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CTD: a resource for predicting chemical-gene-disease networks

CTD: a resource for predicting chemical-gene-disease networks. Carolyn Mattingly North Carolina State University. Chemical landscape. > 60,000 ~2,000 added/year ~8,000 are carcinogens No toxicity data for ~40% of the 3,300 “ high production volume ” chemicals

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CTD: a resource for predicting chemical-gene-disease networks

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  1. CTD: a resource for predicting chemical-gene-disease networks • Carolyn Mattingly • North Carolina State University

  2. Chemical landscape • > 60,000 • ~2,000 added/year • ~8,000 are carcinogens • No toxicity data for ~40% of the 3,300 “high production volume” chemicals • Full toxicity data for only 25% of chemicals in consumer products

  3. Crofton et al. Congenital Anomalies 2012; 52, 140–146

  4. Many disorders are on the rise • Leukemia • Cancers (Brain, breast, childhood) • Asthma • Fertility and full term pregnancies • Birth defects • Autism

  5. How does the environment affect our health?

  6. Genes Environment (chemicals) Disease

  7. ABC + AB BC Evans and Rzhetsky, Science, 329:399 (2010)

  8. C-G interactions C-D Relationships G-D Relationships

  9. 57 curated >1,000 inferred 5,896 Genes 163 Genes Breast Cancer

  10. http://ctdbase.org

  11. +

  12. PLoS One. 2012;7(11):e46524.

  13. Chemical-disease pathways

  14. >300 manuscripts using CTD data >30 public databases incorporating CTD data

  15. Grounding CTD data in “real-world” exposure data Centralizing exposure data Integrating exposure information with other biological data Exposure data

  16. Exposure Stressor Exposure Receptor Interacts with to result in via Exposure Event Exposure Outcome ExO

  17. Exposure data • Status • ~50 data points captured • ~3,000 priority articles: 600 curated, 16,000 exposure statements, 300 unique chemicals, 100 diseases Mattingly CJ, McKone TE, Callahan MA, Blake JA, Hubal EA. Environ Sci Technol. 2012. 46(6):3046.

  18. Exposure data

  19. bisphenol A Exposure Studies Exposure Levels Basics The following are measured exposure levels of bisphenol A or its descendants curated from various Exposure Studies. Click on DETAILS to find more information about the measurement and conditions of the study. displays the actual measurements curated from multiple papers, providing a view of the different ranges data displayed if chemical or its descendant is in the “Stressor”or “Biomarker” column

  20. Blood Pressure Heart Rate Vasoconstriction Disease Phenotype-disease curation Phenotype Hypertension Hypotension Arrhythmias, Cardiac

  21. Phenotype-disease analysis

  22. Phenotype-disease analysis Nagiza Samatova. NCSU

  23. Acknowledgements Scientific Curators Allan Peter Davis Cindy Murphy Cynthia Richards Kelley Lennon-Hopkins Daniela Sciaky Jean Lay Scientific Software Engineers Michael C. Rosenstein Thomas Wiegers Biostatistician Benjamin King, MS System Administrator Roy McMorran Funding

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