In silico health effect prioritization of environmental chemicals through transcriptomics data exploration from a chemo-centric view

With the explosive growth of synthetic compounds, the health effects caused by exogenous chemical exposure have attracted more and more public attention. The prediction of health effect is a never-ending story. Collective resource of transcriptomics data offers an opportunity to understand and identify the multiple health effects of small molecule. Inspired by the fact that environmental chemicals of high health risk frequently share both similar gene expression profile and common structural feature of certain drugs, we here propose a novel computational effect prioritization method for environmental chemicals through transcriptomics data exploration from a chemo-centric view. Specifically, non-negative matrix factorization (NMF) method has been adopted to get the association network linking structural features with transcriptomics characteristics of drugs with specific effects. The model yields 13 pivotal types of effects, so-called components, that represent drug categories with common chemo- and geno-type features. Moreover, the established model effectively prioritizes potential toxic effects for the external chemicals from the endocrine disruptor screening program (EDSP) for their potential estrogenicity and other verified risks. Even if only the highest priority is set for the estrogenic effect, the precision and recall can reach 0.76 and 0.77 respectively for these chemicals. Our effort provides a successful endeavor as to profile potential toxic effects simultaneously for environmental chemicals using both chemical and omics data. (C) 2020 Elsevier B.V. All rights reserved.