Ontology driven integration platform for clinical and translational research

Semantic Web technologies offer a promising framework for integration of disparate biomedical data. In this paper we present the semantic information integration platform under development at the Center for Clinical and Translational Sciences (CCTS) at the University of Texas Health Science Center at Houston (UTHSC-H) as part of our Clinical and Translational Science Award (CTSA) program. We utilize the Semantic Web technologies not only for integrating, repurposing and classification of multi-source clinical data, but also to construct a distributed environment for information sharing, and collaboration online. Service Oriented Architecture (SOA) is used to modularize and distribute reusable services in a dynamic and distributed environment. Components of the semantic solution and its overall architecture are described.

Genome-Wide Analyses Suggest Mechanisms Involving Early B-Cell Development in Canine IgA Deficiency.

Immunoglobulin A deficiency (IgAD) is the most common primary immune deficiency disorder in both humans and dogs, characterized by recurrent mucosal tract infections and a predisposition for allergic and other immune mediated diseases. In several dog breeds, low IgA levels have been observed at a high frequency and with a clinical resemblance to human IgAD. In this study, we used genome-wide association studies (GWAS) to identify genomic regions associated with low IgA levels in dogs as a comparative model for human IgAD. We used a novel percentile groups-approach to establish breed-specific cut-offs and to perform analyses in a close to continuous manner. GWAS performed in four breeds prone to low IgA levels (German shepherd, Golden retriever, Labrador retriever and Shar-Pei) identified 35 genomic loci suggestively associated (p <0.0005) to IgA levels. In German shepherd, three genomic regions (candidate genes include KIRREL3 and SERPINA9) were genome-wide significantly associated (p <0.0002) with IgA levels. A ~20kb long haplotype on CFA28, significantly associated (p = 0.0005) to IgA levels in Shar-Pei, was positioned within the first intron of the gene SLIT1. Both KIRREL3 and SLIT1 are highly expressed in the central nervous system and in bone marrow and are potentially important during B-cell development. SERPINA9 expression is restricted to B-cells and peaks at the time-point when B-cells proliferate into antibody-producing plasma cells. The suggestively associated regions were enriched for genes in Gene Ontology gene sets involving inflammation and early immune cell development.

A Development Methodology to Facilitate the Integration of Smart Spaces into the Web of Things

How to create or integrate large Smart Spaces (considered as mash-ups of sensors and actuators) into the paradigm of ?Web of Things? has been the motivation of many recent works. A cutting-edge approach deals with developing and deploying web-enabled embedded devices with two major objectives: 1) to integrate sensor and actuator technologies into everyday objects, and 2) to allow a diversity of devices to plug to Internet. Currently, developers who want to use this Internet-oriented approach need have solid understanding about sensorial platforms and semantic technologies. In this paper we propose a Resource-Oriented and Ontology-Driven Development (ROOD) methodology, based on Model Driven Architecture (MDA), to facilitate to any developer the development and deployment of Smart Spaces. Early evaluations of the ROOD methodology have been successfully accomplished through a partial deployment of a Smart Hotel.

Ontology driven description and engineering of autonomous systems: application to process system engineering

Autonomous systems refer to systems capable of operating in a real world environment without any form of external control for extended periods of time. Autonomy is a desired goal for every system as it improves its performance, safety and profit. Ontologies are a way to conceptualize the knowledge of a specific domain. In this paper an ontology for the description of autonomous systems as well as for its development (engineering) is presented and applied to a process. This ontology is intended to be applied and used to generate final applications following a model driven methodology.

Bat-MP: An Ontology-Based Energy Management Platform

This paper presents an Ontology-Based multi-technology platform as part of an open energy management system which also comprises a wireless transducer network for control and monitoring. The platform allows the integration of several building automation protocols, eases the development and implementation of different kinds of services and allows sharing of the data of a building. The system has been implemented and tested in the Energy Efficiency Research Facility at CeDInt-UPM.

The NeOn Methodology for Ontology Engineering

In contrast to other approaches that provide methodological guidance for ontology engineering, the NeOn Methodology does not prescribe a rigid workflow, but instead it suggests a variety of pathways for developing ontologies. The nine scenarios proposed in the methodology cover commonly occurring situations, for example, when available ontologies need to be re-engineered, aligned, modularized, localized to support different languages and cultures, and integrated with ontology design patterns and non-ontological resources, such as folksonomies or thesauri. In addition, the NeOn Methodology framework provides (a) a glossary of processes and activities involved in the development of ontologies, (b) two ontology life cycle models, and (c) a set of methodological guidelines for different processes and activities, which are described (a) functionally, in terms of goals, inputs, outputs, and relevant constraints; (b) procedurally, by means of workflow specifications; and (c) empirically, through a set of illustrative examples.

Building an ontology catalogue for smart cities

Apart from providing semantics and reasoning power to data, ontologies enable and facilitate interoperability across heterogeneous systems or environments. A good practice when developing ontologies is to reuse as much knowledge as possible in order to increase interoperability by reducing heterogeneity across models and to reduce development effort. Ontology registries, indexes and catalogues facilitate the task of finding, exploring and reusing ontologies by collecting them from different sources. This paper presents an ontology catalogue for the smart cities and related domains. This catalogue is based on curated metadata and incorporates ontology evaluation features. Such catalogue represents the first approach within this community and it would be highly useful for new ontology developments or for describing and annotating existing ontologies.

Towards the Design of a Textile Chemical Ontology

The main goal of this paper is to present the initial version of a Textile Chemical Ontology, to be used by textile professionals with the purpose of conceptualising and representing the banned and harmful chemical substances that are forbidden in this domain. After analysing different methodologies and determining that “Methontology” is the most appropriate for the purposes, this methodology is explored and applied to the domain. In this manner, an initial set of concepts are defined, together with their hierarchy and the relationships between them. This paper shows the benefits of using the ontology through a real use case in the context of Information Retrieval. The potentiality of the proposed ontology in this preliminary evaluation encourages extending the ontology with a higher number of concepts and relationships, and validating it within other Natural Language Processing applications.

Definition and spatial annotation of the dynamic secretome during early kidney development

The term secretome has been defined as a set of secreted proteins (Grimmond et al. [2003] Genome Res 13:1350-1359). The term secreted protein encompasses all proteins exported from the cell including growth factors, extracellular proteinases, morphogens, and extracellular matrix molecules. Defining the genes encoding secreted proteins that change in expression during organogenesis, the dynamic secretome, is likely to point to key drivers of morphogenesis. Such secreted proteins are involved in the reciprocal interactions between the ureteric bud (UB) and the metanephric mesenchyme (AM) that occur during organogenesis of the metanephros. Some key metanephric secreted proteins have been identified, but many remain to be determined. In this study, microarray expression profiling of E10.5, E11.5, and E13.5 kidney and consensus bioinformatic analysis were used to define a dynamic secretome of early metanephric development. In situ hybridisation was used to confirm microarray results and clarify spatial expression patterns for these genes. Forty-one secreted factors were dynamically expressed between the E10.5 and E13.5 timeframe profiled, and 25 of these factors had not previously been implicated in kidney development. A text-based anatomical ontology was used to spatially annotate the expression pattern of these genes in cultured metanephric explants.

Clinical decision support system for point of care use: ontology driven design and software implementation

OBJECTIVES: The objective of this research was to design a clinical decision support system (CDSS) that supports heterogeneous clinical decision problems and runs on multiple computing platforms. Meeting this objective required a novel design to create an extendable and easy to maintain clinical CDSS for point of care support. The proposed solution was evaluated in a proof of concept implementation. METHODS: Based on our earlier research with the design of a mobile CDSS for emergency triage we used ontology-driven design to represent essential components of a CDSS. Models of clinical decision problems were derived from the ontology and they were processed into executable applications during runtime. This allowed scaling applications' functionality to the capabilities of computing platforms. A prototype of the system was implemented using the extended client-server architecture and Web services to distribute the functions of the system and to make it operational in limited connectivity conditions. RESULTS: The proposed design provided a common framework that facilitated development of diversified clinical applications running seamlessly on a variety of computing platforms. It was prototyped for two clinical decision problems and settings (triage of acute pain in the emergency department and postoperative management of radical prostatectomy on the hospital ward) and implemented on two computing platforms-desktop and handheld computers. CONCLUSIONS: The requirement of the CDSS heterogeneity was satisfied with ontology-driven design. Processing of application models described with the help of ontological models allowed having a complex system running on multiple computing platforms with different capabilities. Finally, separation of models and runtime components contributed to improved extensibility and maintainability of the system.

Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development

Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO) term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4), neurons (Neurofilament M), astrocytes (GFAP) or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals.

A formal model of the Semantic Web Service Ontology (WSMO)

Semantic Web Service, one of the most significant research areas within the Semantic Web vision, has attracted increasing attention from both the research community and industry. The Web Service Modelling Ontology (WSMO) has been proposed as an enabling framework for the total/partial automation of the tasks (e.g., discovery, selection, composition, mediation, execution, monitoring, etc.) involved in both intra- and inter-enterprise integration of Web services. To support the standardisation and tool support of WSMO, a formal model of the language is highly desirable. As several variants of WSMO have been proposed by the WSMO community, which are still under development, the syntax and semantics of WSMO should be formally defined to facilitate easy reuse and future development. In this paper, we present a formal Object-Z formal model of WSMO, where different aspects of the language have been precisely defined within one unified framework. This model not only provides a formal unambiguous model which can be used to develop tools and facilitate future development, but as demonstrated in this paper, can be used to identify and eliminate errors present in existing documentation.

Intelligent Search and Automatic Document Classification and Cataloging Based on Ontology Approach

This paper presents an approach to development of intelligent search system and automatic document classification and cataloging tools for CASE-system based on metadata. The described method uses advantages of ontology approach and traditional approach based on keywords. The method has powerful intelligent means and it can be integrated with existing document search systems.

INFRAWEBS Semantic Web Service Development on the Base of Knowledge Management Layer

The paper gives an overview about the ongoing FP6-IST INFRAWEBS project and describes the main layers and software components embedded in an application oriented realisation framework. An important part of INFRAWEBS is a Semantic Web Unit (SWU) – a collaboration platform and interoperable middleware for ontology-based handling and maintaining of SWS. The framework provides knowledge about a specific domain and relies on ontologies to structure and exchange this knowledge to semantic service development modules. INFRAWEBS Designer and Composer are sub-modules of SWU responsible for creating Semantic Web Services using Case-Based Reasoning approach. The Service Access Middleware (SAM) is responsible for building up the communication channels between users and various other modules. It serves as a generic middleware for deployment of Semantic Web Services. This software toolset provides a development framework for creating and maintaining the full-life-cycle of Semantic Web Services with specific application support.

INFRAWEBS Axiom Editor – A Graphical Ontology-Driven Tool for Creating Complex Logical Expressions

The current INFRAWEBS European research project aims at developing ICT framework enabling software and service providers to generate and establish open and extensible development platforms for Web Service applications. One of the concrete project objectives is developing a full-life-cycle software toolset for creating and maintaining Semantic Web Services (SWSs) supporting specific applications based on Web Service Modelling Ontology (WSMO) framework. According to WSMO, functional and behavioural descriptions of a SWS may be represented by means of complex logical expressions (axioms). The paper describes a specialized userfriendly tool for constructing and editing such axioms – INFRAWEBS Axiom Editor. After discussing the main design principles of the Editor, its functional architecture is briefly presented. The tool is implemented in Eclipse Graphical Environment Framework and Eclipse Rich Client Platform.