Development of KNIME workflow allowing identification of binders at the ecdysone receptor
Citation:
Mellor, C., K. Tollefsen, C. LaLone, M. Cronin, AND J. Firman. Development of KNIME workflow allowing identification of binders at the ecdysone receptor. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, 39(7):1438-1450, (2020).
Impact/Purpose:
The process of molting, also called ecdysis, occurs in invertebrate species allowing for normal growth and development. However, there are chemicals that disrupt this process in invertebrates that lead to improper molting that cause mortality. This work identified and defined characteristics of chemicals that can initiate this adverse molting effect leading to death in invertebrate species. A computational screening workflow was developed using KNIME (Konstanz Information Miner), a free and publicly available data analytics platform, to flag chemicals from a list of 391 chemicals that are likely to disrupt the molting process and therefore act as invertebrate endocrine disruptors. Such information can be used to enhance environmental risk assessment.
Description:
The process of molting, known alternatively as ecdysis, is a feature integral within the life-cycles of species across the arthropod phylum. Regulation occurs as a function of the interaction of ecdysteroid hormones with the arthropod nuclear ecdysone receptor (EcR) and triggering of a series of down-stream events an endocrine signaling pathway highly conserved throughout environmentally-prevalent insect, crustacean and myriapod organisms. Inappropriate EcR binding and activation forms the essential molecular initiating event within posited adverse outcome pathways relating abnormal molting to mortality in arthropods. Definition of the characteristics of chemicals liable to stimulate such activity has potential to be of great utility in mitigation of hazards posed towards vulnerable species. As such, the intention of this investigation has been to develop a series of rule-sets, derived from the key structural and physicochemical features associated with identified EcR ligands, enabling construction within KNIME of workflows permitting the flagging of compounds predisposed to binding at the site. Data describing the activities of 391 distinct chemicals were recovered from a variety of assay formats across ten insect species, allowing for formulation of KNIME screens for potential binding activity at the molecular initiating event and adverse outcome-level of biological organisation.
