Computer applications in the biosciences : CABIOS最新文献

Motivation: Expressed Sequence Tags (ESTs) are short single-pass DNA sequences obtained from either ends of cDNA clones. To exploit these sequences efficiently, a dynamic Web-tool has been developed which uses these data to perform fast virtual cloning of cDNAs.

Results: Starting with a query sequence, the user is able to identify related ESTs and extend the sequence of interest step by step, possibly to a full-length transcript. Graphical views of the clustering are used to monitor the progress of a particular 'cloning' project. Potential open reading frames are detected by positional base preference, and hyperlinks to other Worldwide Web sites allows the user to retrieve information relevant to each EST in a cluster (e.g. sequence traces, clone size, plate position). Apart from cDNA cloning, this tool also provides a mechanism for collating gene families and polymorphism sites.

Motivation: We created Micado, a database for managing genomic information, as part of the Bacillus subtilis genome programs. Its content will be progressively extended to the whole microbial world.

Results: A relational schema is defined for selective queries. It links eubacterial and archaeal sequences, genetic maps for Bacillus subtilis and Escherichia coli, and information on mutants. The latter comes from a new functional analysis project of unknown genes in B subtilis, and the database allows the community to curate information. To help queries from users, a graphical interface is built on SQL access to the database and provided through the WWW. We have automated imports of microbial sequences, and E. coli genetic map, by programming parsers of flat file distributions. These ensure smooth updates from molecular biology repositories on the Internet. Hyperlinks are created as a complement, to reference other general and specialized related information resources.

The problem of predicting protein structure from the sequence remains fundamentally unsolved despite more than three decades of intensive research effort. However, new and promising methods in three-dimensional (3D), 2D and 1D prediction have reopened the field. Mean-force-potentials derived from the protein databases can distinguish between correct and incorrect models (3D). Inter-residue contacts (2D) can be detected by analysis of correlated mutations, albeit with low accuracy. Secondary structure, solvent accessibility and transmembrane helices (1D) can be predicted with significantly improved accuracy using multiple sequence alignments. Some of these new prediction methods have proven accurate and reliable enough to be useful in genome analysis, and in experimental structure determination. Moreover, the new generation of theoretical methods is increasingly influencing experiments in molecular biology.

Motivation: Several methods in molecular population genetics have recently been described to estimate the amount and pattern of the DNA polymorphism in natural populations, and also to test the neutral theory of molecular evolution. These methods are essential for understanding the molecular evolutionary process. However, a comprehensive computer program for the analysis is not currently available.

Results: Here we present DnaSP (DNA Sequence Polymorphism) version 2.0, a software package for Windows that performs extensive population genetics analyses on DNA sequence data. DnaSP estimates several measures of DNA sequence variation within and between populations, linkage disequilibrium, recombination, gene flow and gene conversion (a new algorithm to detect gene conversion tracts has been included). DnaSP can also carry out several tests of neutrality: those of Fu and Li; Hudson, Kreitman and Aguadé; and Tajima. The results of the analyses are displayed in tabular and graphic form.

Availability: For academic uses, DnaSP is available via anonymous ftp: ftp.ebi.ac.uk in the directory/pub/software/dos.

Motivation: To improve the estimation of evolutionary distances between nucleotide sequences by considering the differences in substitution rates among sites.

Results: TREECON for Windows (Van de Peer,Y. and De Wachter,R. Comput. Applic. Biosci., 9, 569-570, 1994) is a software package for the construction and drawing of phylogenetic trees based on distance data computed from nucleic acid and amino acid sequences. For nucleic acids, we here describe the implementation of a recently developed method for estimating evolutionary distances taking into account the substitution rate of individual sites in a sequence alignment.

Availability: TREECON for Windows is available on request from the authors. A small fee is asked in order to support the work and to reinvest in new computer hard- and software. More information about the program and substitution rate calibration can be found at URL http:/(/)bioc-www.uia.ac.be/u/ yvdp/treeconw.html.

Biochemists and molecular biologists have suggested motifs for characterizing the binding of peptide fragments and class II major histocompatibility complex (MHC) molecules based on laboratory results and crystal structures. The iterative algorithm presented here converts a suggested motif into a quantitative data-based model. The database accessed consists of peptide fragments known to bind or not bind to class II MHC molecules of particular haplotypes. Stepwise discriminant analysis is utilized to increase or decrease motif coefficients until the resulting motif classifies all binders and non-binders correctly. Stepwise discriminant analysis is a standard multivariate statistical procedure and is available in comprehensive commercial statistical packages. Program 7M of BMDP Statistical Software was used in this study.