PBAC: A pathway-based attention convolution neural network for predicting clinical drug treatment responses.

Journal: Journal of cellular and molecular medicine
PMID:

Abstract

Precise and personalized drug application is crucial in the clinical treatment of complex diseases. Although neural networks offer a new approach to improving drug strategies, their internal structure is difficult to interpret. Here, we propose PBAC (Pathway-Based Attention Convolution neural network), which integrates a deep learning framework and attention mechanism to address the complex biological pathway information, thereby provide a biology function-based robust drug responsiveness prediction model. PBAC has four layers: gene-pathway layer, attention layer, convolution layer and fully connected layer. PBAC improves the performance of predicting drug responsiveness by focusing on important pathways, helping us understand the mechanism of drug action in diseases. We validated the PBAC model using data from four chemotherapy drugs (Bortezomib, Cisplatin, Docetaxel and Paclitaxel) and 11 immunotherapy datasets. In the majority of datasets, PBAC exhibits superior performance compared to traditional machine learning methods and other research approaches (area under curve = 0.81, the area under the precision-recall curve = 0.73). Using PBAC attention layer output, we identified some pathways as potential core cancer regulators, providing good interpretability for drug treatment prediction. In summary, we presented PBAC, a powerful tool to predict drug responsiveness based on the biology pathway information and explore the potential cancer-driving pathways.

Authors

  • Dexun Deng
    The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
  • Xiaoqiang Xu
  • Ting Cui
    The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
  • Mingcong Xu
    The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
  • Kunpeng Luo
    Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
  • Han Zhang
    Johns Hopkins University, Baltimore, MD, USA.
  • Qiuyu Wang
    School of Mathematics and Statistics, Henan University, Kaifeng, Henan Province, China.
  • Chao Song
    Medical School of Chinese PLA, 100853 Beijing, China.
  • Chao Li
    McGill University Health Centre, McGill Adult Unit for Congenital Heart Disease Excellence, Montreal, Québec, Canada.
  • Guohua Li
    Department of Pathophysiology, Key Laboratory for Arteriosclerology of Hunan Province, MOE Key Lab of Rare Pediatric Diseases, Hengyang Medical School, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, University of South China, Hengyang, Hunan, China.
  • Desi Shang
    The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan, China.