D3EGFR: a webserver for deep learning-guided drug sensitivity prediction and drug response information retrieval for EGFR mutation-driven lung cancer.

Journal: Briefings in bioinformatics
Published Date:

Abstract

As key oncogenic drivers in non-small-cell lung cancer (NSCLC), various mutations in the epidermal growth factor receptor (EGFR) with variable drug sensitivities have been a major obstacle for precision medicine. To achieve clinical-level drug recommendations, a platform for clinical patient case retrieval and reliable drug sensitivity prediction is highly expected. Therefore, we built a database, D3EGFRdb, with the clinicopathologic characteristics and drug responses of 1339 patients with EGFR mutations via literature mining. On the basis of D3EGFRdb, we developed a deep learning-based prediction model, D3EGFRAI, for drug sensitivity prediction of new EGFR mutation-driven NSCLC. Model validations of D3EGFRAI showed a prediction accuracy of 0.81 and 0.85 for patients from D3EGFRdb and our hospitals, respectively. Furthermore, mutation scanning of the crucial residues inside drug-binding pockets, which may occur in the future, was performed to explore their drug sensitivity changes. D3EGFR is the first platform to achieve clinical-level drug response prediction of all approved small molecule drugs for EGFR mutation-driven lung cancer and is freely accessible at https://www.d3pharma.com/D3EGFR/index.php.

Authors

  • Yulong Shi
    CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Chongwu Li
    Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai xxxx, China.
  • Xinben Zhang
    CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Cheng Peng
    School of Electrical and Mechanical Engineering, Hefei Technology College, Hefei, China.
  • Peng Sun
    Department of Microelectronics, Nankai University, Tianjin, 300350, PR China.
  • Qian Zhang
    The Neonatal Intensive Care Unit, Peking Union Medical College Hospital, Peking, China.
  • Leilei Wu
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
  • Ying Ding
    Cockrell School of Engineering, The University of Texas at Austin, Austin, USA.
  • Dong Xie
    Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
  • Zhijian Xu
    Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Weiliang Zhu
    CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.