the number of correct matches found at a given error rate was the same as that found by PSI-BLAST. The advantage of this library is that it uses pairwise sequence comparison methods, such as FASTA or BLAST2, and can, therefore, be searched easily and, in many cases, much more quickly than an iterative multiple sequence comparison method. The procedure is roughly 20 times faster than PSI-BLAST for small genomes and several hundred times for large genomes. AVAILABILITY: Sequences can be submitted to the PDB-ISL servers at http://stash.mrc-lmb.cam.ac.uk/PDB_ISL/ or http://cyrah.ebi.ac.uk:1111/Serv/PDB_ISL/ and can be downloaded from ftp://ftp.ebi.ac.uk/pub/contrib/jong/PDB_+ ++ISL/ CONTACT: sat@mrc-lmb.cam.ac.uk and jong@ebi.ac.uk     

ClusterDraw web server: a tool to identify and visualize clusters of binding motifs for transcription factors

ClusterDraw is a program aimed to identification of binding sites and binding-site clusters. Major difference of the ClusterDraw from existing tools is its ability to scan a wide range of parameter values and weigh statistical significance of all possible clusters, smaller than a selected size. The program produces graphs along with decorated FASTA files. ClusterDraw web server is available at the following URL: http://flydev.berkeley.edu/cgi-bin/cld/submit.cgi     

NNvPDB: Neural Network based Protein Secondary Structure Prediction with PDB Validation

Availabilityhttp://bit.srmuniv.ac.in/cgi-bin/bit/cfpdb/nnsecstruct.pl     

CREDO: a web-based tool for computational detection of conserved sequence motifs in noncoding sequences

SUMMARY: CREDO is a user-friendly, web-based tool that integrates the analysis and results of different algorithms widely used for the computational detection of conserved sequence motifs in noncoding sequences. It enables easy comparison of the individual results. CREDO offers intuitive interfaces for easy and rapid configuration of the applied algorithms and convenient views on the results in graphical and tabular formats. AVAILABILITY: http://mips.gsf.de/proj/regulomips/credo.htm.     

RiDs db: Repeats in diseases database

The non-coding fraction of the human genome, which is approximately 98%, is mainly constituted by repeats. Transpositions, expansions and deletions of these repeat elements contribute to a number of diseases. None of the available databases consolidates information on both tandem and interspersed repeats with the flexibility of FASTA based homology search with reference to disease genes. Repeats in diseases database (RiDs db) is a web accessible relational database, which aids analysis of repeats associated with Mendelian disorders. It is a repository of disease genes, which can be searched by FASTA program or by limitedor free- text keywords. Unlike other databases, RiDs db contains the sequences of these genes with access to corresponding information on both interspersed and tandem repeats contained within them, on a unified platform. Comparative analysis of novel or patient sequences with the reference sequences in RiDs db using FASTA search will indicate change in structure of repeats, if any, with a particular disorder. This database also provides links to orthologs in model organisms such as zebrafish, mouse and Drosophila. AVAILABILITY: The database is available for free at http://115.111.90.196/ridsdb/index.php.     

Compilation of DNA sequences of Escherichia coli K12 (ECD and ECDC; update 1995).

We have compiled the DNA sequence data for Escherichia coli available from the GenBank and EMBL data libraries and independently from the literature. Unlike the previous updates of our E.coli databases, we provide the most recent version preferentially via the World Wide Web System (use URL: http://susi.bio.unigiessen.de/usr/local/www++ +/html/ecdc.html). Our database includes an assembled set of contiguous sequences. Each of these contigs compiles all available sequence information, including those derived from a variety of elder sequences. The organization of the database allows one to find the exact physical location of each individual gene or regulatory region, even regarding discrepancies in nomenclature. The WWW program allows access into the original EMBL and SWISSPROT datafiles. A FASTA and BLAST search may be performed online. Besides the WWW format a flat file version may be obtained via ftp. The complete compilation, including a full set of genetic map data and the E.coli protein index, can be obtained in machine readable form from the EMBL data library as a part of the CD-ROM issue of the EMBL sequence database, released and updated every three months. After deletion of all detected overlaps a total of 3 333 878 individual bp was determined by the end of September 1995. This corresponds to a total of 71.71% of the entire E.coli chromosome consisting of about 4720 kbp. About 94 kbp (2%) are available additionally, but have not yet been definitely mapped.