Prediction of drug adverse events using deep learning in pharmaceutical discovery

Traditional machine learning methods used to detect the side effects of drugs pose significant challenges as feature engineering processes are labor-intensive, expert-dependent, time-consuming and cost-ineffective. Moreover, these methods only focus on detecting the association between drugs and their side effects or classifying drug-drug interaction. Motivated by technological advancements and the availability of big data, we provide a review on the detection and classification of side effects using deep learning approaches. It is shown that the effective integration of heterogeneous, multidimensional drug data sources, together with the innovative deployment of deep learning approaches, helps reduce or prevent the occurrence of adverse drug reactions (ADRs). Deep learning approaches can also be exploited to find replacements for drugs which have side effects or help to diversify the utilization of drugs through drug repurposing.

[1]  Damian Szklarczyk,et al.  STITCH 5: augmenting protein–chemical interaction networks with tissue and affinity data , 2015, Nucleic Acids Res..

[2]  Susumu Goto,et al.  KEGG for representation and analysis of molecular networks involving diseases and drugs , 2009, Nucleic Acids Res..

[3]  Carol Friedman,et al.  Drug-drug interaction through molecular structure similarity analysis , 2012, J. Am. Medical Informatics Assoc..

[4]  Feng Liu,et al.  Predicting potential drug-drug interactions by integrating chemical, biological, phenotypic and network data , 2017, BMC Bioinformatics.

[5]  Pierre Baldi,et al.  Deep Learning for Drug Discovery and Cancer Research: Automated Analysis of Vascularization Images , 2019, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[6]  Roded Sharan,et al.  An Algorithmic Framework for Predicting Side-Effects of Drugs , 2010, RECOMB.

[7]  Yijia Zhang,et al.  A hybrid model based on neural networks for biomedical relation extraction , 2018, J. Biomed. Informatics.

[8]  Thomas Blaschke,et al.  The rise of deep learning in drug discovery. , 2018, Drug discovery today.

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

[10]  Said Ouatik El Alaoui,et al.  An adverse drug effect mentions extraction method based on weighted online recurrent extreme learning machine , 2019, Comput. Methods Programs Biomed..

[11]  Yoshua Bengio,et al.  Learning long-term dependencies with gradient descent is difficult , 1994, IEEE Trans. Neural Networks.

[12]  Arzucan Özgür,et al.  DeepDTA: deep drug–target binding affinity prediction , 2018, Bioinform..

[13]  Hong Yu,et al.  Bidirectional RNN for Medical Event Detection in Electronic Health Records , 2016, NAACL.

[14]  Yi Tay,et al.  Deep Learning based Recommender System: A Survey and New Perspectives , 2018 .

[15]  Sunil Kumar Sahu,et al.  Drug-Drug Interaction Extraction from Biomedical Text Using Long Short Term Memory Network , 2017, J. Biomed. Informatics.

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

[17]  Aaron Finerman An Editorial Note , 1969, CSUR.

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

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

[20]  J. Aronson,et al.  Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature , 2016, BMC Medicine.

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

[22]  Xuejie Zhang,et al.  An Attentive Neural Sequence Labeling Model for Adverse Drug Reactions Mentions Extraction , 2018, IEEE Access.

[23]  Laurence T. Yang,et al.  A survey on deep learning for big data , 2018, Inf. Fusion.

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

[25]  Yong Hu,et al.  Improving drug safety: From adverse drug reaction knowledge discovery to clinical implementation. , 2016, Methods.

[26]  Teun Bousema,et al.  Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy: a systematic review and meta-analysis of individual patient data , 2016, BMC Medicine.

[27]  Carol Hsin,et al.  Implementation and Optimization of Differentiable Neural Computers , 2017 .

[28]  Anne Cocos,et al.  Deep learning for pharmacovigilance: recurrent neural network architectures for labeling adverse drug reactions in Twitter posts , 2017, J. Am. Medical Informatics Assoc..

[29]  Huilong Duan,et al.  Using neural attention networks to detect adverse medical events from electronic health records , 2018, J. Biomed. Informatics.

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

[31]  Kuldip K. Paliwal,et al.  Bidirectional recurrent neural networks , 1997, IEEE Trans. Signal Process..

[32]  Yoshihiro Yamanishi,et al.  Drug-target interaction prediction from chemical, genomic and pharmacological data in an integrated framework , 2010, Bioinform..

[33]  Peer Bork,et al.  The SIDER database of drugs and side effects , 2015, Nucleic Acids Res..

[34]  Jure Leskovec,et al.  Modeling polypharmacy side effects with graph convolutional networks , 2018, bioRxiv.

[35]  Jaques Reifman,et al.  Data-driven prediction of adverse drug reactions induced by drug-drug interactions , 2017, BMC Pharmacology and Toxicology.

[36]  Elena Tutubalina,et al.  Combination of Deep Recurrent Neural Networks and Conditional Random Fields for Extracting Adverse Drug Reactions from User Reviews , 2017, Journal of healthcare engineering.

[37]  Yuemin Bian,et al.  Deep Learning for Drug Design: an Artificial Intelligence Paradigm for Drug Discovery in the Big Data Era , 2018, The AAPS Journal.

[38]  R. Altman,et al.  Data-Driven Prediction of Drug Effects and Interactions , 2012, Science Translational Medicine.

[39]  Gerard de Melo,et al.  Multiple-Weight Recurrent Neural Networks , 2017, IJCAI.

[40]  Geoffrey E. Hinton,et al.  Deep Learning , 2015, Nature.

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

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

[43]  J. Lexchin,et al.  Analysis of the Drugs Withdrawn from the US Market from 1976 to 2010 for Safety Reasons , 2016, Pharmaceutical Medicine.

[44]  Yijia Zhang,et al.  An attention-based effective neural model for drug-drug interactions extraction , 2017, BMC Bioinformatics.

[45]  Jian Wang,et al.  Adverse drug reaction detection via a multihop self-attention mechanism , 2019, BMC Bioinformatics.

[46]  Vasudeva Varma,et al.  Semi-Supervised Recurrent Neural Network for Adverse Drug Reaction mention extraction , 2017, BMC Bioinformatics.

[47]  Wei Wang,et al.  Dependency-based long short term memory network for drug-drug interaction extraction , 2017, BMC Bioinformatics.

[48]  T. J. Moore,et al.  Serious adverse drug events reported to the Food and Drug Administration, 1998-2005. , 2007, Archives of internal medicine.

[49]  Christopher D. Manning,et al.  Generating Typed Dependency Parses from Phrase Structure Parses , 2006, LREC.

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

[51]  Yuan Luo,et al.  Recurrent Neural Networks for Classifying Relations in Clinical Notes , 2017, AMIA.