Bouhifd Mounir, Andersen Melvin E, Baghdikian Christina, Boekelheide Kim, Crofton Kevin M, Fornace Albert J, Kleensang Andre, Li Henghong, Livi Carolina, Maertens Alexandra, McMullen Patrick D, Rosenberg Michael, Thomas Russell, Vantangoli Marguerite, Yager James D, Zhao Liang, Hartung Thomas
Johns Hopkins Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA.
The Hamner Institute, Research Triangle Park, NC, USA.
ALTEX. 2015;32(2):112-24. doi: 10.14573/altex.1502091. Epub 2015 Mar 4.
The Human Toxome Project, funded as an NIH Transformative Research grant 2011-2016, is focused on developing the concepts and the means for deducing, validating and sharing molecular pathways of toxicity (PoT). Using the test case of estrogenic endocrine disruption, the responses of MCF-7 human breast cancer cells are being phenotyped by transcriptomics and mass-spectroscopy-based metabolomics. The bioinformatics tools for PoT deduction represent a core deliverable. A number of challenges for quality and standardization of cell systems, omics technologies and bioinformatics are being addressed. In parallel, concepts for annotation, validation and sharing of PoT information, as well as their link to adverse outcomes, are being developed. A reasonably comprehensive public database of PoT, the Human Toxome Knowledge-base, could become a point of reference for toxicological research and regulatory test strategies.
人类毒物组计划作为美国国立卫生研究院2011 - 2016年的一项变革性研究资助项目,致力于开发推导、验证和共享毒性分子途径(PoT)的概念和方法。以雌激素内分泌干扰为例,通过转录组学和基于质谱的代谢组学对MCF - 7人乳腺癌细胞的反应进行表型分析。用于推导PoT的生物信息学工具是核心成果。目前正在应对细胞系统、组学技术和生物信息学在质量和标准化方面的一些挑战。同时,正在开发PoT信息的注释、验证和共享概念,以及它们与不良后果的联系。一个相当全面的PoT公共数据库——人类毒物组知识库,有望成为毒理学研究和监管测试策略的参考依据。