Databases and software for the analysis of mutations in the human p53 gene, the human hprt gene and both the lacI and lacZ gene in transgenic rodents.

We have created databases and software applications for the analysis of DNA mutations at the humanp53gene, the humanhprtgene and both the rodent transgeniclacIandlacZlocus. The databases themselves are stand-alone dBASE files and the software for analysis of the databases runs on IBM-compatible computers. Each database has a separate software analysis program. The software created for these databases permit the filtering, ordering, report generation and display of information in the database. In addition, a significant number of routines have been developed for the analysis of single base substitutions. One method of obtaining the databases and software is via the World Wide Web (WWW). Open the following home page with a Web Browser: http://sunsite.unc.edu/dnam/mainpage.ht ml . Alternatively, the databases and programs are available via public FTP from: anonymous@sunsite.unc.edu . There is no password required to enter the system. The databases and software are found beneath the subdirectory: pub/academic/biology/dna-mutations. Two other programs are available at the site-a program for comparison of mutational spectra and a program for entry of mutational data into a relational database.     

Databases and software for the analysis of mutations in the human p53 gene, human hprt gene and both the lacI and lacZ gene in transgenic rodents.

We have created databases and software applications for the analysis of DNA mutations at the human p53 gene, the human hprt gene and both the rodent transgenic lacI and lacZ loci. The databases themselves are stand-alone dBASE files and the software for analysis of the databases runs on IBM-compatible computers with Microsoft Windows. Each database has a separate software analysis program. The software created for these databases permit the filtering, ordering, report generation and display of information in the database. In addition, a significant number of routines have been developed for the analysis of single base substitutions. One method of obtaining the databases and software is via the World Wide Web. Open the following home page with a Web Browser: http://sunsite.unc.edu/dnam/mainpage. html . Alternatively, the databases and programs are available via public FTP from: anonymous@sunsite.unc.edu. There is no password required to enter the system. The databases and software are found beneath the subdirectory: pub/academic/biology/dna-mutations. Two other programs are available at the site, a program for comparison of mutational spectra and a program for entry of mutational data into a relational database.     

Databases and software for the analysis of mutations in the human p53 gene, the human hprt gene and the lacZ gene in transgenic rodents.

We have created databases and software applications for the analysis of DNA mutations in the human p53 gene, the human hprt gene and the rodent transgenic lacZ locus. The databases themselves are stand-alone dBase files and the software for analysis of the databases runs on IBM- compatible computers. The software created for these databases permits filtering, ordering, report generation and display of information in the database. In addition, a significant number of routines have been developed for the analysis of single base substitutions. One method of obtaining the databases and software is via the World Wide Web (WWW). Open home page http://sunsite.unc.edu/dnam/mainpage.ht ml with a WWW browser. Alternatively, the databases and programs are available via public ftp from anonymous@sunsite.unc.edu. There is no password required to enter the system. The databases and software are found in subdirectory pub/academic/biology/dna-mutations. Two other programs are available at the WWW site, a program for comparison of mutational spectra and a program for entry of mutational data into a relational database.     

Web-based access to mouse models of human cancers: the Mouse Tumor Biology (MTB) Database

The Mouse Tumor Biology (MTB) Database serves as a curated, integrated resource for information about tumor genetics and pathology in genetically defined strains of mice (i.e., inbred, transgenic and targeted mutation strains). Sources of information for the database include the published scientific literature and direct data submissions by the scientific community. Researchers access MTB using Web-based query forms and can use the database to answer such questions as 'What tumors have been reported in transgenic mice created on a C57BL/6J background?', 'What tumors in mice are associated with mutations in the Trp53 gene?' and 'What pathology images are available for tumors of the mammary gland regardless of genetic background?'. MTB has been available on the Web since 1998 from the Mouse Genome Informatics web site (http://www.informatics.jax.org). We have recently implemented a number of enhancements to MTB including new query options, redesigned query forms and results pages for pathology and genetic data, and the addition of an electronic data submission and annotation tool for pathology data.     

A mutation spectra database for bacterial and mammalian genes.

Each mutation spectrum in this database is a dataset of changes in DNA base sequence in mutations induced in a gene by a particular mutagen (including spontaneous processes) under defined conditions. There are 240 datasets with 24 500 mutants in nine bacterial genes, two phage genes, five mammalian genes and one yeast gene. The database is available on the Web at http://info.med.yale.edu/mutbase/ . The data tables can be viewed on the Web and downloaded in text form for local use. The data are also available in dBASE III, a format which can be utilized by essentially any desktop computer database program or spreadsheet, and makes feasible analyses of a large number of mutants. Researchers are invited to submit additional data. A data entry program, MUTSIN, diagrams each mutation on the computer screen as the data are entered and alerts the user to any discrepancies between the entry and the gene sequence.     

Computational approaches to study the effects of small genomic variations

Advances in DNA sequencing technologies have led to an avalanche-like increase in the number of gene sequences deposited in public databases over the last decade as well as the detection of an enormous number of previously unseen nucleotide variants therein. Given the size and complex nature of the genome-wide sequence variation data, as well as the rate of data generation, experimental characterization of the disease association of each of these variations or their effects on protein structure/function would be costly, laborious, time-consuming, and essentially impossible. Thus, in silico methods to predict the functional effects of sequence variations are constantly being developed. In this review, we summarize the major computational approaches and tools that are aimed at the prediction of the functional effect of mutations, and describe the state-of-the-art databases that can be used to obtain information about mutation significance. We also discuss future directions in this highly competitive field.     

The EMBL nucleotide sequence database

The EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl/) is maintained at the European Bioinformatics Institute (EBI) in an international collaboration with the DNA Data Bank of Japan (DDBJ) and GenBank at the NCBI (USA). Data is exchanged amongst the collaborating databases on a daily basis. The major contributors to the EMBL database are individual authors and genome project groups. Webin is the preferred web-based submission system for individual submitters, whilst automatic procedures allow incorporation of sequence data from large-scale genome sequencing centres and from the European Patent Office (EPO). Database releases are produced quarterly. Network services allow free access to the most up-to-date data collection via ftp, email and World Wide Web interfaces. EBI's Sequence Retrieval System (SRS), a network browser for databanks in molecular biology, integrates and links the main nucleotide and protein databases plus many specialized databases. For sequence similarity searching a variety of tools (e.g. Blitz, Fasta, BLAST) are available which allow external users to compare their own sequences against the latest data in the EMBL Nucleotide Sequence Database and SWISS-PROT.     

KinMutBase, a database of human disease-causing protein kinase mutations.

KinMutBase (http://www.uta.fi/laitokset/imt/KinMut Base.html) is a registry of mutations in human protein kinases related to disorders. Kinases are essential cellular signalling molecules, in which mutations can lead into diseases including, e.g., immunodeficiencies, cancers and endocrine disorders. The first release of KinMutBase contains information for nine protein tyrosine kinases. There are altogether 170 entries representing 273 families and 403 patients. Mutations appear both in conserved hallmark residues of the kinases as well as in non-homologous sites. The KinMutBase WWW pages provide plenty of information, namely mutation statistics and display, clickable sequences with mutations, restriction enzyme patterns and online submission.     

The EMBL Nucleotide Sequence Database: major new developments

The EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl/) incorporates, organizes and distributes nucleotide sequences from all available public sources. The database is located and maintained at the European Bioinformatics Institute (EBI) near Cambridge, UK. In an international collaboration with DDBJ (Japan) and GenBank (USA), data are exchanged amongst the collaborating databases on a daily basis to achieve optimal synchronization. Webin is the preferred web-based submission system for individual submitters, while automatic procedures allow incorporation of sequence data from large-scale genome sequencing centres and from the European Patent Office (EPO). Database releases are produced quarterly. Network services allow free access to the most up-to-date data collection via FTP, Email and World Wide Web interfaces. EBI's Sequence Retrieval System (SRS) integrates and links the main nucleotide and protein databases plus many other specialized molecular biology databases. For sequence similarity searching, a variety of tools (e.g. Fasta, BLAST) are available which allow external users to compare their own sequences against the latest data in the EMBL Nucleotide Sequence Database and SWISS-PROT. All resources can be accessed via the EBI home page at http://www.ebi.ac.uk.     

An inquiry into protein structure and genetic disease: introducing undergraduates to bioinformatics in a large introductory course

This inquiry-based lab is designed around genetic diseases with a focus on protein structure and function. To allow students to work on their own investigatory projects, 10 projects on 10 different proteins were developed. Students are grouped in sections of 20 and work in pairs on each of the projects. To begin their investigation, students are given a cDNA sequence that translates into a human protein with a single mutation. Each case results in a genetic disease that has been studied and recorded in the Online Mendelian Inheritance in Man (OMIM) database. Students use bioinformatics tools to investigate their proteins and form a hypothesis for the effect of the mutation on protein function. They are also asked to predict the impact of the mutation on human physiology and present their findings in the form of an oral report. Over five laboratory sessions, students use tools on the National Center for Biotechnology Information (NCBI) Web site (BLAST, LocusLink, OMIM, GenBank, and PubMed) as well as ExPasy, Protein Data Bank, ClustalW, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the structure-viewing program DeepView. Assessment results showed that students gained an understanding of the Web-based databases and tools and enjoyed the investigatory nature of the lab.     

Biological SOAP servers and web services provided by the public sequence data bank

A number of biological data resources (i.e. databases and data analytical tools) are searchable and usable on-line thanks to the internet and the World Wide Web (WWW) servers. The output from the web server is easy for us to browse. However, it is laborious and sometimes impossible for us to write a computer program that finds a useful data resource, sends a proper query and processes the output. It is a serious obstacle to the integration of distributed heterogeneous data resources. To solve the issue, we have implemented a SOAP (Simple Object Access Protocol) server and web services that provide a program-friendly interface. The web services are accessible at http://www.xml.nig.ac.jp/.     

The protein kinase resource and other bioinformation resources

The Internet, especially the World Wide Web has transformed how today's researchers communicate, share information, and analyze their data. Unfortunately, the vast number of online databases, information resources and analytical tools, some of them masked by unfamiliar titles and Internet addresses, has hindered their universal and effective use by the research community. To overcome these hurdles, subject- and function-specific compendiums are now available which organize information and online tolls in a manner familiar to the biological researcher. The Protein Kinase Resource and the CMS Molecular Biology Resource are two excellent examples of web compendia.     

FisOmics: A portal of fish genomic resources

An online portal, accessible at URL: http://mail.nbfgr.res.in/FisOmics/, was developed that features different genomic databases and tools. The portal, named as FisOmics, acts as a platform for sharing fish genomic sequences and related information in addition to facilitating the access of high-performance computational resources for genome and proteome data analyses. It provides the ability for quarrying, analysing and visualizing genomic sequences and related information. The featured databases in FisOmics are in the World Wide Web domain already. The aim to develop portal was to provide a nodal point to access the featured databases and work conveniently. Presently, FisOmics includes databases on barcode sequences, microsatellite markers, mitogenome sequences, hypoxia-responsive genes and karyology of fishes. Besides, it has a link to other molecular resources and reports on the on-going activities and research achievements.     

Integrated prediction of the effect of mutations on multiple protein characteristics

Site-directed mutagenesis is routinely used in modern biology to elucidate the functional or biophysical roles of protein residues, and plays an important role in the field of rational protein design. Over the past decade, a number of computational tools have been developed that can predict the effect of point mutations on a protein's biophysical characteristics. However, these programs usually provide predictions for only a single characteristic. Furthermore, online versions of these tools are often impractical to use for examination of large and diverse sets of mutants. We have created a new web application, (http://enzyme.ucd.ie/PEAT_SA), that can simultaneously predict the effect of mutations on stability, ligand affinity and pK(a) values. PEAT-SA also provides an expanded feature-set with respect to other online tools which includes the ability to obtain predictions for multiple mutants in one submission. As a result, researchers who use site-directed mutagenesis can access state-of-the-art protein design methods with a fraction of the effort previously required. The results of benchmarking PEAT-SA on standard test-sets demonstrate that its accuracy for all three prediction types compares well to currently available tools. We illustrate PEAT-SA's potential by using it to investigate the influence of mutations on the activity of Subtilisin BPN'. This example demonstrates how the ability to obtain a wide range of information from one source, that can be combined to obtain deeper insight into the influence of mutations, makes PEAT-SA a valuable service to both experimental and computational biologists.     

TreeGeneBrowser: phylogenetic data mining of gene sequences from public databases

MOTIVATION: Sequence databases represent an enormous resource of phylogenetic information, but there is a lack of tools for accessing that information in order to assess the amount of evolutionary information in these databases that may be suitable for phylogenetic reconstruction and for identifying areas of the taxonomy that are under-represented for specific gene sequences. RESULTS: We have developed TreeGeneBrowser which allows inspection and evaluation of gene sequence data for phylogenetic reconstruction. This program improves the efficiency of identification of genes that may be useful for particular phylogenetic studies and identifies taxa and taxonomic branches that are under-represented in sequence databases.     

Web resources for the carbohydrate chemist

Bioinformatics has played a pivotal role in advancing genetics and protein sciences. The large amount of information generated by genomics, and now proteomics, has been a driving force. By comparison, glycobiology still generates small amounts of data. The need to organize our knowledge about carbohydrates is however growing constantly and has given rise to an increasing number of public databases and freely available tools. This review gives an overview of the carbohydrate-oriented resources currently available on the Internet. Many of the resources are seldom referred to in the literature and difficult to find, in part because of the constant flux of the net itself, but also because many efforts have been lead by a single individual. As the World Wide Web has matured the number of 'permanent' resources, maintained by organizations rather than individuals, has increased. In this paper, we present some of the more useful and accessible public tools and databases. There are also a few commercial initiatives but these have not been reviewed.     

The EMBL Nucleotide Sequence Database

The EMBL Nucleotide Sequence Database (aka EMBL-Bank; http://www.ebi.ac.uk/embl/) incorporates, organises and distributes nucleotide sequences from all available public sources. EMBL-Bank is located and maintained at the European Bioinformatics Institute (EBI) near Cambridge, UK. In an international collaboration with DDBJ (Japan) and GenBank (USA), data are exchanged amongst the collaborating databases on a daily basis. Major contributors to the EMBL database are individual scientists and genome project groups. Webin is the preferred web-based submission system for individual submitters, whilst automatic procedures allow incorporation of sequence data from large-scale genome sequencing centres and from the European Patent Office (EPO). Database releases are produced quarterly. Network services allow free access to the most up-to-date data collection via FTP, email and World Wide Web interfaces. EBI’s Sequence Retrieval System (SRS), a network browser for databanks in molecular biology, integrates and links the main nucleotide and protein databases plus many other specialized databases. For sequence similarity searching, a variety of tools (e.g. Blitz, Fasta, BLAST) are available which allow external users to compare their own sequences against the latest data in the EMBL Nucleotide Sequence Database and SWISS-PROT. All resources can be accessed via the EBI home page at http://www.ebi.ac.uk.