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 required properties are not always available.
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…
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…
Drug-drug interactions are preventable causes of medical injuries and often result in doctor and emergency room visits. Computational techniques can be used to predict potential drug-drug interactions. We approach the drug-drug interaction prediction problem as a link prediction problem and present two novel methods for drug-drug interaction prediction based on artificial neural networks and factor propagation over graph nodes: adjacency matrix factorization (AMF) and adjacency matrix factorization with propagation (AMFP). We conduct a retrospective analysis by training our models on a previou…
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…
Sun Yat-sen University（中山大学）；Guangdong Key Laboratory of Big Data Analysis and Processing（广东省大数据分析与处理重点实验室）；Microsoft Research Asia（微软亚洲研究院）；Fudan University（复旦大学）
The identification of active binding drugs for target proteins (termed as drug-target interaction prediction) is the key challenge in virtual screening, which plays an essential role in drug discovery. Although recent deep learning-based approaches achieved better performance than molecular docking, existing models often neglect certain aspects of the intermolecular information, hindering the performance of prediction. We recognize this problem and propose a novel approach named Intermolecular Graph Transformer (IGT) that employs a dedicated attention mechanism to model intermolecular informat…
BVSIMC: Bayesian Variable Selection-Guided Inductive Matrix Completion for Improved and Interpretable Drug Discovery
Department of Statistics University of South Carolina（统计学系南卡罗来纳大学）；Department of Biostatistics University of South Carolina（生物统计学系南卡罗来纳大学）；Department of Biostatistics University of Florida（生物统计学系佛罗里达大学）；Department of Surgery University of Florida（外科医学系佛罗里达大学）；Department of Statistics George Mason University（统计学系乔治·梅森大学）
Enhancing drug and cell line representations via contrastive learning for improved anti-cancer drug prioritization
The Ohio State University（俄亥俄州立大学）；Biomedical Informatics Department, The Ohio State University（俄亥俄州立大学生物医学信息学系）；Computer Science and Engineering Department, The Ohio State University（俄亥俄州立大学计算机科学与工程系）；Translational Data Analytics Institute, The Ohio State University（俄亥俄州立大学转化数据分析研究所）
Hunan University（湖南大学）；Microsoft Research Asia（微软亚洲研究院）；University of Chinese Academy of Sciences（中国科学院大学）；Institute of Information Engineering, Chinese Academy of Sciences（中国科学院信息工程研究所）
Drug-drug interaction (DDI) prediction provides a drug combination strategy for systemically effective treatment. Previous studies usually model drug information constrained on a single view such as the drug itself, leading to incomplete and noisy information, which limits the accuracy of DDI prediction. In this work, we propose a novel multi- view drug substructure network for DDI prediction (MSN-DDI), which learns chemical substructures from both the representations of the single drug (intra-view) and the drug pair (inter-view) simultaneously and utilizes the substructures to update the drug…
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…
Seoul National University（首尔大学）；Seoul National University Hospital（首尔大学医院）
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 develo…
Since multidrug combination is widely applied, the accurate prediction of drug-drug interaction (DDI) is becoming more and more critical. In our method, we use graph to represent drug-drug interaction: nodes represent drug; edges represent drug-drug interactions. Based on our assumption, we convert the prediction of DDI to link prediction problem, utilizing known drug node characteristics and DDI types to predict unknown DDI types. This work proposes a Graph Distance Neural Network (GDNN) to predict drug-drug interactions. Firstly, GDNN generates initial features for nodes via target point met…
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）
School of Electrical Engineering and Computer Science, Gwangju Institute of Science and Technology（光州科学技术院电气与计算机工程学院）
Identification of drug-target interactions (DTIs) plays a key role in drug discovery. The high cost and labor-intensive nature of in vitro and in vivo experiments have highlighted the importance of in silico-based DTI prediction approaches. In several computational models, conventional protein descriptors are shown to be not informative enough to predict accurate DTIs. Thus, in this study, we employ a convolutional neural network (CNN) on raw protein sequences to capture local residue patterns participating in DTIs. With CNN on protein sequences, our model performs better than previous protein…
Jamia Millia Islamia University（贾米亚·米利亚·伊斯兰亚大学）；The Chinese University of Hong Kong（香港中文大学）
Detecting probable Drug Target Interaction (DTI) is a critical task in drug discovery. Conventional DTI studies are expensive, labor-intensive, and take a lot of time, hence there are significant reasons to construct useful computational techniques that may successfully anticipate possible DTIs. Although certain methods have been developed for this cause, numerous interactions are yet to be discovered, and prediction accuracy is still low. To meet these challenges, we propose a DTI prediction model built on molecular structure of drugs and sequence of target proteins. In the proposed model, we…
MSCoD: An Enhanced Bayesian Updating Framework with Multi-Scale Information Bottleneck and Cooperative Attention for Structure-Based Drug Design
Guangxi Key Lab of Human-machine Interaction and Intelligent Decision（广西人机交互与智能决策重点实验室）；Nanning Normal University（南宁师范学院）；College of Big Data and Software Engineering（大数据与软件工程学院）；Zhejiang Wanli University（浙江万里大学）
The University of Texas Health Science Center at Houston（德克萨斯大学休斯顿健康科学中心）
Evaluating the blood-brain barrier (BBB) permeability of drug molecules is a critical step in brain drug development. Traditional methods for the evaluation require complicated in vitro or in vivo testing. Alternatively, in silico predictions based on machine learning have proved to be a cost-efficient way to complement the in vitro and in vivo methods. However, the performance of the established models has been limited by their incapability of dealing with the interactions between drugs and proteins, which play an important role in the mechanism behind the BBB penetrating behaviors. To addres…
Absorption, distribution, metabolism, and excretion (ADME) studies are critical for drug discovery. Conventionally, these tasks, together with other chemical property predictions, rely on domain-specific feature descriptors, or fingerprints. Following the recent success of neural networks, we developed Chemi-Net, a completely data-driven, domain knowledge-free, deep learning method for ADME property prediction. To compare the relative performance of Chemi-Net with Cubist, one of the popular machine learning programs used by Amgen, a large-scale ADME property prediction study was performed on-s…
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…
Drug-drug interactions (DDIs) are a major cause of preventable hospitalizations and deaths. Predicting the occurrence of DDIs helps drug safety professionals allocate investigative resources and take appropriate regulatory action promptly. Traditional DDI prediction methods predict DDIs based on the similarity between drugs. Recently, researchers revealed that predictive performance can be improved by better modeling the interactions between drug pairs with bilinear forms. However, the shallow models leveraging bilinear forms suffer from limitations on capturing complicated nonlinear interacti…
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…
KAIST（韩国科学技术院）；HITS incorporation（HITS 公司）；KI for Artificial Intelligence, KAIST（韩国科学技术院人工智能研究院）
Recently, deep neural network (DNN)-based drug-target interaction (DTI) models were highlighted for their high accuracy with affordable computational costs. Yet, the models' insufficient generalization remains a challenging problem in the practice of in-silico drug discovery. We propose two key strategies to enhance generalization in the DTI model. The first is to predict the atom-atom pairwise interactions via physics-informed equations parameterized with neural networks and provides the total binding affinity of a protein-ligand complex as their sum. We further improved the model generalizat…
Harvard T.H. Chan School of Public Health（哈佛大学陈曾熙公共卫生学院）；IQVIA（艾昆纬）；University of Illinois at Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校）
Drug target interaction (DTI) prediction is a foundational task for in silico drug discovery, which is costly and time-consuming due to the need of experimental search over large drug compound space. Recent years have witnessed promising progress for deep learning in DTI predictions. However, the following challenges are still open: (1) the sole data-driven molecular representation learning approaches ignore the sub-structural nature of DTI, thus produce results that are less accurate and difficult to explain; (2) existing methods focus on limited labeled data while ignoring the value of massi…
Predicting clinical outcomes to anti-cancer drugs on a personalized basis is challenging in cancer treatment due to the heterogeneity of tumors. Traditional computational efforts have been made to model the effect of drug response on individual samples depicted by their molecular profile, yet overfitting occurs because of the high dimension for omics data, hindering models from clinical application. Recent research shows that deep learning is a promising approach to build drug response models by learning alignment patterns between drugs and samples. However, existing studies employed the simpl…
Perelman School of Medicine, University of Pennsylvania（宾夕法尼亚大学佩雷尔曼医学院）；Biodesign Institute, Arizona State University（亚利桑那州立大学生物设计研究所）
Objective: After years of research, Twitter posts are now recognized as an important source of patient-generated data, providing unique insights into population health. A fundamental step to incorporating Twitter data in pharmacoepidemiological research is to automatically recognize medication mentions in tweets. Given that lexical searches for medication names may fail due to misspellings or ambiguity with common words, we propose a more advanced method to recognize them. Methods: We present Kusuri, an Ensemble Learning classifier, able to identify tweets mentioning drug products and dietary …
Indiana University（印第安纳大学）；University of Minho（米尼奥大学）
Background. Drug-drug interaction (DDI) is a major cause of morbidity and mortality. [...] Biomedical literature mining can aid DDI research by extracting relevant DDI signals from either the published literature or large clinical databases. However, though drug interaction is an ideal area for translational research, the inclusion of literature mining methodologies in DDI workflows is still very preliminary. One area that can benefit from literature mining is the automatic identification of a large number of potential DDIs, whose pharmacological mechanisms and clinical significance can then b…
University of Macau（澳门大学）；Central South University（中南大学）
Background: Pharmacokinetic evaluation is one of the key processes in drug discovery and development. However, current absorption, distribution, metabolism, excretion prediction models still have limited accuracy. Aim: This study aims to construct an integrated transfer learning and multitask learning approach for developing quantitative structure-activity relationship models to predict four human pharmacokinetic parameters. Methods: A pharmacokinetic dataset included 1104 U.S. FDA approved small molecule drugs. The dataset included four human pharmacokinetic parameter subsets (oral bioavailab…
Drug-Target Interaction Prediction via Hierarchical Sequential Cross-Attention over Chemical and Protein Language Models
I2A institute, TÉLUQ University（I2A研究所，TÉLUQ大学）；LIO, CRCHUM（LIO，蒙特利尔大学医院研究中心）；LCSI, ESI（LCSI，阿尔及尔国立高等信息学院）；CoMeT UR 24344, Universite de Poitiers（CoMeT UR 24344，普瓦捷大学）；University of Ottawa（渥太华大学）；Lebanese American University（黎巴嫩美国大学）
ProbeMatchDTI: Probe-Driven Multi-Scale Biochemical Pattern Matching for Drug-Target Interaction Prediction
Beijing University of Technology（北京工业大学）；China Academy of Chinese Medical Sciences（中国中医科学院）；National University of Singapore（新加坡国立大学）；University of New South Wales（新南威尔士大学）
University of Electronic Science and Technology of China（电子科技大学）；George Mason University（乔治梅森大学）
Drug-target interaction (DTI) prediction plays a very important role in drug development and drug discovery. Biochemical experiments or \textit{in vitro} methods are very expensive, laborious and time-consuming. Therefore, \textit{in silico} approaches including docking simulation and machine learning have been proposed to solve this problem. In particular, machine learning approaches have attracted increasing attentions recently. However, in addition to the known drug-target interactions, most of the machine learning methods require extra characteristic information such as chemical structures…
Towards Evolutionary-based Automated Machine Learning for Small Molecule Pharmacokinetic Prediction
Baker Heart and Diabetes Institute（贝克心脏与糖尿病研究所）；School of Chemistry & Molecular Biosciences, The University of Queensland（昆士兰大学化学与分子生物科学学院）；The University of Melbourne（墨尔本大学）
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…
Structure-Aware Contrastive Learning with Fine-Grained Binding Representations for Drug Discovery
Department of Health Technology and Informatics, The Hong Kong Polytechnic University（健康科技与信息学系，香港理工大学）；Department of Nuclear Medicine and PET, Hong Kong Sanatorium and Hospital（核医学与PET部，香港疗养院及医院）；Nuclear Medicine Unit, Department of Diagnostic and Interventional Radiology, Queen Elizabeth Hospital（核医学科，诊断与介入放射科，伊丽莎白女王医院）
Detecting and intercepting malicious requests are one of the most widely used ways against attacks in the network security. Most existing detecting approaches, including matching blacklist characters and machine learning algorithms have all shown to be vulnerable to sophisticated attacks. To address the above issues, a more general and rigorous detection method is required. In this paper, we formulate the problem of detecting malicious requests as a temporal sequence classification problem, and propose a novel deep learning model namely Convolutional Neural Network-Bidirectional Long Short-ter…
Generative models for structure-based molecular design hold significant promise for drug discovery, with the potential to speed up the hit-to-lead development cycle, while improving the quality of drug candidates and reducing costs. Data sparsity and bias are, however, two main roadblocks to the development of 3D-aware models. Here we propose a first-in-kind training protocol based on multi-level contrastive learning for improved bias control and data efficiency. The framework leverages the large data resources available for 2D generative modelling with datasets of ligand-protein complexes. Th…
Georgia Institute of Technology（佐治亚理工学院）；Harvard T.H. Chan School of Public Health（哈佛大学陈曾熙公共卫生学院）；IQVIA（艾昆纬）
Thanks to the increasing availability of drug-drug interactions (DDI) datasets and large biomedical knowledge graphs (KGs), accurate detection of adverse DDI using machine learning models becomes possible. However, it remains largely an open problem how to effectively utilize large and noisy biomedical KG for DDI detection. Due to its sheer size and amount of noise in KGs, it is often less beneficial to directly integrate KGs with other smaller but higher quality data (e.g., experimental data). Most of the existing approaches ignore KGs altogether. Some try to directly integrate KGs with other…
FaraAI Company（法拉人工智能公司）；University of Tehran（德黑兰大学）
Optical coherence tomography (OCT) imaging is a well-known technology for visualizing retinal layers and helps ophthalmologists to detect possible diseases. Accurate and early diagnosis of common retinal diseases can prevent the patients from suffering critical damages to their vision. Computer-aided diagnosis (CAD) systems can significantly assist ophthalmologists in improving their examinations. This paper presents a new enhanced deep ensemble convolutional neural network for detecting retinal diseases from OCT images. Our model generates rich and multi-resolution features by employing the l…
FABind+: Enhancing Molecular Docking through Improved Pocket Prediction and Pose Generation
Huazhong University of Science and Technology（华中科技大学）；Renmin University of China（中国人民大学）；University of Science and Technology of China（中国科学技术大学）；Shanghai Artificial Intelligence Laboratory（上海人工智能实验室）
