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.     

SynView: a GBrowse-compatible approach to visualizing comparative genome data

SUMMARY: We present SynView, a simple and generic approach to dynamically visualize multi-species comparative genome data. It is a light-weight application based on the popular and configurable web-based GBrowse framework. It can be used with a variety of databases and provides the user with a high degree of interactivity. The tool is written in Perl and runs on top of the GBrowse framework. It is in use in the PlasmoDB (http://www.PlasmoDB.org) and the CryptoDB (http://www.CryptoDB.org) projects and can be easily integrated into other cross-species comparative genome projects. AVAILABILITY: The program and instructions are freely available at http://www.ApiDB.org/apps/SynView/ CONTACT: jkissing@uga.edu.     

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.     

mmsearch: a motif arrangement language and search program.

This paper presents a language for describing arrangements of motifs in biological sequences, and a program that uses the language to find the arrangements in motif match databases. The program does not by itself search for the constituent motifs, and is thus independent of how they are detected, which allows it to use motif match data of various origins. AVAILABILITY: The program can be tested online at http://hits.isb-sib.ch and the distribution is available from ftp://ftp.isrec.isb-sib.ch/pub/software/unix/mmsearch-1.0.tar.gz CONTACT: Thomas.Junier@isrec.unil.ch SUPPLEMENTARY INFORMATION: The full documentation about mmsearchis available from http://hits.isb-sib.ch/~tjunier/mmsearch/doc.     

GSTaxClassifier: a genomic signature based taxonomic classifier for metagenomic data analysis

GSTaxClassifier (Genomic Signature based Taxonomic Classifier) is a program for metagenomics analysis of shotgun DNA sequences. The program includes

1. a simple but effective algorithm, a modification of the Bayesian method, to predict the most probable genomic origins of sequences at different taxonomical ranks, on the basis of genome databases;
2. a function to generate genomic profiles of reference sequences with tri-, tetra-, penta-, and hexa-nucleotide motifs for setting a user-defined database;
3. two different formats (tabular- and tree-based summaries) to display taxonomic predictions with improved analytical methods; and
4. effective ways to retrieve, search, and summarize results by integrating the predictions into the NCBI tree-based taxonomic information.

GSTaxClassifier takes input nucleotide sequences and using a modified Bayesian model evaluates the genomic signatures between metagenomic query sequences and reference genome databases. The simulation studies of a numerical data sets showed that GSTaxClassifier could serve as a useful program for metagenomics studies, which is freely available at http://helix2.biotech.ufl.edu:26878/metagenomics/.     

Biomarkers used in studying air pollution exposure during pregnancy and perinatal outcomes: a review

Purpose: This review focuses on studies among pregnant women that used biomarkers to assess air pollution exposure, or to understand the mechanisms by which it affects perinatal outcomes.

Methods: We searched PubMed and Google scholar databases to find articles.

Results and conclusions: We found 29 articles, mostly consisting of cohort studies. Interpolation models were most frequently used to assess exposure. The most consistent positive association was between polycyclic aromatic hydrocarbon (PAH) exposure during entire pregnancy and cord blood PAH DNA adducts. Exposure to particulate matter (PM) and nitrogen dioxide (NO₂) showed consistent inverse associations with mitochondrial DNA (mtDNA) content, particularly in the third trimester of pregnancy. No single pollutant showed strong associations with all the biomarkers included in this review. C-reactive proteins (CRPs) and oxidative stress markers increased, whereas telomere length decreased with increasing air pollution exposure. Placental global DNA methylation and mtDNA methylation showed contrasting results with air pollution exposure, the mechanism behind which is unclear. Most studies except those on PAH DNA adducts and mtDNA content provided insufficient evidence for characterizing a critical exposure window. Further research using biomarkers is warranted to understand the relationship between air pollution and perinatal outcomes.     

Development of bioinformatics resources for display and analysis of copy number and other structural variants in the human genome

The discovery of an abundance of copy number variants (CNVs; gains and losses of DNA sequences >1 kb) and other structural variants in the human genome is influencing the way research and diagnostic analyses are being designed and interpreted. As such, comprehensive databases with the most relevant information will be critical to fully understand the results and have impact in a diverse range of disciplines ranging from molecular biology to clinical genetics. Here, we describe the development of bioinformatics resources to facilitate these studies. The Database of Genomic Variants (http://projects.tcag.ca/variation/) is a comprehensive catalogue of structural variation in the human genome. The database currently contains 1,267 regions reported to contain copy number variation or inversions in apparently healthy human cases. We describe the current contents of the database and how it can serve as a resource for interpretation of array comparative genomic hybridization (array CGH) and other DNA copy imbalance data. We also present the structure of the database, which was built using a new data modeling methodology termed Cross-Referenced Tables (XRT). This is a generic and easy-to-use platform, which is strong in handling textual data and complex relationships. Web-based presentation tools have been built allowing publication of XRT data to the web immediately along with rapid sharing of files with other databases and genome browsers. We also describe a novel tool named eFISH (electronic fluorescence in situ hybridization) (http://projects.tcag.ca/efish/), a BLAST-based program that was developed to facilitate the choice of appropriate clones for FISH and CGH experiments, as well as interpretation of results in which genomic DNA probes are used in hybridization-based experiments.     

DNAlive: a tool for the physical analysis of DNA at the genomic scale

SUMMARY: DNAlive is a tool for the analysis and graphical display of structural and physical characteristics of genomic DNA. The web server implements a wide repertoire of metrics to derive physical information from DNA sequences with a powerful interface to derive 3D information on large sequences of both naked and protein-bound DNAs. Furthermore, it implements a mesoscopic Metropolis code which allows the inexpensive study of the dynamic properties of chromatin fibers. In addition, our server also surveys other protein and genomic databases allowing the user to combine and explore the physical properties of selected DNA in the context of functional features annotated on those regions. AVAILABILITY: http://mmb.pcb.ub.es/DNAlive/ ; http://www.inab.org/     

MASV--Multiple (BLAST) Annotation System Viewer

Multiple (BLAST) Annotation System Viewer (MASV) is a tool designed to aid in the annotation of genomic sequences. MASV enables the researcher to compare and analyse differences in annotation and analysis, resulting from changes in databases, analysis program parameters and results. This provides a unique capability for the user to conduct further bioinformatics analysis from the information obtained. AVAILABILITY: http://cbbc.murdoch.edu.au/projects/masv/     

FAIR: A server for internal sequence repeats

An Internet computing server has been developed to identify all the occurrences of the internal sequence repeats in a protein and DNA sequences. Further, an option is provided for the users to check the occurrence(s) of the resultant sequence repeats in the other sequence and structure (Protein Data Bank) databases. The databases deployed in the proposed computing engine are up-to-date and thus the users will get the latest information available in the respective databases. The server is freely accessible over the World Wide Web (WWW). AVAILABILITY: http://bioserver1.physics.iisc.ernet.in/fair/     

GoFigure: automated Gene Ontology annotation

SUMMARY: We have developed a web tool to predict Gene Ontology (GO) terms. The tool accepts an input DNA or protein sequence, and uses BLAST to identify homologous sequences in GO annotated databases. A graph is returned to the user via email. AVAILABILITY: The tool is freely available at: http://udgenome.ags.udel.edu/frm_go.html/     

Cellular senescence induces replication stress with almost no affect on DNA replication timing

Organismal aging entails a gradual decline of normal physiological functions and a major contributor to this decline is withdrawal of the cell cycle, known as senescence. Senescence can result from telomere diminution leading to a finite number of population doublings, known as replicative senescence (RS), or from oncogene overexpression, as a protective mechanism against cancer. Senescence is associated with large-scale chromatin re-organization and changes in gene expression. Replication stress is a complex phenomenon, defined as the slowing or stalling of replication fork progression and/or DNA synthesis, which has serious implications for genome stability, and consequently in human diseases. Aberrant replication fork structures activate the replication stress response leading to the activation of dormant origins, which is thought to be a safeguard mechanism to complete DNA replication on time. However, the relationship between replicative stress and the changes in the spatiotemporal program of DNA replication in senescence progression remains unclear.

Here, we studied the DNA replication program during senescence progression in proliferative and pre-senescent cells from donors of various ages by single DNA fiber combing of replicated DNA, origin mapping by sequencing short nascent strands and genome-wide profiling of replication timing (TRT).

We demonstrate that, progression into RS leads to reduced replication fork rates and activation of dormant origins, which are the hallmarks of replication stress. However, with the exception of a delay in RT of the CREB5 gene in all pre-senescent cells, RT was globally unaffected by replication stress during entry into either oncogene-induced or RS. Consequently, we conclude that RT alterations associated with physiological and accelerated aging, do not result from senescence progression. Our results clarify the interplay between senescence, aging and replication programs and demonstrate that RT is largely resistant to replication stress.     

Human DNA repair genes, 2005

An updated inventory of about 150 human DNA repair genes is described. The compilation includes genes encoding DNA repair enzymes, some genes associated with cellular responses to DNA damage, and other genes associated with genetic instability or sensitivity to DNA damaging agents. The updated human DNA repair genes table (http://www.cgal.icnet.uk/DNA_Repair_Genes.htmlhttp://www.cgal.icnet.uk/DNA_Repair_Genes.html) is a research and reference tool that directly links to several databases: Gene Cards, Online Mendelian Inheritance in Man, the NCBI MapViewer for chromosome position, and the NCBI Entrez database for the reference nucleotide sequence. This article discusses the approximately 25 genes added, since the original version of the table was first produced in 2001, and some other revisions.     

FACIL: Fast and Accurate Genetic Code Inference and Logo

MOTIVATION: The intensification of DNA sequencing will increasingly unveil uncharacterized species with potential alternative genetic codes. A total of 0.65% of the DNA sequences currently in Genbank encode their proteins with a variant genetic code, and these exceptions occur in many unrelated taxa. RESULTS: We introduce FACIL (Fast and Accurate genetic Code Inference and Logo), a fast and reliable tool to evaluate nucleic acid sequences for their genetic code that detects alternative codes even in species distantly related to known organisms. To illustrate this, we apply FACIL to a set of mitochondrial genomic contigs of Globobulimina pseudospinescens. This foraminifer does not have any sequenced close relative in the databases, yet we infer its alternative genetic code with high confidence values. Results are intuitively visualized in a Genetic Code Logo. Availability and implementation: FACIL is available as a web-based service at http://www.cmbi.ru.nl/FACIL/ and as a stand-alone program.     

Flicker image comparison of 2-D gel images for putative protein identification using the 2DWG meta-database

With the availability of two-dimensional (2-D) gel electrophoresis databases that have many characterized proteins, it may be possible to compare a researcher’s gel images with those in relevant databases. This may lead to the putative identification of unknown protein spots in a researcher’s gel with those characterized in a given database, saving the researcher time and money by suggesting monoclonal antibodies to try in confirming these identifications. We have developed two tools to help with this comparison: (1) Flicker, http://www.lecb.ncifcrf.gov/flicker/, a Java applet program running in the researcher’s Web browser, to visually compare their gels against gels on the Internet; and (2) the 2DWG meta-database, http://www.lecb.ncifcrf.gov/2dwgDB/, a searchable database of locations of 2-D electrophoretic gel images found on the Internet. Recent additions to Flicker allow users to click on a protein spot in a gel that is linked to a federated 2D gel database, such as SWISS-2DPAGE, and have it retrieve a report from that Web database for that protein.     

Visualization and analysis of protein interactions

SUMMARY: We have developed a new program called InterViewer for drawing large-scale protein interaction networks in three-dimensional space. Unique features of InterViewer include (1) it is much faster than other recent implementations of drawing algorithms; (2) it can be used not only for visualizing protein interactions but also for analyzing them interactively; and (3) it provides an integrated framework for querying protein interaction databases and directly visualizes the query results. AVAILABILITY: http://wilab.inha.ac.kr/protein/     

BioDownloader: bioinformatics downloads and updates in a few clicks

There are many ftp or http servers storing data required for biological research. While some download applications are available, there is no user-friendly download application with a graphical interface specifically designed and adapted to meet the requirements of bioinformatics. BioDownloader is a program for downloading and updating files from ftp and http servers. It is optimized to work robustly with large numbers of files. It allows the selective retrieval of only the required files (batch downloads, multiple file masks, ls-lR file parsing, recursive search, recent updates, etc.). BioDownloader has a built-in repository containing the settings for common bioinformatics file-synchronization needs, including the Protein Data Bank (PDB) and National Center for Biotechnology Information (NCBI) databases. It can post-process downloaded files, including archive extraction and file conversions. AVAILABILITY: The program can be installed from http://dunbrack.fccc.edu/BioDownloader. The software is freely available for both non-commercial and commercial users under the BSD license.