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 previous release of the DrugBank database with 1,141 drugs and 45,296 drug-drug interactions and evaluate the results on a later version of DrugBank with 1,440 drugs and 248,146 drug-drug interactions. Additionally, we perform a holdout analysis using DrugBank. We report an area under the receiver operating characteristic curve score of 0.807 and 0.990 for the retrospective and holdout analyses respectively. Finally, we create an ensemble-based classifier using AMF, AMFP, and existing link prediction methods and obtain an area under the receiver operating characteristic curve of 0.814 and 0.991 for the retrospective and the holdout analyses. We demonstrate that AMF and AMFP provide state of the art results compared to existing methods and that the ensemble-based classifier improves the performance by combining various predictors. These results suggest that AMF, AMFP, and the proposed ensemble-based classifier can provide important information during drug development and regarding drug prescription given only partial or noisy data. These methods can also be used to solve other link prediction problems. Drug embeddings (compressed representations) created when training our models using the interaction network have been made public.
Aalto University（阿尔托大学）；University of Manchester（曼彻斯特大学）；Kyoto University（京都大学）
Detecting predictive biomarkers from multi-omics data is important for precision medicine, to improve diagnostics of complex diseases and for better treatments. This needs substantial experimental efforts that are made difficult by the heterogeneity of cell lines and huge cost. An effective solution is to build a computational model over the diverse omics data, including genomic, molecular, and environmental information. However, choosing informative and reliable data sources from among the different types of data is a challenging problem. We propose DIVERSE, a framework of Bayesian importance…
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…
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…
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…
Washington University in St. Louis（圣路易斯华盛顿大学）；Washington University School of Medicine（华盛顿大学医学院）
We investigate molecular mechanisms of resistant or sensitive response of cancer drug combination therapies in an inductive and interpretable manner. Though deep learning algorithms are widely used in the drug synergy prediction problem, it is still an open problem to formulate the prediction model with biological meaning to investigate the mysterious mechanisms of synergy (MoS) for the human-AI collaboration in healthcare systems. To address the challenges, we propose a deep graph neural network, IDSP (Interpretable Deep Signaling Pathways), to incorporate the gene-gene as well as gene-drug r…
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…
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…
Central South University（中南大学）；Nanjing Tech University（南京工业大学）；Xinjiang University（新疆大学）
Drug combination therapy has become a increasingly promising method in the treatment of cancer. However, the number of possible drug combinations is so huge that it is hard to screen synergistic drug combinations through wet-lab experiments. Therefore, computational screening has become an important way to prioritize drug combinations. Graph neural network have recently shown remarkable performance in the prediction of compound-protein interactions, but it has not been applied to the screening of drug combinations. In this paper, we proposed a deep learning model based on graph neural networks…
Optimal normalization in quantum-classical hybrid models for anti-cancer drug response prediction
The University of Tokyo（东京大学）；Graduate School of Frontier Sciences（前沿科学研究生院）；Laboratory for Medical Science（医学科学实验室）；Department of Computational Biology and Medical Sciences（计算生物学与医学科学系）；Department of Biological Sciences（生物科学系）；School of Science（科学学校）
Argonne National Laboratory（阿贡国家实验室）；Leidos Biomedical Research, Inc.（莱多斯生物医学研究公司）；National Cancer Institute（美国国家癌症研究所）；The University of Chicago（芝加哥大学）
Transfer learning has been shown to be effective in many applications in which training data for the target problem are limited but data for a related (source) problem are abundant. In this paper, we apply transfer learning to the prediction of anti-cancer drug response. Previous transfer learning studies for drug response prediction focused on building models that predict the response of tumor cells to a specific drug treatment. We target the more challenging task of building general prediction models that can make predictions for both new tumor cells and new drugs. We apply the classic trans…
Penn State University（宾夕法尼亚州立大学）；Penn State College of Medicine（宾夕法尼亚州立大学医学院）
Traditional drug discovery pipeline takes several years and cost billions of dollars. Deep generative and predictive models are widely adopted to assist in drug development. Classical machines cannot efficiently produce atypical patterns of quantum computers which might improve the training quality of learning tasks. We propose a suite of quantum machine learning techniques e.g., generative adversarial network (GAN), convolutional neural network (CNN) and variational auto-encoder (VAE) to generate small drug molecules, classify binding pockets in proteins, and generate large drug molecules, re…
DrugReasoner: Interpretable Drug Approval Prediction with a Reasoning-augmented Language Model
Regenerative Medicine Research Center, Isfahan University of Medical Sciences（再生医学研究中心，伊斯法罕医科大学）；Isfahan University of Medical Sciences（伊斯法罕医科大学）；Isfahan Neuroscience Research Center, Isfahan University of Medical Sciences（伊斯法罕神经科学研究中心，伊斯法罕医科大学）；Department of Electrical and Computer Engineering, Isfahan University of Technology（电气与计算机工程系，伊斯法罕技术大学）
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 …
Fraunhofer FIT（弗劳恩霍夫应用信息技术研究所）；RWTH Aachen University（亚琛工业大学）；University of Dhaka（达卡大学）
Interference between pharmacological substances can cause serious medical injuries. Correctly predicting so-called drug-drug interactions (DDI) does not only reduce these cases but can also result in a reduction of drug development cost. Presently, most drug-related knowledge is the result of clinical evaluations and post-marketing surveillance; resulting in a limited amount of information. Existing data-driven prediction approaches for DDIs typically rely on a single source of information, while using information from multiple sources would help improve predictions. Machine learning (ML) tech…
Drug Release Modeling using Physics-Informed Neural Networks
Division of Applied Mathematics, Brown University（应用数学系，布朗大学）；School of Engineering, Brown University（工程学院，布朗大学）；Institute for Biology, Engineering and Medicine, Brown University（生物、工程与医学研究所，布朗大学）
University of Michigan（密歇根大学）；Argonne National Laboratory（阿贡国家实验室）；University of Chicago（芝加哥大学）
The process of screening molecules for desirable properties is a key step in several applications, ranging from drug discovery to material design. During the process of drug discovery specifically, protein-ligand docking, or chemical docking, is a standard in-silico scoring technique that estimates the binding affinity of molecules with a specific protein target. Recently, however, as the number of virtual molecules available to test has rapidly grown, these classical docking algorithms have created a significant computational bottleneck. We address this problem by introducing Deep Surrogate D…
Greehey Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio（德克萨斯大学圣安东尼奥健康科学中心格里希儿童癌症研究所）；University of Texas at San Antonio（德克萨斯大学圣安东尼奥分校）；Northwestern Polytechnical University（西北工业大学）；Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio（德克萨斯大学圣安东尼奥健康科学中心流行病学与生物统计学系）
The study of high-throughput genomic profiles from a pharmacogenomics viewpoint has provided unprecedented insights into the oncogenic features modulating drug response. A recent screening of ~1,000 cancer cell lines to a collection of anti-cancer drugs illuminated the link between genotypes and vulnerability. However, due to essential differences between cell lines and tumors, the translation into predicting drug response in tumors remains challenging. Here we proposed a DNN model to predict drug response based on mutation and expression profiles of a cancer cell or a tumor. The model contain…
Towards Interpretable Drug-Drug Interaction Prediction: A Graph-Based Approach with Molecular and Network-Level Explanations
Data Science Institute, School of Mathematics, Shandong University（数据科学研究院、数学学院、山东大学）；Academy of Mathematics and Systems Science, Chinese Academy of Sciences（数学与系统科学研究院、中国科学院）；Data Science Institute, Shandong University（数据科学研究院、山东大学）
Zhejiang University（浙江大学）；University of Illinois at Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校）；Hangzhou Dianzi University（杭州电子科技大学）
With the development of computer-assisted techniques, research communities including biochemistry and deep learning have been devoted into the drug discovery field for over a decade. Various applications of deep learning have drawn great attention in drug discovery, such as molecule generation, molecular property prediction, retrosynthesis prediction, and reaction prediction. While most existing surveys only focus on one of the applications, limiting the view of researchers in the community. In this paper, we present a comprehensive review on the aforementioned four aspects, and discuss the re…
While many quantum computing techniques for machine learning have been proposed, their performance on real-world datasets remains to be studied. In this paper, we explore how a variational quantum circuit could be integrated into a classical neural network for the problem of detecting pneumonia from chest radiographs. We substitute one layer of a classical convolutional neural network with a variational quantum circuit to create a hybrid neural network. We train both networks on an image dataset containing chest radiographs and benchmark their performance. To mitigate the influence of differen…
Instituto de Ciencias Matemáticas (ICMAT)（数学科学研究所（ICMAT））；Universidad Autónoma de Madrid（马德里自治大学）；Universidad Politécnica de Madrid（马德里理工大学）；Ingenii Inc.（Ingenii公司）
One of the main challenges in drug discovery is to find molecules that bind specifically and strongly to their target protein while having minimal binding to other proteins. By predicting binding affinity, it is possible to identify the most promising candidates from a large pool of potential compounds, reducing the number of compounds that need to be tested experimentally. Recently, deep learning methods have shown superior performance than traditional computational methods for making accurate predictions on large datasets. However, the complexity and time-consuming nature of these methods ha…
A systematic investigation of molecular encoding methods for drug property predictions across neural network and Transformer encoder-based model
School of Medicine, National Tsing Hua University（国立清华大学医学院）；Institute of Bioinformatics and Structural Biology, National Tsing Hua University（国立清华大学生物信息学与结构生物学研究所）；Department of Life Science, National Tsing Hua University（国立清华大学生命科学系）；Interdisciplinary Program of Life Sciences and Medicine, National Tsing Hua University（国立清华大学生命科学与医学跨学科计划）
In drug discovery, knowledge of the graph structure of chemical compounds is essential. Many thousands of scientific articles in chemistry and pharmaceutical sciences have investigated chemical compounds, but in cases the details of the structure of these chemical compounds is published only as an images. A tool to analyze these images automatically and convert them into a chemical graph structure would be useful for many applications, such drug discovery. A few such tools are available and they are mostly derived from optical character recognition. However, our evaluation of the performance o…
Quantum computing has gained a lot of attention recently, and scientists have seen potential applications in this field using quantum computing for Cryptography and Communication to Machine Learning and Healthcare. Protein folding has been one of the most interesting areas to study, and it is also one of the biggest problems of biochemistry. Each protein folds distinctively, and the difficulty of finding its stable shape rapidly increases with an increase in the number of amino acids in the chain. A moderate protein has about 100 amino acids, and the number of combinations one needs to verify …
Institute of Biochemistry and Biophysics, Polish Academy of Sciences（波兰科学院生物化学与生物物理研究所）；University of Warsaw（华沙大学）
In recent years machine learning (ML) took bio- and cheminformatics fields by storm, providing new solutions for a vast repertoire of problems related to protein sequence, structure, and interactions analysis. ML techniques, deep neural networks especially, were proven more effective than classical models for tasks like predicting binding affinity for molecular complex. In this work we investigated the earlier stage of drug discovery process - finding druggable pockets on protein surface, that can be later used to design active molecules. For this purpose we developed a 3D fully convolutional …
Virginia Tech（弗吉尼亚理工学院暨州立大学）；Argonne National Laboratory（阿贡国家实验室）
As neural networks have begun performing increasingly critical tasks for society, ranging from driving cars to identifying candidates for drug development, the value of their ability to perform uncertainty quantification (UQ) in their predictions has risen commensurately. Permanent dropout, a popular method for neural network UQ, involves injecting stochasticity into the inference phase of the model and creating many predictions for each of the test data. This shifts the computational and energy burden of deep neural networks from the training phase to the inference phase. Recent work has demo…
Molecular property prediction is a fundamental task in the drug and material industries. Physically, the properties of a molecule are determined by its own electronic structure, which is a quantum many-body system and can be exactly described by the Schr"odinger equation. Full-range many-body interactions between electrons have been proven effective in obtaining an accurate solution of the Schr"odinger equation by classical computational chemistry methods, although modeling such interactions consumes an expensive computational cost. Meanwhile, deep learning methods have also demonstrated their…
