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 on representation-model combinations that outperform each of the baseline models.
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）
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…
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）
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…
IBM Research – Zurich（IBM苏黎世研究院）；Institute für Molekulare Systembiologie（分子系统生物学研究所）
We present the Network-based Biased Tree Ensembles (NetBiTE) method for drug sensitivity prediction and drug sensitivity biomarker identification in cancer using a combination of prior knowledge and gene expression data. Our devised method consists of a biased tree ensemble that is built according to a probabilistic bias weight distribution. The bias weight distribution is obtained from the assignment of high weights to the drug targets and propagating the assigned weights over a protein-protein interaction network such as STRING. The propagation of weights, defines neighborhoods of influence …
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）
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…
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…
Texas Tech University（德克萨斯理工大学）；University of Nebraska-Lincoln（内布拉斯加大学林肯分校）
Anti-cancer drug sensitivity prediction using deep learning models for individual cell line is a significant challenge in personalized medicine. REFINED (REpresentation of Features as Images with NEighborhood Dependencies) CNN (Convolutional Neural Network) based models have shown promising results in drug sensitivity prediction. The primary idea behind REFINED CNN is representing high dimensional vectors as compact images with spatial correlations that can benefit from convolutional neural network architectures. However, the mapping from a vector to a compact 2D image is not unique due to var…
Drug-target interaction (DTI) prediction plays a crucial role in drug discovery, and deep learning approaches have achieved state-of-the-art performance in this field. We introduce an ensemble of deep learning models (EnsembleDLM) for DTI prediction. EnsembleDLM only uses the sequence information of chemical compounds and proteins, and it aggregates the predictions from multiple deep neural networks. This approach not only achieves state-of-the-art performance in Davis and KIBA datasets but also reaches cutting-edge performance in the cross-domain applications across different bio-activity typ…
KU Leuven（鲁汶大学）；imec（比利时微电子研究中心）；Aristotle University of Thessaloniki（塞萨洛尼基亚里士多德大学）
Predicting drug-target interactions (DTI) via reliable computational methods is an effective and efficient way to mitigate the enormous costs and time of the drug discovery process. Structure-based drug similarities and sequence-based target protein similarities are the commonly used information for DTI prediction. Among numerous computational methods, neighborhood-based chemogenomic approaches that leverage drug and target similarities to perform predictions directly are simple but promising ones. However, existing similarity-based methods need to be re-trained to predict interactions for any…
TOBB University of Economics and Technology（TOBB经济与技术大学）；Hacettepe University（哈塞特佩大学）
Chemotherapeutic response of cancer cells to a given compound is one of the most fundamental information one requires to design anti-cancer drugs. Recent advances in producing large drug screens against cancer cell lines provided an opportunity to apply machine learning methods for this purpose. In addition to cytotoxicity databases, considerable amount of drug-induced gene expression data has also become publicly available. Following this, several methods that exploit omics data were proposed to predict drug activity on cancer cells. However, due to the complexity of cancer drug mechanisms, n…
In this paper we study the practicality and usefulness of incorporating distributed representations of graphs into models within the context of drug pair scoring. We argue that the real world growth and update cycles of drug pair scoring datasets subvert the limitations of transductive learning associated with distributed representations. Furthermore, we argue that the vocabulary of discrete substructure patterns induced over drug sets is not dramatically large due to the limited set of atom types and constraints on bonding patterns enforced by chemistry. Under this pretext, we explore the eff…
Cornell University（康奈尔大学）；Weill Institute for Cell and Molecular Biology（威尔细胞与分子生物学研究所）
In this study, we intend to solve a mutual information problem in interacting molecules of any type, such as proteins, nucleic acids, and small molecules. Using machine learning techniques, we accurately predict pairwise interactions, which can be of medical and biological importance. Graphs are are useful in this problem for their generality to all types of molecules, due to the inherent association of atoms through atomic bonds. Subgraphs can represent different molecular domains. These domains can be biologically significant as most molecules only have portions that are of functional signif…
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,…
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…
In silico prediction of cardiotoxicity with high sensitivity and specificity for potential drug molecules can be of immense value. Hence, building machine learning classification models, based on some features extracted from the molecular structure of drugs, which are capable of efficiently predicting cardiotoxicity is critical. In this paper, we consider the application of various machine learning approaches, and then propose an ensemble classifier for the prediction of molecular activity on a Drug Discovery Hackathon (DDH) (1st reference) dataset. We have used only 2-D descriptors of SMILE n…
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…
Stanford University（斯坦福大学）；University College London（伦敦大学学院）
Drug-induced liver injury (DILI) describes the adverse effects of drugs that damage liver. Life-threatening results including liver failure or death were also reported in severe DILI cases. Therefore, DILI-related events are strictly monitored for all approved drugs and the liver toxicity became important assessments for new drug candidates. These DILI-related reports are documented in hospital records, in clinical trial results, and also in research papers that contain preliminary in vitro and in vivo experiments. Conventionally, data extraction from previous publications relies heavily on re…
Predicting gene essentiality and drug response from perturbation screens in preclinical cancer models with LEAP: Layered Ensemble of Autoencoders and Predictors
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）
Mila, the Quebec AI Institute（米拉魁北克人工智能研究所）；Relation Therapeutics（Relation Therapeutics公司）；The Scripps Research Institute（斯克里普斯研究所）；Glyde Bio, Inc（Glyde生物公司）；IRIC, Institute for Research in Immunology and Cancer, Université de Montréal（蒙特利尔大学免疫学与癌症研究所（IRIC））；University of Oxford（牛津大学）；Twitter（推特）
For large libraries of small molecules, exhaustive combinatorial chemical screens become infeasible to perform when considering a range of disease models, assay conditions, and dose ranges. Deep learning models have achieved state of the art results in silico for the prediction of synergy scores. However, databases of drug combinations are biased towards synergistic agents and these results do not necessarily generalise out of distribution. We employ a sequential model optimization search utilising a deep learning model to quickly discover synergistic drug combinations active against a cancer …
University of Geneva（日内瓦大学）；BIGCHEM GmbH（BIGCHEM有限公司）；Helmholtz Zentrum Muenchen - German Research Center for Environmental Health (GmbH)（亥姆霍兹慕尼黑中心——德国环境健康研究中心（有限公司））；Firmenich SA（芬美意公司）
In our study, we demonstrate the synergy effect between convolutional neural networks and the multiplicity of SMILES. The model we propose, the so-called Convolutional Neural Fingerprint (CNF) model, reaches the accuracy of traditional descriptors such as Dragon (Mauri et al. [22]), RDKit (Landrum [18]), CDK2 (Willighagen et al. [43]) and PyDescriptor (Masand and Rastija [20]). Moreover the CNF model generally performs better than highly fine-tuned traditional descriptors, especially on small data sets, which is of great interest for the chemical field where data sets are generally small due t…
Currently, approximately 30% of epileptic patients treated with antiepileptic drugs (AEDs) remain resistant to treatment (known as refractory patients). This project seeks to understand the underlying similarities in refractory patients vs. other epileptic patients, identify features contributing to drug resistance across underlying phenotypes for refractory patients, and develop predictive models for drug resistance in epileptic patients. In this study, epileptic patient data was examined to attempt to observe discernable similarities or differences in refractory patients (case) and other non…
School of Informatics, Aristotle University of Thessaloniki（亚里士多德大学信息学院）
In drug discovery, identifying drug-target interactions (DTIs) via experimental approaches is a tedious and expensive procedure. Computational methods efficiently predict DTIs and recommend a small part of potential interacting pairs for further experimental confirmation, accelerating the drug discovery process. Although it has been shown that fusing heterogeneous drug and target similarities can improve the prediction ability, the existing similarity combination methods ignore the interaction consistency for neighbour entities which is more crucial for the DTI prediction model. Furthermore, a…
Scientific Hypothesis Generation by a Large Language Model: Laboratory Validation in Breast Cancer Treatment
University of Cambridge（剑桥大学）；The Alan Turing Institute（艾伦·图灵研究所）；The National Institute of Agricultural Botany（国家农业植物学研究所）；Arctoris Ltd（Arctoris有限公司）；Goldsmiths, University of London（伦敦大学金史密斯学院）；Chalmers University（查尔姆斯理工大学）
Chongqing University of Posts and Telecommunications（重庆邮电大学）；Aristotle University of Thessaloniki（塞萨洛尼基亚里士多德大学）；Paris-Saclay University（巴黎萨克雷大学）；CentraleSupélec（巴黎中央理工-高等电力学院）；Inria（法国国家信息与自动化研究所）
The discovery of drug-target interactions (DTIs) is a very promising area of research with great potential. The accurate identification of reliable interactions among drugs and proteins via computational methods, which typically leverage heterogeneous information retrieved from diverse data sources, can boost the development of effective pharmaceuticals. Although random walk and matrix factorization techniques are widely used in DTI prediction, they have several limitations. Random walk-based embedding generation is usually conducted in an unsupervised manner, while the linear similarity combi…
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…
New York University（纽约大学）；Colton Center for Autoimmunity（科尔顿自身免疫中心）；NYU Grossman School of Medicine（纽约大学格罗斯曼医学院）
Rheumatoid arthritis (RA) is an autoimmune condition caused when patients' immune system mistakenly targets their own tissue. Machine learning (ML) has the potential to identify patterns in patient electronic health records (EHR) to forecast the best clinical treatment to improve patient outcomes. This study introduced a Drug Response Prediction (DRP) framework with two main goals: 1) design a data processing pipeline to extract information from tabular clinical data, and then preprocess it for functional use, and 2) predict RA patient's responses to drugs and evaluate classification models' p…
Deep learning architectures have proved versatile in a number of drug discovery applications, including the modelling of in vitro compound activity. While controlling for prediction confidence is essential to increase the trust, interpretability and usefulness of virtual screening models in drug discovery, techniques to estimate the reliability of the predictions generated with deep learning networks remain largely underexplored. Here, we present Deep Confidence, a framework to compute valid and efficient confidence intervals for individual predictions using the deep learning technique Snapsho…
Harvard University（哈佛大学）；Massachusetts Institute of Technology（麻省理工学院）
Virtual screening can accelerate drug discovery by identifying promising candidates for experimental evaluation. Machine learning is a powerful method for screening, as it can learn complex structure-property relationships from experimental data and make rapid predictions over virtual libraries. Molecules inherently exist as a three-dimensional ensemble and their biological action typically occurs through supramolecular recognition. However, most deep learning approaches to molecular property prediction use a 2D graph representation as input, and in some cases a single 3D conformation. Here we…
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 …
Massive molecular simulations of drug-target proteins have been used as a tool to understand disease mechanism and develop therapeutics. This work focuses on learning a generative neural network on a structural ensemble of a drug-target protein, e.g. SARS-CoV-2 Spike protein, obtained from computationally expensive molecular simulations. Model tasks involve characterizing the distinct structural fluctuations of the protein bound to various drug molecules, as well as efficient generation of protein conformations that can serve as an complement of a molecular simulation engine. Specifically, we …
Advancing Tabular Stroke Modelling Through a Novel Hybrid Architecture and Feature-Selection Synergy
Department of Computer Science and Engineering, Leading University, Sylhet 3112, Bangladesh（计算机科学与工程系，领先大学，锡尔het 3112，孟加拉国）；DeepNet Research and Development Lab, Sylhet 3100, Bangladesh（深网研究与发展实验室，锡尔het 3100，孟加拉国）
Contrastive Multi-Task Learning with Solvent-Aware Augmentation 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）；School of Data Science, Lingnan University（数据科学学院，岭南大学）
From Static to Dynamic Structures: Improving Binding Affinity Prediction with Graph-Based Deep Learning
Institute for Interdisciplinary Information Sciences, Tsinghua University（清华大学交叉信息研究院）；School of Medicine, Tsinghua University（清华大学医学院）；KTH Stockholm（瑞典皇家理工学院）；Microsoft Research Asia（微软亚洲研究院）；School of Life Science and Technology, Xidian University（西安电子科技大学生命科学技术学院）；School of Engineering, Westlake University（西湖大学工程学院）
Measuring AI Progress in Drug Discovery: A Reproducible Leaderboard for the Tox21 Challenge
ELLIS Unit Linz and LIT AI Lab, Institute for Machine Learning（ELLIS单位林茨和LIT AI实验室，机器学习研究所）；Clinical Research Institute for Medical AI（医学人工智能临床研究 institutes）；Johannes Kepler University（约翰·开普勒大学）
Prediction of a molecule's 3D conformer ensemble from the molecular graph holds a key role in areas of cheminformatics and drug discovery. Existing generative models have several drawbacks including lack of modeling important molecular geometry elements (e.g. torsion angles), separate optimization stages prone to error accumulation, and the need for structure fine-tuning based on approximate classical force-fields or computationally expensive methods such as metadynamics with approximate quantum mechanics calculations at each geometry. We propose GeoMol--an end-to-end, non-autoregressive and S…
