Embracing assay heterogeneity with neural processes for markedly improved bioactivity predictions (2308.09086v1)

Abstract: Predicting the bioactivity of a ligand is one of the hardest and most important challenges in computer-aided drug discovery. Despite years of data collection and curation efforts by research organizations worldwide, bioactivity data remains sparse and heterogeneous, thus hampering efforts to build predictive models that are accurate, transferable and robust. The intrinsic variability of the experimental data is further compounded by data aggregation practices that neglect heterogeneity to overcome sparsity. Here we discuss the limitations of these practices and present a hierarchical meta-learning framework that exploits the information synergy across disparate assays by successfully accounting for assay heterogeneity. We show that the model achieves a drastic improvement in affinity prediction across diverse protein targets and assay types compared to conventional baselines. It can quickly adapt to new target contexts using very few observations, thus enabling large-scale virtual screening in early-phase drug discovery.