GxVAEs: Two Joint VAEs Generate Hit Molecules from Gene Expression Profiles

The de novo generation of hit-like molecules that show bioactivity and drug-likeness is an important task in computer-aided drug discovery. Although artificial intelligence can generate molecules with desired chemical properties, most previous studies have ignored the influence of disease-related cellular environments. This study proposes a novel deep generative model called GxVAEs to generate hit-like molecules from gene expression profiles by leveraging two joint variational autoencoders (VAEs). The first VAE, ProfileVAE, extracts latent features from gene expression profiles. The extracted features serve as the conditions that guide the second VAE, which is called MolVAE, in generating hit-like molecules. GxVAEs bridge the gap between molecular generation and the cellular environment in a biological system, and produce molecules that are biologically meaningful in the context of specific diseases. Experiments and case studies on the generation of therapeutic molecules show that GxVAEs outperforms current state-of-the-art baselines and yield hit-like molecules with potential bioactivity and drug-like properties. We were able to successfully generate the potential molecular structures with therapeutic effects for various diseases from patients’ disease profiles.