Predicting Drug-Target Affinity Based on Recurrent Neural Networks and Graph Convolutional Neural Networks.

Journal: Combinatorial chemistry & high throughput screening
Published Date:

Abstract

BACKGROUND: Drug development requires a lot of money and time, and the outcome of the challenge is unknown. So, there is an urgent need for researchers to find a new approach that can reduce costs. Therefore, the identification of drug-target interactions (DTIs) has been a critical step in the early stages of drug discovery. These computational methods aim to narrow the search space for novel DTIs and to elucidate the functional background of drugs. Most of the methods developed so far use binary classification to predict the presence or absence of interactions between the drug and the target. However, it is more informative but also more challenging to predict the strength of the binding between a drug and its target. If the strength is not strong enough, such a DTI may not be useful. Hence, the development of methods to predict drug-target affinity (DTA) is of significant importance Method: We have improved the GraphDTA model from a dual-channel model to a triple-channel model. We interpreted the target/protein sequences as time series and extracted their features using the LSTM network. For the drug, we considered both the molecular structure and the local chemical background, retaining the four variant networks used in GraphDTA to extract the topological features of the drug and capturing the local chemical background of the atoms in the drug by using BiGRU. Thus, we obtained the latent features of the target and two latent features of the drug. The connection of these three feature vectors is then inputted into a 2 layer FC network, and a valuable binding affinity is the output.

Authors

  • Qingyu Tian
    College of Computer Science and Technology, China University of Petroleum (East China), Qingdao 266580, Shandong,China.
  • Mao Ding
    Department of Neurology Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033,China | College of Computer Science and Technology, China University of Petroleum (East China), Qingdao 266580, Shandong, China.
  • Hui Yang
    Department of Neurology, The Second Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, China.
  • Caibin Yue
    Department of Infectious Diseases and Hepatology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Medical Insurance Office, The Second Hospital, Cheeloo College of Medicine, Shandong University Jinan 250033,China.
  • Yue Zhong
    Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People's Republic of China.
  • Zhenzhen Du
    College of Computer Science and Technology, China University of Petroleum, Qingdao 266580, Shandong,China.
  • Dayan Liu
    College of Computer Science and Technology, China University of Petroleum, Qingdao 266580, China.
  • Jiali Liu
    Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
  • Yufeng Deng
    Infervision, Beijing, China.