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PubMed2002

IMGT, the international ImMunoGeneTics database: a high-quality information system for comparative immunogenetics and immunology.

IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr), is a high quality integrated information system specializing in Immunoglobulins (IG), T cell Receptors (TR) and Major Histocompatibility Complex (MHC) of human and other vertebrates, created in 1989, by LIGM, at the Université Montpellier II, CNRS, Montpellier, France. IMGT provides a common access to standardized data, which include nucleotide and protein sequences, oligonucleotide primers, gene maps, genetic polymorphisms, specificities, 2D and 3D structures. IMGT includes several databases (IMGT/LIGM-DB, IMGT/HLA-DB, IMGT/3Dstructure-DB), Web resources ('IMGT Marie-Paule page') which comprise IMGT Scientific Chart, IMGT Repertoire, IMGT Bloc-notes, IMGT Education, IMGT Aide-mémoire and IMGT Index, and interactive tools (IMGT/V-QUEST, IMGT/JunctionAnalysis). These expertly annotated data on the genome, proteome, genetics and structure of the IG, TR and MHC are of high value for comparative genome evolution studies of the adaptative immune response.

Animals↗

PubMed1998

Database tools for integrating and searching membrane property data correlated with neuronal morphology.

A critical problem in neuroscience is the lack of database tools for integrating neuronal property data. We report here the development of a combined object oriented-relational database (NeuronDB, http://senselab.med.yale.edu/neurondb) that meets these needs by providing tools for integrating data within neurons and comparing data across neurons. It focuses on three types of neuronal properties voltage-gated channels, neurotransmitter receptors, and neurotransmitters. The data are organized in relation to different regions of neurons as represented in canonical forms; using simple canonical models of complex cells as a vehicle for indexing information permits the database to be searchable across different neurons. Using these multidimensional search tools, users can locate specific properties in specific regions of a neuron; obtain integrated summaries of all properties within a region; and carry out searches to compare properties across equivalent compartments in different neurons. These tools thus permit searches of the multidimensional neuron property space equivalent to homology searches of sequence databases. NeuronDB is accessible over the Internet; it provides immediate links to citation indexes and abstracts supporting the deposited data, and annotations that indicate the state of acceptance of the data. Users are encouraged to contribute data. The ability to input the data from NeuronDB directly to NEURON and GENESIS is being developed. As a shared Web resource, NeuronDB should enhance the efforts of neuroscientists and neuronal modellers to analyze and compare the functional operations of different types of neurons.

Automation↗

PubMed2003

Membrane protein crystallization.

The need for high-resolution structure information on membrane proteins is immediate and growing. Currently, the only reliable way to get it is crystallographically. The rate-limiting step from protein to structure is crystal production. An overview of the current ideas and experimental approaches prevailing in the area of membrane protein crystallization is presented. The long-established surfactant-based method has been reviewed extensively and is not examined in detail here. The focus instead is on the latest methods, all of which exploit the spontaneous self-assembling properties of lipids and detergent as vesicles (vesicle-fusion method), discoidal micelles (bicelle method), and liquid crystals or mesophases (in meso or cubic-phase method). In the belief that a knowledge of the underlying phase science is integral to understanding the molecular basis of these assorted crystallization strategies, the article begins with a brief primer on lipids, mesophases, and phase science, and the related issue of form and function as applied to lipids is addressed. The experimental challenges associated with and the solutions for procuring adequate amounts of homogeneous membrane proteins, or parts thereof, are examined. The cubic-phase method is described from the following perspectives: how it is done in practice, its general applicability and successes to date, and the nature of the mesophases integral to the process. Practical aspects of the method are examined with regard to salt, detergent, and screen solution effects; crystallization at low temperatures; tailoring the cubic phase to suit the target protein; different cubic-phase types; dealing with low-protein samples, colorless proteins, microcrystals, and radiation damage; transport within the cubic phase for drug design, cofactor retention, and phasing; using spectroscopy for quality control; harvesting crystals; and miniaturization and robotization for high-throughput screening. The section ends with a hypothesis for nucleation and growth of membrane protein crystals in meso. Thus far, the bicelle and vesicle-fusion methods have produced crystals of one membrane protein, bacteriorhodopsin. The experimental details of both methods are reviewed and their general applicability in the future is commented on. The three new methods are rationalized by analogy to crystallization in microgravity and with respect to epitaxy. A list of Web resources in the area of membrane protein crystallogenesis is included.

Crystallization↗

PubMed2003

Institutionalizing pain management: the Post-Operative Pain Management Quality Improvement Project.

Clinical practice and quality improvement (QI) guidelines for acute postoperative pain management have been developed to address the well-documented problem of undertreatment of postoperative pain. The Post-Operative Pain Management Quality Improvement Project (the POP Project) was initiated to determine whether an intervention designed to support hospitals in the development of QI efforts would lead to improvements in structures, processes, and outcomes consistent with recommended guidelines. A nationwide sample of 233 hospitals joined the project. The intervention consisted of written resource materials accompanied by support services that included an e-mail list server, a resource Web page, and assistance from POP Project staff via telephone. Data regarding critical structures, processes (practice patterns), and patient outcomes were collected at baseline before the intervention began and at follow-up 12 to 18 months later. Results showed a statistically significant increase from baseline (45%) to follow-up (72%) in the presence of structural elements that are critical to improving pain management. There were statistically significant improvements in practices including documented use of pain rating scales, decreased use of intramuscular opioids, and increased use of nonpharmacologic strategies. Patient survey data showed no change in pain outcomes. Evaluation data showed that 70% of hospitals were very or extremely satisfied with their participation in the POP Project and 90% of them planned to continue efforts to improve pain management after the POP Project ended. Further research is needed to determine how to translate the excellent results obtained for structure and process into meaningful outcomes for patients.

Data Collection↗

PubMed2003

Parent education after newborn congenital heart surgery.

The moment an infant is diagnosed with a congenital heart defect, parents experience a mixture of shock, disbelief, fear, anger, and often a profound sense of sadness. In the midst of these emotions they must learn to provide for the special needs of their infant. Providing parents with the knowledge and skills to care for their infant during this stressful time requires the concerted effort of a multidisciplinary team who can provide clear, concise, and consistent communication. This article provides a step-by-step guide to the information needs of families who are preparing to take their infants home after cardiac surgery. Parents must understand the underlying cardiac defect and the goals and objectives of the surgical repair. In addition to normal newborn care, parents need to learn about care of the incision, nutritional support, and how to safely administer prescribed medications. Potential complications and when to call their health care provider or seek emergency care are an important focus of teaching. Information about infant development, challenges specific to their infant, and pragmatic strategies to support normal development are of prime interest to parents. Written reference materials, a Web resource list, and a family discharge teaching tool provide tangible resources for the family after discharge.

Adult↗

PubMed2005

Complex trait analysis of gene expression uncovers polygenic and pleiotropic networks that modulate nervous system function.

Patterns of gene expression in the central nervous system are highly variable and heritable. This genetic variation among normal individuals leads to considerable structural, functional and behavioral differences. We devised a general approach to dissect genetic networks systematically across biological scale, from base pairs to behavior, using a reference population of recombinant inbred strains. We profiled gene expression using Affymetrix oligonucleotide arrays in the BXD recombinant inbred strains, for which we have extensive SNP and haplotype data. We integrated a complementary database comprising 25 years of legacy phenotypic data on these strains. Covariance among gene expression and pharmacological and behavioral traits is often highly significant, corroborates known functional relations and is often generated by common quantitative trait loci. We found that a small number of major-effect quantitative trait loci jointly modulated large sets of transcripts and classical neural phenotypes in patterns specific to each tissue. We developed new analytic and graph theoretical approaches to study shared genetic modulation of networks of traits using gene sets involved in neural synapse function as an example. We built these tools into an open web resource called WebQTL that can be used to test a broad array of hypotheses.

Animals↗

PubMed2006

Our favourite alternative splice site.

Alternative splicing is a widespread mechanism in mammals that generates several mRNAs from one gene, thereby creating genetic diversity of the genome. Variant splice patterns are often specific to different stages of development or particular tissues, and alternative splicing defects are being more frequently detected in genetic diseases and cancers. The increasingly important role of alternative splicing in the function and the regulation of cellular process makes it critical to have an easy-to-use data repository for the biological and medical research communities. We have compared web resources that give access to information on alternatively spliced genes, and the FAST DB (Friendly Alternative Splicing and Transcripts DataBase) site came out as our favourite.

Alternative Splicing↗

PubMed2006

Internet organ solicitation, explained.

The growth of internet-based communications and the increasing demand for living organ donors are resulting in more use of Web sites for organ solicitation. Web resources have the capacity to improve public awareness about both organ donations and transplant outcomes. Rules for organ donation and fair allocation must follow legal principles regarding organ solicitation. Categories of internet recipient/donor matching services include "clearing house," "membership," and "individual" sites. All these raise ethical concerns related to the individual recipient/donor relationship and to the current system of organ allocation. However, a lack of rules and regulations regarding internet solicitation exists. Several pragmatic steps are proposed.

Health Knowledge, Attitudes, Practice↗

PubMed2002

Tools for clinical toxicology on the World Wide Web: review and scenario.

Clinical toxicologists are entrusted with the health and safety of humans and animals exposed to toxic substances. To do their jobs well they need a solid knowledge of toxicological principles, an ability to handle emergent situations, a "bedside" manner that results in a good rapport with patients, and the ability to access current and accurate information in order to properly care for the afflicted. An information armamentarium that is increasingly digital and Web-based is becoming a necessity. This article reviews Web resources that can assist the toxicologist. A case scenario is presented to provide a practical perspective to the information tools outlined.

Chemical Phenomena↗

PubMedDate not supplied

Conformational and physicochemical DNA features specific for transcription factor binding sites.

MOTIVATION: A reliable recognition of transcription factor binding sites is essential for analysis of regulatory genomic sequences. The experimental data make evident an important role of DNA conformational features for site functioning. However, Internet-available tools for revealing conformational and physicochemical DNA features significant for the site functioning and subsequent use of these features for site recognition have not been developed up to now. RESULTS: We suggest an approach for revealing significant conformational and physicochemical properties of functional sites implemented in the database B-DNA-VIDEO. This database is designed to study the sets of various transcription factor binding sites, providing evidence that transcription factor binding sites are characterized by specific sets of significant conformational and physicochemical DNA properties. For a fixed site, by using the B-DNA features selected for this site recognition, the C-program recognizing this site may be generated, control tested and stored in the database B-DNA-VIDEO. Each B-DNA-VIDEO entry links to the Web-applet recognizing the site, whose significant B-DNA features are stored in this entry as the 'site recognition programs'. The pairwise linked entry-applet pairs are compiled within the B-DNA-VIDEO system, which is simultaneously the database and the program tools package applicable immediately for recognizing the sites stored in the database. Indeed, this is the novelty. Hence, B-DNA-VIDEO is the Web resource of both 'searching for static data' and 'active computation' type, that is why it was called an 'activated database'. AVAILABILITY: B-DNA-VIDEO is available at http://wwwmgs.bionet.nsc.ru/systems/BDNAVideo/ and the mirror site at http://www.cbil.upenn.edu/mgs/systems/c onsfreq/.

Base Sequence↗

PubMed1999

Genomes OnLine Database (GOLD 1.0): a monitor of complete and ongoing genome projects world-wide.

UNLABELLED: GOLD (Genomes On Line Database) is a World Wide Web resource for comprehensive access to information regarding complete and ongoing genome projects around the world. AVAILABILITY: GOLD is based at the University of Illinois at Urbana-Champaign and is available at http://geta.life.uiuc.edu/ approximately nikos/genomes. html. It is also mirrored at the European Bioinformatics Institute at http://www.ebi.ac.uk/research/cgg/genomes.html. CONTACT: genomes@ebi.ac.uk

Databases, Factual↗

PubMed2000

Modeling splice sites with Bayes networks.

MOTIVATION: The main goal in this paper is to develop accurate probabilistic models for important functional regions in DNA sequences (e.g. splice junctions that signal the beginning and end of transcription in human DNA). These methods can subsequently be utilized to improve the performance of gene-finding systems. The models built here attempt to model long-distance dependencies between non-adjacent bases. RESULTS: An efficient modeling method is described which models biological data more accurately than a first-order Markov model without increasing the number of parameters. Intuitively, a small number of parameters helps a learning system to avoid overfitting. Several experiments with the model are presented, which show a small improvement in the average accuracy as compared with a simple Markov model. These experiments suggest that single long distance dependencies do not help the recognition problem, thus confirming several previous studies which have used more heuristic modeling techniques. AVAILABILITY: This software is available for downloaded and as a web resource at http://www.ai.uic.edu/software CONTACT: kasif@eecs.uic.edu

Bayes Theorem↗

PubMed2004

A web portal for classification of expression data using maximal margin linear programming.

The Maximal Margin (MAMA) linear programming classification algorithm has recently been proposed and tested for cancer classification based on expression data. It demonstrated sound performance on publicly available expression datasets. We developed a web interface to allow potential users easy access to the MAMA classification tool. Basic and advanced options provide flexibility in exploitation. The input data format is the same as that used in most publicly available datasets. This makes the web resource particularly convenient for non-expert machine learning users working in the field of expression data analysis.

Algorithms↗

PubMed2005

IntegratedMap: a Web interface for integrating genetic map data.

SUMMARY: IntegratedMap is a Web application and database schema for storing and interactively displaying genetic map data. Its Web interface includes a menu for direct chromosome/linkage group selection, a search form for selection based on mapped object location and linkage group displays. An overview display provides convenient access to the full range of mapped and anchored object types with genetic locus details, such as numbers, types and names of mapped/anchored objects displayed in a compact scrollable list box that automatically updates based on selected map location and object type. Also, multilinkage group and localized map views are available along with links that can be configured for integration with other Web resources. AVAILABILITY: IntegratedMap is implemented in C#/ASP.NET and the package, including a MySQL schema creation script, is available from http://cggc.agtec.uga.edu/Data/download.asp

Algorithms↗

PubMed2006

HaptenDB: a comprehensive database of haptens, carrier proteins and anti-hapten antibodies.

UNLABELLED: The key requirement for successful immunochemical assay is the availability of antibodies with high specificity and desired affinity. Small molecules, when used as haptens, are not immunogenic. However, on conjugating with carrier molecule they elicit antibody response. The production of anti-hapten antibodies of desired specificity largely depends on the hapten design (preserving greatly the chemical structure and spatial conformation of target compound), selection of the appropriate carrier protein and the conjugation method. This manuscript describes a curated database HaptenDB, where information is collected from published literature and web resources. The current version of the database has 2021 entries for 1087 haptens and 25 carrier proteins, where each entry provides comprehensive details about (1) nature of the hapten, (2) 2D and 3D structures of haptens, (3) carrier proteins, (4) coupling method, (5) method of anti-hapten antibody production, (6) assay method (used for characterization) and (7) specificities of antibodies. The current version of HaptenDB covers a wide array of haptens including pesticides, herbicides, insecticides, drugs, vitamins, steroids, hormones, toxins, dyes, explosives, etc. It provides internal and external links to various databases/resources to obtain further information about the nature of haptens, carriers and respective antibodies. For structure similarity comparison of haptens, the database also integrates tools like JME Editor and JMOL for sketching, displaying and manipulating hapten 2D/3D structures online. So the database would be of great help in identifying functional group(s) in smaller molecules using antibodies as well as for the development of immunodiagnostics/therapeutics by providing data and procedures available so far for the generation of specific or cross-reactive antibodies. AVAILABILITY: HaptenDB is available on http://www.imtech.res.in/raghava/haptendb/ and http://bioinformatics.uams.edu/raghava/haptendb/ (Mirror site).

Antibodies↗

PubMed2005

OxfordGrid: a web interface for pairwise comparative map views.

SUMMARY: OxfordGrid is a web application and database schema for storing and interactively displaying genetic map data in a comparative, dot-plot, fashion. Its display is composed of a matrix of cells, each representing a pairwise comparison of mapped probe data for two linkage groups or chromosomes. These are arranged along the axes with one forming grid columns and the other grid rows with the degree and pattern of synteny/colinearity between the two linkage groups manifested in the cell's dot density and structure. A mouse click over the selected grid cell launches an image map-based display for the selected cell. Both individual and linear groups of mapped probes can be selected and displayed. Also, configurable links can be used to access other web resources for mapped probe information. AVAILABILITY: OxfordGrid is implemented in C#/ASP.NET and the package, including MySQL schema creation scripts, is available at ftp://cggc.agtec.uga.edu/OxfordGrid/.

Algorithms↗

PubMed2005

VIS-O-BAC: exploratory visualization of functional genome studies from bacteria.

UNLABELLED: The visualization-aided exploration of complex datasets will allow the research community to formulate novel functional hypotheses leading to a better understanding of biological processes at all levels. Therefore, we have developed a web resource termed VIS-O-BAC designed for the functional investigation of expression data for model systems, such as bacterial pathogens based on a graphical display. Genome-scale datasets derived from typical 'omic' approaches can directly be explored with respect to three biologically relevant aspects, the genome structure (operon organization), the organization of genes in pathways (KEGG) and the gene function with Gene Ontology (GO) terms. The integrated viewers can be used in parallel and combine expression data and functional annotations from different external data repositories. The graphical visualizations evidently accelerate both the validation of regulatory information and the detection of affected biological processes. AVAILABILITY: http://leger2.gbf.de/cgi-bin/vis-o-bac.pl. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Chromosome Mapping↗

PubMed2006

DomainSieve: a protein domain-based screen that led to the identification of dam-associated genes with potential link to DNA maintenance.

MOTIVATION: The Dam methyltransferase (DamMT) activity, broadly distributed in association with restriction endonucleases, as part of the restriction-modification defense systems, has evolved to become intimately associated with essential biological functions in a few organisms. In Escherichia coli, DamMT is involved in multiple aspects of DNA maintenance, replication initiation, daughter chromosome segregation, DNA mismatch repair, gene expression control, etc. The participation of DamMT in such a diverse set of functions required that other genes adapted, or emerged through evolution, in response to the DamMT-induced modification of the genomic environment. One example is SeqA, a protein that senses the methylation status of the origin of replication of the chromosome to control the timing of replication initiation. Interestingly, seqA is only present in a few DamMT-specifying proteobacteria. This observation led us to hypothesize that other genes, specifying related functions, might also be found in these organisms. To test this hypothesis, we implemented a large-scale comparative genomic screen meant to identify genes specifying DNA methylation sensing domains, probably involved in DNA maintenance functions. RESULTS: We carried out a phylogenetic analysis of DamMT, identifying two contrasting behaviors of the protein. Based on this phylogeny, we defined precisely a set of genomes, in which the protein activity is likely to be involved in DNA maintenance functions, the 'resident' dam genomes. We defined a second set of genomes, in which DamMT is not resident. We developped a new tool, 'DomainSieve', in order to screen these two sets for protein domains that are strictly associated with 'resident' dam genomes. This approach was rewarding and generated a list of genes, among which some, at least, specify activities with clear linkage to DamMT-dependent DNA methylation and DNA maintenance. AVAILABILITY: DomainSieve is implemented as a web resource and is accessible at http://stat.genopole.cnrs.fr/ds/.

Algorithms↗