BioAct-Het: A Heterogeneous Siamese Neural Network for Bioactivity Prediction Using Novel Bioactivity Representation

[Image: see text] Drug failure during experimental procedures due to low bioactivity presents a significant challenge. To mitigate this risk and enhance compound bioactivities, predicting bioactivity classes during lead optimization is essential. The existing studies on structure–activity relationships have highlighted the connection between the chemical structures of compounds and their bioactivity. However, these studies often overlook the intricate relationship between drugs and bioactivity, which encompasses multiple factors beyond the chemical structure alone. To address this issue, we propose the BioAct-Het model, employing a heterogeneous siamese neural network to model the complex relationship between drugs and bioactivity classes, bringing them into a unified latent space. In particular, we introduce a novel representation for the bioactivity classes, called Bio-Prof, and enhance the original bioactivity data sets to tackle data scarcity. These innovative approaches resulted in our model outperforming the previous ones. The evaluation of BioAct-Het is conducted through three distinct strategies: association-based, bioactivity class-based, and compound-based. The association-based strategy utilizes supervised learning classification, while the bioactivity class-based strategy adopts a retrospective study evaluation approach. On the other hand, the compound-based strategy demonstrates similarities to the concept of meta-learning. Furthermore, the model’s effectiveness in addressing real-world problems is analyzed through a case study on the application of vancomycin and oseltamivir for COVID-19 treatment as well as molnupiravir’s potential efficacy in treating COVID-19 patients. The data and code underlying this article are available on https://github.com/CBRC-lab/BioAct-Het. However, data sets were derived from sources in the public domain.