Adverse Drug Reaction (ADR) is a significant public health concern world-wide. Numerous graph-based methods have been applied to biomedical graphs for predicting ADRs in pre-marketing phases. ADR detection in post-market surveillance is no less important than pre-marketing assessment, and ADR detection with large-scale clinical data have attracted much attention in recent years. However, there are not many studies considering graph structures from clinical data for detecting an ADR signal, which is a pair of a prescription and a diagnosis that might be a potential ADR. In this study, we develop a novel graph-based framework for ADR signal detection using healthcare claims data. We construct a Drug-disease graph with nodes representing the medical codes. The edges are given as the relationships between two codes, computed using the data. We apply Graph Neural Network to predict ADR signals, using labels from the Side Effect Resource database. The model shows improved AUROC and AUPRC performance of 0.795 and 0.775, compared to other algorithms, showing that it successfully learns node representations expressive of those relationships. Furthermore, our model predicts ADR pairs that do not exist in the established ADR database, showing its capability to supplement the ADR database.
Research on Adverse Drug Reaction Prediction Model Combining Knowledge Graph Embedding and Deep Learning
University of Southampton（南安普顿大学）；University of Science and Technology of China（中国科学技术大学）；San Francisco Bay University（旧金山湾大学）；Trine University（特莱恩大学）；The Hong Kong University of Science and Technology（香港科技大学）；SouthWest JiaoTong University（西南交通大学）
KU Leuven（鲁汶大学）；CRACS INESC-TEC and FCUP Universidade do Porto（CRACS INESC-TEC与波尔图大学理学院）；Marshfield Clinic（马什菲尔德诊所）；University of Wisconsin - Madison（威斯康星大学麦迪逊分校）
Learning from electronic medical records (EMR) is challenging due to their relational nature and the uncertain dependence between a patient's past and future health status. Statistical relational learning is a natural fit for analyzing EMRs but is less adept at handling their inherent latent structure, such as connections between related medications or diseases. One way to capture the latent structure is via a relational clustering of objects. We propose a novel approach that, instead of pre-clustering the objects, performs a demand-driven clustering during learning. We evaluate our algorithm …
CrossADR: enhancing adverse drug reactions prediction for combination pharmacotherapy with cross-layer feature integration and cross-level associative learning
School of Mathematical Sciences（数学科学学院）；Shanghai Key Laboratory of PMMP（PMMP上海重点实验室）；East China Normal University（华东师范大学）；Shanghai（上海）；China（中国）
A pharmacological effect of a drug on cells, organs and systems refers to the specific biochemical interaction produced by a drug substance, which is called its mechanism of action. Drug repositioning (or drug repurposing) is a fundamental problem for the identification of new opportunities for the use of already approved or failed drugs. In this paper, we present a method based on a multi-relation unsupervised graph embedding model that learns latent representations for drugs and diseases so that the distance between these representations reveals repositioning opportunities. Once representati…
The 2019 novel coronavirus (SARS-CoV-2) pandemic has resulted in more than a million deaths, high morbidities, and economic distress worldwide. There is an urgent need to identify medications that would treat and prevent novel diseases like the 2019 coronavirus disease (COVID-19). Drug repurposing is a promising strategy to discover new medical indications of the existing approved drugs due to several advantages in terms of the costs, safety factors, and quick results compared to new drug design and discovery. In this work, we explore computational data-driven methods for drug repurposing and …
Drug repositioning holds great promise because it can reduce the time and cost of new drug development. While drug repositioning can omit various R&D processes, confirming pharmacological effects on biomolecules is essential for application to new diseases. Biomedical explainability in a drug repositioning model can support appropriate insights in subsequent in-depth studies. However, the validity of the XAI methodology is still under debate, and the effectiveness of XAI in drug repositioning prediction applications remains unclear. In this study, we propose GraphIX, an explainable drug reposi…
The drug discovery and development process is a long and expensive one, costing over 1 billion USD on average per drug and taking 10-15 years. To reduce the high levels of attrition throughout the process, there has been a growing interest in applying machine learning methodologies to various stages of drug discovery and development in the recent decade, especially at the earliest stage identification of druggable disease genes. In this paper, we have developed a new tensor factorisation model to predict potential drug targets (genes or proteins) for treating diseases. We created a three dimen…
Drug repurposing is more relevant than ever due to drug development's rising costs and the need to respond to emerging diseases quickly. Knowledge graph embedding enables drug repurposing using heterogeneous data sources combined with state-of-the-art machine learning models to predict new drug-disease links in the knowledge graph. As in many machine learning applications, significant work is still required to understand the predictive models' behavior. We propose a structured methodology to understand better machine learning models' results for drug repurposing, suggesting key elements of the…
We study the problem of detecting adverse drug events in electronic healthcare records. The challenge in this work is to aggregate heterogeneous data types involving diagnosis codes, drug codes, as well as lab measurements. An earlier framework proposed for the same problem demonstrated promising predictive performance for the random forest classifier by using only lab measurements as data features. We extend this framework, by additionally including diagnosis and drug prescription codes, concurrently. In addition, we employ a recursive feature selection mechanism on top, that extracts the top…
Shandong Polytechnic University（山东理工大学）；University of Nottingham（诺丁汉大学）
Adverse drug reaction (ADR) is widely concerned for public health issue. In this study we propose an original approach to detect the ADRs using feature matrix and feature selection. The experiments are carried out on the drug Simvastatin. Major side effects for the drug are detected and better performance is achieved compared to other computerized methods. The detected ADRs are based on the computerized method, further investigation is needed.
University of Manchester（曼彻斯特大学）；Manchester Institute of Innovation Research, Alliance Manchester Business School, The University of Manchester（曼彻斯特大学联盟曼彻斯特商学院曼彻斯特创新研究所）
Adverse drug reactions (ADRs) are unwanted or harmful effects experienced after the administration of a certain drug or a combination of drugs, presenting a challenge for drug development and drug administration. In this paper, we present a set of taggers for extracting adverse drug reactions and related entities, including factors, severity, negations, drug class and animal. The systems used a mix of rule-based, machine learning (CRF) and deep learning (BLSTM with word2vec embeddings) methodologies in order to annotate the data. The systems were submitted to adverse drug reaction shared task,…
Indiana University - Purdue University Indianapolis（印第安纳大学-普渡大学印第安纳波利斯分校）；University of Pennsylvania（宾夕法尼亚大学）；Ohio State University（俄亥俄州立大学）
Background: The problem of predicting whether a drug combination of arbitrary orders is likely to induce adverse drug reactions is considered in this manuscript. Methods: Novel kernels over drug combinations of arbitrary orders are developed within support vector machines for the prediction. Graph matching methods are used in the novel kernels to measure the similarities among drug combinations, in which drug co-medication patterns are leveraged to measure single drug similarities. Results: The experimental results on a real-world dataset demonstrated that the new kernels achieve an area under…
The increased adoption of Electronic Health Records(EHRs) has brought changes to the way the patient care is carried out. The rich heterogeneous and temporal data space stored in EHRs can be leveraged by machine learning models to capture the underlying information and make clinically relevant predictions. This can be exploited to support public health activities such as pharmacovigilance and specifically mitigate the public health issue of Adverse Drug Events(ADEs). The aim of this article is, therefore, to investigate the various ways of handling temporal data for the purpose of detecting AD…
Drug repositioning is an attractive cost-efficient strategy for the development of treatments for human diseases. Here, we propose an interpretable model that learns disease self-representations for drug repositioning. Our self-representation model represents each disease as a linear combination of a few other diseases. We enforce proximity in the learnt representations in a way to preserve the geometric structure of the human phenome network - a domain-specific knowledge that naturally adds relational inductive bias to the disease self-representations. We prove that our method is globally opt…
University of Cambridge（剑桥大学）；Mila – Québec Artificial Intelligence Institute（Mila-魁北克人工智能研究所）；HEC Montréal（蒙特利尔高等商学院）
Complex or co-existing diseases are commonly treated using drug combinations, which can lead to higher risk of adverse side effects. The detection of polypharmacy side effects is usually done in Phase IV clinical trials, but there are still plenty which remain undiscovered when the drugs are put on the market. Such accidents have been affecting an increasing proportion of the population (15% in the US now) and it is thus of high interest to be able to predict the potential side effects as early as possible. Systematic combinatorial screening of possible drug-drug interactions (DDI) is challeng…
Monitoring the biomedical literature for cases of Adverse Drug Reactions (ADRs) is a critically important and time consuming task in pharmacovigilance. The development of computer assisted approaches to aid this process in different forms has been the subject of many recent works. One particular area that has shown promise is the use of Deep Neural Networks, in particular, Convolutional Neural Networks (CNNs), for the detection of ADR relevant sentences. Using token-level convolutions and general purpose word embeddings, this architecture has shown good performance relative to more traditional…
National Sun Yat-sen University（国立中山大学）；Kaohsiung Medical University（高雄医学大学）
Patients with Acute Kidney Injury (AKI) increase mortality, morbidity, and long-term adverse events. Therefore, early identification of AKI may improve renal function recovery, decrease comorbidities, and further improve patients' survival. To control certain risk factors and develop targeted prevention strategies are important to reduce the risk of AKI. Drug-drug interactions and drug-disease interactions are critical issues for AKI. Typical statistical approaches cannot handle the complexity of drug-drug and drug-disease interactions. In this paper, we propose a novel learning algorithm, Dee…
Drug repositioning is designed to discover new uses of known drugs, which is an important and efficient method of drug discovery. Researchers only use one certain type of Collaborative Filtering (CF) models for drug repositioning currently, like the neighborhood based approaches which are good at mining the local information contained in few strong drug-disease associations, or the latent factor based models which are effectively capture the global information shared by a majority of drug-disease associations. Few researchers have combined these two types of CF models to derive a hybrid model …
Qilu University of Technology（齐鲁工业大学）；University of Nottingham（诺丁汉大学）
Adverse drug reaction (ADR) is widely concerned for public health issue. ADRs are one of most common causes to withdraw some drugs from market. Prescription event monitoring (PEM) is an important approach to detect the adverse drug reactions. The main problem to deal with this method is how to automatically extract the medical events or side effects from high-throughput medical events, which are collected from day to day clinical practice. In this study we propose a novel concept of feature matrix to detect the ADRs. Feature matrix, which is extracted from big medical data from The Health Impr…
Adverse drug interactions are largely preventable causes of medical accidents, which frequently result in physician and emergency room encounters. The detection of drug interactions in a lab, prior to a drug's use in medical practice, is essential, however it is costly and time-consuming. Machine learning techniques can provide an efficient and accurate means of predicting possible drug-drug interactions and combat the growing problem of adverse drug interactions. Most existing models for predicting interactions rely on the chemical properties of drugs. While such models can be accurate, the r…
Data-mining techniques have frequently been developed for Spontaneous reporting databases. These techniques aim to find adverse drug events accurately and efficiently. Spontaneous reporting databases are prone to missing information, under reporting and incorrect entries. This often results in a detection lag or prevents the detection of some adverse drug events. These limitations do not occur in electronic health-care databases. In this paper, existing methods developed for spontaneous reporting databases are implemented on both a spontaneous reporting database and a general practice electron…
We present an algorithm based on multi-layer transformers for identifying Adverse Drug Reactions (ADR) in social media data. Our model relies on the properties of the problem and the characteristics of contextual word embeddings to extract two views from documents. Then a classifier is trained on each view to label a set of unlabeled documents to be used as an initializer for a new classifier in the other view. Finally, the initialized classifier in each view is further trained using the initial training examples. We evaluated our model in the largest publicly available ADR dataset. The experi…
The automation of adverse drug reaction (ADR) detection in social media would revolutionize the practice of pharmacovigilance, supporting drug regulators, the pharmaceutical industry and the general public in ensuring the safety of the drugs prescribed in daily practice. Following from the published proceedings of the Social Media Mining for Health (SMM4H) Applications Workshop & Shared Task in August 2019, we aimed to develop a deep learning model to classify ADRs within Twitter tweets that contain drug mentions. Our approach involved fine-tuning $BERT_{LARGE}$ and two domain-specific BERT im…
University of Udine（乌迪内大学）；The Hong Kong Polytechnic University（香港理工大学）；DSIG - Bayer Pharmaceuticals（拜耳制药DSIG）
Adverse Drug Event (ADE) extraction models can rapidly examine large collections of social media texts, detecting mentions of drug-related adverse reactions and trigger medical investigations. However, despite the recent advances in NLP, it is currently unknown if such models are robust in face of negation, which is pervasive across language varieties. In this paper we evaluate three state-of-the-art systems, showing their fragility against negation, and then we introduce two possible strategies to increase the robustness of these models: a pipeline approach, relying on a specific component fo…
University of Udine（乌迪内大学）；CSAIL MIT（麻省理工学院计算机科学与人工智能实验室）；The Hong Kong Polytechnic University（香港理工大学）
In recent years, Internet users are reporting Adverse Drug Events (ADE) on social media, blogs and health forums. Because of the large volume of reports, pharmacovigilance is seeking to resort to NLP to monitor these outlets. We propose for the first time the use of the SpanBERT architecture for the task of ADE extraction: this new version of the popular BERT transformer showed improved capabilities with multi-token text spans. We validate our hypothesis with experiments on two datasets (SMM4H and CADEC) with different text typologies (tweets and blog posts), finding that SpanBERT combined wit…
Evaluating the Robustness of Adverse Drug Event Classification Models Using Templates
German Research Center for Artificial Intelligence (DFKI)（德国人工智能研究中心）；Technische Universität Berlin（柏林工业大学）；BIFOLD – Berlin Institute for the Foundations of Learning and Data（柏林学习与数据基础研究所）
Combination therapy has shown to improve therapeutic efficacy while reducing side effects. Importantly, it has become an indispensable strategy to overcome resistance in antibiotics, anti-microbials, and anti-cancer drugs. Facing enormous chemical space and unclear design principles for small-molecule combinations, the computational drug-combination design has not seen generative models to meet its potential to accelerate resistance-overcoming drug combination discovery. We have developed the first deep generative model for drug combination design, by jointly embedding graph-structured domain …
Multimodal Model with Text and Drug Embeddings for Adverse Drug Reaction Classification
Kazan Federal University（喀山联邦大学）；Lomonosov Moscow State University（莫斯科罗蒙诺索夫国立大学）；Sber AI；National Research University Higher School of Economics（国立研究型大学高等经济学院）
ADRNet: A Generalized Collaborative Filtering Framework Combining Clinical and Non-Clinical Data for Adverse Drug Reaction Prediction
Peking University（北京大学）；Yale University（耶鲁大学）；University of California, San Diego（加利福尼亚大学圣迭戈分校）；University of Science and Technology of China（中国科学技术大学）
In this work, we present the first corpus for German Adverse Drug Reaction (ADR) detection in patient-generated content. The data consists of 4,169 binary annotated documents from a German patient forum, where users talk about health issues and get advice from medical doctors. As is common in social media data in this domain, the class labels of the corpus are very imbalanced. This and a high topic imbalance make it a very challenging dataset, since often, the same symptom can have several causes and is not always related to a medication intake. We aim to encourage further multi-lingual effort…
In this work we present a deep learning approach to conduct hypothesis-free, transcriptomics-based matching of drugs for diseases. Our proposed neural network architecture is trained on approved drug-disease indications, taking as input the relevant disease and drug differential gene expression profiles, and learns to identify novel indications. We assemble an evaluation dataset of disease-drug indications spanning 68 diseases and evaluate in silico our approach against the most widely used transcriptomics-based matching baselines, CMap and the Characteristic Direction. Our results show a more…
Computational drug repositioning aims to discover new therapeutic diseases for marketed drugs and has the advantages of low cost, short development cycle, and high controllability compared to traditional drug development. The matrix factorization model has become the cornerstone technique for computational drug repositioning due to its ease of implementation and excellent scalability. However, the matrix factorization model uses the inner product to represent the association between drugs and diseases, which is lacking in expressive ability. Moreover, the degree of similarity of drugs or disea…
Computational Approaches for Predicting Drug-Disease Associations: A Comprehensive Review
School of Computer Science and Technology, Xidian University（西安电子科技大学计算机科学与技术学院）；Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China（电子科技大学基础与前沿研究院）
A Dataset for Pharmacovigilance in German, French, and Japanese: Annotating Adverse Drug Reactions across Languages
BIFOLD；TU Berlin（柏林工业大学）；German Research Center for Artificial Intelligence (DFKI)（德国人工智能研究中心（DFKI））；Université Paris-Saclay（巴黎萨克雷大学）；Nara Institute of Science and Technology（奈良科学技术研究所）；RIKEN（理化学研究所）
Boosting drug-disease association prediction for drug repositioning via dual-feature extraction and cross-dual-domain decoding
Institute of Computing Science and Technology, Guangzhou University（广州大学计算科学与技术学院）；School of Computer Science and Technology, Dalian University of Technology（大连理工大学计算机科学与技术学院）；Electronics and Communication Sciences Unit, Indian Statistical Institute（印度统计研究所电子与通信科学部）
University of Western Australia（西澳大学）；Fiona Stanley Hospital（菲奥娜·斯坦利医院）；Harry Perkins Institute of Medical Research（哈里·珀金斯医学研究所）
Explainable Artificial Intelligence (XAI) has been identified as a viable method for determining the importance of features when making predictions using Machine Learning (ML) models. In this study, we created models that take an individual's health information (e.g. their drug history and comorbidities) as inputs, and predict the probability that the individual will have an Acute Coronary Syndrome (ACS) adverse outcome. Using XAI, we quantified the contribution that specific drugs had on these ACS predictions, thus creating an XAI-based technique for pharmacovigilance monitoring, using ACS as…
The Chinese University of Hong Kong（香港中文大学）；Tencent AI Lab（腾讯人工智能实验室）；Hunan Normal University（湖南师范大学）；Hong Kong University of Science and Technology (Guangzhou)（香港科技大学（广州））
Many patients with chronic diseases resort to multiple medications to relieve various symptoms, which raises concerns about the safety of multiple medication use, as severe drug-drug antagonism can lead to serious adverse effects or even death. This paper presents a Decision Support System, called DSSDDI, based on drug-drug interactions to support doctors prescribing decisions. DSSDDI contains three modules, Drug-Drug Interaction (DDI) module, Medical Decision (MD) module and Medical Support (MS) module. The DDI module learns safer and more effective drug representations from the drug-drug int…
Background: Children are frequently prescribed medication off-label, meaning there has not been sufficient testing of the medication to determine its safety or effectiveness. The main reason this safety knowledge is lacking is due to ethical restrictions that prevent children from being included in the majority of clinical trials. Objective: The objective of this paper is to investigate whether an ensemble of simple study designs can be implemented to signal acutely occurring side effects effectively within the paediatric population by using historical longitudinal data. The majority of pharma…
Hunter College, The City University of New York（纽约城市大学亨特学院）；The Graduate Center, The City University of New York（纽约城市大学研究生中心）；Weill Cornell Medicine, Cornell University（康奈尔大学威尔康奈尔医学院）
Many multi-genic systemic diseases such as neurological disorders, inflammatory diseases, and the majority of cancers do not have effective treatments yet. Reinforcement learning powered systems pharmacology is a potentially effective approach to design personalized therapies for untreatable complex diseases. In this survey, state-of-the-art reinforcement learning methods and their latest applications to drug design are reviewed. The challenges on harnessing reinforcement learning for systems pharmacology and personalized medicine are discussed. Potential solutions to overcome the challenges a…
Evaluating the Effectiveness of Artificial Intelligence in Predicting Adverse Drug Reactions among Cancer Patients: A Systematic Review and Meta-Analysis
National Polytechnic School of Oran - Maurice Audin（奥兰国家理工学院 - 莫里斯·奥丹）
DrugGen 2: A disease-aware language model for enhancing drug discovery
Regenerative Medicine Research Center（再生医学研究中心）；Isfahan University of Medical Sciences（伊斯法罕医科大学）；Isfahan Neuroscience Research Center（伊斯法罕神经科学研究中心）；School of Pharmacy（药学院）；Department of Medicinal Chemistry（药理化学系）；Cardiovascular Research Institute（心血管研究学院）；Department of Genetics and Molecular Biology（基因与分子生物学系）；Bioinformatics Research Center（生物信息学研究中心）
Adverse drug reactions / events (ADR/ADE) have a major impact on patient health and health care costs. Detecting ADR's as early as possible and sharing them with regulators, pharma companies, and healthcare providers can prevent morbidity and save many lives. While most ADR's are not reported via formal channels, they are often documented in a variety of unstructured conversations such as social media posts by patients, customer support call transcripts, or CRM notes of meetings between healthcare providers and pharma sales reps. In this paper, we propose a natural language processing (NLP) so…
BiBLDR: Bidirectional Behavior Learning for Drug Repositioning
School of Computer Science, Hunan First Normal University（湖南第一师范学院计算机科学学院）；School of Computer Science and Engineering, Central South University（中南大学计算机科学与工程学院）
The electronic healthcare databases are starting to become more readily available and are thought to have excellent potential for generating adverse drug reaction signals. The Health Improvement Network (THIN) database is an electronic healthcare database containing medical information on over 11 million patients that has excellent potential for detecting ADRs. In this paper we apply four existing electronic healthcare database signal detecting algorithms (MUTARA, HUNT, Temporal Pattern Discovery and modified ROR) on the THIN database for a selection of drugs from six chosen drug families. Thi…
Isfahan University of Technology（伊斯法罕理工大学）；Amirkabir University of Technology（阿米尔卡比尔理工大学）；Isfahan University of Medical Sciences（伊斯法罕医科大学）；Carleton University（卡尔顿大学）
Drug repositioning offers an effective solution to drug discovery, saving both time and resources by finding new indications for existing drugs. Typically, a drug takes effect via its protein targets in the cell. As a result, it is necessary for drug development studies to conduct an investigation into the interrelationships of drugs, protein targets, and diseases. Although previous studies have made a strong case for the effectiveness of integrative network-based methods for predicting these interrelationships, little progress has been achieved in this regard within drug repositioning researc…
Computational drug repositioning technology is an effective tool to accelerate drug development. Although this technique has been widely used and successful in recent decades, many existing models still suffer from multiple drawbacks such as the massive number of unvalidated drug-disease associations and the inner product. The limitations of these works are mainly due to the following two reasons: firstly, previous works used negative sampling techniques to treat unvalidated drug-disease associations as negative samples, which is invalid in real-world settings; secondly, the inner product cann…
