Mark A. Musen

The evolution of Protégé: an environment for knowledge-based systems development

The Protege project has come a long way since Mark Musen first built the Protege 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 Protege system has evolved into a durable, extensible platform for knowledge-based systems development and research. The current version, Protege-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 Protege 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: Protege is a flexible, well-supported, and robust development environment. Using Protege, developers and domain experts can easily build effective knowledge-based systems, and researchers can explore ideas in a variety of knowledge-based domains.

Creating Semantic Web contents with Protege-2000

As researchers continue to create new languages in the hope of developing a Semantic Web, they still lack consensus on a standard. The authors describe how Protege-2000, a tool for ontology development and knowledge acquisition, can be adapted for editing models in different Semantic Web languages.

The protégé OWL plugin: an open development environment for semantic web applications

We introduce the OWL Plugin, a Semantic Web extension of the Protege ontology development platform. The OWL Plugin can be used to edit ontologies in the Web Ontology Language (OWL), to access description logic reasoners, and to acquire instances for semantic markup. In many of these features, the OWL Plugin has created and facilitated new practices for building Semantic Web contents, often driven by the needs of and feedback from our users. Furthermore, Proteges flexible open-source platform means that it is easy to integrate custom-tailored components to build real-world applications. This document describes the architecture of the OWL Plugin, walks through its most important features, and discusses some of our design decisions.

Network Analysis of Intrinsic Functional Brain Connectivity in Alzheimer's Disease

Functional brain networks detected in task-free (“resting-state”) functional magnetic resonance imaging (fMRI) have a small-world architecture that reflects a robust functional organization of the brain. Here, we examined whether this functional organization is disrupted in Alzheimers 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.

The PROMPT suite: interactive tools for ontology merging and mapping

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.

The Knowledge Model of Protégé-2000: Combining Interoperability and Flexibility

Knowledge-based systems have become ubiquitous in recent years. Knowledge-base developers need to be able to share and reuse knowledge bases that they build. Therefore, interoperability among different knowledge-representation systems is essential. The Open Knowledge-Base Connectivity protocol (OKBC) is a common query and construction interface for frame-based systems that facilitates this interoperability. ProtEgE-2000 is an OKBC-compatible knowledge-base-editing environment developed in our laboratory. We describe ProtEgE-2000 knowledge model that makes the import and export of knowledge bases from and to other knowledge-base servers easy. We discuss how the requirements of being a usable and configurable knowledge-acquisition tool affected our decisions in the knowledge-model design. ProtEgE-2000 also has a flexible metaclass architecture which provides configurable templates for new classes in the knowledge base. The use of metaclasses makes ProtEgE-2000 easily extensible and enables its use with other knowledge models. We demonstrate that we can resolve many of the differences between the knowledge models of ProtEgE-2000 and Resource Description Framework (RDF)--a system for annotating Web pages with knowledge elements--by defining a new metaclass set. Resolving the differences between the knowledge models in declarative way enables easy adaptation of ProtEgE-2000 as an editor for other knowledge-representation systems.

BioPortal: ontologies and integrated data resources at the click of a mouse

Biomedical ontologies provide essential domain knowledge to drive data integration, information retrieval, data annotation, natural-language processing and decision support. BioPortal (http://bioportal.bioontology.org) is an open repository of biomedical ontologies that provides access via Web services and Web browsers to ontologies developed in OWL, RDF, OBO format and Protégé frames. BioPortal functionality includes the ability to browse, search and visualize ontologies. The Web interface also facilitates community-based participation in the evaluation and evolution of ontology content by providing features to add notes to ontology terms, mappings between terms and ontology reviews based on criteria such as usability, domain coverage, quality of content, and documentation and support. BioPortal also enables integrated search of biomedical data resources such as the Gene Expression Omnibus (GEO), ClinicalTrials.gov, and ArrayExpress, through the annotation and indexing of these resources with ontologies in BioPortal. Thus, BioPortal not only provides investigators, clinicians, and developers ‘one-stop shopping’ to programmatically access biomedical ontologies, but also provides support to integrate data from a variety of biomedical resources.

BioPortal: enhanced functionality via new Web services from the National Center for Biomedical Ontology to access and use ontologies in software applications

The National Center for Biomedical Ontology (NCBO) is one of the National Centers for Biomedical Computing funded under the NIH Roadmap Initiative. Contributing to the national computing infrastructure, NCBO has developed BioPortal, a web portal that provides access to a library of biomedical ontologies and terminologies (http://bioportal.bioontology.org) via the NCBO Web services. BioPortal enables community participation in the evaluation and evolution of ontology content by providing features to add mappings between terms, to add comments linked to specific ontology terms and to provide ontology reviews. The NCBO Web services (http://www.bioontology.org/wiki/index.php/NCBO_REST_services) enable this functionality and provide a uniform mechanism to access ontologies from a variety of knowledge representation formats, such as Web Ontology Language (OWL) and Open Biological and Biomedical Ontologies (OBO) format. The Web services provide multi-layered access to the ontology content, from getting all terms in an ontology to retrieving metadata about a term. Users can easily incorporate the NCBO Web services into software applications to generate semantically aware applications and to facilitate structured data collection.

EON: A Component-Based Approach to Automation of Protocol-Directed Therapy

Provision of automated support for planning protocol-directed therapy requires a computer program to take as input clinical data stored in an electronic patient-record system and to generate as output recommendations for therapeutic interventions and laboratory testing that are defined by applicable protocols. This paper presents a synthesis of research carried out at Stanford University to model the therapy-planning task and to demonstrate a component-based architecture for building protocol-based decision-support systems. We have constructed general-purpose software components that (1) interpret abstract protocol specifications to construct appropriate patient-specific treatment plans; (2) infer from time-stamped patient data higher-level, interval-based, abstract concepts; (3) perform time-oriented queries on a time-oriented patient database; and (4) allow acquisition and maintenance of protocol knowledge in a manner that facilitates efficient processing both by humans and by computers. We have implemented these components in a computer system known as EON. Each of the components has been developed, evaluated, and reported independently. We have evaluated the integration of the components as a composite architecture by implementing T-HELPER, a computer-based patient-record system that uses EON to offer advice regarding the management of patients who are following clinical trial protocols for AIDS or HIV infection. A test of the reuse of the software components in a different clinical domain demonstrated rapid development of a prototype application to support protocol-based care of patients who have breast cancer.

Dimensions of knowledge sharing and reuse

Many workers in medical informatics are seeking to reuse knowledge in new applications and to share encoded knowledge across software environments. Knowledge reuse involves many dimensions, including the reapplication of lexicons, ontologies, inference syntax, tasks, and problem-solving methods. Principal obstacles to all current work in knowledge sharing involve the difficulties of achieving consensus regarding what knowledge representations mean, of enumerating the context features and background knowledge required to ascribe meaning to a particular knowledge representation, and of describing knowledge independent of specific interpreters or inference engines. Progress in the area of knowledge sharing will necessitate more practical experience with attempts to interchange knowledge as well as better tools for viewing and editing knowledge representations at appropriate levels of abstraction. The PROTEGE-II project is one attempt to provide a knowledge-base authoring environment in which developers can experiment with the reuse of knowledge-level problem-solving methods, task models, and domain ontologies.