The Protein Structure Initiative Structural Biology Knowledgebase Technology Portal: a structural biology web resource

The Technology Portal of the Protein Structure Initiative Structural Biology Knowledgebase (PSI SBKB; http://technology.sbkb.org/portal/ ) is a web resource providing information about methods and tools that can be used to relieve bottlenecks in many areas of protein production and structural biology research. Several useful features are available on the web site, including multiple ways to search the database of over 250 technological advances, a link to videos of methods on YouTube, and access to a technology forum where scientists can connect, ask questions, get news, and develop collaborations. The Technology Portal is a component of the PSI SBKB ( http://sbkb.org ), which presents integrated genomic, structural, and functional information for all protein sequence targets selected by the Protein Structure Initiative. Created in collaboration with the Nature Publishing Group, the SBKB offers an array of resources for structural biologists, such as a research library, editorials about new research advances, a featured biological system each month, and a functional sleuth for searching protein structures of unknown function. An overview of the various features and examples of user searches highlight the information, tools, and avenues for scientific interaction available through the Technology Portal.     

The Supramap project: linking pathogen genomes with geography to fight emergent infectious diseases

Novel pathogens have the potential to become critical issues of national security, public health and economic welfare. As demonstrated by the response to Severe Acute Respiratory Syndrome (SARS) and influenza, genomic sequencing has become an important method for diagnosing agents of infectious disease. Despite the value of genomic sequences in characterizing novel pathogens, raw data on their own do not provide the information needed by public health officials and researchers. One must integrate knowledge of the genomes of pathogens with host biology and geography to understand the etiology of epidemics. To these ends, we have created an application called Supramap ( http://supramap.osu.edu ) to put information on the spread of pathogens and key mutations across time, space and various hosts into a geographic information system (GIS). To build this application, we created a web service for integrated sequence alignment and phylogenetic analysis as well as methods to describe the tree, mutations, and host shifts in Keyhole Markup Language (KML). We apply the application to 239 sequences of the polymerase basic 2 (PB2) gene of recent isolates of avian influenza (H5N1). We map a mutation, glutamic acid to lysine at position 627 in the PB2 protein (E627K), in H5N1 influenza that allows for increased replication of the virus in mammals. We use a statistical test to support the hypothesis of a correlation of E627K mutations with avian‐mammalian host shifts but reject the hypothesis that lineages with E627K are moving westward. Data, instructions for use, and visualizations are included as supplemental materials at: http://supramap.osu.edu/sm/supramap/publications . © The Willi Hennig Society 2010.     

Prediction of protein stability changes for single-site mutations using support vector machines

Accurate prediction of protein stability changes resulting from single amino acid mutations is important for understanding protein structures and designing new proteins. We use support vector machines to predict protein stability changes for single amino acid mutations leveraging both sequence and structural information. We evaluate our approach using cross-validation methods on a large dataset of single amino acid mutations. When only the sign of the stability changes is considered, the predictive method achieves 84% accuracy-a significant improvement over previously published results. Moreover, the experimental results show that the prediction accuracy obtained using sequence alone is close to the accuracy obtained using tertiary structure information. Because our method can accurately predict protein stability changes using primary sequence information only, it is applicable to many situations where the tertiary structure is unknown, overcoming a major limitation of previous methods which require tertiary information. The web server for predictions of protein stability changes upon mutations (MUpro), software, and datasets are available at http://www.igb.uci.edu/servers/servers.html.     

MUTYH Associated Polyposis (MAP)

MUTYH Associated Polyposis (MAP), a Polyposis predisposition caused by biallelic mutations in the Base Excision Repair (BER) gene MUTYH, confers a marked risk of colorectal cancer (CRC). The MAP phenotype is difficult to distinguish from other hereditary CRC syndromes. Especially from Familial Adenomatous Polyposis (FAP) and to a lesser extend Lynch Syndrome, which are caused by germline mutations in the APC and Mismatch Repair (MMR) genes, respectively.     

« Biology/medicine 2.0 »: an overview

In the last decade, the applications known as "web 2.0" (Facebook, Youtube, Twitter…) have changed our daily life and gradually influence the field of research. This article aims at proposing a critical overview of these new services, and emphasizes the changes induced for researchers (practice of scientific publication, sharing and mutualization of research data and discussion between researchers…) especially in the field of biology/medicine. A focus is done on the limitations that prevent most of scientists from using these services in their common practice (lack of knowledge about these tools, time-consuming, fear of sharing data and ideas). Despite these restrictions, some mutations affecting researcher's information uses are unavoidable, and these new tools may rapidly contribute to scientific advances.     

Selecton: a server for detecting evolutionary forces at a single amino-acid site

SUMMARY: We present an algorithmic tool for the identification of biologically significant amino acids in proteins of known three dimensional structure. We estimate the degree of purifying selection and positive Darwinian selection at each site and project these estimates onto the molecular surface of the protein. Thus, patches of functional residues (undergoing either positive or purifying selection), which may be discontinuous in the linear sequence, are revealed. We test for the statistical significance of the site-specific scores in order to obtain reliable and valid estimates. AVAILABILITY: The Selecton web server is available at: http://selecton.bioinfo.tau.ac.il SUPPLEMENTARY INFORMATION: More information is available at http://selecton.bioinfo.tau.ac.il/overview.html. A set of examples is available at http://selecton.bioinfo.tau.ac.il/gallery.html.     

WWW and the aerobiologist: operating instructions

For several years now, the World Wide Web (WWW) has left the realm of information technology and represents a fundamental everyday working tool for a wide variety of disciplines. Aerobiology, though a newcomer in this virtual space, is proceeding at a fast pace towards the creation of an easily accessible and effective information network. The web gives access to text, imagery, movie and sound with relatively low-cost and user-friendly interfaces conceived as graphical magazines. A practical way to start navigating and looking for information is to operate a ‘search engine’ which is a large database containing addresses on a wide spectrum of subjects. As an alternative, a few selected sites exist that can initialize your search by providing a thematic list of addresses. After leaving the entry ‘port’ you are directed from site to site and eventually end up with a lot more information than you initially thought. Excerpts: information on public and private institutions, access to databases and image catalogs, bibliographical information, overview of monitoring networks, directions on national and international research programs, news (calendar of meetings, courses, etc.). Information is provided for the non-expert user who asks himself the key questions: ‘Where do I start to browse the net?’ or ‘Can I become a provider of information on the net and, if so, is it terribly difficult?’ The idea is that everybody can in principle become a ‘surfer’ or a ‘provider’ dedicating a reasonable amount of time and effort to the task. What one ends up with is an easy-to-use and powerful tool that is already helping the whole aerobiological community to pursue its goals and reach out for necessary interdisciplinary approaches to unsolved scientific issues. The server AEROBIOLOGY INTERNATIONAL (http://www.fisbat.bo.cnr.it/AERO/) is presented as an example on how to proceed with the creation of a new server and its management.     

ZCURVE_CoV: a new system to recognize protein coding genes in coronavirus genomes,and its applications in analyzing SARS-CoV genomes

A new system to recognize protein coding genes in the coronavirus genomes, specially suitable for the SARS-CoV genomes, has been proposed in this paper. Compared with some existing systems, the new program package has the merits of simplicity, high accuracy, reliability, and quickness. The system ZCURVE_CoV has been run for each of the 11 newly sequenced SARS-CoV genomes. Consequently, six genomes not annotated previously have been annotated, and some problems of previous annotations in the remaining five genomes have been pointed out and discussed. In addition to the polyprotein chain ORFs 1a and 1b and the four genes coding for the major structural proteins, spike (S), small envelop (E), membrane (M), and nuleocaspid (N), respectively, ZCURVE_CoV also predicts 5-6 putative proteins in length between 39 and 274 amino acids with unknown functions. Some single nucleotide mutations within these putative coding sequences have been detected and their biological implications are discussed. A web service is provided, by which a user can obtain the annotated result immediately by pasting the SARS-CoV genome sequences into the input window on the web site (http://tubic.tju.edu.cn/sars/). The software ZCURVE_CoV can also be downloaded freely from the web address mentioned above and run in computers under the platforms of Windows or Linux.     

Research resource: Update and extension of a glycoprotein hormone receptors web application

The SSFA-GPHR (Sequence-Structure-Function-Analysis of Glycoprotein Hormone Receptors) database provides a comprehensive set of mutation data for the glycoprotein hormone receptors (covering the lutropin, the FSH, and the TSH receptors). Moreover, it provides a platform for comparison and investigation of these homologous receptors and helps in understanding protein malfunctions associated with several diseases. Besides extending the data set (> 1100 mutations), the database has been completely redesigned and several novel features and analysis tools have been added to the web site. These tools allow the focused extraction of semiquantitative mutant data from the GPHR subtypes and different experimental approaches. Functional and structural data of the GPHRs are now linked interactively at the web interface, and new tools for data visualization (on three-dimensional protein structures) are provided. The interpretation of functional findings is supported by receptor morphings simulating intramolecular changes during the activation process, which thus help to trace the potential function of each amino acid and provide clues to the local structural environment, including potentially relocated spatial counterpart residues. Furthermore, double and triple mutations are newly included to allow the analysis of their functional effects related to their spatial interrelationship in structures or homology models. A new important feature is the search option and data visualization by interactive and user-defined snake-plots. These new tools allow fast and easy searches for specific functional data and thereby give deeper insights in the mechanisms of hormone binding, signal transduction, and signaling regulation. The web application "Sequence-Structure-Function-Analysis of GPHRs" is accessible on the internet at http://www.ssfa-gphr.de/.     

The DT40 web site: sampling and connecting the genes of a B cell line

Thousands of new vertebrate genes have been discovered and genetic systems are needed to address their functions at the cellular level. The chicken B cell line DT40 allows efficient gene disruptions due to its high homologous recombination activity. However, cloning the gene of interest is often cumbersome, since relatively few chicken cDNA sequences are present in the public databases. In addition, the accumulation of multiple mutations within the same cell clone is limited by the consumption of one drug-resistance marker for each transfection. Here, we present the DT40 web site (http://genetics.hpi.uni-hamburg.de/dt40.html), which includes a comprehensive database of chicken bursal ESTs to identify disruption candidate genes and recyclable marker cassettes based on the loxP system. These freely available resources greatly facilitate the analysis of genes and genetic networks.     

Comparative Genometrics (CG): a database dedicated to biometric comparisons of whole genomes

The ever increasing rate at which whole genome sequences are becoming accessible to the scientific community has created an urgent need for tools enabling comparison of chromosomes of different species. We have applied biometric methods to available chromosome sequences and posted the results on our Comparative Genometrics (CG) web site. By genometrics, a term coined by Elston and Wilson [Genet. Epidemiol. (1990), 7, 17–19], we understand a biometric analysis of chromosomes. During the initial phase, our web site displays, for all completely sequenced prokaryotic genomes, three genometric analyses: the DNA walk [Lobry (1999) Microbiology Today, 26, 164–165] and two complementary representations, i.e. the cumulative GC- and TA-skew analyses, capable of identifying, at the level of whole genomes, features inherent to chromosome organization and functioning. It appears that the latter features are taxon-specific. Although primarily focused on prokaryotic chromosomes, the CG web site contains genometric information on paradigm plasmids, phages, viruses and eukaryotic organelles. Relevant data and methods can be readily used by the scientific community for further analyses as well as for tutorial purposes. Our data posted at the CG web site are freely available on the World Wide Web at http://www.unil.ch/comparativegenometrics.     

GALT Protein Database, a Bioinformatics Resource for the Management and Analysis of Structural Features of a Galactosemia-related Protein and Its Mutants

We describe the GALT-Prot database and its related web-based application that have been developed to collect information about the structural and functional effects of mutations on the human enzyme galactose-1-phosphate uridyltransferase (GALT) involved in the genetic disease named galactosemia type Ⅰ. Besides a list of missense mutations at gene and protein sequence levels, GALT-Prot reports the analysis results of mutant GALT structures. In addition to the structural information about the wild-type enzyme, the database also includes structures of over 100 single point mutants simulated by means of a computational procedure, and the analysis to each mutant was made with several bioinformatics programs in order to investigate the effect of the mutations. The web-based interface allows querying of the database, and several links are also provided in order to guarantee a high integration with other resources already present on the web. Moreover, the architecture of the database and the web application is flexible and can be easily adapted to store data related to other proteins with point mutations. GALT-Prot is freely available at http://bioinformatica.isa.cnr.it/GALT/.     

A tool for gene expression based PubMed search through combining data sources

SUMMARY: We present a new tool for the semi-automated querying of PubMed using a batch of tens to thousands of GenBank accession numbers or UniGene cluster ids. By combining information from UniGene and SWISS-PROT, microGENIE obtains information on the biological relevance of expressed genes, as identified by micro-array experiments, with minimal user intervention and time investment. AVAILABILITY: microGENIE is freely available from http://www.cs.vu.nl/microgenie SUPPLEMENTARY INFORMATION: The web site above supplies examples of input and output files.     

ASAP: automated sequence annotation pipeline for web-based updating of sequence information with a local dynamic database

The automated sequence annotation pipeline (ASAP) is designed to ease routine investigation of new functional annotations on unknown sequences, such as expressed sequence tags (ESTs), through querying of web-accessible resources and maintenance of a local database. The system allows easy use of the output from one search as the input for a new search, as well as the filtering of results. The database is used to store formats and parameters and information for parsing data from web sites. The database permits easy updating of format information should a site modify the format of a query or of a returned web page.     

Digestive system disorders: gastroesophageal reflux disease

This article comes from Clinical Evidence (1999; 1 : 145-153), a new resource for clinicians produced jointly by the BMJ Publishing Group and the American College of Physicians-American Society of Internal Medicine. Clinical Evidence is an extensively peer-reviewed publication that summarizes the best available evidence on the effects of common clinical interventions gleaned from thorough searches and appraisal of the world literature. It became available in the United States late last year. Please see advertisement for more information or, alternatively, visit the web site at www. evidence.org.     

GeneReporter--sequence-based document retrieval and annotation

GeneReporter is a web tool that reports functional information and relevant literature on a protein-coding sequence of interest. Its purpose is to support both manual genome annotation and document retrieval. PubMed references corresponding to a sequence are detected by the extraction of query words from UniProt entries of homologous sequences. Data on protein families, domains, potential cofactors, structure, function, cellular localization, metabolic contribution and corresponding DNA binding sites complement the information on a given gene product of interest. Availability and implementation: GeneReporter is available at http://www.genereporter.tu-bs.de. The web site integrates databases and analysis tools as SOAP-based web services from the EBI (European Bioinformatics Institute) and NCBI (National Center for Biotechnology Information).     

ParIS Genome Rearrangement server

SUMMARY: ParIS Genome Rearrangement is a web server for a Bayesian analysis of unichromosomal genome pairs. The underlying model allows inversions, transpositions and inverted transpositions. The server generates a Markov chain using a Partial Importance Sampler technique, and samples trajectories of mutations from this chain. The user can specify several marginalizations to the posterior: the posterior distribution of number of mutations needed to transform one genome into another, length distribution of mutations, number of mutations that have occurred at a given site. Both text and graphical outputs are available. We provide a limited server, a downloadable unlimited server that can be installed locally on any linux/Unix operating system, and a database of mitochondrial gene orders.     

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.