In this mini-review, we explore the new prediction methods for drug combination synergy relying on high-throughput combinatorial screens. The fast progress of the field is witnessed in the more than thirty original machine learning methods published since 2021, a clear majority of them based on deep learning techniques. We aim to put these papers under a unifying lens by highlighting the core technologies, the data sources, the input data types and synergy scores used in the methods, as well as the prediction scenarios and evaluation protocols that the papers deal with. Our finding is that the best methods accurately solve the synergy prediction scenarios involving known drugs or cell lines while the scenarios involving new drugs or cell lines still fall short of an accurate prediction level.
CongFu: Conditional Graph Fusion for Drug Synergy Prediction
University of Toronto（多伦多大学）；Vector Institute for Artificial Intelligence（向量人工智能研究所）；The Hospital for Sick Children（病童医院）；University Health Network（大学健康网络）；Peter Munk Cardiac Centre, University Health Network（彼得·蒙克心脏中心，大学健康网络）
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…
VQSynery: Robust Drug Synergy Prediction With Vector Quantization Mechanism
School of Data Science and Engineering（数据科学与工程学院）；East China Normal University（华东师范大学）；School of Medicine（医学院）；College of Design&Engineering（设计与工程学院）；National University of Singapore（新加坡国立大学）
Drug combinations play an important role in therapeutics due to its better efficacy and reduced toxicity. Recent approaches have applied machine learning to identify synergistic combinations for cancer, but they are not applicable to new diseases with limited combination data. Given that drug synergy is closely tied to biological targets, we propose a \emph{biological bottleneck} model that jointly learns drug-target interaction and synergy. The model consists of two parts: a drug-target interaction and target-disease association module. This design enables the model to \emph{explain} how a bi…
TOBB University of Economics and Technology（TOBB经济与技术大学）
One of the promising methods for the treatment of complex diseases such as cancer is combinational therapy. Due to the combinatorial complexity, machine learning models can be useful in this field, where significant improvements have recently been achieved in determination of synergistic combinations. In this study, we investigate the effectiveness of different compound representations in predicting the drug synergy. On a large drug combination screen dataset, we first demonstrate the use of a promising representation that has not been used for this problem before, then we propose an ensemble …
SynerGPT: In-Context Learning for Personalized Drug Synergy Prediction and Drug Design
University of Illinois Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校）；Allen Institute for Artificial Intelligence（艾伦人工智能研究所）；The Hebrew University of Jerusalem（耶路撒冷希伯来大学）
We propose the molecular omics network (MOOMIN) a multimodal graph neural network used by AstraZeneca oncologists to predict the synergy of drug combinations for cancer treatment. Our model learns drug representations at multiple scales based on a drug-protein interaction network and metadata. Structural properties of compounds and proteins are encoded to create vertex features for a message-passing scheme that operates on the bipartite interaction graph. Propagated messages form multi-resolution drug representations which we utilized to create drug pair descriptors. By conditioning the drug c…
CancerGPT: Few-shot Drug Pair Synergy Prediction using Large Pre-trained Language Models
University of Texas at Austin（德克萨斯大学奥斯汀分校）；University of Massachusetts Amherst（马萨诸塞大学阿默斯特分校）；University of Texas Health Science Center at Houston（德克萨斯大学休斯顿健康科学中心）
MD-Syn: Synergistic drug combination prediction based on the multidimensional feature fusion method and attention mechanisms
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）
Washington University School of Medicine, Washington University in St. Louis（圣路易斯华盛顿大学医学院）；Dalian University of Technology（大连理工大学）
Drug resistance is still a major challenge in cancer therapy. Drug combination is expected to overcome drug resistance. However, the number of possible drug combinations is enormous, and thus it is infeasible to experimentally screen all effective drug combinations considering the limited resources. Therefore, computational models to predict and prioritize effective drug combinations is important for combinatory therapy discovery in cancer. In this study, we proposed a novel deep learning model, AuDNNsynergy, to prediction drug combinations by integrating multi-omics data and chemical structur…
University of Southern California, Information Sciences Institute（南加州大学信息科学研究所）；Yerevan State University（埃里温国立大学）
Scientists often seek simplified representations of complex systems to facilitate prediction and understanding. If the factors comprising a representation allow us to make accurate predictions about our system, but obscuring any subset of the factors destroys our ability to make predictions, we say that the representation exhibits informational synergy. We argue that synergy is an undesirable feature in learned representations and that explicitly minimizing synergy can help disentangle the true factors of variation underlying data. We explore different ways of quantifying synergy, deriving new…
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）
Background. The Drug Discovery Unit (DDU) of Cancer Research UK (CRUK) is using the software Dotmatics for storage and analysis of scientific data during drug discovery process. Whilst the data include event logs, time stamps, activities, and user information are mostly sitting in the database without fully utilising their potential value. Aims. This dissertation aims at extracting knowledge from event logs data which recorded during drug discovery process, to capture the operational business process of the DDU of Cancer Research UK (CRUK) as it was being executed. It provides the evaluations …
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）
University of Florence（佛罗伦萨大学）；University of Siena（锡耶纳大学）；University of Cambridge（剑桥大学）
Drug Side-Effects (DSEs) have a high impact on public health, care system costs, and drug discovery processes. Predicting the probability of side-effects, before their occurrence, is fundamental to reduce this impact, in particular on drug discovery. Candidate molecules could be screened before undergoing clinical trials, reducing the costs in time, money, and health of the participants. Drug side-effects are triggered by complex biological processes involving many different entities, from drug structures to protein-protein interactions. To predict their occurrence, it is necessary to integrat…
University of Cambridge（剑桥大学）；Google Research（谷歌研究院）
Capturing the microscopic interactions that determine molecular reactivity poses a challenge across the physical sciences. Even a basic understanding of the underlying reaction mechanisms can substantially accelerate materials and compound design, including the development of new catalysts or drugs. Given the difficulties routinely faced by both experimental and theoretical investigations that aim to improve our mechanistic understanding of a reaction, recent advances have focused on data-driven routes to derive structure-property relationships directly from high-throughput screens. However, e…
Nanjing University（南京大学）；The University of Iowa（爱荷华大学）
Wind farm needs prediction models for predictive maintenance. There is a need to predict values of non-observable parameters beyond ranges reflected in available data. A prediction model developed for one machine many not perform well in another similar machine. This is usually due to lack of generalizability of data-driven models. To increase generalizability of predictive models, this research integrates the data mining with first-principle knowledge. Physics-based principles are combined with machine learning algorithms through feature engineering, strong rules and divide-and-conquer. The p…
Classification is one of the most popular and widely used supervised learning tasks, which categorizes objects into predefined classes based on known knowledge. Classification has been an important research topic in machine learning and data mining. Different classification methods have been proposed and applied to deal with various real-world problems. Unlike unsupervised learning such as clustering, a classifier is typically trained with labeled data before being used to make prediction, and usually achieves higher accuracy than unsupervised one. In this paper, we first define classification…
Virus infection is one of the major diseases that seriously threaten human health. To meet the growing demand for mining and sharing data resources related to antiviral drugs and to accelerate the design and discovery of new antiviral drugs, we presented an open-access antiviral drug resource and machine learning platform (VDDB), which, to the best of our knowledge, is the first comprehensive dedicated resource for experimentally verified potential drugs/molecules based on manually curated data. Currently, VDDB highlights 848 clinical vaccines, 199 clinical antibodies, as well as over 710,000 …
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…
European Molecular Biology Laboratory（欧洲分子生物学实验室）；European Bioinformatics Institute（欧洲生物信息研究所）；University of Cambridge（剑桥大学）
Estimating the reliability of individual predictions is key to increase the adoption of computational models and artificial intelligence in preclinical drug discovery, as well as to foster its application to guide decision making in clinical settings. Among the large number of algorithms developed over the last decades to compute prediction errors, Conformal Prediction (CP) has gained increasing attention in the computational drug discovery community. A major reason for its recent popularity is the ease of interpretation of the computed prediction errors in both classification and regression t…
Harvard T. H. Chan School of Public Health, Harvard University（哈佛大学陈曾熙公共卫生学院）；IQVIA（艾昆纬）；MIT-IBM Watson AI Lab, IBM Research（IBM研究院麻省理工学院-IBM沃森人工智能实验室）；Georgia Institute of Technology（佐治亚理工学院）
Adverse drug-drug interactions (DDIs) remain a leading cause of morbidity and mortality. Identifying potential DDIs during the drug design process is critical for patients and society. Although several computational models have been proposed for DDI prediction, there are still limitations: (1) specialized design of drug representation for DDI predictions is lacking; (2) predictions are based on limited labelled data and do not generalize well to unseen drugs or DDIs; and (3) models are characterized by a large number of parameters, thus are hard to interpret. In this work, we develop a ChemicA…
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）
University of Nottingham（诺丁汉大学）；Nottingham City Hospital（诺丁汉城市医院）
Longitudinal observational databases have become a recent interest in the post marketing drug surveillance community due to their ability of presenting a new perspective for detecting negative side effects. Algorithms mining longitudinal observation databases are not restricted by many of the limitations associated with the more conventional methods that have been developed for spontaneous reporting system databases. In this paper we investigate the robustness of four recently developed algorithms that mine longitudinal observational databases by applying them to The Health Improvement Network…
Predicting how a drug-like molecule binds to a specific protein target is a core problem in drug discovery. An extremely fast computational binding method would enable key applications such as fast virtual screening or drug engineering. Existing methods are computationally expensive as they rely on heavy candidate sampling coupled with scoring, ranking, and fine-tuning steps. We challenge this paradigm with EquiBind, an SE(3)-equivariant geometric deep learning model performing direct-shot prediction of both i) the receptor binding location (blind docking) and ii) the ligand's bound pose and o…
Universitas Indonesia（印度尼西亚大学）；Universitas Mercu Buana（默库布阿纳大学）
One essential task in information extraction from the medical corpus is drug name recognition. Compared with text sources come from other domains, the medical text is special and has unique characteristics. In addition, the medical text mining poses more challenges, e.g., more unstructured text, the fast growing of new terms addition, a wide range of name variation for the same drug. The mining is even more challenging due to the lack of labeled dataset sources and external knowledge, as well as multiple token representations for a single drug name that is more common in the real application s…
CoFEND: A Cross-Modal Fusion End-to-End Network for Cold-Start Drug-Drug Interaction Prediction
College of Computer and Information Science, Southwest University（西南大学计算机与信息科学学院）；Beihang University（北京航空航天大学）；School of Computing, Southern Illinois University Carbondale（南伊利诺伊大学卡本代尔分校计算机学院）；School of Physics and Electronic Science, Zunyi Normal University（遵义师范学院物理与电子科学学院）
DATA Consortium（DATA联盟）；Kansas State University Olathe（堪萨斯州立大学奥拉西校区）；Kansas State University（堪萨斯州立大学）；University of Colombo（科伦坡大学）；University of California, Davis（加利福尼亚大学戴维斯分校）；National University of La Plata（拉普拉塔国立大学）；King Faisal University（费萨尔国王大学）
Extra-label drug use in food animal medicine is authorized by the US Animal Medicinal Drug Use Clarification Act (AMDUCA), and estimated withdrawal intervals are based on published scientific pharmacokinetic data. Occasionally there is a paucity of scientific data on which to base a withdrawal interval or a large number of animals being treated, driving the need to test for drug residues. Rapid assay commercial farm-side tests are essential for monitoring drug residues in animal products to protect human health. Active ingredients, sensitivity, matrices, and species that have been evaluated fo…
Siemens AG（西门子股份公司）；Technical University of Munich（慕尼黑工业大学）
Focusing on comprehensive networking, big data, and artificial intelligence, the Industrial Internet-of-Things (IIoT) facilitates efficiency and robustness in factory operations. Various sensors and field devices play a central role, as they generate a vast amount of real-time data that can provide insights into manufacturing. The synergy of complex event processing (CEP) and machine learning (ML) has been developed actively in the last years in IIoT to identify patterns in heterogeneous data streams and fuse raw data into tangible facts. In a traditional compute-centric paradigm, the raw fiel…
Side effects of prescribed medications are a common occurrence. Electronic healthcare databases present the opportunity to identify new side effects efficiently but currently the methods are limited due to confounding (i.e. when an association between two variables is identified due to them both being associated to a third variable). In this paper we propose a proof of concept method that learns common associations and uses this knowledge to automatically refine side effect signals (i.e. exposure-outcome associations) by removing instances of the exposure-outcome associations that are caused b…
The collection and examination of social media has become a useful mechanism for studying the mental activity and behavior tendencies of users. Through the analysis of collected Twitter data, models were developed for classifying drug-related tweets. Using topic pertaining keywords, such as slang and methods of drug consumption, a set of tweets was generated. Potential candidates were then preprocessed resulting in a dataset of 3,696,150 rows. The classification power of multiple methods was compared including support vector machines (SVM), XGBoost, and convolutional neural network (CNN) based…
