Chemical Space Networks Enhance Toxicity Recognition via Graph Embedding

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Abstract
Chemical space networks (CSNs) are a new effective strategy for detecting latent chemical patterns irrespective of defined coordinate systems based on molecular descriptors and fingerprints. CSNs can be a new powerful option as a new approach method and increase the capacity of assessing potential adverse impacts of chemicals on human health. Here, CSNs are shown to effectively characterize the toxicity of chemicals toward several human health end points, namely chromosomal aberrations, mutagenicity, carcinogenicity, developmental toxicity, skin irritation, estrogenicity, androgenicity, and hepatoxicity. In this work, we report how the content from CSNs structure can be embedded through graph neural networks into a metric space, which, for eight different toxicological human health end points, allows better discrimination of toxic and nontoxic chemicals. In fact, using embeddings returns, on average, an increase in predictive performances. In fact, embedding employment enhances the learning, leading to an increment of the classification performance of +12% in terms of the area under the ROC curve. Moreover, through a dedicated eXplainable Artificial Intelligence framework, a straight interpretation of results is provided through the detection of putative structural alerts related to a given toxicity. Hence, the proposed approach represents a step forward in the area of alternative methods and could lead to breakthrough innovations in the design of safer chemicals and drugs.

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