Bioassay Ontology and Software Tools to Integrate and Analyze Diverse Data Sets

描述（由申请人提供）：越来越多的大型和多样化的数据集正在使用各种高通量和低通量筛选技术由医疗资助的筛选中心生成。这些数据大部分都是可以访问的。最大的小分子筛选结果公共库是PubChem，目前涵盖了37万种化合物的1,500多种检测。预计在未来五年内，可用于临床的检测方法数量将增长10倍以上。这一宝贵资源的效用目前是有限的，因为复杂多样的生物测定数据集所包含的知识尚未正式化，因此无法进行全面的计算分析或与其他数据源整合。这个建议就是要打破这个限制。 在过去的十年中，生物学家已经开发了本体，以便于分析和讨论从各种基因组计划中出现的大量信息。本体是对象和概念及其属性和关系的受控词汇表表示。其目的是建模和共享特定领域的知识，使软件代理可以自动提取和关联的信息。 本建议的目的是开发一个生物测定本体，软件工具，并证明其效用。生物测定本体将连贯地描述各种生物测定（例如PubChem中的生物测定），重点关注复杂的基于细胞的测定，特别是高含量的筛选数据。软件支持和开发包括构建本体术语和管理数据集的模块，将本体映射到筛选实验和其他本体的工具，以及在本体的上下文中标准化，重新格式化和聚合数据集的工具。我们将通过创建PubChem衍生的数据库并通过搜索界面向社区提供该数据库来演示我们方法的实用性。本体和软件工具将有助于在各种情况下分析生物测定筛选数据，例如信号或代谢途径以及间接的人类疾病。这些工具将使人们能够提取数据集，用于模拟干扰剂和生物靶点（或途径）之间的特定相互作用，或模拟分析技术相关的干扰。最终用户软件需要为生物学家和化学生物学家提供易用性，以便在他们自己和外部数据集的上下文中利用本体。它将是模块化和开源的。我们将发展各种合作，在社区中传播生物测定本体和软件，并促进其持续发展。 公共卫生相关性：该项目将开发一个生物测定本体，以连贯地描述用于研究干扰剂（如药物）如何改变细胞功能的数百种不同测定。沿着搜索现有检测数据库的新软件，这将使科学家能够更有效地识别和优先考虑化学品，以进一步开发为化学探针或治疗的起点。

DESCRIPTION (provided by applicant): Increasingly large and diverse data sets are being generated by publically funded screening centers using various high- and low-throughput screening technologies. Much of this data is accessible. The largest public repository of small molecule screening results is PubChem, currently covering over 1,500 assays for 370,000 compounds. The number of publically available assays is expected to grow more than 10 fold during the next five years. The utility of this invaluable resource is currently limited, because the knowledge contained in complex and diverse bioassay data sets is not formalized and therefore cannot be accessed for comprehensive computational analysis or integration with other data sources. This proposal is to attack this limitation. For the past ten years ontologies have been developed by biologists to facilitate the analysis and discussion of the massive amounts of information emerging from the various genome projects. An ontology is a controlled vocabulary representation of the objects and concepts and their properties and relationships. The purpose is to model and share domain-specific knowledge so that software agents can automatically extract and associate information. The aim of this proposal is to develop a bioassay ontology, software tools, and to demonstrate their utility. The bioassay ontology will coherently describe diverse biological assays (such as those in PubChem) with a focus on complex cell-based assays and in particular high-content screening data. Software support and development includes modules to build ontology terms and to curate data sets, tools to map the ontology onto screening experiments and other ontologies, and tools to standardize, reformat, and aggregate data sets in the context of the ontology. We will demonstrate the utility of our approach by creating a PubChem-derived database and making it available to the community via a search interface. The ontology and software tools will facilitate the analysis of bioassay screening data in various contexts, for example signaling or metabolic pathways and indirectly human disease. The tools will enable one to extract data sets for modeling specific interactions between perturbing agents and biological targets (or pathways), or to model assay technology-dependent interferences. End user software needs to provide ease of use for biologists and chemical biologists to utilize the ontology in the context of their own and external data sets. It will be modular and open source. We will develop various collaborations to disseminate the bioassay ontology and software in the community and to facilitate their ongoing development. PUBLIC HEALTH RELEVANCE: This project will develop a bioassay ontology to coherently describe the hundreds of different assays used to study how perturbing agents, such as drugs, alter cell function. Along with new software to search existing assay databases, this will enable scientists to more effectively identify and prioritize chemicals for further development into chemical probes or starting points for therapeutics.