Exposome and health: characterization and network-based exploration of diverse environmental chemical spaces[HBNI Th212]

Abstract

Humans are exposed to environmental chemicals in their everyday life and such exposure can contribute to the incidence of several chronic diseases. Characterization, monitoring and regulation of the ever increasing space of environmental chemicals for their potential adverse health effects is both necessary and challenging. In other words, characterization of the chemical exposome from a health perspective is necessary for human well-being.

To this end, there has been growing interest in characterizing the human exposome along with the genome to better understand the environmental factors crucial for human health and disease.

In this thesis, we focus on environmental chemicals that have gained significant attention from scientists, regulatory authorities, and the general public, due to their potential health concerns. In order to link chemical exposomes to health effects, we have undertaken a systematic compilation, curation and exploration of the existing information contained in published toxicological studies on diverse groups of environmental chemicals.

Specifically, we focus on five groups of chemicals with toxicological relevance, namely endocrine disrupting chemicals (EDCs), environmental neurotoxicants, human milk contaminants, fragrance chemicals in children’s products, and exogenous chemicals detected in human tissues.

Furthermore, there is recent recognition of the need to leverage network science and systems biology approaches in characterizing the chemical exposome. Therefore, we extensively employ these approaches on the compiled toxicological information for the five groups of environmental chemicals studied in this thesis. Specifically, we investigated similarity networks of these environmental chemicals based on similarity in chemical structures or similarity of target genes. Further, we constructed bipartite networks of environmental chemicals and their target genes, and tripartite networks of environmental chemicals, their target genes and associated diseases, to reveal perturbed pathways and potential disease comorbidities related to chemical exposure. Moreover, we derive a comprehensive adverse outcome pathway (AOP) network for endocrine-mediated perturbations, and thereafter, employ graph-theoretic measures to identify the critical biological events associated with endocrine disruption upon chemical exposure.

To further demonstrate the utility of our research for chemical risk assessment, we perform a comparative study using several chemical lists that are a part of inventories, guidelines or regulations to assess the regulatory status and source of the diverse groups of environmental chemicals considered in this thesis. These analyses reveal that several environmental chemicals of concern are part of everyday exposures, and moreover, many of these chemicals are found to be produced in high volume.

In sum, the curated resources and multi-pronged analyses of diverse environmental chemical spaces described in this thesis will facilitate research in toxicology and human exposome.