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An introduction is presented in which the editor discusses various reports within the issue on topics related to domain specific business ontologies that have emerged in multiple fields.

Abstract: Intense interest in knowledge-acquisition research began 25 years ago, stimulated by the excitement about knowledge-based systems that emerged in the 1970s followed by the realities of the “AI Winter” that arrived in the 1980s. The knowledge-acquisition workshops that responded to this interest led to the formation of a vibrant research community that has achieved remarkable consensus on a number of issues. These viewpoints include (1) the rejection of the notion of knowledge as a commodity to be transferred from one locus to another, (2) an acceptance of the situated nature of human expertise, (3) emphasis on knowledge acquisition as the modeling of problem solving, and (4) the pursuit of reusable patterns in problem solving and in domain descriptions that can facilitate both modeling and system implementation. The Semantic Web community will benefit greatly by incorporating these perspectives in its work. [Copyright &y& Elsevier]

Background: Researchers in biomedical informatics use ontologies and terminologies to annotate their data in order to facilitate data integration and translational discoveries. As the use of ontologies for annotation of biomedical datasets has risen, a common challenge is to identify ontologies that are best suited to annotating specific datasets. The number and variety of biomedical ontologies is large, and it is cumbersome for a researcher to figure out which ontology to use. Methods: We present the Biomedical Ontology Recommender web service. The system uses textual metadata or a set of keywords describing a domain of interest and suggests appropriate ontologies for annotating or representing the data. The service makes a decision based on three criteria. The first one is coverage, or the ontologies that provide most terms covering the input text. The second is connectivity, or the ontologies that are most often mapped to by other ontologies. The final criterion is size, or the number of concepts in the ontologies. The service scores the ontologies as a function of scores of the annotations created using the National Center for Biomedical Ontology (NCBO) Annotator web service. We used all the ontologies from the UMLS Metathesaurus and the NCBO BioPortal. Results: We compare and contrast our Recommender by an exhaustive functional comparison to previously published efforts. We evaluate and discuss the results of several recommendation heuristics in the context of three real world use cases. The best recommendations heuristics, rated 'very relevant' by expert evaluators, are the ones based on coverage and connectivity criteria. The Recommender service (alpha version) is available to the community and is embedded into BioPortal. [ABSTRACT FROM AUTHOR]

The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar ''small-world'' organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism. [ABSTRACT FROM AUTHOR]

Summary: Objective: In the context of the Semantic Web, ontologies have to be usable by software agents as well as by humans. Therefore, they must meet explicit representation and consistency requirements. This article describes a method for managing the semantic consistency of an ontology of brain–cortex anatomy. Method: The methodology relies on the explicit identification of the relationship properties and of the dependencies that might exist among concepts or relationships. These dependencies have to be respected for insuring the semantic consistency of the model. We propose a method for automatically generating all the dependent items. As a consequence, knowledge base updates are easier and safer. Result: Our approach is composed of three main steps: (1) providing a realistic representation, (2) ensuring the intrinsic consistency of the model and (3) checking its incremental consistency. The corner stone of ontological modeling lies in the expressiveness of the model and in the sound principles that structure it. This part defines the ideal possibilities of the ontology and is called realism of representation. Regardless of how well a model represents reality, the intrinsic consistency of a model corresponds to its lack of contradiction. This step is particularly important as soon as dependencies between relationships or concepts have to be fulfilled. Eventually, the incremental consistency encompasses the respect of the two previous criteria during the successive updates of the ontology. Conclusion: The explicit representation of dependencies among concepts and relationships in an ontology can be helpfully used to assist in the management of the knowledge base and to ensure the model’s semantic consistency. [Copyright &y& Elsevier]

Abstract: Many ontology-development tools allow users to supplement frame-based representations with arbitrary logical sentences. However, few users actually take advantage of this opportunity. For example, in the Ontolingua ontology library, only 20% of the ontologies have any user-defined axioms. We believe the difficulty of composing axioms primarily accounts for the lack of axioms in these knowledge bases: Many domain experts cannot translate their thoughts into abstract and symbolic representations. We attempt to remedy the difficulties by identifying groups of axioms that manifest common patterns, creating “templates” that allow users to compose axioms by “filling in the blanks.” We studied axioms in two public ontology libraries, and derived 20 templates that cover 85% of all the user-defined axioms. We describe our methodology for identifying the templates and present examples. We constructed an interface that allows users to create constraints on knowledge bases by “filling in blanks;” our usability testing shows that users could use templates to encode axioms with a success rate similar to that of experts writing directly in an axiom language. Our approach should foster the introduction of axioms and constraints that are currently missing in many ontologies. [Copyright &y& Elsevier]

Introduces topics and articles discussed in the March 2005 issue of the journal "Applied Ontology," including an article which focuses on the need to establish well-designed metrics, methodologies, and experiments for evaluating the practical benefits of ontologies.

One of the main threads in the history of knowledge-representation formalisms is the trade-off between the expressiveness of first-order logic on the one hand and the tractability and ease-of-use of frame-based systems on the other hand. Frame-based systems provide intuitive, cognitively easy-to-understand, and scalable means for modeling a domain. However, when a domain model is particularly complex, frame-based representation may lead to complicated and sometimes awkward solutions. We have encountered such problems when developing the Digital Anatomist Foundational Model, an ontology aimed at representing comprehensively the physical organization of the human body. We show that traditional frame-based techniques such as is-a hierarchies, slots (roles) and role restrictions are not sufficient for a comprehensive model of this domain. The diverse modeling challenges and problems in this project required us to use such knowledge-representation techniques as reified relations, metaclasses and a metaclass hierarchy, different propagation patterns for template and own slots, and so on. We posit that even though the modeling structure imposed by frame-based systems may sometimes lead to complicated solutions, it is still worthwhile to use frame-based representation for very large-scale projects such as this one. [Copyright &y& Elsevier]

Researchers in the ontology-design field have developed the content for ontologies in many domain areas. This distributed nature of ontology development has led to a large number of ontologies covering overlapping domains. In order for these ontologies to be reused, they first need to be merged or aligned to one another. We developed a suite of tools for managing multiple ontologies. These suite provides users with a uniform framework for comparing, aligning, and merging ontologies, maintaining versions, translating between different formalisms. Two of the tools in the suite support semi-automatic ontology merging: iPrompt is an interactive ontology-merging tool that guides the user through the merging process, presenting him with suggestions for next steps and identifying inconsistencies and potential problems. AnchorPrompt uses a graph structure of ontologies to find correlation between concepts and to provide additional information for iPrompt. [Copyright &y& Elsevier]

The Prote´ge´ project has come a long way since Mark Musen first built the Prote´ge´ meta-tool for knowledge-based systems in 1987. The original tool was a small application, aimed at building knowledge-acquisition tools for a few specialized programs in medical planning. From this initial tool, the Prote´ge´ system has evolved into a durable, extensible platform for knowledge-based systems development and research. The current version, Prote´ge´-2000, can be run on a variety of platforms, supports customized user-interface extensions, incorporates the Open Knowledge-Base Connectivity (OKBC) knowledge model, interacts with standard storage formats such as relational databases, XML, and RDF, and has been used by hundreds of individuals and research groups. In this paper, we follow the evolution of the Prote´ge´ project through three distinct re-implementations. We describe our overall methodology, our design decisions, and the lessons we have learned over the duration of the project. We believe that our success is one of infrastructure: Prote´ge´ is a flexible, well-supported, and robust development environment. Using Prote´ge´, developers and domain experts can easily build effective knowledge-based systems, and researchers can explore ideas in a variety of knowledge-based domains. [Copyright &y& Elsevier]

The article focuses on the increase in the number of data breaches of protected health information in the U.S. Topics mentioned include evaluation of an online database of the U.S. Department of Health and Human Services on data breaches of unencrypted protected health information, an overview of the Health Insurance Portability and accountability Act, and the need to implement strategies to mitigate health care data breaches.

Compares different prototype metatools in computer software knowledge acquisition. Effectiveness of the different metatools; Qualities of metatools; Description of metatools such as Protege, Dots, Dash and Spark.

An introduction is presented in which the editor discusses various reports within the issue on topics including ontologies, the use of ontologies in the Internet of Things, and applied ontology.

A letter to the editor is presented in response to an article on biomedical research concerning ontology by Larisa Soldatova and Ross King in the September 2006 issue.

Advanced statisticalmethods used to analyze high-throughput data such as gene-expression assays result in long lists of ''significant genes.'' One way to gain insight into the significance of altered expression levels is to determine whether Gene Ontology (GO) terms associated with a particular biological process, molecular function, or cellular component are over- or under-represented in the set of genes deemed significant. This process, referred to as enrichment analysis, profiles a gene-set, and is widely used to makes sense of the results of high-throughput experiments. The canonical example of enrichment analysis is when the output dataset is a list of genes differentially expressed in some condition. To determine the biological relevance of a lengthy gene list, the usual solution is to perform enrichment analysis with the GO. We can aggregate the annotating GO concepts for each gene in this list, and arrive at a profile of the biological processes or mechanisms affected by the condition under study. While GO has been the principal target for enrichment analysis, the methods of enrichment analysis are generalizable. We can conduct the same sort of profiling along other ontologies of interest. Just as scientists can ask ''Which biological process is over-represented in my set of interesting genes or proteins?'' we can also ask ''Which disease (or class of diseases) is over-represented in my set of interesting genes or proteins?''. For example, by annotating known protein mutations with disease terms from the ontologies in BioPortal,Mort et al. recently identified a class of diseases--blood coagulation disorders--that were associated with a 14-fold depletion in substitutions at O-linked glycosylation sites. With the availability of tools for automatic annotation of datasets with terms from disease ontologies, there is no reason to restrict enrichment analyses to the GO. In this chapter, we will discuss methods to perform enrichment analysis using any ontology available in the biomedical domain. We will review the general methodology of enrichment analysis, the associated challenges, and discuss the novel translational analyses enabled by the existence of public, national computational infrastructure and by the use of disease ontologies in such analyses. [ABSTRACT FROM AUTHOR]

Background: Ontologies in biomedicine facilitate information integration, data exchange, search and query of biomedical data, and other critical knowledgeintensive tasks. The OBO Foundry is a collaborative effort to establish a set of principles for ontology development with the eventual goal of creating a set of interoperable reference ontologies in the domain of biomedicine. One of the key requirements to achieve this goal is to ensure that ontology developers reuse term definitions that others have already created rather than create their own definitions, thereby making the ontologies orthogonal. Methods: We used a simple lexical algorithm to analyze the extent to which the set of OBO Foundry candidate ontologies identified from September 2009 to September 2010 conforms to this vision. Specifically, we analyzed (1) the level of explicit term reuse in this set of ontologies, (2) the level of overlap, where two ontologies define similar terms independently, and (3) how the levels of reuse and overlap changed during the course of this year. Results: We found that 30% of the ontologies reuse terms from other Foundry candidates and 96% of the candidate ontologies contain terms that overlap with terms from the other ontologies. We found that while term reuse increased among the ontologies between September 2009 and September 2010, the level of overlap among the ontologies remained relatively constant. Additionally, we analyzed the six ontologies announced as OBO Foundry members on March 5, 2010, and identified that the level of overlap was extremely low, but, notably, so was the level of term reuse. Conclusions: We have created a prototype web application that allows OBO Foundry ontology developers to see which classes from their ontologies overlap with classes from other ontologies in the OBO Foundry (http://obomap.bioontology.org). From our analysis, we conclude that while the OBO Foundry has made significant progress toward orthogonality during the period of this study through increased adoption of explicit term reuse, a large amount of overlap remains among these ontologies. Furthermore, the characteristics of the identified overlap, such as the terms it comprises and its distribution among the ontologies, indicate that the achieving orthogonality will be exceptionally difficult, if not impossible. [ABSTRACT FROM AUTHOR]

Background: Public biomedical data repositories often provide web-based interfaces to collect experimental metadata. However, these interfaces typically reflect the ad hoc metadata specification practices of the associated repositories, leading to a lack of standardization in the collected metadata. This lack of standardization limits the ability of the source datasets to be broadly discovered, reused, and integrated with other datasets. To increase reuse, discoverability, and reproducibility of the described experiments, datasets should be appropriately annotated by using agreed-upon terms, ideally from ontologies or other controlled term sources. Results: This work presents "CEDAR OnDemand", a browser extension powered by the NCBO (National Center for Biomedical Ontology) BioPortal that enables users to seamlessly enter ontology-based metadata through existing web forms native to individual repositories. CEDAR OnDemand analyzes the web page contents to identify the text input fields and associate them with relevant ontologies which are recommended automatically based upon input fields' labels (using the NCBO ontology recommender) and a pre-defined list of ontologies. These field-specific ontologies are used for controlling metadata entry. CEDAR OnDemand works for any web form designed in the HTML format. We demonstrate how CEDAR OnDemand works through the NCBI (National Center for Biotechnology Information) BioSample web-based metadata entry. Conclusion: CEDAR OnDemand helps lower the barrier of incorporating ontologies into standardized metadata entry for public data repositories. CEDAR OnDemand is available freely on the Google Chrome store https://chrome.google.com/webstore/search/CEDAROnDemand [ABSTRACT FROM AUTHOR]

Many vocabularies and ontologies are produced to represent and annotate agronomic data. However, those ontologies are spread out, in different formats, of different size, with different structures and from overlapping domains. Therefore, there is need for a common platform to receive and host them, align them, and enabling their use in agro-informatics applications. By reusing the National Center for Biomedical Ontologies (NCBO) BioPortal technology, we have designed AgroPortal, an ontology repository for the agronomy domain. The AgroPortal project re-uses the biomedical domain’s semantic tools and insights to serve agronomy, but also food, plant, and biodiversity sciences. We offer a portal that features ontology hosting, search, versioning, visualization, comment, and recommendation; enables semantic annotation; stores and exploits ontology alignments; and enables interoperation with the semantic web. The AgroPortal specifically satisfies requirements of the agronomy community in terms of ontology formats (e.g., SKOS vocabularies and trait dictionaries) and supported features (offering detailed metadata and advanced annotation capabilities). In this paper, we present our platform’s content and features, including the additions to the original technology, as well as preliminary outputs of five driving agronomic use cases that participated in the design and orientation of the project to anchor it in the community. By building on the experience and existing technology acquired from the biomedical domain, we can present in AgroPortal a robust and feature-rich repository of great value for the agronomic domain. [ABSTRACT FROM AUTHOR]

Background: Structured data acquisition is a common task that is widely performed in biomedicine. However, current solutions for this task are far from providing a means to structure data in such a way that it can be automatically employed in decision making (e.g., in our example application domain of clinical functional assessment, for determining eligibility for disability benefits) based on conclusions derived from acquired data (e.g., assessment of impaired motor function). To use data in these settings, we need it structured in a way that can be exploited by automated reasoning systems, for instance, in the Web Ontology Language (OWL); the de facto ontology language for the Web. Results: We tackle the problem of generating Web-based assessment forms from OWL ontologies, and aggregating input gathered through these forms as an ontology of "semantically-enriched" form data that can be queried using an RDF query language, such as SPARQL. We developed an ontology-based structured data acquisition system, which we present through its specific application to the clinical functional assessment domain. We found that data gathered through our system is highly amenable to automatic analysis using queries. Conclusions: We demonstrated how ontologies can be used to help structuring Web-based forms and to semantically enrich the data elements of the acquired structured data. The ontologies associated with the enriched data elements enable automated inferences and provide a rich vocabulary for performing queries. [ABSTRACT FROM AUTHOR]

Background: Ontologies and controlled terminologies have become increasingly important in biomedical research. Researchers use ontologies to annotate their data with ontology terms, enabling better data integration and interoperability across disparate datasets. However, the number, variety and complexity of current biomedical ontologies make it cumbersome for researchers to determine which ones to reuse for their specific needs. To overcome this problem, in 2010 the National Center for Biomedical Ontology (NCBO) released the Ontology Recommender, which is a service that receives a biomedical text corpus or a list of keywords and suggests ontologies appropriate for referencing the indicated terms. Methods: We developed a new version of the NCBO Ontology Recommender. Called Ontology Recommender 2.0, it uses a novel recommendation approach that evaluates the relevance of an ontology to biomedical text data according to four different criteria: (1) the extent to which the ontology covers the input data; (2) the acceptance of the ontology in the biomedical community; (3) the level of detail of the ontology classes that cover the input data; and (4) the specialization of the ontology to the domain of the input data. Results: Our evaluation shows that the enhanced recommender provides higher quality suggestions than the original approach, providing better coverage of the input data, more detailed information about their concepts, increased specialization for the domain of the input data, and greater acceptance and use in the community. In addition, it provides users with more explanatory information, along with suggestions of not only individual ontologies but also groups of ontologies to use together. It also can be customized to fit the needs of different ontology recommendation scenarios. Conclusions: Ontology Recommender 2.0 suggests relevant ontologies for annotating biomedical text data. It combines the strengths of its predecessor with a range of adjustments and new features that improve its reliability and usefulness. Ontology Recommender 2.0 recommends over 500 biomedical ontologies from the NCBO BioPortal platform, where it is openly available (both via the user interface at http://bioportal.bioontology.org/recommender, and via a Web service API). [ABSTRACT FROM AUTHOR]

With the growing popularity of large-scale collaborative ontology-engineering projects, such as the creation of the 11th revision of the International Classification of Diseases, we need new methods and insights to help project- and community-managers to cope with the constantly growing complexity of such projects. In this paper, we present a novel application of Markov chains to model sequential usage patterns that can be found in the change-logs of collaborative ontology-engineering projects. We provide a detailed presentation of the analysis process, describing all the required steps that are necessary to apply and determine the best fitting Markov chain model. Amongst others, the model and results allow us to identify structural properties and regularities as well as predict future actions based on usage sequences. We are specifically interested in determining the appropriate Markov chain orders which postulate on how many previous actions future ones depend on. To demonstrate the practical usefulness of the extracted Markov chains we conduct sequential pattern analyses on a large-scale collaborative ontology-engineering dataset, the International Classification of Diseases in its 11th revision. To further expand on the usefulness of the presented analysis, we show that the collected sequential patterns provide potentially actionable information for user-interface designers, ontology-engineering tool developers and project-managers to monitor, coordinate and dynamically adapt to the natural development processes that occur when collaboratively engineering an ontology. We hope that presented work will spur a new line of ontology-development tools, evaluation-techniques and new insights, further taking the interactive nature of the collaborative ontology-engineering process into consideration. [ABSTRACT FROM AUTHOR]

The life science industries (including pharmaceuticals, agrochemicals and consumer goods) are exploring new business models for research and development that focus on external partnerships. In parallel, there is a desire to make better use of data obtained from sources such as human clinical samples to inform and support early research programmes. Success in both areas depends upon the successful integration of heterogeneous data from multiple providers and scientific domains, something that is already a major challenge within the industry. This issue is exacerbated by the absence of agreed standards that unambiguously identify the entities, processes and observations within experimental results. In this article we highlight the risks to future productivity that are associated with incomplete biological and chemical vocabularies and suggest a new model to address this long-standing issue. [ABSTRACT FROM AUTHOR]

Background: Translational medicine requires the integration of knowledge using heterogeneous data from health care to the life sciences. Here, we describe a collaborative effort to produce a prototype Translational Medicine Knowledge Base (TMKB) capable of answering questions relating to clinical practice and pharmaceutical drug discovery. Results: We developed the Translational Medicine Ontology (TMO) as a unifying ontology to integrate chemical, genomic and proteomic data with disease, treatment, and electronic health records. We demonstrate the use of Semantic Web technologies in the integration of patient and biomedical data, and reveal how such a knowledge base can aid physicians in providing tailored patient care and facilitate the recruitment of patients into active clinical trials. Thus, patients, physicians and researchers may explore the knowledge base to better understand therapeutic options, efficacy, and mechanisms of action. Conclusions: This work takes an important step in using Semantic Web technologies to facilitate integration of relevant, distributed, external sources and progress towards a computational platform to support personalized medicine. [ABSTRACT FROM AUTHOR]

Problem solving methods (PSMs) are software components that represent and encode reusable algorithms. They can be combined with representations of domain knowledge to produce intelligent application systems. A goal of research on PSMs is to provide principled methods and tools for composing and reusing algorithms in knowledge-based systems. The ultimate objective is to produce libraries of methods that can be easily adapted for use in these systems. Despite the intuitive appeal of PSMs as conceptual building blocks, in practice, these goals are largely unmet. There are no widely available tools for building applications using PSMs and no public libraries of PSMs available for reuse. This paper analyzes some of the reasons for the lack of widespread adoptions of PSM techniques and illustrate our analysis by describing our experiences developing a complex, high-throughput software system based on PSM principles. We conclude that many fundamental principles in PSM research are useful for building knowledge-based systems. In particular, the task--method decomposition process, which provides a means for structuring knowledge-based tasks, is a powerful abstraction for building systems of analytic methods. However, despite the power of PSMs in the conceptual modeling of knowledge-based systems, software engineering challenges have been seriously underestimated. The complexity of integrating control knowledge modeled by developers using PSMs with the domain knowledge that they model using ontologies creates a barrier to widespread use of PSM-based systems. Nevertheless, the surge of recent interest in ontologies has led to the production of comprehensive domain ontologies and of robust ontology-authoring tools. These developments present new opportunities to leverage the PSM approach. [ABSTRACT FROM AUTHOR]

The National Center for Biomedical Ontology (NCBO) is developing a system for automated, ontology-based access to online biomedical resources (Shah NH, et al.: Ontology-driven indexing of public datasets for translational bioinformatics. BMC Bioinformatics 2009, 10 (Suppl 2):S1). The system's indexing workflow processes the text metadata of diverse resources such as datasets from GEO and ArrayExpress to annotate and index them with concepts from appropriate ontologies. This indexing requires the use of a concept-recognition tool to identify ontology concepts in the resource's textual metadata. In this paper, we present a comparison of two concept recognizers -- NLM's MetaMap and the University of Michigan's Mgrep. We utilize a number of data sources and dictionaries to evaluate the concept recognizers in terms of precision, recall, speed of execution, scalability and customizability. Our evaluations demonstrate that Mgrep has a clear edge over MetaMap for large-scale service oriented applications. Based on our analysis we also suggest areas of potential improvements for Mgrep. We have subsequently used Mgrep to build the Open Biomedical Annotator service. The Annotator service has access to a large dictionary of biomedical terms derived from the United Medical Language System (UMLS) and NCBO ontologies. The Annotator also leverages the hierarchical structure of the ontologies and their mappings to expand annotations. The Annotator service is available to the community as a REST Web service for creating ontology-based annotations of their data. [ABSTRACT FROM AUTHOR]

Background: A critical challenge in neuroscience is organizing, managing, and accessing the explosion in neuroscientific knowledge, particularly anatomic knowledge. We believe that explicit knowledge-based approaches to make neuroscientific knowledge computationally accessible will be helpful in tackling this challenge and will enable a variety of applications exploiting this knowledge, such as surgical planning. Results: We developed ontology-based models of neuroanatomy to enable symbolic lookup, logical inference and mathematical modeling of neural systems. We built a prototype model of the motor system that integrates descriptive anatomic and qualitative functional neuroanatomical knowledge. In addition to modeling normal neuroanatomy, our approach provides an explicit representation of abnormal neural connectivity in disease states, such as common movement disorders. The ontology-based representation encodes both structural and functional aspects of neuroanatomy. The ontology-based models can be evaluated computationally, enabling development of automated computer reasoning applications. Conclusion: Neuroanatomical knowledge can be represented in machine-accessible format using ontologies. Computational neuroanatomical approaches such as described in this work could become a key tool in translational informatics, leading to decision support applications that inform and guide surgical planning and personalized care for neurological disease in the future. [ABSTRACT FROM AUTHOR]

The volume of publicly available genomic scale data is increasing. Genomic datasets in public repositories are annotated with free-text fields describing the pathological state of the studied sample. These annotations are not mapped to concepts in any ontology, making it difficult to integrate these datasets across repositories. We have previously developed methods to map text-annotations of tissue microarrays to concepts in the NCI thesaurus and SNOMED-CT. In this work we generalize our methods to map text annotations of gene expression datasets to concepts in the UMLS. We demonstrate the utility of our methods by processing annotations of datasets in the Gene Expression Omnibus. We demonstrate that we enable ontology-based querying and integration of tissue and gene expression microarray data. We enable identification of datasets on specific diseases across both repositories. Our approach provides the basis for ontology-driven data integration for translational research on gene and protein expression data. Based on this work we have built a prototype system for ontology based annotation and indexing of biomedical data. The system processes the text metadata of diverse resource elements such as gene expression data sets, descriptions of radiology images, clinical-trial reports, and PubMed article abstracts to annotate and index them with concepts from appropriate ontologies. The key functionality of this system is to enable users to locate biomedical data resources related to particular ontology concepts. [ABSTRACT FROM AUTHOR]

The National Cancer Institute's (NCI) Thesaurus is a biomedical reference ontology. The NCI Thesaurus is represented using description logic, more specifically Ontylog, a description logic implemented by Apelon, Inc. We are exploring the use of the DL species of the Web Ontology Language (OWL DL) – a W3C recommended standard for ontology representation – instead of Ontylog for representing the NCI Thesaurus. We have studied the requirements for knowledge representation of the NCI Thesaurus, and considered how OWL DL (and its implementation in Protégé-OWL) satisfies these requirements. In this paper, we discuss the areas where OWL DL was sufficient for representing required components, where tool support that would hide some of the complexity and extra levels of indirection would be required, and where language expressiveness is not sufficient given the representation requirements. Because many of the knowledge-representation issues that we encountered are very similar to the issues in representing other biomedical terminologies and ontologies in general, we believe that the lessons that we learned and the approaches that we developed will prove useful and informative for other researchers. [ABSTRACT FROM AUTHOR]

Functional brain networks detected in task-free (''resting-state'') functional magnetic resonance imaging (fMRI) have a smallworld architecture that reflects a robust functional organization of the brain. Here, we examined whether this functional organization is disrupted in Alzheimer's disease (AD). Task-free fMRI data from 21 AD subjects and 18 age-matched controls were obtained. Wavelet analysis was applied to the fMRI data to compute frequency-dependent correlation matrices. Correlation matrices were thresholded to create 90-node undirected-graphs of functional brain networks. Small-world metrics (characteristic path length and clustering coefficient) were computed using graph analytical methods. In the low frequency interval 0.01 to 0.05 Hz, functional brain networks in controls showed small-world organization of brain activity, characterized by a high clustering coefficient and a low characteristic path length. In contrast, functional brain networks in AD showed loss of small-world properties, characterized by a significantly lower clustering coefficient (p<0.01), indicative of disrupted local connectivity. Clustering coefficients for the left and right hippocampus were significantly lower (p<0.01) in the AD group compared to the control group. Furthermore, the clustering coefficient distinguished AD participants from the controls with a sensitivity of 72% and specificity of 78%. Our study provides new evidence that there is disrupted organization of functional brain networks in AD. Small-world metrics can characterize the functional organization of the brain in AD, and our findings further suggest that these network measures may be useful as an imaging-based biomarker to distinguish AD from healthy aging. [ABSTRACT FROM AUTHOR]

The advancement of the computational biology field hinges on progress in three fundamental directions - the development of new computational algorithms, the availability of informatics resource management infrastructures and the capability of tools to interoperate and synergize. There is an explosion in algorithms and tools for computational biology, which makes it difficult for biologists to find, compare and integrate such resources. We describe a new infrastructure, iTools, for managing the query, traversal and comparison of diverse computational biology resources. Specifically, iTools stores information about three types of resources-data, software tools and web-services. The iTools design, implementation and resource meta - data content reflect the broad research, computational, applied and scientific expertise available at the seven National Centers for Biomedical Computing. iTools provides a system for classification, categorization and integration of different computational biology resources across space-and-time scales, biomedical problems, computational infrastructures and mathematical foundations. A large number of resources are already iTools-accessible to the community and this infrastructure is rapidly growing. iTools includes human and machine interfaces to its resource meta-data repository. Investigators or computer programs may utilize these interfaces to search, compare, expand, revise and mine meta-data descriptions of existent computational biology resources. We propose two ways to browse and display the iTools dynamic collection of resources. The first one is based on an ontology of computational biology resources, and the second one is derived from hyperbolic projections of manifolds or complex structures onto planar discs. iTools is an open source project both in terms of the source code development as well as its meta-data content. iTools employs a decentralized, portable, scalable and lightweight framework for long-term resource management. We demonstrate several applications of iTools as a framework for integrated bioinformatics. iTools and the complete details about its specifications, usage and interfaces are available at the iTools web page http://iTools.ccb.ucla.edu. [ABSTRACT FROM AUTHOR]

Background: The Stanford Tissue Microarray Database (TMAD) is a repository of data serving a consortium of pathologists and biomedical researchers. The tissue samples in TMAD are annotated with multiple free-text fields, specifying the pathological diagnoses for each sample. These text annotations are not structured according to any ontology, making future integration of this resource with other biological and clinical data difficult. Results: We developed methods to map these annotations to the NCI thesaurus. Using the NCIT we can effectively represent annotations for about 86% of the samples. We demonstrate how this mapping enables ontology driven integration and querying of tissue microarray data. We have deployed the mapping and ontology driven querying tools at the TMAD site for general use. Conclusion: We have demonstrated that we can effectively map the diagnosis-related terms describing a sample in TMAD to the NCI-T. The NCI thesaurus terms have a wide coverage and provide terms for about 86% of the samples. In our opinion the NCI thesaurus can facilitate integration of this resource with other biological data. [ABSTRACT FROM AUTHOR]

Timely detection of an inhalational anthrax outbreak is critical for clinical and public health management. Syndromic surveillance has received considerable investment, but little is known about how it will perform relative to routine clinical case finding for detection of an inhalational anthrax outbreak. We conducted a simulation study to compare clinical case finding with syndromic surveillance for detection of an outbreak of inhalational anthrax. After simulated release of 1 kg of anthrax spores, the proportion of outbreaks detected first by syndromic surveillance was 0.59 at a specificity of 0.9 and 0.28 at a specificity of 0.975. The mean detection benefit of syndromic surveillance was 1.0 day at a specificity of 0.9 and 0.32 days at a specificity of 0.975. When syndromic surveillance was sufficiently sensitive to detect a substantial proportion of outbreaks before clinical case finding, it generated frequent false alarms. [ABSTRACT FROM AUTHOR]

Objective: Medical assessment of penetrating injuries is a difficult and knowledge-intensive task, and rapid determination of the extent of internal injuries is vital for triage and for determining the appropriate treatment. Physical examination and computed tomographic (CT) imaging data must be combined with detailed anatomic, physiologic, and biomechanical knowledge to assess the injured subject. We are developing a methodology to automate reasoning about penetrating injuries using canonical knowledge combined with specific subject image data. Methods and Material: In our approach, we build a three-dimensional geometric model of a subject from segmented images. We link regions in this model to entities in two knowledge sources: (1) a comprehensive ontology of anatomy containing organ identities, adjacencies, and other information useful for anatomic reasoning and (2) an ontology of regional perfusion containing formal definitions of arterial anatomy and corresponding regions of perfusion. We created computer reasoning services ("problem solvers") that use the ontologies to evaluate the geometric model of the subject and deduce the consequences of penetrating injuries. Results: We developed and tested our methods using data from the Visible Human. Our problem solvers can determine the organs that are injured given particular trajectories of projectiles, whether vital structures--such as a coronary artery--are injured, and they can predict the propagation of injury ensuing after vital structures are injured. Conclusion: We have demonstrated the capability of using ontologies with medical images to support computer reasoning about injury based on those images. Our methodology demonstrates an approach to creating intelligent computer applications that reason with image data, and it may have value in helping practitioners in the assessment of penetrating injury. [ABSTRACT FROM AUTHOR]

Abstract Objectives: To determine the characteristics of popular breast cancer related websites and whether more popular sites are of higher quality. Design: The search engine Google was used to generate a list of websites about breast cancer. Google ranks search results by measures of link popularity--the number of links to a site from other sites. The top 200 sites returned in response to the query "breast cancer" were divided into "more popular" and "less popular" subgroups by three different measures of link popularity: Google rank and number of links reported independently by Google and by AltaVista (another search engine). Main outcome measures: Type and quality of content. Results: More popular sites according to Google rank were more likely than less popular ones to contain information on ongoing clinical trials (27% v 12%, P = 0.01 ), results of trials (12% v 3%, P = 0.02), and opportunities for psychosocial adjustment (48% v 23%, P < 0.01). These characteristics were also associated with higher number of links as reported by Google and AltaVista. More popular sites by number of linking sites were also more likely to provide updates on other breast cancer research, information on legislation and advocacy, and a message board service. Measures of quality such as display of authorship, attribution or references, currency of information, and disclosure did not differ between groups. Conclusions: Popularity of websites is associated with type rather than quality of content. Sites that include content correlated with popularity may best meet the public's desire for information about breast cancer. [ABSTRACT FROM AUTHOR]

Metadata—the machine-readable descriptions of the data—are increasingly seen as crucial for describing the vast array of biomedical datasets that are currently being deposited in public repositories. While most public repositories have firm requirements that metadata must accompany submitted datasets, the quality of those metadata is generally very poor. A key problem is that the typical metadata acquisition process is onerous and time consuming, with little interactive guidance or assistance provided to users. Secondary problems include the lack of validation and sparse use of standardized terms or ontologies when authoring metadata. There is a pressing need for improvements to the metadata acquisition process that will help users to enter metadata quickly and accurately. In this paper, we outline a recommendation system for metadata that aims to address this challenge. Our approach uses association rule mining to uncover hidden associations among metadata values and to represent them in the form of association rules. These rules are then used to present users with real-time recommendations when authoring metadata. The novelties of our method are that it is able to combine analyses of metadata from multiple repositories when generating recommendations and can enhance those recommendations by aligning them with ontology terms. We implemented our approach as a service integrated into the CEDAR Workbench metadata authoring platform, and evaluated it using metadata from two public biomedical repositories: US-based National Center for Biotechnology Information BioSample and European Bioinformatics Institute BioSamples. The results show that our approach is able to use analyses of previously entered metadata coupled with ontology-based mappings to present users with accurate recommendations when authoring metadata. [ABSTRACT FROM AUTHOR]

Summary: WebProtégé is an open-source Web application for editing OWL 2 ontologies. It contains several features to aid collaboration, including support for the discussion of issues, change notification and revision-based change tracking. WebProtégé also features a simple user interface, which is geared towards editing the kinds of class descriptions and annotations that are prevalent throughout biomedical ontologies. Moreover, it is possible to configure the user interface using views that are optimized for editing Open Biomedical Ontology (OBO) class descriptions and metadata. Some of these views are shown in the Supplementary Material and can be seen in WebProtégé itself by configuring the project as an OBO project.Availability and implementation: WebProtégé is freely available for use on the Web at http://webprotege.stanford.edu. It is implemented in Java and JavaScript using the OWL API and the Google Web Toolkit. All major browsers are supported. For users who do not wish to host their ontologies on the Stanford servers, WebProtégé is available as a Web app that can be run locally using a Servlet container such as Tomcat. Binaries, source code and documentation are available under an open-source license at http://protegewiki.stanford.edu/wiki/WebProtege.Contact: matthew.horridge@stanford.eduSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM PUBLISHER]