Graph-augmented Convolutional Networks on Drug-Drug Interactions Prediction

We propose an end-to-end model to predict drug-drug interactions (DDIs) by employing graph-augmented convolutional networks. And this is implemented by combining graph CNN with an attentive pooling network to extract structural relations between drug pairs and make DDI predictions. The experiment results suggest a desirable performance achieving ROC at 0.988, F1-score at 0.956, and AUPR at 0.986. Besides, the model can tell how the two DDI drugs interact structurally by varying colored atoms. And this may be helpful for drug design during drug discovery.

[1]  Adrià Cereto-Massagué,et al.  Molecular fingerprint similarity search in virtual screening. , 2015, Methods.

[2]  Oguz Dikenelli,et al.  Evaluation of knowledge graph embedding approaches for drug-drug interaction prediction using Linked Open Data , 2018, SWAT4LS.

[3]  Kaizhu Huang,et al.  Siamese network ensemble for visual tracking , 2018, Neurocomputing.

[4]  William L. Jorgensen,et al.  Journal of Chemical Information and Modeling , 2005, J. Chem. Inf. Model..

[5]  J. Barthélémy,et al.  A drug interaction study between ticlopidine and cyclosporin in heart transplant recipients , 1997, European Journal of Clinical Pharmacology.

[6]  Ping Zhang,et al.  Interpretable Drug Target Prediction Using Deep Neural Representation , 2018, IJCAI.

[7]  Nigam H. Shah,et al.  Mining clinical text for signals of adverse drug-drug interactions , 2014, J. Am. Medical Informatics Assoc..

[8]  David Rogers,et al.  Extended-Connectivity Fingerprints , 2010, J. Chem. Inf. Model..

[9]  Vijay S. Pande,et al.  Low Data Drug Discovery with One-Shot Learning , 2016, ACS central science.

[10]  David S. Wishart,et al.  DrugBank 5.0: a major update to the DrugBank database for 2018 , 2017, Nucleic Acids Res..

[11]  C. Moura,et al.  Drug-drug interactions associated with length of stay and cost of hospitalization. , 2009, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[12]  J. Balian,et al.  Metabolic drug-drug interactions: perspective from FDA medical and clinical pharmacology reviewers. , 1997, Advances in pharmacology.

[13]  Alexander Peysakhovich,et al.  PyTorch-BigGraph: A Large-scale Graph Embedding System , 2019, SysML.

[14]  M. Hao,et al.  Celecoxib is a substrate of CYP2D6: Impact on celecoxib metabolism in individuals with CYP2C9*3 variants. , 2018, Drug metabolism and pharmacokinetics.

[15]  Lior Rokach,et al.  Detecting drug-drug interactions using artificial neural networks and classic graph similarity measures , 2019, PloS one.

[16]  中尾 光輝,et al.  KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース) , 2000 .

[17]  Alán Aspuru-Guzik,et al.  Convolutional Networks on Graphs for Learning Molecular Fingerprints , 2015, NIPS.

[18]  Heiko Paulheim,et al.  RDF2Vec: RDF graph embeddings and their applications , 2019, Semantic Web.

[19]  Yoshua Bengio,et al.  Understanding the difficulty of training deep feedforward neural networks , 2010, AISTATS.

[20]  Ping Zhang,et al.  DDI-CPI, a server that predicts drug–drug interactions through implementing the chemical–protein interactome , 2014, Nucleic Acids Res..

[21]  Esa Rahtu,et al.  Siamese network features for image matching , 2016, 2016 23rd International Conference on Pattern Recognition (ICPR).

[22]  Laurens van der Maaten,et al.  Modeling Time Series Similarity with Siamese Recurrent Networks , 2016, ArXiv.

[23]  Yi Pan,et al.  IDNDDI: An Integrated Drug Similarity Network Method for Predicting Drug-Drug Interactions , 2019, ISBRA.

[24]  G. Vargas-Alarcón,et al.  The relationship between potential drug-drug interactions and mortality rate of elderly hospitalized patients. , 2011, Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion.

[25]  David S. Wishart,et al.  DrugBank: a comprehensive resource for in silico drug discovery and exploration , 2005, Nucleic Acids Res..

[26]  Jae Yong Ryu,et al.  Deep learning improves prediction of drug–drug and drug–food interactions , 2018, Proceedings of the National Academy of Sciences.

[27]  Hossein Afarideh,et al.  Journal of Pharmacy & Pharmaceutical Sciences A Publication of the Canadian Society for Pharmaceutical Sciences Société canadienne des sciences pharmaceutiques , 2000 .

[28]  Jianying Hu,et al.  Predicting adverse drug reactions through interpretable deep learning framework , 2018, BMC Bioinformatics.

[29]  Stefan Decker,et al.  Drug-Drug Interaction Prediction Based on Knowledge Graph Embeddings and Convolutional-LSTM Network , 2019, BCB.