Christian Darabos1,2, Jingya Qiu1, Jason H. Moore2
1The Geisel School of Medicine, Dartmouth College
2The Perelman School of Medicine, University of Pennsylvania
Email: jhmoore@upenn.edu
Pacific Symposium on Biocomputing 21:9-20(2016)
© 2016 World Scientific
Open Access chapter published by World Scientific Publishing Company and distributed under the terms of the Creative Commons Attribution (CC BY) 4.0 License.
Complex diseases are the result of intricate interactions between genetic, epigenetic and environ- mental factors. In previous studies, we used epidemiological and genetic data linking environmental exposure or genetic variants to phenotypic disease to construct Human Phenotype Networks and separately analyze the effects of both environment and genetic factors on disease interactions. To better capture the intricacies of the interactions between environmental exposure and the biological pathways in complex disorders, we integrate both aspects into a single “tripartite” network. Despite extensive research, the mechanisms by which chemical agents disrupt biological pathways are still poorly understood. In this study, we use our integrated network model to identify specific biolog- ical pathway candidates possibly disrupted by environmental agents. We conjecture that a higher number of co-occurrences between an environmental substance and biological pathway pair can be associated with a higher likelihood that the substance is involved in disrupting that pathway. We validate our model by demonstrating its ability to detect known arsenic and signal transduction pathway interactions and speculate on candidate cell-cell junction organization pathways disrupted by cadmium. The validation was supported by distinct publications of cell biology and genetic studies that associated environmental exposure to pathway disruption. The integrated network approach is a novel method for detecting the biological effects of environmental exposures. A better understanding of the molecular processes associated with specific environmental exposures will help in developing targeted molecular therapies for patients who have been exposed to the toxicity of environmental chemicals.