Multi-source transfer learning with Graph Neural Network for excellent modelling the bioactivities of ligands targeting orphan G protein-coupled receptors

Abstract

<abstract> <p>G protein-coupled receptors (GPCRs) have been the targets for more than 40% of the currently approved drugs. Although neural networks can effectively improve the accuracy of prediction with the biological activity, the result is undesirable in the limited orphan GPCRs (oGPCRs) datasets. To this end, we proposed Multi-source Transfer Learning with Graph Neural Network, called MSTL-GNN, to bridge this gap. Firstly, there are three ideal sources of data for transfer learning, oGPCRs, experimentally validated GPCRs, and invalidated GPCRs similar to the former one. Secondly, the SIMLEs format GPCRs convert to graphics, and they can be the input of Graph Neural Network (GNN) and ensemble learning for improving prediction accuracy. Finally, our experiments show that MSTL-GNN remarkably improves the prediction of GPCRs ligand activity value compared with previous studies. On average, the two evaluation indexes we adopted, R2 and Root-mean-square deviation (RMSE). Compared with the state-of-the-art work MSTL-GNN increased up to 67.13% and 17.22%, respectively. The effectiveness of MSTL-GNN in the field of GPCR Drug discovery with limited data also paves the way for other similar application scenarios.</p> </abstract>