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TranScreen: Transfer Learning on Graph-Based Anti-Cancer Virtual Screening Model

Milad Salem    
Aminollah Khormali    
Arash Keshavarzi Arshadi    
Julia Webb and Jiann-Shiun Yuan    

Resumen

Deep learning?s automatic feature extraction has proven its superior performance over traditional fingerprint-based features in the implementation of virtual screening models. However, these models face multiple challenges in the field of early drug discovery, such as over-training and generalization to unseen data, due to the inherently unbalanced and small datasets. In this work, the TranScreen pipeline is proposed, which utilizes transfer learning and a collection of weight initializations to overcome these challenges. An amount of 182 graph convolutional neural networks are trained on molecular source datasets and the learned knowledge is transferred to the target task for fine-tuning. The target task of p53-based bioactivity prediction, an important factor for anti-cancer discovery, is chosen to showcase the capability of the pipeline. Having trained a collection of source models, three different approaches are implemented to compare and rank them for a given task before fine-tuning. The results show improvement in performance of the model in multiple cases, with the best model increasing the area under receiver operating curve ROC-AUC from 0.75 to 0.91 and the recall from 0.25 to 1. This improvement is vital for practical virtual screening via lowering the false negatives and demonstrates the potential of transfer learning. The code and pre-trained models are made accessible online.

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