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The Make 2D-DB II package: conversion of federated two-dimensional gel electrophoresis databases into a relational format and interconnection of distributed databases.

The Make 2D-DB tool has been previously developed to help build federated two-dimensional gel electrophoresis (2-DE) databases on one's own web site. The purpose of our work is to extend the strength of the first package and to build a more efficient environment. Such an environment should be able to fulfill the different needs and requirements arising from both the growing use of 2-DE techniques and the increasing amount of distributed experimental data.

Databases, Protein↗

OLDERADO: on-line database of ensemble representatives and domains. On Line Database of Ensemble Representatives And DOmains.

In cases where the structure of a single protein is represented by an ensemble of conformations, there is often a need to determine the common features and to choose a "representative" conformation. This occurs, for example, with structures determined by NMR spectroscopy, analysis of the trajectory from a molecular dynamics simulation, or an ensemble of structures produced by comparative modeling. We reported previously automatic methods for (1) defining the atoms with low spatial variance across an ensemble (i.e., the "core" atoms) and the domains in which these atoms lie, and (2) clustering an ensemble into conformationally related subfamilies. To extend the utility of these methods, we have developed a freely available server on the World Wide Web at http:/(/)neon.chem.le.ac.uk/olderado/. This (1) contains an automatically generated database of representative structures, core atoms, and domains determined for 449 ensembles of NMR-derived protein structures in the Protein Data Bank (PDB) in May 1997, and (2) allows the user to upload a PDB-formatted file containing the coordinates of an ensemble of structures. The server returns in real time: (1) information on the residues constituting domains: (2) the structures that constitute each conformational subfamily; and (3) an interactive java-based three-dimensional viewer to visualise the domains and clusters. Such information is useful, for example, when selecting conformations to be used in comparative modeling and when choosing parts of structures to be used in molecular replacement. Here we describe the OLDERADO server.

Computer Communication Networks↗

Lessons learned from process incident databases and the process safety incident database (PSID) approach sponsored by the Center for Chemical Process Safety.

Learning from the experiences of others has long been recognized as a valued and relatively painless process. In the world of process safety, this learning method is an essential tool since industry has neither the time and resources nor the willingness to experience an incident before taking corrective or preventative steps. This paper examines the need for and value of process safety incident databases that collect incidents of high learning value and structure them so that needed information can be easily and quickly extracted. It also explores how they might be used to prevent incidents by increasing awareness and by being a tool for conducting PHAs and incident investigations. The paper then discusses how the CCPS PSID meets those requirements, how PSID is structured and managed, and its attributes and features.

Accident Prevention↗

A RAPID algorithm for sequence database comparisons: application to the identification of vector contamination in the EMBL databases.

MOTIVATION: Word-matching algorithms such as BLAST are routinely used for sequence comparison. These algorithms typically use areas of matching words to seed alignments which are then used to assess the degree of sequence similarity. In this paper, we show that by formally separating the word-matching and sequence-alignment process, and using information about word frequencies to generate alignments and similarity scores, we can create a new sequence-comparison algorithm which is both fast and sensitive. The formal split between word searching and alignment allows users to select an appropriate alignment method without affecting the underlying similarity search. The algorithm has been used to develop software for identifying entries in DNA sequence databases which are contaminated with vector sequence. RESULTS: We present three algorithms, RAPID, PHAT and SPLAT, which together allow vector contaminations to be found and assessed extremely rapidly. RAPID is a word search algorithm which uses probabilities to modify the significance attached to different words; PHAT and SPLAT are alignment algorithms. An initial implementation has been shown to be approximately an order of magnitude faster than BLAST. The formal split between word searching and alignment not only offers considerable gains in performance, but also allows alignment generation to be viewed as a user interface problem, allowing the most useful output method to be selected without affecting the underlying similarity search. Receiver Operator Characteristic (ROC) analysis of an artificial test set allows the optimal score threshold for identifying vector contamination to be determined. ROC curves were also used to determine the optimum word size (nine) for finding vector contamination. An analysis of the entire expressed sequence tag (EST) subset of EMBL found a contamination rate of 0.27%. A more detailed analysis of the 50 000 ESTs in est10.dat (an EST subset of EMBL) finds an error rate of 0.86%, principally due to two large-scale projects. AVAILABILITY: A Web page for the software exists at http://bioinf.man.ac.uk/rapid, or it can be downloaded from ftp://ftp.bioinf.man.ac.uk/RAPID CONTACT: crispin@cs.man.ac.uk

Algorithms↗

Marfan Database (second edition): software and database for the analysis of mutations in the human FBN1 gene.

Fibrillin is the major component of extracellular microfibrils. Mutations in the fibrillin gene on chromosome 15 (FBN1) were described at first in the heritable connective tissue disorder, Marfan syndrome (MFS). More recently, FBN1 has also been shown to harbor mutations related to a spectrum of conditions phenotypically related to MFS. These mutations are private, essentially missense, generally non-recurrent and widely distributed throughout the gene. To date no clear genotype/phenotype relationship has been observed excepted for the localization of neonatal mutations in a cluster between exons 24 and 32. The second version of the computerized Marfan database contains 89 entries. The software has been modified to accomodate new functions and routines.

Animals↗

Cancer gene expression database (CGED): a database for gene expression profiling with accompanying clinical information of human cancer tissues.

Gene expression profiling of cancer tissues is expected to contribute to our understanding of cancer biology as well as developments of new methods of diagnosis and therapy. Our collaborative efforts in Japan have been mainly focused on solid tumors such as breast, colorectal and hepatocellular cancers. The expression data are obtained by a high-throughput RT-PCR technique, and patients are recruited mainly from a single hospital. In the cancer gene expression database (CGED), the expression and clinical data are presented in a way useful for scientists interested in specific genes or biological functions. The data can be retrieved either by gene identifiers or by functional categories defined by Gene Ontology terms or the Swiss-Prot annotation. Expression patterns of multiple genes, selected by names or similarity search of the patterns, can be compared. Visual presentation of the data with sorting function enables users to easily recognize of relationships between gene expression and clinical parameters. Data for other cancers such as lung and thyroid cancers will be added in the near future. The URL of CGED is http://cged.hgc.jp.

Databases, Genetic↗

BioModels Database: a free, centralized database of curated, published, quantitative kinetic models of biochemical and cellular systems.

BioModels Database (http://www.ebi.ac.uk/biomodels/), part of the international initiative BioModels.net, provides access to published, peer-reviewed, quantitative models of biochemical and cellular systems. Each model is carefully curated to verify that it corresponds to the reference publication and gives the proper numerical results. Curators also annotate the components of the models with terms from controlled vocabularies and links to other relevant data resources. This allows the users to search accurately for the models they need. The models can currently be retrieved in the SBML format, and import/export facilities are being developed to extend the spectrum of formats supported by the resource.

Biochemical Phenomena↗

'The surface management system' (SuMS) database: a surface-based database to aid cortical surface reconstruction, visualization and analysis.

Surface reconstructions of the cerebral cortex are increasingly widely used in the analysis and visualization of cortical structure, function and connectivity. From a neuroinformatics perspective, dealing with surface-related data poses a number of challenges. These include the multiplicity of configurations in which surfaces are routinely viewed (e.g. inflated maps, spheres and flat maps), plus the diversity of experimental data that can be represented on any given surface. To address these challenges, we have developed a surface management system (SuMS) that allows automated storage and retrieval of complex surface-related datasets. SuMS provides a systematic framework for the classification, storage and retrieval of many types of surface-related data and associated volume data. Within this classification framework, it serves as a version-control system capable of handling large numbers of surface and volume datasets. With built-in database management system support, SuMS provides rapid search and retrieval capabilities across all the datasets, while also incorporating multiple security levels to regulate access. SuMS is implemented in Java and can be accessed via a Web interface (WebSuMS) or using downloaded client software. Thus, SuMS is well positioned to act as a multiplatform, multi-user 'surface request broker' for the neuroscience community.

Brain Mapping↗

The rice kinase database. A phylogenomic database for the rice kinome.

The rice (Oryza sativa) genome contains 1,429 protein kinases, the vast majority of which have unknown functions. We created a phylogenomic database (http://rkd.ucdavis.edu) to facilitate functional analysis of this large gene family. Sequence and genomic data, including gene expression data and protein-protein interaction maps, can be displayed for each selected kinase in the context of a phylogenetic tree allowing for comparative analysis both within and between large kinase subfamilies. Interaction maps are easily accessed through links and displayed using Cytoscape, an open source software platform. Chromosomal distribution of all rice kinases can also be explored via an interactive interface.

Amino Acid Motifs↗

Exploring Potential Causality and Molecular Mechanisms between Heart Failure and Renal Failure: Insights from Mendelian Randomization Studies, the MIMIC-IV Database and the Gene Expression Omnibus Database.

UNLABELLED: Introduction: Heart failure (HF) and renal failure (RF) frequently coexist as cardiorenal syndrome, but their underlying causal mechanisms remain poorly defined. METHODS: This study applied Mendelian randomization (MR) using genome-wide association study (GWAS) datasets to investigate the causal effect of HF on RF. The inverse variance weighted method assessed causality, and summary-data-based MR (SMR) was used to identify therapeutic targets. Additional analyses included 211 gut microbiota traits and 1,400 serum metabolites. Validation was performed using the MIMIC-IV database. Transcriptomic data were analyzed to identify differentially expressed genes (DEGs) and key transcription factors (TFs). RESULTS: This study found that HF significantly increases the risk of RF (OR = 1.54, 95% CI: 1.07-2.23, p = 0.020). SMR analysis identified SURF1 and MAP3K11 as potential therapeutic targets for HF and RF. One gut microbiota genus and one serum metabolite showed causal associations with both diseases. MIMIC-IV data supported the HF-RF association (OR = 2.94, 95% CI: 2.81-3.07, p < 0.001). A total of 11 overlapping DEGs were enriched in the MAPK cascade, with RELA identified as a key TF. CONCLUSION: This study provides genetic and molecular evidence supporting a causal role of HF in RF, highlighting microbial, metabolic, and immune mechanisms as potential therapeutic targets. .

Humans↗

Achieving maximum ROI from corporate databases: exploiting your databases with integrated querying for better decision-making.

In order to increase the rate of drug discovery, pharmaceutical and biotechnology companies spend billions of dollars a year assembling research databases. Current trends still indicate a falling rate in the discovery of New Molecular Entities (NMEs). It is widely accepted that the data need to be integrated in order for it to add value. The degree to which this must be achieved is often misunderstood. The true goal of data integration must be to provide accessible knowledge. If knowledge cannot be gained from these data, then it will invalidate the business case for gathering it. Current data integration solutions focus on the initial task of integrating the actual data and to some extent, also address the need to allow users to access integrated information. Typically the search tools that are provided are either restrictive forms or free text based. While useful, neither of these solutions is suitable for providing full coverage of large numbers of integrated structured data sources. One solution to this accessibility problem is to present the integrated data in a collated manner that allows users to browse and explore it and also perform complex ad-hoc searches on it within a scientific context and without the need for advanced Information Technology (IT) skills. Additionally, the solution should be maintainable by 'in-house' administrators rather than requiring expensive consultancy. This paper examines the background to this problem, investigates the requirements for effective exploitation of corporate data and presents a novel effective solution.

Databases, Factual↗

A database in private practice: the Brooklyn Outcomes of Arthritis Rheumatology Database (BOARD).

Rheumatologists generally use few quantitative measures in making clinical decisions. In the US, fewer than 10% use questionnaires in routine clinical care, and fewer than 15% perform a formal joint count at each visit. Patient questionnaires are the quantitative tools rheumatologists have to monitor their patients' health status and response to therapy. The health assessment questionnaire (HAQ) and its derivatives have been shown to be the best predictors of functional and work disability, costs, joint replacement surgery and mortality; they are as good as and usually better predictors than joint counts, radiographs and laboratory tests. The Brooklyn Outcomes of Arthritis Registry Database was initiated with the aim of collecting quantitative data using a multi-dimensional health assessment questionnire (MDHAQ) from all rheumatology patients seen as part of routine care, each and every time the patient was seen. Data that are feasible to collect in routine clinical care provide the only way to assess quantitatively how our patients are doing. If data are not collected and recorded, an opportunity is lost forever. If there is a reason for the visit, there is a reason to complete a questionnaire.

Arthritis↗

UK National Transplant Database: a digest of published audit material. UKTSSA National Transplant Database.

The analyses undertaken on the national transplant database for the UK and Republic of Ireland on behalf of the participating transplant units have shown some factors influencing survival to be common to all organ types, and an improvement in survival over the last ten years for all organ transplant groups. The increasing use of older donors is also a general problem, despite the differing definition of 'old donors' for each organ group. The main findings from the multifactorial analysis are summarised below, both for those factors influencing 1-year transplant survival, and survival over distinct posttransplant epochs. The number of previous transplants had a significant influence on survival across all organ types. For heart transplants, the effects of recipient sex, age, primary disease and donor cause of death were strongest during the first 28 days, and donor age influenced survival from 29 days onwards. The number of previous transplants was found to be the only influence on heart/lung transplants but for lung(s) transplants, the weight of the recipient was also found to influence survival throughout. Recipient primary disease was found to influence survival in the first 21 days, while donor sex, CMV match and donor cause of death influenced survival over 21 days. The majority of factors influencing liver transplant survival were present in both the first 21 days and beyond. Differences were found between the early and late epochs, with younger recipients influencing early survival, and recipients over age 40 influencing survival after 21 days. Analyses of factors associated with kidney transplant survival have shown significant improvement over time. Retransplantation, and the use of kidneys from older (>55 years), younger (<19 years), and non-trauma victim donors continue to carry significantly higher risks of failure. Female donor to male recipient, exchanged and non-beneficially matched transplants, along with grafts given to younger and older recipients, were also associated with inferior survival. The analysis of 4 distinct posttransplant intervals further confirmed that, for some factors, the risk persisted while, for others, their effect was transient.

Adolescent↗