We propose a new approach for integrating protocol care schedules into patients' personal calendars. This approach could provide patients with greater control over their current and future scheduling ...demands as they seek and receive protocol-based care.
PROTÉGÉ-II is a suite of tools and a methodology for building knowledge-based systems and domain-specific knowledge-acquisition tools. In this paper, we show how PROTÉGÉ-II can be applied to the task ...of providing protocol-based decision support in the domain of treating HIV-infected patients. To apply PROTÉGÉ-II, (1) we construct a decomposable problem-solving method called
episodic skeletal-plan refinement, (2) we build an
application ontology that consists of the terms and relations in the domain, and of method-specific distinctions not already captured in the domain terms, and (3) we specify
mapping relations that link terms from the application ontology to the domain-independent terms used in the problem-solving method. From the application ontology, we automatically generate a domain-specific knowledge-acquisition tool that is custom-tailored for the application. The knowledge-acquisition tool is used for the creation and maintenance of domain knowledge used by the problem-solving method. The general goal of the PROTÉGÉ-II approach is to produce systems and components that are reusable and easily maintained. This is the rationale for constructing ontologies and problem-solving methods that can be composed from a set of smaller-grained methods and mechanisms. This is also why we tightly couple the knowledge-acquisition tools to the application ontology that specifies the domain terms used in the problem-solving systems. Although our evaluation is still preliminary, for the application task of providing protocol-based decision support, we show that these goals of reusability and easy maintenance can be achieved. We discuss design decisions and the tradeoffs that have to be made in the development of the system.
Modern genomic research has access to a plethora of knowledge sources. Often, it is imperative that researchers combine and integrate knowledge from multiple perspectives. Although some technology ...exists for connecting data and knowledge bases, these methods are only just beginning to be successfully applied to research in modem cell biology. In this paper, we argue that one way to integrate multiple knowledge sources is through anatomy--both generic cellular anatomy, as well as anatomic knowledge about the tissues and organs that may be studied via microarray gene expression experiments. We present two examples where we have combined a large ontology of human anatomy (the FMA) with other genomic knowledge sources: the gene ontology (GO) and the mouse genomic databases (MGD) of the Jackson Labs. These two initial examples of knowledge integration provide a proof of concept that anatomy can act as a hub through which we can usefully combine a variety of genomic knowledge and data.
Currently, biosimulation researchers use a variety of computational environments and languages to model biological processes. Ideally, researchers should be able to semiautomatically merge models to ...more effectively build larger, multi-scale models. However, current modeling methods do not capture the underlying semantics of these models sufficiently to support this type of model construction. In this paper, we both propose a general approach to solve this problem, and we provide a specific example that demonstrates the benefits of our methodology. In particular, we describe three biosimulation models: (1) a cardio-vascular fluid dynamics model, (2) a model of heart rate regulation via baroreceptor control, and (3) a sub-cellular-level model of the arteriolar smooth muscle. Within a light-weight ontological framework, we leverage reference ontologies to match concepts across models. The light-weight ontology then helps us combine our three models into a merged model that can answer questions beyond the scope of any single model.
When different groups create models or ontologies of the same knowledge domain, this creates challenges for knowledge sharing. To identify these challenges, we compare cellular structure as modeled ...by the Foundational Model of Anatomy(FMA), the Gene Ontology (GO), and the Cell Component Ontology (CCO). These ontologies all model the physical anatomy of a cell, and we expected them to be similar in scope. However, we discovered that the actual differences among the mare substantial. These differences represent variations based on theory-driven vs. emergent construction,as well as differences in how small application ontologies like the CCO are created from reference ontologies. In this paper, we provide a description and analysis of these differences. By studying differences in language, granularity, breadth of coverage,and model organization, we hope to gain a better understanding of how to map between related ontologies.
In previous work, we proposed an approach called the Structural Difference Method (SDM) to correlating the anatomy of Homo sapiens with selected species, using the Foundational Model of Anatomy (FMA) ...as a framework and graph matching as a method, for determining similarities and differences between species. In this paper, we present the design of a comparative anatomy information system that utilizes the SDM and allows users to issue queries to determine the similarities and differences between two species. Our system will serve as a pilot project for cross-species anatomical information collection, storage, and retrieval. The underlying data structure of a mapping, and the syntax and semantics of the system's query language, are presented.
Paget's disease of bone (PDB) is a common disorder characterized by focal abnormalities of bone remodeling. We previously identified variants at the CSF1, OPTN and TNFRSF11A loci as risk factors for ...PDB by genome-wide association study. Here we extended this study, identified three new loci and confirmed their association with PDB in 2,215 affected individuals (cases) and 4,370 controls from seven independent populations. The new associations were with rs5742915 within PML on 15q24 (odds ratio (OR) = 1.34, P = 1.6 × 10−14), rs10498635 within RIN3 on 14q32 (OR = 1.44, P = 2.55 × 10−11) and rs4294134 within NUP205 on 7q33 (OR = 1.45, P = 8.45 × 10−10). Our data also confirmed the association of TM7SF4 (rs2458413, OR = 1.40, P = 7.38 × 10−17) with PDB. These seven loci explained ∼13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB.
Clinical trial protocol documents play an important role in clinical research. However, clinical protocol writing remains a complex and relatively un-studied process. Protocols are often written by ...teams of people, yet little prior research has captured the problems or analyzed the collaboration support needs of protocol writers. Here we present the results of an initial ethnographic study into the clinical trial protocol writing processes at a representative cooperative clinical trial group funded by National Cancer Institute (NCI). We analyzed the collaborative nature of the writing process, identified common problems, derived information and communication support needs of collaborative clinical protocol writers, and provided recommendations to streamline the process. We believe that this paper contributes useful implications for the design of future collaborative clinical protocol writing tools.
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