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Columba: an integrated database of proteins, structures, and annotations.

BACKGROUND: Structural and functional research often requires the computation of sets of protein structures based on certain properties of the proteins, such as sequence features, fold classification, or functional annotation. Compiling such sets using current web resources is tedious because the necessary data are spread over many different databases. To facilitate this task, we have created COLUMBA, an integrated database of annotations of protein structures. DESCRIPTION: COLUMBA currently integrates twelve different databases, including PDB, KEGG, Swiss-Prot, CATH, SCOP, the Gene Ontology, and ENZYME. The database can be searched using either keyword search or data source-specific web forms. Users can thus quickly select and download PDB entries that, for instance, participate in a particular pathway, are classified as containing a certain CATH architecture, are annotated as having a certain molecular function in the Gene Ontology, and whose structures have a resolution under a defined threshold. The results of queries are provided in both machine-readable extensible markup language and human-readable format. The structures themselves can be viewed interactively on the web. CONCLUSION: The COLUMBA database facilitates the creation of protein structure data sets for many structure-based studies. It allows to combine queries on a number of structure-related databases not covered by other projects at present. Thus, information on both many and few protein structures can be used efficiently. The web interface for COLUMBA is available at http://www.columba-db.de.

Base Sequence↗

Ligand Depot: a data warehouse for ligands bound to macromolecules.

UNLABELLED: Ligand Depot is an integrated data resource for finding information about small molecules bound to proteins and nucleic acids. The initial release (version 1.0, November, 2003) focuses on providing chemical and structural information for small molecules found as part of the structures deposited in the Protein Data Bank. Ligand Depot accepts keyword-based queries and also provides a graphical interface for performing chemical substructure searches. A wide variety of web resources that contain information on small molecules may also be accessed through Ligand Depot. AVAILABILITY: Ligand Depot is available at http://ligand-depot.rutgers.edu/. Version 1.0 supports multiple operating systems including Windows, Unix, Linux and the Macintosh operating system. The current drawing tool works in Internet Explorer, Netscape and Mozilla on Windows, Unix and Linux.

Binding Sites↗

BEAUTY: an enhanced BLAST-based search tool that integrates multiple biological information resources into sequence similarity search results.

BEAUTY (BLAST enhanced alignment utility) is an enhanced version of the NCBI's BLAST data base search tool that facilitates identification of the functions of matched sequences. We have created new data bases of conserved regions and functional domains for protein sequences in NCBI's Entrez data base, and BEAUTY allows this information to be incorporated directly into BLAST search results. A Conserved Regions Data Base, containing the locations of conserved regions within Entrez protein sequences, was constructed by (1) clustering the entire data base into families, (2) aligning each family using our PIMA multiple sequence alignment program, and (3) scanning the multiple alignments to locate the conserved regions within each aligned sequence. A separate Annotated Domains Data Base was constructed by extracting the locations of all annotated domains and sites from sequences represented in the Entrez, PROSITE, BLOCKS, and PRINTS data bases. BEAUTY performs a BLAST search of those Entrez sequences with conserved regions and/or annotated domains. BEAUTY then uses the information from the Conserved Regions and Annotated Domains data bases to generate, for each matched sequence, a schematic display that allows one to directly compare the relative locations of (1) the conserved regions, (2) annotated domains and sites, and (3) the locally aligned regions matched in the BLAST search. In addition, BEAUTY search results include World-Wide Web hypertext links to a number of external data bases that provide a variety of additional types of information on the function of matched sequences. This convenient integration of protein families, conserved regions, annotated domains, alignment displays, and World-Wide Web resources greatly enhances the biological informativeness of sequence similarity searches. BEAUTY searches can be performed remotely on our system using the "BCM Search Launcher" World-Wide Web pages (URL is < http:/ /gc.bcm.tmc.edu:8088/ search-launcher/launcher.html > ).

Amino Acid Sequence↗

The Protein Kinase Resource: everything you always wanted to know about protein kinases but were afraid to ask.

Protein kinases and phosphatases play crucial roles in all the major cellular processes, such as signal transduction, cell differentiation, cell proliferation and cell cycle progression. Protein phosphorylation or dephosphorylation can form the basis of many critical processes, including enzyme activation or inactivation, protein localization and protein degradation. Given the importance of protein kinases to cellular development and function, it is critical that there are effective ways of disseminating information on protein kinases to the research community. This review describes such a web resource, 'The Protein Kinase Resource' (http://pkr.sdsc.edu/html/index.shtml), which serves as a repository for cellular and molecular data on protein kinases.

Animals↗

Expert searching in public health.

OBJECTIVE: The article explores the characteristics of public health information needs and the resources available to address those needs that distinguish it as an area of searching requiring particular expertise. METHODS: Public health searching activities from reference questions and literature search requests at a large, urban health department library were reviewed to identify the challenges in finding relevant public health information. RESULTS: The terminology of the information request frequently differed from the vocabularies available in the databases. Searches required the use of multiple databases and/or Web resources with diverse interfaces. Issues of the scope and features of the databases relevant to the search questions were considered. CONCLUSION: Expert searching in public health differs from other types of expert searching in the subject breadth and technical demands of the databases to be searched, the fluidity and lack of standardization of the vocabulary, and the relative scarcity of high-quality investigations at the appropriate level of geographic specificity. Health sciences librarians require a broad exposure to databases, gray literature, and public health terminology to perform as expert searchers in public health.

Evidence-Based Medicine↗

Gene2EST: a BLAST2 server for searching expressed sequence tag (EST) databases with eukaryotic gene-sized queries.

Expressed sequence tags (ESTs) are randomly sequenced cDNA clones. Currently, nearly 3 million human and 2 million mouse ESTs provide valuable resources that enable researchers to investigate the products of gene expression. The EST databases have proven to be useful tools for detecting homologous genes, for exon mapping, revealing differential splicing, etc. With the increasing availability of large amounts of poorly characterised eukaryotic (notably human) genomic sequence, ESTs have now become a vital tool for gene identification, sometimes yielding the only unambiguous evidence for the existence of a gene expression product. However, BLAST-based Web servers available to the general user have not kept pace with these developments and do not provide appropriate tools for querying EST databases with large highly spliced genes, often spanning 50 000-100 000 bases or more. Here we describe Gene2EST (http://woody.embl-heidelberg.de/gene2est/), a server that brings together a set of tools enabling efficient retrieval of ESTs matching large DNA queries and their subsequent analysis. RepeatMasker is used to mask dispersed repetitive sequences (such as Alu elements) in the query, BLAST2 for searching EST databases and Artemis for graphical display of the findings. Gene2EST combines these components into a Web resource targeted at the researcher who wishes to study one or a few genes to a high level of detail.

Amino Acid Sequence↗

IMGT, the international ImMunoGeneTics information system, http://imgt.cines.fr.

IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr), is a high quality integrated knowledge resource specializing in immunoglobulins (IG), T cell receptors (TR) and major histocompatibility complexes (MHC) and related proteins of the immune system (RPI) 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, and 2D and 3D structures. IMGT includes five databases (IMGT/LIGM-DB, IMGT/3Dstructure-DB, IMGT/MHC-DB, IMGT/PRIMER-DB, IMGT/GENE-DB) Web resources ('IMGT Marie-Paule page') and interactive tools (IMGT/V-QUEST, IMGT/JunctionAnalysis, IMGT/PhyloGene, IMGT/LocusView, IMGT/GeneView, IMGT/GeneSearch, IMGT/StructureQuery). IMGT data are expertly annotated according to the rules of the IMGT Scientific chart based on IMGTONTOLOGY. IMGT tools are particularly useful for the analysis of the IG and TR repertoires in physiological normal and pathological situations. IMGT has important applications in medical research (autoimmune diseases, AIDS, leukaemias, lymphomas, myelomas), biotechnology related to antibody engineering (phage displays, combinatorial libraries) and therapeutic approaches (graft, immunotherapy). IMGT is freely available at http://imgt.cines.fr.

Animals↗

Teaching evidence-based medicine on a busy hospitalist service: residents rate a pilot curriculum.

PURPOSE: To increase evidence-based medicine (EBM) instruction within the confines of reduced resident work hours. METHOD: In 2001-02, the authors designed and implemented an EBM curriculum for residents on an inpatient medicine service at Stanford University Medical Center. Thirty-six residents were assigned the hospitalist rotation in its pilot year. Attendings introduced EBM concepts and Internet resources. During daily rounds, housestaff presented patient-based EBM literature search results. After the rotation, residents were given a questionnaire on which they were asked to rate the impact of the curriculum on their understanding of 20 EBM terms or practice skills (1 = no effect to 5 = strong effect). RESULTS: Twenty-three residents (64%) completed the questionnaire. The results were very positive with average effect of more than 4 (somewhat strong effect/impact) for 16 of the 20 questions. High-speed Internet access and EBM Web resources were critical to efficient delivery of the curriculum during inpatient care. CONCLUSION: The pilot curriculum successfully introduced the practice of EBM during active inpatient care without requiring additional hours from housestaff schedules. To further evaluate and expand this project, EBM skills will be tested before and after the rotation, and faculty development will allow consistent delivery in additional clinical settings.

Attitude of Health Personnel↗

IMGT-ONTOLOGY for immunogenetics and immunoinformatics.

IMGT, the international ImMunoGeneTics information system(R) (http://imgt.cines.fr), is a high quality integrated knowledge resource specializing in immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC) and related proteins of the immune system (RPI) of human and other vertebrates, created in 1989, by the Laboratoire d'ImmunoGenetique Moleculaire LIGM. 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 consists of several sequence databases (IMGT/LIGM-DB, IMGT/MHC-DB, IMGT/PRIMER-DB), one genome database (IMGT/GENE-DB) and one three-dimensional structure database (IMGT/3Dstructure-DB), interactive tools for sequence analysis (IMGT/V-QUEST, IMGT/JunctionAnalysis, IMGT/PhyloGene, IMGT/Allele-Align), for genome analysis (IMGT/GeneSearch, IMGT/GeneView, IMGT/LocusView) and for 3D structure analysis (IMGT/StructuralQuery), and Web resources ("IMGT Marie-Paule page") comprising 8000 HTML pages. IMGT other accesses include SRS, FTP, search by BLAST, etc. By its high quality and its easy data distribution, IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas, myelomas), veterinary research, genome diversity and genome evolution studies of the adaptive immune responses, biotechnology related to antibody engineering (scFv, phage displays, combinatorial libraries) and therapeutical approaches (grafts, immunotherapy). IMGT is freely available at http://imgt.cines.fr.

Animals↗

Map of dermatology: 'first-impression' user feedback and agenda for further development.

BACKGROUND: Map of Dermatology (http://healthcybermap.org/dermap/) is a free web resource that enables users to search for images of skin conditions by body region and morphology rather than by condition name, which is much more useful and natural in answering questions about unknown clinical presentations/diagnoses, especially for non-specialists. OBJECTIVES AND METHODS: This paper presents responses received from twelve users, including specialist dermatologists, non-specialists (some with interests in health informatics), and lay persons, who provided their 'first-impression' feedback on Map of Dermatology by responding to a very short e-mail questionnaire covering service usefulness and interface usability. The paper also provides a brief review of the gaps in current online dermatology information service provision in general. RESULTS: The overall user feedback received was very positive. An exploratory discussion of the arguments and possibilities for radically improving Map of Dermatology to produce 'the ultimate web-based dermatology diagnostic tool' is also provided, together with some desiderata and preliminary 'design and feature specifications' for such a tool based on users' suggestions, the gaps highlighted in other existing online dermatology tools, and the author's own reflections and experience. CONCLUSIONS: When successfully developed, the proposed tool is expected to have significant potential for efficiently and effectively addressing many of the currently unmet educational needs of clinicians.

Atlases as Topic↗

Design and evaluation of SchoolhealthLink, a Web-based health information resource.

SchoolhealthLink, a Web-based information service for Missouri school nurses, is a promising resource to reach school nurses isolated from traditional professional networks. It also may serve as an important adjunct to stay abreast of the latest health information. Using a strategy to identify the health information needs of school nurses and to test the site early in its development, this pilot study found school nurses reported SchoolhealthLink was an easy-to-use method to find high-quality, up-to-date information relevant to school nursing practice, was better than existing methods to access information, and could change the way they practiced. In order to continue to build SchoolhealthLink, a partnership with Barnes College of Nursing and the Missouri Association of School Nurses has been established to work together to continue to add health information resources useful to school nursing practice.

Attitude of Health Personnel↗

Can examination of WWW usage statistics and other indirect quality indicators distinguish the relative quality of medical web sites?

BACKGROUND: The Internet offers a great amount of health related websites, but concern has been raised about their reliability. Several subjective evaluation criteria and websites rating systems have been proposed as a help for the Internet users to distinguish among web resources with different quality, but their efficacy has not been proven. OBJECTIVES: To evaluate the agreement of a subset of Internet rating systems editorial boards regarding their evaluations of a sample of pediatric websites. To evaluate certain websites characteristics as possible quality indicators for pediatric websites. METHODS: Comparative survey of the Results of systematic evaluations of the contents and formal aspects of a sample of pediatric websites, with the number of daily visits to those websites, the time since their last update, the impact factor of their authors or editors, and the number of websites linked to them. RESULTS: 363 websites were compiled from eight rating systems. Only 25 were indexed and evaluated by at least two rating systems. This subset included more updated and more linked websites. There was no correlation among the Results of the evaluation of these 25 websites by the rating systems. The number of inbound links to the websites significantly correlated with their updating frequency (p<.001), with the number of daily visits (p=.005), and with the Results of their evaluation by the largest rating system, HealthAtoZ (p<.001). The websites updating frequency also significantly correlated with the RESULTS of the websites evaluation by HealthAtoZ, both about their contents (p=.001) and their total values (p<.05). The number of daily visits significantly correlated (p<.05) with the Results of the evaluations by Medical Matrix. CONCLUSIONS: Some websites characteristics as the number of daily visits, their updating frequency and, overall, the number of websites linked to them, correlate with their evaluation by some of the largest rating systems on the Internet, what means that certain indexes obtained from the usage analysis of pediatric websites could be used as quality indicators. On the other hand, the citation analysis on the Web by the quantification of inbound links to medical websites could be an objective and feasible tool in rating great amounts of websites.

Health Education↗

The surgeon and AIDS: twenty years later.

BACKGROUND: Since the first reports on indications and outcome for abdominal procedures in the HIV/AIDS patient were published 20 years ago, the epidemiology and presentation of surgical illness have changed remarkably with the advent of new antiviral regimens. A review of the now occasional, but still important, role of the surgeon in contemporary treatment of HIV/AIDS is presented. DATA SOURCES: Information was obtained by PubMed searches of medical journals, examination of reference lists, and Web resources. STUDY SELECTION: Articles on operative indications, outcomes, precautions, source of transmission, and pathophysiology of HIV/AIDS were selected. DATA EXTRACTION: Data was obtained from peer-reviewed articles and references. DATA SYNTHESIS: The last 2 decades have seen a decrease in operative mortality from as high as 85% to approximately 15% with a corresponding improvement in morbidity. Surgical emergencies such as appendicitis occur in HIV patients with the same frequency as non-HIV patients and are treated with equivalent results. Concern about transmission of HIV in the operating room has lessened somewhat. Although still a hazard, the probability of HIV transmission with accidental exposure is low, with risks below 0.5% for percutaneous hollow-bore needles and less than 0.1% risk for mucus membrane exposure. CONCLUSIONS: Improved surgical outcomes together with of accurate data on the modes and likelihood of accidental transmission of HIV to members of the surgery team have resulted in the treatment of HIV/AIDS patients becoming an accepted part of routine surgical practice.

Abdomen, Acute↗

[Training and continuing education via the Internet].

A world-wide homogeneous level of knowledge for all members of an expert community is the proposed aim of academic education. The potential of the World Wide Web (WWW) with respect to under- and postgraduate education maybe accomplished if its use will become a definite part of cultural skills. Additionally, the process of simple collection of information should be added by the process of gaining knowledge and experience. Adaptation to the target group and a high degree of inter-activity are the two main characteristics of high-quality technology-based learning materials. Considering both most of the web-resources show deficits. Instructional design as well as information technology have means to overcome these deficits. With respect to the didactic principles of materials for beginners and advanced students, the architecture of computerised learning programs plays a significant role. However, costs to develop high-level learning materials is extremely high. Therefore it is necessary, to use synergetic effects with other digitized clinical and scientific materials.

Computer-Assisted Instruction↗

A combined strategy of "in silico" transcriptome analysis and web search engine optimization allows an agile identification of reference genes suitable for normalization in gene expression studies.

Traditionally housekeeping genes have been employed as endogenous reference (internal control) genes for normalization in gene expression studies. Since the utilization of single housekeepers cannot assure an unbiased result, new normalization methods involving multiple housekeeping genes and normalizing using their mean expression have been recently proposed. Moreover, since a gold standard gene suitable for every experimental condition does not exist, it is also necessary to validate the expression stability of every putative control gene on the specific requirements of the planned experiment. As a consequence, finding a good set of reference genes is for sure a non-trivial problem requiring quite a lot of lab-based experimental testing. In this work we identified novel candidate barley reference genes suitable for normalization in gene expression studies. An advanced web search approach aimed to collect, from publicly available web resources, the most interesting information regarding the expression profiling of candidate housekeepers on a specific experimental basis has been set up and applied, as an example, on stress conditions. A complementary lab-based analysis has been carried out to verify the expression profile of the selected genes in different tissues and during heat shock response. This combined dry/wet approach can be applied to any species and physiological condition of interest and can be considered very helpful to identify putative reference genes to be shortlisted every time a new experimental design has to be set up.

Base Sequence↗

The role of informatics in glycobiology research with special emphasis on automatic interpretation of MS spectra.

This paper reviews the current status of bioinformatics applications and databases in glycobiology, which are based on bioinformatics approaches as well as informatics for glycobiology where an explicit encoding of glycan structures is required. The availability of the complete sequence of the human genome has accelerated the systematic identification of so far unidentified glycogenes considerably in many areas of glycobiology using well-established bioinfomatics tools. Although there has been an immense development of new glyco-related data collections as well as informatics tools and several efforts have been started to cross-link and reference the various data deposited in distributed databases, informatics for glycobiology and glycomics is still poorly developed compared to the genomics and proteomics area. The development of algorithms for the automatic interpretation of MS spectra - currently, a severe bottleneck, which hampers the rapid and reliable interpretation of MS data in high-throughput glycomics projects - is reviewed. A comprehensive list of web resources is given. Several lines of progression are discussed. There is an urgent need for the development of decentralised input facilities of experimentally determined glycan structures. Simultaneously, agreements of standards for the structural description of glycans as well as formats for the related data have to be established. The integration of glycomics with genomics/proteomics has to increase.

Computational Biology↗

A single-cell meta-analysis evidences transposable element dysregulation in sex-based differences in Parkinson's disease.

Transposable elements (TEs) (mobile genetic elements comprising &#x223c;45% of the human genome) have recently emerged as potential contributors to Parkinson's disease (PD); however their role and sex-specific impact remain poorly understood. Here, we present the first integrative meta-analysis of TE expression across 4 substantia nigra single-nucleus RNA-seq datasets, comprising a total of 66 donors, generating a cell-type-resolved atlas of TE dysregulation in PD. We identified widespread TE activation across major brain cell types (i.e. neurons, astrocytes, oligodendrocytes and microglia), with marked upregulation of L1s in neurons and HERVs in oligodendrocytes. Sex-stratified analyses revealed distinct male- and female-biased TE signatures, indicating regulatory programs uniquely affected in each sex, including MIR elements in microglia and Alu subfamilies in neurons. Correlation and genomic proximity analyses also uncovered TE-gene associations linked to important PD pathways such as neuroinflammation or myelination. Collectively, our study positions TEs as potential sex-modulated contributors to PD pathology and also provides a public web resource (PATOSS) to explore PD-associated TE transcriptional deregulation.

Parkinson's disease↗

Plastid proteomics.

Plastids are essential organelles present in virtually all cells in plants and in green algae. The proteomes of plastids, and in particular of chloroplasts, have received significant amounts of attention in recent years. Various fractionation and mass spectrometry (MS) techniques have been applied to catalogue the chloroplast proteome and its membrane compartments. Neural network and hidden Markov models, in combination with experimentally derived filters, were used to try to predict the chloroplast subproteomes. Some of the many protein-protein interaction, as well as post-translational modifications have been characterized. Nevertheless, our understanding of the chloroplast proteome and its dynamics is very incomplete. Rapid improvements and wide-scale implementation of MS and new tools for comparative proteomics will undoubtedly accelerate this understanding in the near future. Proteomics studies often generate a large amount of data and these data are only meaningful if they can be easily accessed via the 'world-wide-web' and connected to other types of biological information. The plastid proteome data base (PPDB at http://www.ppdb.tc.cornell.edu/) and other web resources are discussed. This review will briefly summarize recent experimental and theoretical efforts, attempt to translate these data into the functions of the chloroplast and outline expectations and possibilities for (comparative) chloroplast proteomics.

Chloroplasts↗