学位论文详细信息
Systems Toxicology: Beyond Animal Models
Systems Toxicology;Bioinformatics;Machine Learning;Genetic Regulatory Networks;not listed
Maertens, AlexandraScott, Alan L. ;
Johns Hopkins University
关键词: Systems Toxicology;    Bioinformatics;    Machine Learning;    Genetic Regulatory Networks;    not listed;   
Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/37194/MAERTENS-DISSERTATION-2014.pdf?sequence=1&isAllowed=y
瑞士|英语
来源: JOHNS HOPKINS DSpace Repository
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【 摘 要 】

Toxicology – much like the rest of biology – is undergoing a profound change as new technologies begin to offer a more systems oriented view of cellular physiology.For toxicology in particular, this means moving away from black-box animal models that provide limited information about mechanisms of toxicity towards the use of in vitro approaches which can both expedite hazard assessment while at the same time providing a more data –rich insight into toxic effects at the molecular level. One motivator of this shift is Green Toxciology, which seeks to support the Green Chemistry movement. In order for this approach to succeed, it will require two separate but parallel efforts. The first is an Integrated Testing Strategy which seeks to use machine learning and data mining techniques to combine QSARs and in vitro tests in the most efficient way possible to accurately estimate hazard, which is discussed both theoretically and demonstrated practically with the example of skin sensitization. Secondly, toxicology will require new approaches that exploit the insights of network biology to look at toxic mechanisms from a systems perspective. The theoretical concept of a Pathway of Toxicity is outlined, and an example of how to extract a suggested Pathway of Toxicity is given, using a Weighted Gene Correlation Network Analysis of a small microarray study of MPTP toxicity combined with text-mining and other high-throughput data to suggest novel candidate transcription factors and proteins. In conclusion, it discusses some of the current limitations of another promising –omics technology, metabolomics.

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