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

Abstract

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.

Reporting biological assay screening results for maximum impact

“…In addition, some MLP assay screening campaign details were missing or difficult to discern, such as differentiation between a confirmatory screen and a counter screen. Furthermore, while the vocabularies necessary to consistently annotate the data did not exist at the start of the project, they exist now (15). Through BARD, the MLP screening centers set about to consider how to best improve the representation of their data for improved reuse.…”

“…In its latest form, BAO 2.0 (15) emphasizes six major parts of an assay: Bioassay Component, Format, Method, Biological Component, Screened Entity Component , and Endpoint Component . It includes other constructs that help to define the organization (screening center, equipment/reagent manufacturer, etc.…”

Standardization of High Content Imaging and Informatics

“…The BioAssay Ontology (BAO) project is a recently published example of concepts and challenges in the standardization process. 12,13 With the guidance and leadership of one of the principle investigators of the BAO project, Vance Lemmon at the University of Miami, SBI 2 will undertake to advance the development of standardized data analysis descriptors and naming conventions for HCA methods.…”

Using the BioAssay Ontology for Analyzing High-Throughput Screening Data

“…For example, new relationships for thorough annotation of detection wavelengths, restructuring the annotation of target protein primary structure, and the addition of assay kits and instruments used within AstraZeneca have been added to the ontology. BAO 2.0 classes and properties 8 have then been used to represent our in-house drug discovery data annotations as semantic triples. In-house HTS assays are represented as new instances of "bioassay," "screening campaign," and "measure group," which are the core of the screening cascade and assay annotations in BAO 2.0.…”

“…BAO enables classification of screening assays to facilitate data analysis and comparison between different HTS data sets. 7,8 The ontology includes information about the assay design and technology, end point (result) and metadata to describe a target, such as protein origin and cell line background. BAO annotation enables the analysis of biological activity based on various relevant characteristics such as the assay format and type (e.g.…”