Enhancing chemogenomics with predictive pharmacology.

One of the grand challenges in contemporary chemical biology is the generation of a probe for every member of the human proteome. Probe selection and optimization strategies typically rely on experimental bioactivity data to determine the potency and selectivity of candidate molecules. However, this approach is profoundly limited by the sparsity of the known data, the annotation bias often found in the literature and the cost of physical screening. Recent advancements in predictive pharmacology, such as the application of multitask and transfer learning, as well as the use of biologically motivated, structure-agnostic features to characterize molecules, should serve to mitigate these issues. Computational modelling likely offers the only cost effective approach to substantially increasing the bioactivity annotation density both on the local and global scale and thus, we argue, will need to make a substantial contribution if the ambitious goals of probing the human proteome are to be realized in the foreseeable future.