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bioRxiv · 10.1101/619163

A curated knowledgebase enabling a network perspective on endocrine disrupting chemicals and their biological systems-level perturbations

Karthikeyan, B. S.·Ravichandran, J.·Mohanraj, K.·Vivek-Ananth, R. P.·Samal, A.
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Abstract

Human well-being can be affected by exposure to several chemicals in the environment. One such group is endocrine disrupting chemicals (EDCs) that can perturb the hormonal homeostasis leading to adverse health effects. In this work, we have developed a detailed workflow to identify EDCs with supporting evidence of endocrine disruption in published experiments in humans or rodents. Thereafter, this workflow was used to manually evaluate more than 16000 published research articles and identify 686 potential EDCs with published evidence in humans or rodents. Importantly, we have compiled the observed adverse effects or endocrine-specific perturbations along with the dosage information for the potential EDCs from their supporting published experiments. Subsequently, the potential EDCs were classified based on the type of supporting evidence, their environmental source and their chemical properties. Additional compiled information for potential EDCs include their chemical structure, physicochemical properties, predicted ADMET properties and target genes. In order to enable future research based on this compiled information on potential EDCs, we have built an online knowledgebase, Database of Endocrine Disrupting Chemicals and their Toxicity profiles (DEDuCT), accessible at: https://cb.imsc.res.in/deduct/. After building this comprehensive resource, we employed a network biology approach to study the chemical space of EDCs and its potential link to the biological space of target genes of EDCs. Specifically, we have constructed two networks of EDCs using our resource based on similarity of chemical structures or target genes. Ensuing analysis of these two networks revealed that EDCs can differ both in their chemical structure and set of target genes. Though our detailed results highlight potential challenges in developing predictive models for EDCs, the compiled information in our resource will undoubtedly enable future research in the field, especially, those focussed towards mechanistic understanding of the systems-level perturbations caused by EDCs.

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Karthikeyan, B. S., Ravichandran, J., Mohanraj, K., Vivek-Ananth, R. P., Samal, A.. 2019-04-26. A curated knowledgebase enabling a network perspective on endocrine disrupting chemicals and their biological systems-level perturbations. https://doi.org/10.1101/619163

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