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High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents HPHC
Published on: May 10, 2016
The human toxome project
Mounir Bouhifd1, Melvin E Andersen2, Christina Baghdikian3
1Johns Hopkins Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA.
Abstract:
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.
Insights
The Human Toxome Project develops methods to identify molecular pathways of toxicity (PoT). This research aims to create a public knowledge base for toxicology and regulatory testing.
Area of Science:
- Toxicology
- Molecular Biology
- Bioinformatics
Background:
- The Human Toxome Project, funded by NIH, aims to establish methods for identifying, validating, and sharing molecular pathways of toxicity (PoT).
- Existing toxicological research faces challenges in standardization and data sharing, hindering progress.
Purpose of the Study:
- To develop concepts and tools for deducing, validating, and sharing molecular pathways of toxicity (PoT).
- To create a comprehensive public database, the Human Toxome Knowledge-base, for toxicological research and regulatory strategies.
Main Methods:
- Utilizing estrogenic endocrine disruption as a test case.
- Phenotyping MCF-7 human breast cancer cells using transcriptomics and mass-spectroscopy-based metabolomics.
- Developing bioinformatics tools for PoT deduction and addressing challenges in data quality and standardization.
Main Results:
- Progress in developing bioinformatics tools for PoT deduction.
- Addressing challenges in cell system quality, omics technologies, and bioinformatics standardization.
- Developing concepts for annotating, validating, and sharing PoT information and linking them to adverse outcomes.
Conclusions:
- The Human Toxome Knowledge-base has the potential to become a central reference for toxicological research.
- Standardization and data sharing are crucial for advancing toxicological understanding and regulatory science.
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