Transferring knowledge across aquatic species via clustering techniques to unravel patterns of pesticide toxicity

In silico modelling takes the advantage of accelerating ecotoxicological assessments on hazardous chemicals without conducting risky in vivo experiments under ethic regulation. To date, the prevailing strategy of one model for one species cannot be well generalized to multi-species modelling. In this work, we propose a new strategy of one model for multiple species to facilitate knowledge transfer across aquatic species. The available lethal concentration values of 4952 pesticides on 651 fish species are aggregated into one toxicity response matrix, purely through which we attempt to unravel fish toxicosis-phylogenesis relationships and pesticide toxicity-structure relationships via clustering techniques including non-negative matrix factorization (NMF) and hierarchical clustering. The clustering results suggest that (1) close NMF weights indicate close species-toxicosis and pesticide-toxicity profiles; (2) and that species toxicosis patterns are related with species phylogenetic relationships; (3) and that close pesticide-toxicity profiles indicate similar atom-pair structural fingerprints. These environmental, chemical and biological insights can be used as expert knowledge for environmentalists to manually gain knowledge about untested species/pesticides from tested species/pesticides, and meanwhile provide support for us to build in silico models from species phylogenetic and pesticide structural points of view. Besides unravelling the mechanisms behind toxicity response, we also adopt stratified cross validation and external test to validate the reliability of using NMF to predict missing toxicity values. Independent test on external data shows that NMF achieves 0.8404-0.9397 R² on four fish species. In the context of toxicity prediction, non-negative matrix factorization can be viewed as a model based on quantitative activity-activity relationships (QAAR), and provides an alternative approach of inferring toxicity values on untested species from tested species.