Advancing mechanism-based studies with cross-species chemical-phenotype data

描述(由申请人提供)：我们的目标是提供一个集中的、公开可用的资源，提供全面的、注释良好的数据和分析工具，为环境健康研究的设计和解释提供信息，并促进对环境影响疾病的病因的新见解。大多数人类疾病涉及遗传和环境因素之间的相互作用；然而，这些复杂相互作用的基础还没有得到很好的了解，并限制了毒性预测、风险评估、研究优先顺序和治疗干预方面的改进。我们开发了比较毒理基因组学数据库(CTD；http://ctdbase.org))，通过提供来自同行评审文献的描述化学-基因相互作用以及化学-基因-疾病关系的手动精选数据，并将这些数据与选定的外部数据集(例如，通路和生物过程数据)和新的数据分析工具相集成，来增强对环境-疾病联系的理解。我们建议开发和实施一个新的手动精选数据模块，描述跨物种的化学表型信息和分析能力，将这些数据纳入更广泛的CTD生物学背景。这些增加将显著增加CTD的影响，并特别旨在促进：a)通过病前表型了解环境疾病的进展，b)确定潜在的暴露生物标记物，c)跨物种和实验系统进行和解释研究的能力，以及d)发展将化学物质、基因、表型和疾病联系在一起的生物网络。该项目将利用我们的跨学科团队在毒理学、软件开发、管理、生物信息学和统计学方面的专业知识，以及CTD灵活的基础设施和已证明的价值，以促进对关键环境健康问题的理解，并直接与新兴的研究优先事项保持一致。

DESCRIPTION (provided by applicant): Our objective is to provide a centralized, publicly available resource with comprehensive, well-annotated data and analysis tools that informs design and interpretation of environmental health studies and promotes novel insights into the etiologies of environmentally influenced diseases. Most human diseases involve interactions between genetic and environmental factors; however, the basis of these complex interactions are not well understood and limit improvements in toxicity prediction, risk assessment, research prioritization and therapeutic interventions. We developed the Comparative Toxicogenomics Database (CTD; http://ctdbase.org) to enhance understanding about environment-disease connections by providing manually curated data describing chemical-gene interactions and chemical- and gene-disease relationships from the peer-reviewed literature and integrating these data with select external data sets (e.g., pathways and biological process data) and novel data analysis tools. We propose to develop and implement a new module of manually curated data describing cross-species chemical-phenotype information and analytical capabilities that will incorporate these data into the broader biological context of CTD. These additions will significantly increase the impact of CTD and specifically aim to advance: a) understanding of environmental disease progression via pre-disease phenotypes, b) identification of potential biomarkers of exposure, c) the capacity to conduct and interpret studies across species and experimental systems, and d) development of biological networks that associate chemicals, genes, phenotypes, and diseases. This project will leverage our interdisciplinary team's expertise in toxicology, software development, curation, bioinformatics and statistics, as well as the flexible infrastructure and demonstrated value of CTD to facilitate understanding of critical environmental health issues in direct alignment with emerging research priorities.