Chemical-induced phenotypes at CTD help inform the pre-disease state and construct adverse outcome pathways

Chemical-induced phenotypes at CTD help inform the pre-disease state and construct adverse... Abstract The Comparative Toxicogenomics Database (CTD; http://ctdbase.org) is a public resource that manually curates the scientific literature to provide content that illuminates the molecular mechanisms by which environmental exposures affect human health. We introduce our new chemical-phenotype module that describes how chemicals can affect molecular, cellular, and physiological phenotypes. At CTD, we operationally distinguish between phenotypes and diseases, wherein a phenotype refers to a non-disease biological event: e.g., decreased cell cycle arrest (phenotype) vs. liver cancer (disease), increased fat cell proliferation (phenotype) vs. morbid obesity (disease), etc. Chemical-phenotype interactions are expressed in a formal structured notation using controlled terms for chemicals, phenotypes, taxon, and anatomical descriptors. Combining this information with CTD’s chemical-disease module allows inferences to be made between phenotypes and diseases, yielding potential insight into the pre-disease state. Integration of all four CTD modules furnishes unique opportunities for toxicologists to generate computationally predictive adverse outcome pathways, linking chemical-gene molecular initiating events with phenotypic key events, adverse diseases, and population-level health outcomes. As examples, we present three diverse case studies discerning the effect of vehicle emissions on altered leukocyte migration, the role of cadmium in influencing phenotypes preceding Alzheimer disease, and the connection of arsenic-induced glucose metabolic phenotypes with diabetes. To date, CTD contains over 165,000 interactions that connect more than 6,400 chemicals to 3,900 phenotypes for 760 anatomical terms in 215 species, from over 19,000 scientific articles. To our knowledge, this is the first comprehensive set of manually curated, literature-based, contextualized, chemical-induced, non-disease phenotype data provided to the public. phenotype, database, curation, chemical, disease, adverse outcome pathway © The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Toxicological Sciences Oxford University Press

Chemical-induced phenotypes at CTD help inform the pre-disease state and construct adverse outcome pathways

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Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
ISSN
1096-6080
eISSN
1096-0929
D.O.I.
10.1093/toxsci/kfy131
Publisher site
See Article on Publisher Site

Abstract

Abstract The Comparative Toxicogenomics Database (CTD; http://ctdbase.org) is a public resource that manually curates the scientific literature to provide content that illuminates the molecular mechanisms by which environmental exposures affect human health. We introduce our new chemical-phenotype module that describes how chemicals can affect molecular, cellular, and physiological phenotypes. At CTD, we operationally distinguish between phenotypes and diseases, wherein a phenotype refers to a non-disease biological event: e.g., decreased cell cycle arrest (phenotype) vs. liver cancer (disease), increased fat cell proliferation (phenotype) vs. morbid obesity (disease), etc. Chemical-phenotype interactions are expressed in a formal structured notation using controlled terms for chemicals, phenotypes, taxon, and anatomical descriptors. Combining this information with CTD’s chemical-disease module allows inferences to be made between phenotypes and diseases, yielding potential insight into the pre-disease state. Integration of all four CTD modules furnishes unique opportunities for toxicologists to generate computationally predictive adverse outcome pathways, linking chemical-gene molecular initiating events with phenotypic key events, adverse diseases, and population-level health outcomes. As examples, we present three diverse case studies discerning the effect of vehicle emissions on altered leukocyte migration, the role of cadmium in influencing phenotypes preceding Alzheimer disease, and the connection of arsenic-induced glucose metabolic phenotypes with diabetes. To date, CTD contains over 165,000 interactions that connect more than 6,400 chemicals to 3,900 phenotypes for 760 anatomical terms in 215 species, from over 19,000 scientific articles. To our knowledge, this is the first comprehensive set of manually curated, literature-based, contextualized, chemical-induced, non-disease phenotype data provided to the public. phenotype, database, curation, chemical, disease, adverse outcome pathway © The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

Toxicological SciencesOxford University Press

Published: May 28, 2018

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