LGICdb: the ligand-gated ion channel database

Ligand-Gated Ion Channels (LGIC) are polymeric transmembrane proteins involved in the fast response to numerous neurotransmitters. All these receptors are formed by homologous subunits and the last two decades revealed an unexpected wealth of genes coding for these subunits. The Ligand-Gated Ion Channel database (LGICdb) has been developed to handle this increasing amount of data. The database aims to provide only one entry for each gene, containing annotated nucleic acid and protein sequences. The repository is carefully structured and the entries can be retrieved by various criteria. In addition to the sequences, the LGICdb provides multiple sequence alignments, phylogenetic analyses and atomic coordinates when available. The database is accessible via the World Wide Web (http://www.pasteur.fr/recherche/banques/LGIC /LGIC.html), where it is continuously updated. The version 16 (September 2000) available for download contained 333 entries covering 34 species.     

SubViral RNA: a database of the smallest known auto-replicable RNA species

We describe here the establishment of an online database containing a large number of sequences and related data on viroids, viroid-like RNAs and human hepatitis delta virus (vHDV) in a customizable and user-friendly format. This database is available on the World Wide Web at http://penelope.med.usherb.ca/subviral.     

Histone and histone fold sequences and structures: a database.

A database of aligned histone protein sequences has been constructed based on the results of homology searches of the major public sequence databases. In addition, sequences of proteins identified as containing the histone fold motif and structures of all known histone and histone fold proteins have been included in the current release. Database resources include information on conflicts between similar sequence entries in different source databases, multiple sequence alignments, and links to the Entrez integrated information retrieval system at the National Center for Biotechnology Information (NCBI). The database currently contains over 1000 protein sequences. All sequences and alignments in this database are available through the World Wide Web at: http: //www.ncbi.nlm.nih.gov/Baxevani/HISTONES/ .     

HUGE: a database for human large proteins identified in the Kazusa cDNA sequencing project

We have been developing a HUGE database to summarize results from the sequence analysis of human novel large (>4 kb) cDNAs identified in the Kazusa cDNA sequencing project, systematically designated KIAA plus a four-digit number. HUGE currently contains nearly 2000 gene/protein characteristic tables harboring the results of the computer-assisted analysis of the cDNA and the predicted protein sequences together with those of expression profiling and chromosomal mapping. In the updated version of HUGE, we made it possible to compare each KIAA cDNA sequence with the corresponding entry in the human draft genome sequence that was published recently. Approximately 90% of KIAA cDNAs in HUGE can be localized along the human genome for at least half or more of the cDNA’s length. Any nucleotide differences between the cDNA and the corresponding genomic sequences are also presented in detail. This new version of HUGE greatly helps us evaluate the completeness of cDNA clones and the accuracy of cDNA/genomic sequences. More interestingly, in some cases, the ability to compare cDNA with genomic sequences allows us to identify candidate sites of RNA editing. HUGE is available on the World Wide Web at http://www.kazusa.or.jp/huge.     

Decoding of superimposed traces produced by direct sequencing of heterozygous indels

Direct Sanger sequencing of a diploid template containing a heterozygous insertion or deletion results in a difficult-to-interpret mixed trace formed by two allelic traces superimposed onto each other. Existing computational methods for deconvolution of such traces require knowledge of a reference sequence or the availability of both direct and reverse mixed sequences of the same template. We describe a simple yet accurate method, which uses dynamic programming optimization to predict superimposed allelic sequences solely from a string of letters representing peaks within an individual mixed trace. We used the method to decode 104 human traces (mean length 294 bp) containing heterozygous indels 5 to 30 bp with a mean of 99.1% bases per allelic sequence reconstructed correctly and unambiguously. Simulations with artificial sequences have demonstrated that the method yields accurate reconstructions when (1) the allelic sequences forming the mixed trace are sufficiently similar, (2) the analyzed fragment is significantly longer than the indel, and (3) multiple indels, if present, are well-spaced. Because these conditions occur in most encountered DNA sequences, the method is widely applicable. It is available as a free Web application Indelligent at http://ctap.inhs.uiuc.edu/dmitriev/indel.asp.     

Identifying the 3'-terminal exon in human DNA.

MOTIVATION: We present JTEF, a new program for finding 3' terminal exons in human DNA sequences. This program is based on quadratic discriminant analysis, a standard non-linear statistical pattern recognition method. The quadratic discriminant functions used for building the algorithm were trained on a set of 3' terminal exons of type 3tuexon (those containing the true STOP codon). RESULTS: We showed that the average predictive accuracy of JTEF is higher than the presently available best programs (GenScan and Genemark.hmm) based on a test set of 65 human DNA sequences with 121 genes. In particular JTEF performs well on larger genomic contigs containing multiple genes and significant amounts of intergenic DNA. It will become a valuable tool for genome annotation and gene functional studies. AVAILABILITY: JTEF is available free for academic users on request from ftp://cshl.org/pub/science/mzhanglab/JTEF and will be made available through the World Wide Web (http://argon.cshl.org/).     

BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequences

'BLAST 2 Sequences', a new BLAST-based tool for aligning two protein or nucleotide sequences, is described. While the standard BLAST program is widely used to search for homologous sequences in nucleotide and protein databases, one often needs to compare only two sequences that are already known to be homologous, coming from related species or, e.g. different isolates of the same virus. In such cases searching the entire database would be unnecessarily time-consuming. 'BLAST 2 Sequences' utilizes the BLAST algorithm for pairwise DNA-DNA or protein-protein sequence comparison. A World Wide Web version of the program can be used interactively at the NCBI WWW site (http://www.ncbi.nlm.nih.gov/gorf/bl2.++ +html). The resulting alignments are presented in both graphical and text form. The variants of the program for PC (Windows), Mac and several UNIX-based platforms can be downloaded from the NCBI FTP site (ftp://ncbi.nlm.nih.gov).     

JDotter: a Java interface to multiple dotplots generated by dotter

Java-Dotter (JDotter) is a platform-independent Java interactive interface for the Linux version of Dotter, a widely used program for generating dotplots of large DNA or protein sequences. JDotter runs as a client-server application and can send new sequences to the Dotter program for alignment as well as rapidly access a repository of preprocessed dotplots. JDotter also interfaces with a sequence database or file system to display supplementary feature data. Thus, JDotter greatly simplifies access to dotplot data in laboratories that deal with large numbers of genomes and have a multi-platform organization. AVAILABILITY: Currently, JDotter is used via Java Web Start by the Poxvirus Bioinformatics Resource for examining dotplots of complete poxvirus genomes; http://athena.bioc.uvic.ca/pbr/jdotter/. The software is available for download from the same location. SUPPLEMENTARY INFORMATION: Installation instructions, the User's Manual, screenshots and examples are available at the JDotter home page http://athena.bioc.uvic.ca/pbr/jdotter/. The software and source code is free for non-commercial applications.     

TREE-PUZZLE: maximum likelihood phylogenetic analysis using quartets and parallel computing

SUMMARY: TREE-PUZZLE is a program package for quartet-based maximum-likelihood phylogenetic analysis (formerly PUZZLE, Strimmer and von Haeseler, Mol. Biol. Evol., 13, 964-969, 1996) that provides methods for reconstruction, comparison, and testing of trees and models on DNA as well as protein sequences. To reduce waiting time for larger datasets the tree reconstruction part of the software has been parallelized using message passing that runs on clusters of workstations as well as parallel computers. AVAILABILITY: http://www.tree-puzzle.de. The program is written in ANSI C. TREE-PUZZLE can be run on UNIX, Windows and Mac systems, including Mac OS X. To run the parallel version of PUZZLE, a Message Passing Interface (MPI) library has to be installed on the system. Free MPI implementations are available on the Web (cf. http://www.lam-mpi.org/mpi/implementations/).     

BAliBASE (Benchmark Alignment dataBASE): enhancements for repeats, transmembrane sequences and circular permutations

BAliBASE is specifically designed to serve as an evaluation resource to address all the problems encountered when aligning complete sequences. The database contains high quality, manually constructed multiple sequence alignments together with detailed annotations. The alignments are all based on three-dimensional structural superpositions, with the exception of the transmembrane sequences. The first release provided sets of reference alignments dealing with the problems of high variability, unequal repartition and large N/C-terminal extensions and internal insertions. Here we describe version 2.0 of the database, which incorporates three new reference sets of alignments containing structural repeats, trans-membrane sequences and circular permutations to evaluate the accuracy of detection/prediction and alignment of these complex sequences. BAliBASE can be viewed at the web site http://www-igbmc.u-strasbg. fr/BioInfo/BAliBASE2/index.html or can be downloaded from ftp://ftp-igbmc.u-strasbg.fr/pub/BAliBASE2 /.     

CAST: an iterative algorithm for the complexity analysis of sequence tracts. Complexity analysis of sequence tracts

MOTIVATION: Sensitive detection and masking of low-complexity regions in protein sequences. Filtered sequences can be used in sequence comparison without the risk of matching compositionally biased regions. The main advantage of the method over similar approaches is the selective masking of single residue types without affecting other, possibly important, regions. RESULTS: A novel algorithm for low-complexity region detection and selective masking. The algorithm is based on multiple-pass Smith-Waterman comparison of the query sequence against twenty homopolymers with infinite gap penalties. The output of the algorithm is both the masked query sequence for further analysis, e.g. database searches, as well as the regions of low complexity. The detection of low-complexity regions is highly specific for single residue types. It is shown that this approach is sufficient for masking database query sequences without generating false positives. The algorithm is benchmarked against widely available algorithms using the 210 genes of Plasmodium falciparum chromosome 2, a dataset known to contain a large number of low-complexity regions. AVAILABILITY: CAST (version 1.0) executable binaries are available to academic users free of charge under license. Web site entry point, server and additional material: http://www.ebi.ac.uk/research/cgg/services/cast/     

Histone Sequence Database: a compilation of highly-conserved nucleoprotein sequences.

By searching the current protein sequence databases using sequences from human and chicken histones H1/H5, H2A, H2B, H3 and H4, a database of aligned histone protein sequences with statistically significant sequence similarity to the search sequence was constructed. In addition, a nucleotide sequence database of the corresponding coding regions for these proteins has been assembled. The region of each of the core histones containing the histone fold motif is identified in the protein alignments. The database contains >1300 protein and nucleotide sequences. All sequences and alignments in this database are available through the World Wide Web at http://www.ncbi.nlm.nih.gov/Baxevani/HISTO NES.     

The Organelle Genome Database Project (GOBASE).

The taxonomically broad organelle genome database (GOBASE) organizes and integrates diverse data related to organelles (mitochondria and chloroplasts). The current version of GOBASE focuses on the mitochondrial subset of data and contains molecular sequences, RNA secondary structures and genetic maps, as well as taxonomic information for all eukaryotic species represented. The database has been designed so that complex biological queries, especially ones posed in a comparative genomics context, are supported. GOBASE has been implemented as a relational database with a web-based user interface (http://megasun.bch.umontreal.ca/gobase/gobas e.html ). Custom software tools have been written in house to assist in the population of the database, data validation, nomenclature standardization and front-end design. The database is fully operational and publicly accessible via the World Wide Web, allowing interactive browsing, sophisticated searching and easy downloading of data.     

MICROFAMILY (version 1): a computer program for detecting flanking‐region similarities among different microsatellite loci

Microsatellite flanking regions are not necessarily unique sequences, but they may group into sequence families. Microsatellites occurring within such families are likely to give multiple banding patterns during polymerase chain reaction amplifications. microfamily (version 1) is a program that detects flanking‐region similarities between different microsatellite‐containing sequences, thus allowing for potentially problematic sequences to be eliminated prior to primer design. The program also accomplishes some otherwise tedious sequence editing, such as checking for nonpermitted characters, and eliminates poorly readable extremities or potential vector/adapter contamination. microfamily is written in Perl and available for Linux and Windows systems at http://www.up.univ‐mrs.fr/local/egee/dir/meglecz/microfamily.html .     

VIR.II: a new interface with the antibody sequences in the Kabat database.

The Kabat database is the source of information par excellence on antibody sequences. In 1995, we developed an interface with the Kabat database, called VIR. VIR has been very useful in conducting studies aiming to find structure-function relationships in antibodies. Here we report a new version adapted to the World Wide Web, called VIR.II. VIR.II allows searches by type of chain (V(H) or V(L)), by species, and by specificity. The species are selected using a pulldown menu, whereas the specificities can be selected from a list containing the unique specificities reported in the Kabat database. These facilities avoid mistakes and redundancies in the searches. Another feature, and probably the most important one, is that VIR.II introduces a classification of specificities in terms of the chemical and biochemical nature of the antigen, like anti-protein, anti-peptide, anti-hapten, etc. This classification has been useful in discovering patterns in the antigen-binding site of antibodies that correlate with the type of antigen the antibody interacts with. To illustrate this, while showing the capabilities of VIR.II, we analyze all the murine anti-peptide and anti-protein antibody sequences compiled as of July, 2000 in the Kabat database.     

The guide RNA database (3.0).

The RNA editing process within the mitochondria of kinetoplastid organisms is controlled by small, trans -acting RNA molecules referred to as guide RNAs. The guide RNA database is a compilation of published guide RNA sequences, currently containing 254 entries from 11 different organisms. Additional information includes RNA secondary and tertiary structure models, information on the gene localisation, literature citations and other relevant facts. The database can be accessed through the World Wide Web (WWW) at http://www.biochem.mpg.de/ goeringe/