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Evolving BioAssay Ontology (BAO): modularization, integration and applications.

Journal of biomedical semantics | 2014

The lack of established standards to describe and annotate biological assays and screening outcomes in the domain of drug and chemical probe discovery is a severe limitation to utilize public and proprietary drug screening data to their maximum potential. We have created the BioAssay Ontology (BAO) project (http://bioassayontology.org) to develop common reference metadata terms and definitions required for describing relevant information of low-and high-throughput drug and probe screening assays and results. The main objectives of BAO are to enable effective integration, aggregation, retrieval, and analyses of drug screening data. Since we first released BAO on the BioPortal in 2010 we have considerably expanded and enhanced BAO and we have applied the ontology in several internal and external collaborative projects, for example the BioAssay Research Database (BARD). We describe the evolution of BAO with a design that enables modeling complex assays including profile and panel assays such as those in the Library of Integrated Network-based Cellular Signatures (LINCS). One of the critical questions in evolving BAO is the following: how can we provide a way to efficiently reuse and share among various research projects specific parts of our ontologies without violating the integrity of the ontology and without creating redundancies. This paper provides a comprehensive answer to this question with a description of a methodology for ontology modularization using a layered architecture. Our modularization approach defines several distinct BAO components and separates internal from external modules and domain-level from structural components. This approach facilitates the generation/extraction of derived ontologies (or perspectives) that can suit particular use cases or software applications. We describe the evolution of BAO related to its formal structures, engineering approaches, and content to enable modeling of complex assays and integration with other ontologies and datasets.

Pubmed ID: 25093074 RIS Download

Research resources used in this publication

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Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS080145
  • Agency: NHGRI NIH HHS, United States
    Id: RC2 HG005668

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This is a list of tools and resources that we have found mentioned in this publication.


Bioassay Ontology (tool)

RRID:SCR_002638

Ontology to describe and categorize chemical biology and drug screening assays and their results including high-throughput screening (HTS) data for the purpose of categorizing assays and data analysis. BAO is an extensible, knowledge-based, highly expressive (currently SHOIQ(D)) description of biological assays making use of descriptive logic based features of the Web Ontology Language (OWL). BAO currently has over 700 classes and also makes use of several other ontologies. It describes several concepts related to biological screening, including Perturbagen, Format, Meta Target, Design, Detection Technology, and Endpoint. Perturbagens are perturbing agents that are screened in an assay; they are mostly small molecules. Assay Meta Target describes what is known about the biological system and / or its components interrogated in the assay (and influenced by the Perturbagen). Meta target can be directly described as a molecular entity (e.g. a purified protein or a protein complex), or indirectly by a biological process or event (e.g. phosphorylation). Format describes the biological or chemical features common to each test condition in the assay and includes biochemical, cell-based, organism-based, and variations thereof. The assay Design describes the assay methodology and implementation of how the perturbation of the biological system is translated into a detectable signal. Detection Technology relates to the physical method and technical details to detect and record a signal. Endpoints are the final HTS results as they are usually published (such as IC50, percent inhibition, etc). BAO has been designed to accommodate multiplexed assays. All main BAO components include multiple levels of sub-categories and specification classes, which are linked via object property relationships forming an expressive knowledge-based representation.

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Protege (tool)

RRID:SCR_003299

Protege is a free, open-source platform that provides a growing user community with a suite of tools to construct domain models and knowledge-based applications with ontologies. At its core, Protege implements a rich set of knowledge-modeling structures and actions that support the creation, visualization, and manipulation of ontologies in various representation formats. Protege can be customized to provide domain-friendly support for creating knowledge models and entering data. Further, Protege can be extended by way of a plug-in architecture and a Java-based Application Programming Interface (API) for building knowledge-based tools and applications. An ontology describes the concepts and relationships that are important in a particular domain, providing a vocabulary for that domain as well as a computerized specification of the meaning of terms used in the vocabulary. Ontologies range from taxonomies and classifications, database schemas, to fully axiomatized theories. In recent years, ontologies have been adopted in many business and scientific communities as a way to share, reuse and process domain knowledge. Ontologies are now central to many applications such as scientific knowledge portals, information management and integration systems, electronic commerce, and semantic web services. The Protege platform supports two main ways of modeling ontologies: * The Protege-Frames editor enables users to build and populate ontologies that are frame-based, in accordance with the Open Knowledge Base Connectivity protocol (OKBC). In this model, an ontology consists of a set of classes organized in a subsumption hierarchy to represent a domain's salient concepts, a set of slots associated to classes to describe their properties and relationships, and a set of instances of those classes - individual exemplars of the concepts that hold specific values for their properties. * The Protege-OWL editor enables users to build ontologies for the Semantic Web, in particular in the W3C's Web Ontology Language (OWL). An OWL ontology may include descriptions of classes, properties and their instances. Given such an ontology, the OWL formal semantics specifies how to derive its logical consequences, i.e. facts not literally present in the ontology, but entailed by the semantics. These entailments may be based on a single document or multiple distributed documents that have been combined using defined OWL mechanisms (see the OWL Web Ontology Language Guide). Protege is based on Java, is extensible, and provides a plug-and-play environment that makes it a flexible base for rapid prototyping and application development.

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HUGO (tool)

RRID:SCR_012800

Human Genome Organisation (HUGO) is the international organization of scientists involved in human genetics. HUGO was conceived in 1988, at the first meeting on genome mapping and sequencing at Cold Spring Harbor. From a 42 scientists of 17 countries membership association, HUGO has increased its membership base to over 1,200 members, both established and aspiring of 69 countries after two decades. HUGO has, over the years, played an essential role behind the scenes of the human genome project. With its mission to promote international collaborative effort to study the human genome and the myriad issues raised by knowledge of the genome, HUGO has had noteworthy successes in some of the less glamorous, but nonetheless vital, aspects of the human genome project. As a truly international organization, HUGO is entering its 20th year of its history by making an inflection in its direction seeking the biological meaning of its information content. To this end, HUGO is focusing on the medical implications of genomic knowledge. Moving forward, HUGO is also working to enhance the genomic capabilities in the emerging countries of the world. The excitement and interest in genomic sciences in Asia, Middle East, South America and Africa are palpable and the hope is that these technologies will help in national development and health.

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