Multiple Similarity Drug-Target Interaction Prediction with Random Walks and Matrix Factorization
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）
Bin Liu, Dimitrios Papadopoulos, Fragkiskos D. Malliaros, Grigorios Tsoumakas, Apostolos N. Papadopoulos
发表信息：
Briefings in Bioinformatics, Volume 23, Issue 5, 2022
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 combination in matrix factorization distorts individual insights offered by different views. To tackle these issues, we take a multi-layered network approach to handle diverse drug and target similarities, and propose a novel optimization framework, called Multiple similarity DeepWalk-based Matrix Factorization (MDMF), for DTI prediction. The framework unifies embedding generation and interaction prediction, learning vector representations of drugs and targets that not only retain higher-order proximity across all hyper-layers and layer-specific local invariance, but also approximate the interactions with their inner product. Furthermore, we develop an ensemble method (MDMF2A) that integrates two instantiations of the MDMF model, optimizing the area under the precision-recall curve (AUPR) and the area under the receiver operating characteristic curve (AUC) respectively. The empirical study on real-world DTI datasets shows that our method achieves statistically significant improvement over current state-of-the-art approaches in four different settings. Moreover, the validation of highly ranked non-interacting pairs also demonstrates the potential of MDMF2A to discover novel DTIs.
Inria Saclay（法国国家信息与自动化研究所萨克莱分所）；Univ. Paris Saclay（巴黎萨克雷大学）；IIIT - Delhi（德里英迪拉·甘地信息技术学院）
Co-administration of two or more drugs simultaneously can result in adverse drug reactions. Identifying drug-drug interactions (DDIs) is necessary, especially for drug development and for repurposing old drugs. DDI prediction can be viewed as a matrix completion task, for which matrix factorization (MF) appears as a suitable solution. This paper presents a novel Graph Regularized Probabilistic Matrix Factorization (GRPMF) method, which incorporates expert knowledge through a novel graph-based regularization strategy within an MF framework. An efficient and sounded optimization algorithm is pro…
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…
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…
Helsinki Institute for Information Technology HIIT（赫尔辛基信息技术研究所）；Aalto University（阿尔托大学）；Institute for Molecular Medicine Finland FIMM（芬兰分子医学研究所）；University of Helsinki（赫尔辛基大学）；Science for Life Laboratory（生命科学实验室）；Karolinska Institutet（卡罗林斯卡学院）；University of Turku（图尔库大学）
A key goal of computational personalized medicine is to systematically utilize genomic and other molecular features of samples to predict drug responses for a previously unseen sample. Such predictions are valuable for developing hypotheses for selecting therapies tailored for individual patients. This is especially valuable in oncology, where molecular and genetic heterogeneity of the cells has a major impact on the response. However, the prediction task is extremely challenging, raising the need for methods that can effectively model and predict drug responses. In this study, we propose a no…
Predicting the novel effects of drugs based on information about approved drugs can be regarded as a recommendation system. Matrix factorization is one of the most used recommendation systems and various algorithms have been devised for it. A literature survey and summary of existing algorithms for predicting drug effects demonstrated that most such methods, including neighborhood regularized logistic matrix factorization, which was the best performer in benchmark tests, used a binary matrix that considers only the presence or absence of interactions. However, drug effects are known to have tw…
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…
Global Blood Therapeutics（Global Blood Therapeutics（全球血液治疗公司））
The approval success rate of drug candidates is very low with the majority of failure due to safety and efficacy. Increasingly available high dimensional information on targets, drug molecules and indications provides an opportunity for ML methods to integrate multiple data modalities and better predict clinically promising drug targets. Notably, drug targets with human genetics evidence are shown to have better odds to succeed. However, a recent tensor factorization-based approach found that additional information on targets and indications might not necessarily improve the predictive accurac…
Tigerlily is a TigerGraph based system designed to solve the drug interaction prediction task. In this machine learning task, we want to predict whether two drugs have an adverse interaction. Our framework allows us to solve this highly relevant real-world problem using graph mining techniques in these steps: (a) Using PyTigergraph we create a heterogeneous biological graph of drugs and proteins. (b) We calculate the personalized PageRank scores of drug nodes in the TigerGraph Cloud. (c) We embed the nodes using sparse non-negative matrix factorization of the personalized PageRank matrix. (d) …
University of Virginia（弗吉尼亚大学）；McGill University（麦吉尔大学）
Predicting the response of cancer cells to drugs is an important problem in pharmacogenomics. Recent efforts in generation of large scale datasets profiling gene expression and drug sensitivity in cell lines have provided a unique opportunity to study this problem. However, one major challenge is the small number of samples (cell lines) compared to the number of features (genes) even in these large datasets. We propose a collaborative filtering (CF) like algorithm for modeling gene-drug relationship to identify patients most likely to benefit from a treatment. Due to the correlation of gene ex…
IIIT - Delhi（德里印度理工学院）；Inria Saclay（法国国家信息与自动化研究所萨克雷分部）；Univ. Paris Saclay（巴黎萨克雷大学）
This work formulates antiviral repositioning as a matrix completion problem where the antiviral drugs are along the rows and the viruses along the columns. The input matrix is partially filled, with ones in positions where the antiviral has been known to be effective against a virus. The curated metadata for antivirals (chemical structure and pathways) and viruses (genomic structure and symptoms) is encoded into our matrix completion framework as graph Laplacian regularization. We then frame the resulting multiple graph regularized matrix completion problem as deep matrix factorization. This i…
Indiana University - Purdue University Indianapolis（印第安纳大学-普渡大学印第安纳波利斯分校）
Opioid overdose rates have increased in the United States over the past decade and reflect a major public health crisis. Modeling and prediction of drug and opioid hotspots, where a high percentage of events fall in a small percentage of space-time, could help better focus limited social and health services. In this work we present a spatial-temporal point process model for drug overdose clustering. The data input into the model comes from two heterogeneous sources: 1) high volume emergency medical calls for service (EMS) records containing location and time, but no information on the type of …
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…
Memorial Sloan Kettering Cancer Center（纪念斯隆-凯特琳癌症中心）；Columbia University（哥伦比亚大学）
Exploratory cancer drug studies test multiple tumor cell lines against multiple candidate drugs. The goal in each paired (cell line, drug) experiment is to map out the dose-response curve of the cell line as the dose level of the drug increases. We propose Bayesian Tensor Filtering (BTF), a hierarchical Bayesian model for dose-response modeling in multi-sample, multi-treatment cancer drug studies. BTF uses low-dimensional embeddings to share statistical strength between similar drugs and similar cell lines. Structured shrinkage priors in BTF encourage smoothness in the dose-response curves whi…
We introduce a probabilistic model with implicit norm regularization for learning nonnegative matrix factorization (NMF) that is commonly used for predicting missing values and finding hidden patterns in the data, in which the matrix factors are latent variables associated with each data dimension. The nonnegativity constraint for the latent factors is handled by choosing priors with support on the nonnegative subspace, e.g., exponential density or distribution based on exponential function. Bayesian inference procedure based on Gibbs sampling is employed. We evaluate the model on several real…
The vast majority of current machine learning algorithms are designed to predict single responses or a vector of responses, yet many types of response are more naturally organized as matrices or higher-order tensor objects where characteristics are shared across modes. We present a new machine learning algorithm BaTFLED (Bayesian Tensor Factorization Linked to External Data) that predicts values in a three-dimensional response tensor using input features for each of the dimensions. BaTFLED uses a probabilistic Bayesian framework to learn projection matrices mapping input features for each mode…
Word2vec, as an efficient tool for learning vector representation of words has shown its effectiveness in many natural language processing tasks. Mikolov et al. issued Skip-Gram and Negative Sampling model for developing this toolbox. Perozzi et al. introduced the Skip-Gram model into the study of social network for the first time, and designed an algorithm named DeepWalk for learning node embedding on a graph. We prove that the DeepWalk algorithm is actually factoring a matrix M where each entry M_{ij} is logarithm of the average probability that node i randomly walks to node j in fix steps.
Joint NTU-UBC Research Centre of Excellence in Active Living for the Elderly (LILY)（南洋理工大学-不列颠哥伦比亚大学活跃老年生活卓越联合研究中心（LILY））；Alibaba-NTU Singapore Joint Research Institute（阿里巴巴-南洋理工大学新加坡联合研究院）；Nanyang Technological University（南洋理工大学）；ShanghaiTech University（上海科技大学）；A*Star（新加坡科技研究局）；Singapore Management University（新加坡管理大学）
Synthetic lethality (SL) is a promising concept for novel discovery of anti-cancer drug targets. However, wet-lab experiments for detecting SLs are faced with various challenges, such as high cost, low consistency across platforms or cell lines. Therefore, computational prediction methods are needed to address these issues. This paper proposes a novel SL prediction method, named SL2MF, which employs logistic matrix factorization to learn latent representations of genes from the observed SL data. The probability that two genes are likely to form SL is modeled by the linear combination of gene l…
Motivation: Combination therapies have been widely used to treat cancers. However, it is cost- and time-consuming to experimentally screen synergistic drug pairs due to the enormous number of possible drug combinations. Thus, computational methods have become an important way to predict and prioritize synergistic drug pairs. Results: We proposed a Deep Tensor Factorization (DTF) model, which integrated a tensor factorization method and a deep neural network (DNN), to predict drug synergy. The former extracts latent features from drug synergy information while the latter constructs a binary cla…
University of Washington（华盛顿大学）；Carnegie Mellon University（卡内基梅隆大学）
Relational learning can be used to augment one data source with other correlated sources of information, to improve predictive accuracy. We frame a large class of relational learning problems as matrix factorization problems, and propose a hierarchical Bayesian model. Training our Bayesian model using random-walk Metropolis-Hastings is impractically slow, and so we develop a block Metropolis-Hastings sampler which uses the gradient and Hessian of the likelihood to dynamically tune the proposal. We demonstrate that a predictive model of brain response to stimuli can be improved by augmenting it…
CentraleSupélec（中央理工-高等电力学院）；Inria Saclay（法国国家信息与自动化研究所萨克雷中心）；University of Paris-Saclay（巴黎-萨克雷大学）
Learning representations of nodes in a low dimensional space is a crucial task with many interesting applications in network analysis, including link prediction and node classification. Two popular approaches for this problem include matrix factorization and random walk-based models. In this paper, we aim to bring together the best of both worlds, towards learning latent node representations. In particular, we propose a weighted matrix factorization model which encodes random walk-based information about the nodes of the graph. The main benefit of this formulation is that it allows to utilize …
Institute of Artificial Intelligence, Medical University of Vienna（维也纳医科大学人工智能研究所）
Learning good quality neural graph embeddings has long been achieved by minimizing the point-wise mutual information (PMI) for co-occurring nodes in simulated random walks. This design choice has been mostly popularized by the direct application of the highly-successful word embedding algorithm word2vec to predicting the formation of new links in social, co-citation, and biological networks. However, such a skeuomorphic design of graph embedding methods entails a truncation of information coming from pairs of nodes with low PMI. To circumvent this issue, we propose an improved approach to lear…
Pacific Northwest National Laboratory（西北太平洋国家实验室）；Stanford University（斯坦福大学）；University of Massachusetts Amherst（马萨诸塞大学阿默斯特分校）
Representation learning methods that transform encoded data (e.g., diagnosis and drug codes) into continuous vector spaces (i.e., vector embeddings) are critical for the application of deep learning in healthcare. Initial work in this area explored the use of variants of the word2vec algorithm to learn embeddings for medical concepts from electronic health records or medical claims datasets. We propose learning embeddings for medical concepts by using graph-based representation learning methods on SNOMED-CT, a widely popular knowledge graph in the healthcare domain with numerous operational an…
University of Science and Technology of China（中国科学技术大学）
Recent advances in the field of network embedding have shown the low-dimensional network representation is playing a critical role in network analysis. However, most of the existing principles of network embedding do not incorporate auxiliary information such as content and labels of nodes flexibly. In this paper, we take a matrix factorization perspective of network embedding, and incorporate structure, content and label information of the network simultaneously. For structure, we validate that the matrix we construct preserves high-order proximities of the network. Label information can be f…
Since the invention of word2vec, the skip-gram model has significantly advanced the research of network embedding, such as the recent emergence of the DeepWalk, LINE, PTE, and node2vec approaches. In this work, we show that all of the aforementioned models with negative sampling can be unified into the matrix factorization framework with closed forms. Our analysis and proofs reveal that: (1) DeepWalk empirically produces a low-rank transformation of a network's normalized Laplacian matrix; (2) LINE, in theory, is a special case of DeepWalk when the size of vertices' context is set to one; (3) …
Technical University of Denmark（丹麦技术大学）；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）；University of California, Irvine（加州大学欧文分校）
Learning representations of nodes in a low dimensional space is a crucial task with numerous interesting applications in network analysis, including link prediction, node classification, and visualization. Two popular approaches for this problem are matrix factorization and random walk-based models. In this paper, we aim to bring together the best of both worlds, towards learning node representations. In particular, we propose a weighted matrix factorization model that encodes random walk-based information about nodes of the network. The benefit of this novel formulation is that it enables us …
AI Department, Ant Financial Services Group（蚂蚁金融服务集团人工智能部门）
Points of interest (POI) recommendation has been drawn much attention recently due to the increasing popularity of location-based networks, e.g., Foursquare and Yelp. Among the existing approaches to POI recommendation, Matrix Factorization (MF) based techniques have proven to be effective. However, existing MF approaches suffer from two major problems: (1) Expensive computations and storages due to the centralized model training mechanism: the centralized learners have to maintain the whole user-item rating matrix, and potentially huge low rank matrices. (2) Privacy issues: the users' prefere…
Random-walk based network embedding algorithms like DeepWalk and node2vec are widely used to obtain Euclidean representation of the nodes in a network prior to performing downstream inference tasks. However, despite their impressive empirical performance, there is a lack of theoretical results explaining their large-sample behavior. In this paper, we study node2vec and DeepWalk through the perspective of matrix factorization. In particular, we analyze these algorithms in the setting of community detection for stochastic blockmodel graphs (and their degree-corrected variants). By exploiting the…
Massachusetts Institute of Technology（麻省理工学院）；University of Illinois at Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校）；Georgia Institute of Technology（佐治亚理工学院）
Structure-based drug design (SBDD) aims to discover drug candidates by finding molecules (ligands) that bind tightly to a disease-related protein (targets), which is the primary approach to computer-aided drug discovery. Recently, applying deep generative models for three-dimensional (3D) molecular design conditioned on protein pockets to solve SBDD has attracted much attention, but their formulation as probabilistic modeling often leads to unsatisfactory optimization performance. On the other hand, traditional combinatorial optimization methods such as genetic algorithms (GA) have demonstrate…
National Laboratory for Scientific Computing (LNCC)（国家科学计算实验室）；Federal University of Juiz de Fora (UFJF)（茹伊斯迪福拉联邦大学）
Embedding static graphs in low-dimensional vector spaces plays a key role in network analytics and inference, supporting applications like node classification, link prediction, and graph visualization. However, many real-world networks present dynamic behavior, including topological evolution, feature evolution, and diffusion. Therefore, several methods for embedding dynamic graphs have been proposed to learn network representations over time, facing novel challenges, such as time-domain modeling, temporal features to be captured, and the temporal granularity to be embedded. In this survey, we…
The University of Texas at Austin（得克萨斯大学奥斯汀分校）；Amazon（亚马逊）；Technicolor Research Bay Area（特艺集团湾区研究院）
Predicting unobserved entries of a partially observed matrix has found wide applicability in several areas, such as recommender systems, computational biology, and computer vision. Many scalable methods with rigorous theoretical guarantees have been developed for algorithms where the matrix is factored into low-rank components, and embeddings are learned for the row and column entities. While there has been recent research on incorporating explicit side information in the low-rank matrix factorization setting, often implicit information can be gleaned from the data, via higher-order interactio…
