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PubMed2003

Applying database technology to clinical and basic research bioinformatics projects.

This paper describes the application of database technology to medical information with the goal of providing medical and clinical researchers with the tools necessary to plan bioinformatics projects. Commercial database management systems were utilized, standard database design practices were applied, a user interface was created, data entered, and the development of analysis tools, including data mining technologies is underway. Databases were constructed based on animal and cell culture models of diabetes and clinical data. Bioinformatics is a useful tool in both basic research and clinical settings. The advantages of relational databases and an approach to managing bioinformatics projects are discussed.

Animals↗
PubMed2002

Grouping and identification of sequence tags (GRIST): bioinformatics tools for the NEIBank database.

NEIBank is a project to develop and organize genomics and bioinformatics resources for the eye. As part of this effort, tools have been developed for bioinformatics analysis and web based display of data from expressed sequence tag (EST) analyses. EST sequences are identified and formed into groups or clusters representing related transcripts from the same gene. This is carried out by a rules-based procedure called GRIST (GRouping and Identification of Sequence Tags) that uses sequence match parameters derived from BLAST programs. Linked procedures are used to eliminate non-mRNA contaminants. All data are assembled in a relational database and assembled for display as web pages with annotations and links to other informatics resources. Genome projects generate huge amounts of data that need to be classified and organized to become easily accessible to the research community. GRIST provides a useful tool for assembling and displaying the results of EST analyses. The NEIBank web site contains a growing set of pages cataloging the known transcriptional repertoire of eye tissues, derived from new NEIBank cDNA libraries and from eye-related data deposited in the dbEST section of GenBank.

Animals↗
PubMed2002

SeqHound: biological sequence and structure database as a platform for bioinformatics research.

BACKGROUND: SeqHound has been developed as an integrated biological sequence, taxonomy, annotation and 3-D structure database system. It provides a high-performance server platform for bioinformatics research in a locally-hosted environment. RESULTS: SeqHound is based on the National Center for Biotechnology Information data model and programming tools. It offers daily updated contents of all Entrez sequence databases in addition to 3-D structural data and information about sequence redundancies, sequence neighbours, taxonomy, complete genomes, functional annotation including Gene Ontology terms and literature links to PubMed. SeqHound is accessible via a web server through a Perl, C or C++ remote API or an optimized local API. It provides functionality necessary to retrieve specialized subsets of sequences, structures and structural domains. Sequences may be retrieved in FASTA, GenBank, ASN.1 and XML formats. Structures are available in ASN.1, XML and PDB formats. Emphasis has been placed on complete genomes, taxonomy, domain and functional annotation as well as 3-D structural functionality in the API, while fielded text indexing functionality remains under development. SeqHound also offers a streamlined WWW interface for simple web-user queries. CONCLUSIONS: The system has proven useful in several published bioinformatics projects such as the BIND database and offers a cost-effective infrastructure for research. SeqHound will continue to develop and be provided as a service of the Blueprint Initiative at the Samuel Lunenfeld Research Institute. The source code and examples are available under the terms of the GNU public license at the Sourceforge site http://sourceforge.net/projects/slritools/ in the SLRI Toolkit.

Amino Acid Sequence↗
PubMed2005

Update in bioinformatics. Toward a digital database of plant cell signalling networks: advantages, limitations and predictive aspects of the digital model.

The process of signal integration, which contributes to the regulation of multiple cellular activities, can be described in a digital language by a set of connected digital operations. In this article we delineate the basic concepts of cell signalling in the context of a logical description of information processing. Newly described instances of signal integration in plants are given as examples. The different advantages, limitations and predictive aspects of the digital modeling of signal transduction networks, as well as the minimal architecture of a computer database for plant signalling networks are discussed.

Computational Biology↗
PubMed2003

E-MSD: the European Bioinformatics Institute Macromolecular Structure Database.

The E-MSD macromolecular structure relational database (http://www.ebi.ac.uk/msd) is designed to be a single access point for protein and nucleic acid structures and related information. The database is derived from Protein Data Bank (PDB) entries. Relational database technologies are used in a comprehensive cleaning procedure to ensure data uniformity across the whole archive. The search database contains an extensive set of derived properties, goodness-of-fit indicators, and links to other EBI databases including InterPro, GO, and SWISS-PROT, together with links to SCOP, CATH, PFAM and PROSITE. A generic search interface is available, coupled with a fast secondary structure domain search tool.

Animals↗
PubMed2006

Bioinformatics and its applications in plant biology.

Bioinformatics plays an essential role in today's plant science. As the amount of data grows exponentially, there is a parallel growth in the demand for tools and methods in data management, visualization, integration, analysis, modeling, and prediction. At the same time, many researchers in biology are unfamiliar with available bioinformatics methods, tools, and databases, which could lead to missed opportunities or misinterpretation of the information. In this review, we describe some of the key concepts, methods, software packages, and databases used in bioinformatics, with an emphasis on those relevant to plant science. We also cover some fundamental issues related to biological sequence analyses, transcriptome analyses, computational proteomics, computational metabolomics, bio-ontologies, and biological databases. Finally, we explore a few emerging research topics in bioinformatics.

Computational Biology↗
PubMed1998

The EMBL nucleotide sequence database.

The EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl. html ) constitutes Europe's primary nucleotide sequence resource. DNA and RNA sequences are directly submitted from researchers and genome sequencing groups and collected from the scientific literature and patent applications (Fig. 1). In collaboration with DDBJ and GenBank the database is produced, maintained and distributed at the European Bioinformatics Institute. Database releases are produced quarterly and are distributed on CD-ROM. EBI's network services allow access to the most up-to-date data collection via Internet and World Wide Web interface, providing database searching and sequence similarity facilities plus access to a large number of additional databases.

Base Sequence↗
PubMed2005

Apolipoprotein l6, a novel proapoptotic Bcl-2 homology 3-only protein, induces mitochondria-mediated apoptosis in cancer cells.

Cancer cells frequently possess defects in the genetic and biochemical pathways of apoptosis. Members of the Bcl-2 family play pivotal roles in regulating apoptosis and possess at least one of four Bcl-2 homology (BH) domains, designated BH1 to BH4. The BH3 domain is the only one conserved in proapoptotic BH3-only proteins and plays an important role in protein-protein interactions in apoptosis by regulating homodimerization and heterodimerization of the Bcl-2 family members. To date, 10 BH3-only proapoptotic proteins have been identified and characterized in the human genome. The completion of the Human Genome Project and the availability of various public databases and sequence analysis algorithms allowed us to use the bioinformatic database-mining approach to identify one novel BH3-only protein, apolipoprotein L6 (ApoL6). The full-length cDNA of ApoL6 was identified, cloned, and functionally expressed in p53-null colorectal cancer cells (DLD-1). We found that overexpression of wild-type ApoL6 induced mitochondria-mediated apoptosis in DLD-1 cells characterized by release of cytochrome c and Smac/DIABLO from mitochondria and activation of caspase-9, whereas ApoL6 BH3 domain deletion allele did not. In addition, overexpression of ApoL6 also induced activation of caspase-8. Furthermore, we showed that adenovirus harboring the full-length cDNA of ApoL6 induced marked apoptosis in a variety of cancer cell types, and ApoL6 recruited and interacted with lipid/fatty acid components during the induction of apoptosis. To our knowledge, this is the first example that intracellular overproduction of an apolipoprotein induces marked apoptosis.

Alleles↗
PubMed2004

A web services choreography scenario for interoperating bioinformatics applications.

BACKGROUND: Very often genome-wide data analysis requires the interoperation of multiple databases and analytic tools. A large number of genome databases and bioinformatics applications are available through the web, but it is difficult to automate interoperation because: 1) the platforms on which the applications run are heterogeneous, 2) their web interface is not machine-friendly, 3) they use a non-standard format for data input and output, 4) they do not exploit standards to define application interface and message exchange, and 5) existing protocols for remote messaging are often not firewall-friendly. To overcome these issues, web services have emerged as a standard XML-based model for message exchange between heterogeneous applications. Web services engines have been developed to manage the configuration and execution of a web services workflow. RESULTS: To demonstrate the benefit of using web services over traditional web interfaces, we compare the two implementations of HAPI, a gene expression analysis utility developed by the University of California San Diego (UCSD) that allows visual characterization of groups or clusters of genes based on the biomedical literature. This utility takes a set of microarray spot IDs as input and outputs a hierarchy of MeSH Keywords that correlates to the input and is grouped by Medical Subject Heading (MeSH) category. While the HTML output is easy for humans to visualize, it is difficult for computer applications to interpret semantically. To facilitate the capability of machine processing, we have created a workflow of three web services that replicates the HAPI functionality. These web services use document-style messages, which means that messages are encoded in an XML-based format. We compared three approaches to the implementation of an XML-based workflow: a hard coded Java application, Collaxa BPEL Server and Taverna Workbench. The Java program functions as a web services engine and interoperates with these web services using a web services choreography language (BPEL4WS). CONCLUSION: While it is relatively straightforward to implement and publish web services, the use of web services choreography engines is still in its infancy. However, industry-wide support and push for web services standards is quickly increasing the chance of success in using web services to unify heterogeneous bioinformatics applications. Due to the immaturity of currently available web services engines, it is still most practical to implement a simple, ad-hoc XML-based workflow by hard coding the workflow as a Java application. For advanced web service users the Collaxa BPEL engine facilitates a configuration and management environment that can fully handle XML-based workflow.

Computational Biology↗
PubMed1997

Cell cycle and apoptosis: possible roles of Gadd45 and MyD118 proteins inferred from their homology to ribosomal proteins.

The function and structure of many disease gene products are currently poorly understood, and the easiest way to proceed is to search databases for homologous proteins to infer function or structure from the closest database match. Bioinformatics provides a variety of methods that reach beyond the standard database searches with single query sequences. The identification of a large superfamily of ribosome-associated proteins by computer analysis enabled Eugene Koonin to infer functional information for Gadd45, which is part of a cell-cycle checkpoint pathway defective in ataxia-telangiectasia.

Amino Acid Sequence↗
PubMed2003

Panel of human cancer cell lines provides valuable database for drug discovery and bioinformatics.

Studies conducted at the US National Cancer Institute (NCI) and in our laboratory show that databases including the drug sensitivities of panels of many human cancer cell lines provide valuable information on the molecular pharmacology of anticancer drugs. We established a panel of 39 cell lines of various human cancers and developed a database of their chemosensitivities. Drugs were profiled in terms of their "fingerprints", patterns of differential activity against the cell lines. There was a significant correlation between a drug's fingerprint and its mode of action, as observed in the NCI panel of 60 cell lines. Therefore our cell-line panel is a powerful tool to predict the modes of action of new compounds. We have been using this system for drug discovery, coupled with various target-based drug screenings. We used the system to identify a novel DNA minor-groove binder, MS-247, which has inhibitory activity against topoisomerases I and II, and potent in vivo antitumor activity against various human cancer xenografts. We also discovered a potent novel telomerase inhibitor, FJ5002, by mining our database with the COMPARE algorithm, followed by experimental validation. We investigated the gene expression profiles of the cell lines by using DNA microarrays to find profiles determining cellular chemosensitivity and new targets for anticancer drugs. Our integrated database, including the chemosensitivities and gene expression profiles of the cell-line panel, could provide a basis for drug discovery and personalized therapy.

Databases, Factual↗
PubMed2003

Bioinformatics in neurosurgery.

WITH THE COMPLETION of the Human Genome Project, the amount of molecular biological sequence data available in public databases has reached staggering proportions. Data continue to accumulate at an exponential rate in the postgenomic era. Compilation, storage, searching, sharing, studying, and transmitting of all these data present formidable challenges. To keep pace with this extant database, the science of bioinformatics (sometimes called computational biology) has evolved. Bioinformatics is the combination of biology and computers and usually involves the storage or analysis of molecular biological sequence data at either the deoxyribonucleic acid, ribonucleic acid, or protein (amino acid) level. Most bioinformatics tools are freely available on the Internet for use by investigators around the globe. The collective wisdom from bioinformatics databases worldwide will continue to spawn advances in the neurological sciences for generations to come. Neurosurgeons must be aware of the power and potential applications of bioinformatics for the analysis of neurosurgical diseases.

Animals↗
PubMed2005

Databases and information integration for the Medicago truncatula genome and transcriptome.

An international consortium is sequencing the euchromatic genespace of Medicago truncatula. Extensive bioinformatic and database resources support the marker-anchored bacterial artificial chromosome (BAC) sequencing strategy. Existing physical and genetic maps and deep BAC-end sequencing help to guide the sequencing effort, while EST databases provide essential resources for genome annotation as well as transcriptome characterization and microarray design. Finished BAC sequences are joined into overlapping sequence assemblies and undergo an automated annotation process that integrates ab initio predictions with EST, protein, and other recognizable features. Because of the sequencing project's international and collaborative nature, data production, storage, and visualization tools are broadly distributed. This paper describes databases and Web resources for the project, which provide support for physical and genetic maps, genome sequence assembly, gene prediction, and integration of EST data. A central project Web site at medicago.org/genome provides access to genome viewers and other resources project-wide, including an Ensembl implementation at medicago.org, physical map and marker resources at mtgenome.ucdavis.edu, and genome viewers at the University of Oklahoma (www.genome.ou.edu), the Institute for Genomic Research (www.tigr.org), and Munich Information for Protein Sequences Center (mips.gsf.de).

Base Sequence↗
PubMed2002

Mobile access to biological databases on the Internet.

We have developed a new way of accessing biological databases and bioinformatics applications on the Internet. This new service, bioinformatics wireless application protocol (BioWAP) service, which is accessible by mobile devices makes it possible to access bioinformatics services, where normal PC or personal digital assistant (PDA) connections are not feasible. The BioWAP service includes major biological databases and applications demonstrating a simple method of implementing WAP interfaces to uncompliant applications, i.e. the applications that are not WAP or Internet based. The BioWAP service can be browsed with any WAP terminal.

Computational Biology↗
PubMed2003

BioWareDB: the biomedical software and database search engine.

UNLABELLED: A wealth of bioinformatics tools and databases has been created over the last decade and most are freely available to the general public. However, these valuable resources live a shadow existence compared to experimental results and methods that are widely published in journals and relatively easily found through publication databases such as PubMed. For the general scientist as well as bioinformaticists, these tools can deliver great value to the design and analysis of biological and medical experiments, but there is no inventory presenting an up-to-date and easily searchable index of all these resources. To remedy this, the BioWareDB search engine has been created. BioWareDB is an extensive and current catalog of software and databases of relevance to researchers in the fields of biology and medicine, and presently consists of 2800 validated entries. AVAILABILITY: BioWareDB is freely available over the Internet at http://www.biowaredb.org/

Abstracting and Indexing↗
PubMed2006

CryptoDB: a Cryptosporidium bioinformatics resource update.

The database, CryptoDB (http://CryptoDB.org), is a community bioinformatics resource for the AIDS-related apicomplexan-parasite, Cryptosporidium. CryptoDB integrates whole genome sequence and annotation with expressed sequence tag and genome survey sequence data and provides supplemental bioinformatics analyses and data-mining tools. A simple, yet comprehensive web interface is available for mining and visualizing the data. CryptoDB is allied with the databases PlasmoDB and ToxoDB via ApiDB, an NIH/NIAID-fundedBioinformatics Resource Center. Recent updates to CryptoDB include the deposition of annotated genome sequences for Cryptosporidium parvum and Cryptosporidium hominis, migration to a relational database (GUS), a new query and visualization interface and the introduction of Web services.

Animals↗
PubMed2025

KSHVbook: An Information-Sharing Database for Kaposi's Sarcoma-Associated Herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus belonging to the γ-herpesvirus subfamily. KSHV is the causative agent of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD), and KSHV inflammatory cytokine syndrome (KICS). Since its discovery, research on KSHV has rapidly progressed, but existing information platforms relatively lack comprehensiveness and do not provide efficient analysis tools tailored for KSHV. To further promote the research on KSHV more effectively, we have developed KSHVbook (http://www.kshvbook.com), a specialized information-sharing database dedicated to KSHV. This platform offers extensive information on genes, coding sequences, proteins, and the gene regulatory region. Besides, the KSHVbook includes about 35 010 transcription factor binding sites (TFBSs), 342 010 pairs of KSHV miRNA-host target gene relationships, protein structures predicted by AlphaFold3, qPCR primers, and so on. We also develop analytical tools for viral genome regions, TFBSs, and KSHV miRNA target genes to discover previously unknown biological functions of KSHV. These analytical tools can effectively identify the potential regulatory relationships between host transcription factors and viral genes. Overall, this platform provides a centralized data resource for KSHV research by integrating multiple databases, offering accessible analysis tools, and simplifying data acquisition. The KSHVbook will continue to be updated, and more features can be found on the website.

Herpesvirus 8, Human↗