Drug-Drug Interaction Extraction via Recurrent Hybrid Convolutional Neural Networks with an Improved Focal Loss

Drug-drug interactions (DDIs) may bring huge health risks and dangerous effects to a patient’s body when taking two or more drugs at the same time or within a certain period of time. Therefore, the automatic extraction of unknown DDIs has great potential for the development of pharmaceutical agents and the safety of drug use. In this article, we propose a novel recurrent hybrid convolutional neural network (RHCNN) for DDI extraction from biomedical literature. In the embedding layer, the texts mentioning two entities are represented as a sequence of semantic embeddings and position embeddings. In particular, the complete semantic embedding is obtained by the information fusion between a word embedding and its contextual information which is learnt by recurrent structure. After that, the hybrid convolutional neural network is employed to learn the sentence-level features which consist of the local context features from consecutive words and the dependency features between separated words for DDI extraction. Lastly but most significantly, in order to make up for the defects of the traditional cross-entropy loss function when dealing with class imbalanced data, we apply an improved focal loss function to mitigate against this problem when using the DDIExtraction 2013 dataset. In our experiments, we achieve DDI automatic extraction with a micro F-score of 75.48% on the DDIExtraction 2013 dataset, outperforming the state-of-the-art approach by 2.49%.

[1]  Makoto Miwa,et al.  Enhancing Drug-Drug Interaction Extraction from Texts by Molecular Structure Information , 2018, ACL.

[2]  Yoon Kim,et al.  Convolutional Neural Networks for Sentence Classification , 2014, EMNLP.

[3]  Andrew McCallum,et al.  Fast and Accurate Entity Recognition with Iterated Dilated Convolutions , 2017, EMNLP.

[4]  Rabab Kreidieh Ward,et al.  Deep Sentence Embedding Using Long Short-Term Memory Networks: Analysis and Application to Information Retrieval , 2015, IEEE/ACM Transactions on Audio, Speech, and Language Processing.

[5]  Jun Zhao,et al.  Recurrent Convolutional Neural Networks for Text Classification , 2015, AAAI.

[6]  Jürgen Schmidhuber,et al.  Long Short-Term Memory , 1997, Neural Computation.

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

[8]  Ugo Moretti,et al.  Epidemiology and characteristics of adverse drug reactions caused by drug–drug interactions , 2012, Expert opinion on drug safety.

[9]  Hongfei Lin,et al.  Extracting Drug-Drug Interaction from the Biomedical Literature Using a Stacked Generalization-Based Approach , 2013, PloS one.

[10]  Xiaolong Wang,et al.  Drug-Drug Interaction Extraction via Convolutional Neural Networks , 2016, Comput. Math. Methods Medicine.

[11]  Jeffrey Pennington,et al.  GloVe: Global Vectors for Word Representation , 2014, EMNLP.

[12]  Zhiting Hu,et al.  Improved Variational Autoencoders for Text Modeling using Dilated Convolutions , 2017, ICML.

[13]  N. Laachfoubi EXTRACTING DRUG-DRUG INTERACTIONS FROM BIOMEDICAL TEXT USING A FEATURE-BASED KERNEL APPROACH , 2016 .

[14]  Yue Zhang,et al.  Target-Dependent Twitter Sentiment Classification with Rich Automatic Features , 2015, IJCAI.

[15]  Alan L. Yuille,et al.  Recurrent Saliency Transformation Network: Incorporating Multi-stage Visual Cues for Small Organ Segmentation , 2017, 2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition.

[16]  Russ B Altman,et al.  PharmGKB: the Pharmacogenomics Knowledge Base. , 2013, Methods in molecular biology.

[17]  Jun'ichi Tsujii,et al.  Dependency Parsing and Domain Adaptation with LR Models and Parser Ensembles , 2007, EMNLP.

[18]  Danqi Chen,et al.  A Fast and Accurate Dependency Parser using Neural Networks , 2014, EMNLP.

[19]  Paloma Martínez,et al.  Lessons learnt from the DDIExtraction-2013 Shared Task , 2014, J. Biomed. Informatics.

[20]  Francesco Carlo Morabito,et al.  Deep Learning Representation from Electroencephalography of Early-Stage Creutzfeldt-Jakob Disease and Features for Differentiation from Rapidly Progressive Dementia , 2017, Int. J. Neural Syst..

[21]  Bowen Zhou,et al.  Classifying Relations by Ranking with Convolutional Neural Networks , 2015, ACL.

[22]  Alberto Lavelli,et al.  FBK-irst : A Multi-Phase Kernel Based Approach for Drug-Drug Interaction Detection and Classification that Exploits Linguistic Information , 2013, *SEMEVAL.

[23]  Jimmy Ba,et al.  Adam: A Method for Stochastic Optimization , 2014, ICLR.

[24]  Shasha Li,et al.  Drug-Drug Interaction Extraction via Recurrent Neural Network with Multiple Attention Layers , 2017, ADMA.

[25]  Ross B. Girshick,et al.  Focal Loss for Dense Object Detection , 2017, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[26]  Ralf Zimmer,et al.  RelEx - Relation extraction using dependency parse trees , 2007, Bioinform..

[27]  Deyu Zhou,et al.  Position-aware deep multi-task learning for drug-drug interaction extraction , 2018, Artif. Intell. Medicine.

[28]  Jun Zhao,et al.  Relation Classification via Convolutional Deep Neural Network , 2014, COLING.

[29]  Isabel Segura-Bedmar,et al.  The 1st DDIExtraction-2011 challenge task: Extraction of Drug-Drug Interactions from biomedical texts , 2011 .

[30]  Xiao Sun,et al.  Multichannel Convolutional Neural Network for Biological Relation Extraction , 2016, BioMed research international.

[31]  Paloma Martínez,et al.  SemEval-2013 Task 9 : Extraction of Drug-Drug Interactions from Biomedical Texts (DDIExtraction 2013) , 2013, *SEMEVAL.

[32]  Stewart E. Glaspole Stockley’s Drug Interactions , 2018 .

[33]  Wei Zheng,et al.  Drug–drug interaction extraction via hierarchical RNNs on sequence and shortest dependency paths , 2017, Bioinform..

[34]  César de Pablo-Sánchez,et al.  Using a shallow linguistic kernel for drug-drug interaction extraction , 2011, J. Biomed. Informatics.

[35]  Paloma Martínez,et al.  A linguistic rule-based approach to extract drug-drug interactions from pharmacological documents , 2011, BMC Bioinformatics.

[36]  U. Rajendra Acharya,et al.  Automated EEG-based screening of depression using deep convolutional neural network , 2018, Comput. Methods Programs Biomed..

[37]  Alex Graves,et al.  Neural Machine Translation in Linear Time , 2016, ArXiv.

[38]  Alberto Lavelli,et al.  Exploiting the Scope of Negations and Heterogeneous Features for Relation Extraction: A Case Study for Drug-Drug Interaction Extraction , 2013, HLT-NAACL.

[39]  Tapio Salakoski,et al.  Distributional Semantics Resources for Biomedical Text Processing , 2013 .

[40]  Jason Weston,et al.  Natural Language Processing (Almost) from Scratch , 2011, J. Mach. Learn. Res..

[41]  Jeffrey Dean,et al.  Distributed Representations of Words and Phrases and their Compositionality , 2013, NIPS.

[42]  Andrew Y. Ng,et al.  CheXNet: Radiologist-Level Pneumonia Detection on Chest X-Rays with Deep Learning , 2017, ArXiv.

[43]  Yoshua Bengio,et al.  Word Representations: A Simple and General Method for Semi-Supervised Learning , 2010, ACL.

[44]  Haibin Liu,et al.  Extracting drug-drug interactions from literature using a rich feature-based linear kernel approach , 2015, AMIA.

[45]  Zhenchao Jiang,et al.  Drug-drug interaction extraction from biomedical literature using support vector machine and long short term memory networks , 2017, Inf. Sci..

[46]  R. Lucas,et al.  Glycosidic enzymes enhance retinal transduction following intravitreal delivery of AAV2 , 2010, Molecular vision.

[47]  Paloma Martínez,et al.  The DDI corpus: An annotated corpus with pharmacological substances and drug-drug interactions , 2013, J. Biomed. Informatics.

[48]  Jun'ichi Tsujii,et al.  Feature Forest Models for Probabilistic HPSG Parsing , 2008, CL.

[49]  Jari Björne,et al.  UTurku: Drug Named Entity Recognition and Drug-Drug Interaction Extraction Using SVM Classification and Domain Knowledge , 2013, *SEMEVAL.

[50]  Isabelle Ragueneau-Majlessi,et al.  A useful tool for drug interaction evaluation: The University of Washington Metabolism and Transport Drug Interaction Database , 2010, Human Genomics.

[51]  Hongfei Lin,et al.  Drug drug interaction extraction from biomedical literature using syntax convolutional neural network , 2016, Bioinform..