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UNLABELLED: An integrated database and search system has been developed for protein family identification and information retrieval, as an approach to undertake the highly complex, genomic-scale problem of molecular sequence database search and organization. AVAILABILITY: http://diana.uthct.edu CONTACT: wu@uthct.edu
We present a methodology and database mediator tool for integrating modern knowledge-based systems, such as the Stanford EON architecture for automated guideline-based decision-support, with legacy databases, such as the Veterans Health Information Systems & Technology Architecture (VISTA) systems, which are used nation-wide. Specifically, we discuss designs for database integration in ATHENA, a system for hypertension care based on EON, at the VA Palo Alto Health Care System. We describe a new database mediator that affords the EON system both physical and logical data independence from the legacy VA database. We found that to achieve our design goals, the mediator requires two separate mapping levels and must itself involve a knowledge-based component.
SUMMARY: Besides classical clustering methods such as hierarchical clustering, in recent years biclustering has become a popular approach to analyze biological data sets, e.g. gene expression data. The Biclustering Analysis Toolbox (BicAT) is a software platform for clustering-based data analysis that integrates various biclustering and clustering techniques in terms of a common graphical user interface. Furthermore, BicAT provides different facilities for data preparation, inspection and postprocessing such as discretization, filtering of biclusters according to specific criteria or gene pair analysis for constructing gene interconnection graphs. The possibility to use different biclustering algorithms inside a single graphical tool allows the user to compare clustering results and choose the algorithm that best fits a specific biological scenario. The toolbox is described in the context of gene expression analysis, but is also applicable to other types of data, e.g. data from proteomics or synthetic lethal experiments. AVAILABILITY: The BicAT toolbox is freely available at http://www.tik.ee.ethz.ch/sop/bicat and runs on all operating systems. The Java source code of the program and a developer's guide is provided on the website as well. Therefore, users may modify the program and add further algorithms or extensions.
MOTIVATION: A Robot Scientist is a physically implemented robotic system that can automatically carry out cycles of scientific experimentation. We are commissioning a new Robot Scientist designed to investigate gene function in S. cerevisiae. This Robot Scientist will be capable of initiating >1,000 experiments, and making >200,000 observations a day. Robot Scientists provide a unique test bed for the development of methodologies for the curation and annotation of scientific experiments: because the experiments are conceived and executed automatically by computer, it is possible to completely capture and digitally curate all aspects of the scientific process. This new ability brings with it significant technical challenges. To meet these we apply an ontology driven approach to the representation of all the Robot Scientist's data and metadata. RESULTS: We demonstrate the utility of developing an ontology for our new Robot Scientist. This ontology is based on a general ontology of experiments. The ontology aids the curation and annotating of the experimental data and metadata, and the equipment metadata, and supports the design of database systems to hold the data and metadata. AVAILABILITY: EXPO in XML and OWL formats is at: http://sourceforge.net/projects/expo/. All materials about the Robot Scientist project are available at: http://www.aber.ac.uk/compsci/Research/bio/robotsci/.
MITOMAP (http://www.MITOMAP.org), a database for the human mitochondrial genome, has grown rapidly in data content over the past several years as interest in the role of mitochondrial DNA (mtDNA) variation in human origins, forensics, degenerative diseases, cancer and aging has increased dramatically. To accommodate this information explosion, MITOMAP has implemented a new relational database and an improved search engine, and all programs have been rewritten. System administrative changes have been made to improve security and efficiency, and to make MITOMAP compatible with a new automatic mtDNA sequence analyzer known as Mitomaster.
In the Department of Defense (DoD), US Army Medical Command is now embarking on an extremely exciting new project--creating a virtual radiology environment (VRE) for the management of radiology examinations. The business of radiology in the military is therefore being reengineered on several fronts by the VRE Project. In the VRE Project, a set of intelligent agent algorithms determine where examinations are to routed for reading bases on a knowledge base of the entire VRE. The set of algorithms, called the Meta-Manager, is hierarchical and uses object-based communications between medical treatment facilities (MTFs) and medical centers that have digital imaging network picture archiving and communications systems (DIN-PACS) networks. The communications is based on use of common object request broker architecture (CORBA) objects and services to send patient demographics and examination images from DIN-PACS networks in the MTFs to the DIN-PACS networks at the medical centers for diagnosis. The Meta-Manager is also responsible for updating the diagnosis at the originating MTF. CORBA services are used to perform secure message communications between DIN-PACS nodes in the VRE network. The Meta-Manager has a fail-safe architecture that allows the master Meta-Manager function to float to regional Meta-Manager sites in case of server failure. A prototype of the CORBA-based Meta-Manager is being developed by the University of Arizona's Computer Engineering Research Laboratory using the unified modeling language (UML) as a design tool. The prototype will implement the main functions described in the Meta-Manager design specification. The results of this project are expected to reengineer the process of radiology in the military and have extensions to commercial radiology environments.
The solution to many of the problems of the computer-based recording of the medical record has been elusive, largely due to difficulties in the capture of those data elements that comprise the records of the Present Illness and of the Physical Findings. Reliable input of data has proven to be more complex than originally envisioned by early work in the field. This has led to more research and development into better data collection protocols and easy to use human-computer interfaces as support tools. The Medical Examination Direct Iconic and Graphic Augmented Text Entry System (MEDIGATE System) is a computer enhanced interactive graphic and textual record of the findings from physical examinations designed to provide ease of user input and to support organization and processing of the data characterizing these findings. The primary design objective of the MEDIGATE System is to develop and evaluate different interface designs for recording observations from the physical examination in an attempt to overcome some of the deficiencies in this major component of the individual record of health and illness.
UNLABELLED: FigSearch is a prototype text-mining and classification system for figures from any corpus of full-text biological papers. The system allows users to search for figures that contain genes of interest and illustrate protein interactions. The retrieved figures are ranked by a score representing the likelihood to be of a certain type, in this case, schematic illustrations of protein interactions and signaling events. The system contains a Web interface for search, a module for classification of figures based on vector representations of figure legends and a module for indexing gene names. In a preliminary validation, the FigSearch system showed satisfactory performance according to domain experts in providing the most relevant graphical representations. This strategy may be easily extended to other figure types. Moreover, as more full-text data become available, such a system will find increased usefulness in identifying and presenting compressed biological knowledge. AVAILABILITY: A searchable Web interface, FigSearch, is accessible via http://pubgeneserver.uio.no/figsearch/ for all figures from the available corpus.
BACKGROUND: Translational research requires taking basic science observations and developing them into clinically useful tests and therapeutics. We have developed a process to develop molecular biomarkers for diagnosis and prognosis by integrating tissue microarray (TMA) technology and an internet-database tool, Profiler. TMA technology allows investigators to study hundreds of patient samples on a single glass slide resulting in the conservation of tissue and the reduction in inter-experimental variability. The Profiler system allows investigator to reliably track, store, and evaluate TMA experiments. Here within we describe the process that has evolved through an empirical basis over the past 5 years at two academic institutions. RESULTS: The generic design of this system makes it compatible with multiple organ system (e.g., prostate, breast, lung, renal, and hematopoietic system,). Studies and folders are restricted to authorized users as required. Over the past 5 years, investigators at 2 academic institutions have scanned 656 TMA experiments and collected 63,311 digital images of these tissue samples. 68 pathologists from 12 major user groups have accessed the system. Two groups directly link clinical data from over 500 patients for immediate access and the remaining groups choose to maintain clinical and pathology data on separate systems. Profiler currently has 170 K data points such as staining intensity, tumor grade, and nuclear size. Due to the relational database structure, analysis can be easily performed on single or multiple TMA experimental results. The TMA module of Profiler can maintain images acquired from multiple systems. CONCLUSION: We have developed a robust process to develop molecular biomarkers using TMA technology and an internet-based database system to track all steps of this process. This system is extendable to other types of molecular data as separate modules and is freely available to academic institutions for licensing.
Databases continue to grow but the metrics available to evaluate information retrieval systems have not changed. Large collections such as MEDLINE and the World Wide Web contain many relevant documents for common queries. Ranking is therefore increasingly important and successful information retrieval systems, such as Google, have emphasized ranking. However, existing evaluation metrics such as precision and recall, do not directly account for ranking. This paper describes a novel way of measuring information retrieval performance using weighted hit curves adapted from the field of statistical detection to reflect multiple desirable characteristics such as relevance, importance, and methodologic quality. In statistical detection, hit curves have been proposed to represent occurrence of interesting events during a detection process. Similarly, hit curves can be used to study the position of relevant documents within large result sets. We describe hit curves in light of a formal model of information retrieval, show how hit curves represent system performance including ranking, and define ways to statistically compare performance of multiple systems using hit curves. We provide example scenarios where traditional measures are less suitable than hit curves and conclude that hit curves may be useful for evaluating retrieval from large collections where ranking performance is crucial.
SUMMARY: MACiE (mechanism, annotation and classification in enzymes) is a publicly available web-based database, held in CMLReact (an XML application), that aims to help our understanding of the evolution of enzyme catalytic mechanisms and also to create a classification system which reflects the actual chemical mechanism (catalytic steps) of an enzyme reaction, not only the overall reaction. AVAILABILITY: http://www-mitchell.ch.cam.ac.uk/macie/.
BACKGROUND: Analysis of inherited diseases and their associated phenotypes is of great importance to gain knowledge of underlying genetic interactions and could ultimately give clinically useful insights into disease processes, including complex diseases influenced by multiple genetic loci. Nevertheless, to date few computational contributions have been proposed for this purpose, mainly due to lack of controlled clinical information easily accessible and structured for computational genome-wise analyses. To allow performing phenotype analyses of inherited disorder related genes we implemented new original modules within GFINDer http://www.bioinformatics.polimi.it/GFINDer/, a Web system we previously developed that dynamically aggregates functional annotations of user uploaded gene lists and allows performing their statistical analysis and mining. RESULTS: New GFINDer modules allow annotating large numbers of user classified biomolecular sequence identifiers with morbidity and clinical information, classifying them according to genetic disease phenotypes and their locations of occurrence, and statistically analyzing the obtained classifications. To achieve this we exploited, normalized and structured the information present in textual form in the Clinical Synopsis sections of the Online Mendelian Inheritance in Man (OMIM) databank. Such valuable information delineates numerous signs and symptoms accompanying many genetic diseases and it is divided into phenotype location categories, either by organ system or type of finding. CONCLUSION: Supporting phenotype analyses of inherited diseases and biomolecular functional evaluations, GFINDer facilitates a genomic approach to the understanding of fundamental biological processes and complex cellular mechanisms underlying patho-physiological phenotypes.
Hereditary angioneurotic edema (HAE) is an autosomal dominant disorder characterized by episodic local subcutaneous and submucosal edema and is caused by the deficiency of the activated C1 esterase inhibitor protein (C1-INH or C1INH; approved gene symbol SERPING1). Published C1-INH mutations are represented in large universal databases (e.g., OMIM, HGMD), but these databases update their data rather infrequently, they are not interactive, and they do not allow searches according to different criteria. The HAEdb, a C1-INH gene mutation database (http://hae.biomembrane.hu) was created to contribute to the following expectations: 1) help the comprehensive collection of information on genetic alterations of the C1-INH gene; 2) create a database in which data can be searched and compared according to several flexible criteria; and 3) provide additional help in new mutation identification. The website uses MySQL, an open-source, multithreaded, relational database management system. The user-friendly graphical interface was written in the PHP web programming language. The website consists of two main parts, the freely browsable search function, and the password-protected data deposition function. Mutations of the C1-INH gene are divided in two parts: gross mutations involving DNA fragments >1 kb, and micro mutations encompassing all non-gross mutations. Several attributes (e.g., affected exon, molecular consequence, family history) are collected for each mutation in a standardized form. This database may facilitate future comprehensive analyses of C1-INH mutations and also provide regular help for molecular diagnostic testing of HAE patients in different centers.
Computational analysis of the bonding, geometric, and topological relationships within proteins typically takes on the order of hours, mainly devoted to the writing of scripts and code to correctly parse the data. The Structured Query Language (SQL) built into modern database management systems eliminates the need for data parsing, effectively reducing the analysis time to seconds. To this end, we have formulated a conceptual data model (CDM) for proteins based on the IUPAC recommendations for biochemical nomenclature. This conceptual data model makes explicit the inherent bonding relationships between the atoms of a protein, as well as the geometric (bond angle and torsion angle) and topological (chirality) relationships between the bonds. The validity of the CDM has been tested with a reduced implementation using commercial database software. The ease in both populating the database with data from the Protein Data Bank and formulating/executing queries supports the correctness of the model. The ability to conduct truly interactive analyses of protein structure is essential to fully capitalize on the explosion in postgenomic protein structure data.
Entries in biological databases are usually linked to scientific references. To generate those links and to keep them up-to-date, database maintainers have to continuously scan the scientific literature to select references that are relevant for each single database entry. The continuous growth of both the corpus of scientific literature and the size of biological databases makes this task very hard. We present a protocol intended to assist the updating of an existing set of literature (abstract) links from a single database entry with new references. It consists of taking the set of MEDLINE neighbour references of the existing linked abstracts and evaluating their relevance according to the existing set of abstracts. To test the applicability of the algorithm, we did a simple benchmark of the system using the references associated with the entries of a protein domain database. Human experts found the references that the algorithm scored highly were more relevant to the database entry than those scored lowly, suggesting that the algorithm was useful.
Current research in the biosciences depends heavily on the effective exploitation of huge amounts of data. These are in disparate formats, remotely dispersed, and based on the different vocabularies of various disciplines. Furthermore, data are often stored or distributed using formats that leave implicit many important features relating to the structure and semantics of the data. Conceptual data modelling involves the development of implementation-independent models that capture and make explicit the principal structural properties of data. Entities such as a biopolymer or a reaction, and their relations, eg catalyses, can be formalised using a conceptual data model. Conceptual models are implementation-independent and can be transformed in systematic ways for implementation using different platforms, eg traditional database management systems. This paper describes the basics of the most widely used conceptual modelling notations, the ER (entity-relationship) model and the class diagrams of the UML (unified modelling language), and illustrates their use through several examples from bioinformatics. In particular, models are presented for protein structures and motifs, and for genomic sequences.
Systems Biology aims to understand quantitatively how properties of biological systems can be understood as functions of the characteristics of, and interactions between their macromolecular components. Whereas, traditional biochemistry focused on isolation and characterization of cellular components, the challenge for Systems Biology lies in integration of this knowledge and the knowledge about molecular interactions. Computer models play an important role in this integration. We here discuss an approach with which we aim to link kinetic models on small parts of metabolism together, so as to form detailed kinetic models of larger chunks of metabolism, and ultimately of the entire living cell. Specifically, we will discuss techniques that can be used to model a sub-network in isolation of a larger network of which it is a part, while still maintaining the dynamics of the larger complete network. We will start by outlining the JWS online system, the silicon cell project, and the type of models we propose. JWS online is a model repository, which can be used for the storage, simulation and analysis of kinetic models. We advocate to integrate a top-down approach, where measurements on the complete system are used to derive fluxes in a detailed structural model, with a bottom-up approach, consisting of the integration of molecular mechanism-based detailed kinetic models into the structural model.
MOTIVATION: The biological literature is a major repository of knowledge. Many biological databases draw much of their content from a careful curation of this literature. However, as the volume of literature increases, the burden of curation increases. Text mining may provide useful tools to assist in the curation process. To date, the lack of standards has made it impossible to determine whether text mining techniques are sufficiently mature to be useful. RESULTS: We report on a Challenge Evaluation task that we created for the Knowledge Discovery and Data Mining (KDD) Challenge Cup. We provided a training corpus of 862 articles consisting of journal articles curated in FlyBase, along with the associated lists of genes and gene products, as well as the relevant data fields from FlyBase. For the test, we provided a corpus of 213 new ('blind') articles; the 18 participating groups provided systems that flagged articles for curation, based on whether the article contained experimental evidence for gene expression products. We report on the evaluation results and describe the techniques used by the top performing groups.