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. 2015;32(2):112-24.
doi: 10.14573/altex.1502091. Epub 2015 Mar 4.

The human toxome project

Mounir Bouhifd  1 , Melvin E Andersen  2 , Christina Baghdikian  3 , Kim Boekelheide  4 , Kevin M Crofton  5 , Albert J Fornace Jr  6 , Andre Kleensang  1 , Henghong Li  6 , Carolina Livi  7 , Alexandra Maertens  1 , Patrick D McMullen  2 , Michael Rosenberg  7 , Russell Thomas  5 , Marguerite Vantangoli  4 , James D Yager  8 , Liang Zhao  1 , Thomas Hartung  1   9
Affiliations

The human toxome project

Mounir Bouhifd et al. ALTEX. 2015.

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.

Keywords: alternative methods; metabolomics; regulatory toxicology; safety sciences; transcriptomics.

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Conflict of interest statement

Declaration of interest

The employment affiliations of the authors of this paper are as shown on the cover page. Ten of the authors are affiliated with universities that have traditional roles of teaching, research and service. Two of the authors are associated with the U.S. Environmental Protection Agency. Two of the authors are associated with a non-profit institution, The Hamner Institute, which has an interest in advancing the science of toxicology and risk assessment. And two of the authors are employees of Agilent Technologies, Inc., a for-profit company that provides advanced bio-analytical equipment and measurement services to a wide range of clients. The individual authors were compensated by their respective employers. In some cases, funding was provided by an NIH Transformation Research Grant, “Mapping the Human Toxome by Systems Toxicology” (RO1 ES 020750) to Johns Hopkins Bloomberg School of Public Health (PI Thomas Hartung) and Food and Drug Administration Grant “DNTox-21c Identification of Pathways of Developmental Neurotoxicity for High Throughput Testing by Metabolomies” (U01 FD 004230) to Johns Hopkins Bloomberg School of Public Health (PI Thomas Hartung). The analyses, interpretations and conclusions presented in this paper are the professional work product of the authors and may not necessarily represent the views of their employers.

Figures

Fig. 1
Fig. 1
Components of the project “Mapping the Human Toxome by Systems Toxicology” (http://humantoxome.com)
Fig. 2
Fig. 2
Good correlation between three laboratories in the targeted analysis of 108 genes related to estrogenic effects
See this image and copyright information in PMC

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