Deep learning prediction of Quantmap clusters

Abstract: The hypothesis that similar chemicals exert similar biological activities has been widely adopted in the field of drug discovery and development. Quantitative Structure-Activity Relationship (QSAR) models have been used ubiquitously in drug discovery to understand the function of chemicals in biological systems. A common QSAR modeling method calculates similarity scores between chemicals to assess their biological function. However, due to the fact that some chemicals can be similar and yet have different biological activities, or conversely can be structurally different yet have similar biological functions, various methods have instead been developed to quantify chemical similarity at the functional level. Quantmap is one such method, which utilizes biological databases to quantify the biological similarity between chemicals. Quantmap uses quantitative molecular network topology analysis to cluster chemical substances based on their bioactivities. This method by itself, unfortunately, cannot assign new chemicals (those which may not yet have biological data) to the derived clusters. Owing to the fact that there is a lack of biological data for many chemicals, deep learning models were explored in this project with respect to their ability to correctly assign unknown chemicals to Quantmap clusters. The deep learning methods explored included both convolutional and recurrent neural networks. Transfer learning/pretraining based approaches and data augmentation methods were also investigated. The best performing model, among those considered, was the Seq2seq model (a recurrent neural network containing two joint networks, a perceiver and an interpreter network) without pretraining, but including data augmentation.