scholarly journals A miRNA-Driven Inference Model to Construct Potential Drug-Disease Associations for Drug Repositioning

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Hailin Chen ◽  
Zuping Zhang
Keyword(s):  
Case Studies ◽  
Drug Repositioning ◽  
Disease Association ◽  
Potential Drug ◽  
Inference Model ◽  
Excellent Performance ◽  
Model Case ◽  
Disease Associations ◽  
New Perspective ◽  
Inappropriate Expression

Increasing evidence discovered that the inappropriate expression of microRNAs (miRNAs) will lead to many kinds of complex diseases and drugs can regulate the expression level of miRNAs. Therefore human diseases may be treated by targeting some specific miRNAs with drugs, which provides a new perspective for drug repositioning. However, few studies have attempted to computationally predict associations between drugs and diseases via miRNAs for drug repositioning. In this paper, we developed an inference model to achieve this aim by combining experimentally supported drug-miRNA associations and miRNA-disease associations with the assumption that drugs will form associations with diseases when they share some significant miRNA partners. Experimental results showed excellent performance of our model. Case studies demonstrated that some of the strongly predicted drug-disease associations can be confirmed by the publicly accessible database CTD (www.ctdbase.org), which indicated the usefulness of our inference model. Moreover, candidate miRNAs as molecular hypotheses underpinning the associations were listed to guide future experiments. The predicted results were released for further studies. We expect that this study will provide help in our understanding of drug-disease association prediction and in the roles of miRNAs in drug repositioning.

Computational drug repositioning based on multi-similarities bilinear matrix factorization

2020 ◽  
Author(s):  
Mengyun Yang ◽  
Gaoyan Wu ◽  
Qichang Zhao ◽  
Yaohang Li ◽  
Jianxin Wang
Keyword(s):  
Matrix Factorization ◽  
Drug Repositioning ◽  
Disease Association ◽  
Biological Entity ◽  
Biomedical Data ◽  
Supplementary Data ◽  
Practical Applications ◽  
Disease Associations ◽  
Association Matrix ◽  
Similarity Matrices

Abstract With the development of high-throughput technology and the accumulation of biomedical data, the prior information of biological entity can be calculated from different aspects. Specifically, drug–drug similarities can be measured from target profiles, drug–drug interaction and side effects. Similarly, different methods and data sources to calculate disease ontology can result in multiple measures of pairwise disease similarities. Therefore, in computational drug repositioning, developing a dynamic method to optimize the fusion process of multiple similarities is a crucial and challenging task. In this study, we propose a multi-similarities bilinear matrix factorization (MSBMF) method to predict promising drug-associated indications for existing and novel drugs. Instead of fusing multiple similarities into a single similarity matrix, we concatenate these similarity matrices of drug and disease, respectively. Applying matrix factorization methods, we decompose the drug–disease association matrix into a drug-feature matrix and a disease-feature matrix. At the same time, using these feature matrices as basis, we extract effective latent features representing the drug and disease similarity matrices to infer missing drug–disease associations. Moreover, these two factored matrices are constrained by non-negative factorization to ensure that the completed drug–disease association matrix is biologically interpretable. In addition, we numerically solve the MSBMF model by an efficient alternating direction method of multipliers algorithm. The computational experiment results show that MSBMF obtains higher prediction accuracy than the state-of-the-art drug repositioning methods in cross-validation experiments. Case studies also demonstrate the effectiveness of our proposed method in practical applications. Availability: The data and code of MSBMF are freely available at https://github.com/BioinformaticsCSU/MSBMF. Corresponding author: Jianxin Wang, School of Computer Science and Engineering, Central South University, Changsha, Hunan 410083, P. R. China. E-mail: [email protected] Supplementary Data: Supplementary data are available online at https://academic.oup.com/bib.

scholarly journals The Performance of Gene Expression Signature-Guided Drug–Disease Association in Different Categories of Drugs and Diseases

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2776
Author(s):  
Xiguang Qi ◽  
Mingzhe Shen ◽  
Peihao Fan ◽  
Xiaojiang Guo ◽  
Tianqi Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Drug Repositioning ◽  
Gene Expression Signature ◽  
Disease Association ◽  
Mtor Signaling Pathway ◽  
Immune System Diseases ◽  
Expression Signature ◽  
Chemotherapy Drugs ◽  
Disease Associations

A gene expression signature (GES) is a group of genes that shows a unique expression profile as a result of perturbations by drugs, genetic modification or diseases on the transcriptional machinery. The comparisons between GES profiles have been used to investigate the relationships between drugs, their targets and diseases with quite a few successful cases reported. Especially in the study of GES-guided drugs–disease associations, researchers believe that if a GES induced by a drug is opposite to a GES induced by a disease, the drug may have potential as a treatment of that disease. In this study, we data-mined the crowd extracted expression of differential signatures (CREEDS) database to evaluate the similarity between GES profiles from drugs and their indicated diseases. Our study aims to explore the application domains of GES-guided drug–disease associations through the analysis of the similarity of GES profiles on known pairs of drug–disease associations, thereby identifying subgroups of drugs/diseases that are suitable for GES-guided drug repositioning approaches. Our results supported our hypothesis that the GES-guided drug–disease association method is better suited for some subgroups or pathways such as drugs and diseases associated with the immune system, diseases of the nervous system, non-chemotherapy drugs or the mTOR signaling pathway.

scholarly journals Hybrid attentional memory network for computational drug repositioning

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jieyue He ◽  
Xinxing Yang ◽  
Zhuo Gong ◽  
lbrahim Zamit
Keyword(s):  
Drug Repositioning ◽  
Cold Start ◽  
New Drugs ◽  
Data Sets ◽  
Latent Factor ◽  
Disease Associations ◽  
Memory Network ◽  
Predicted Values ◽  
New Perspective ◽  
Cold Start Problem

Abstract Background Drug repositioning has been an important and efficient method for discovering new uses of known drugs. Researchers have been limited to one certain type of collaborative filtering (CF) models for drug repositioning, like the neighborhood based approaches which are good at mining the local information contained in few strong drug–disease associations, or the latent factor based models which are effectively capture the global information shared by a majority of drug–disease associations. Few researchers have combined these two types of CF models to derive a hybrid model which can offer the advantages of both. Besides, the cold start problem has always been a major challenge in the field of computational drug repositioning, which restricts the inference ability of relevant models. Results Inspired by the memory network, we propose the hybrid attentional memory network (HAMN) model, a deep architecture combining two classes of CF models in a nonlinear manner. First, the memory unit and the attention mechanism are combined to generate a neighborhood contribution representation to capture the local structure of few strong drug–disease associations. Then a variant version of the autoencoder is used to extract the latent factor of drugs and diseases to capture the overall information shared by a majority of drug–disease associations. During this process, ancillary information of drugs and diseases can help alleviate the cold start problem. Finally, in the prediction stage, the neighborhood contribution representation is coupled with the drug latent factor and disease latent factor to produce predicted values. Comprehensive experimental results on two data sets demonstrate that our proposed HAMN model outperforms other comparison models based on the AUC, AUPR and HR indicators. Conclusions Through the performance on two drug repositioning data sets, we believe that the HAMN model proposes a new solution to improve the prediction accuracy of drug–disease associations and give pharmaceutical personnel a new perspective to develop new drugs.

scholarly journals In silico drug repositioning using deep learning and comprehensive similarity measures

2021 ◽  
Vol 22 (S3) ◽  
Author(s):  
Hai-Cheng Yi ◽  
Zhu-Hong You ◽  
Lei Wang ◽  
Xiao-Rui Su ◽  
Xi Zhou ◽  
...  
Keyword(s):  
Drug Repositioning ◽  
Similarity Measures ◽  
Predictive Ability ◽  
New Drugs ◽  
Potential Drug ◽  
Proposed Model ◽  
Disease Associations ◽  
Benchmark Datasets ◽  
Gated Recurrent Units ◽  
New Treatments

Abstract Background Drug repositioning, meanings finding new uses for existing drugs, which can accelerate the processing of new drugs research and development. Various computational methods have been presented to predict novel drug–disease associations for drug repositioning based on similarity measures among drugs and diseases. However, there are some known associations between drugs and diseases that previous studies not utilized. Methods In this work, we develop a deep gated recurrent units model to predict potential drug–disease interactions using comprehensive similarity measures and Gaussian interaction profile kernel. More specifically, the similarity measure is used to exploit discriminative feature for drugs based on their chemical fingerprints. Meanwhile, the Gaussian interactions profile kernel is employed to obtain efficient feature of diseases based on known disease-disease associations. Then, a deep gated recurrent units model is developed to predict potential drug–disease interactions. Results The performance of the proposed model is evaluated on two benchmark datasets under tenfold cross-validation. And to further verify the predictive ability, case studies for predicting new potential indications of drugs were carried out. Conclusion The experimental results proved the proposed model is a useful tool for predicting new indications for drugs or new treatments for diseases, and can accelerate drug repositioning and related drug research and discovery.

scholarly journals Predicting Drug-Disease Association Based on Ensemble Strategy

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianlin Wang ◽  
Wenxiu Wang ◽  
Chaokun Yan ◽  
Junwei Luo ◽  
Ge Zhang
Keyword(s):  
Prediction Models ◽  
Drug Repositioning ◽  
Predictive Ability ◽  
Disease Association ◽  
New Drugs ◽  
Similarity Network ◽  
Disease Similarity ◽  
Ensemble Strategy ◽  
Disease Associations ◽  
Reducing Costs

Drug repositioning is used to find new uses for existing drugs, effectively shortening the drug research and development cycle and reducing costs and risks. A new model of drug repositioning based on ensemble learning is proposed. This work develops a novel computational drug repositioning approach called CMAF to discover potential drug-disease associations. First, for new drugs and diseases or unknown drug-disease pairs, based on their known neighbor information, an association probability can be obtained by implementing the weighted K nearest known neighbors (WKNKN) method and improving the drug-disease association information. Then, a new drug similarity network and new disease similarity network can be constructed. Three prediction models are applied and ensembled to enable the final association of drug-disease pairs based on improved drug-disease association information and the constructed similarity network. The experimental results demonstrate that the developed approach outperforms recent state-of-the-art prediction models. Case studies further confirm the predictive ability of the proposed method. Our proposed method can effectively improve the prediction results.

scholarly journals Predicting Drug-Disease Associations via Using Gaussian Interaction Profile and Kernel-Based Autoencoder

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Han-Jing Jiang ◽  
Yu-An Huang ◽  
Zhu-Hong You
Keyword(s):  
Case Studies ◽  
Computational Models ◽  
Cross Validation ◽  
Drug Repositioning ◽  
Feature Learning ◽  
Superior Performance ◽  
Reliable Model ◽  
Disease Associations ◽  
The Cost ◽  
Fold Cross Validation

Computational drug repositioning, designed to identify new indications for existing drugs, significantly reduced the cost and time involved in drug development. Prediction of drug-disease associations is promising for drug repositioning. Recent years have witnessed an increasing number of machine learning-based methods for calculating drug repositioning. In this paper, a novel feature learning method based on Gaussian interaction profile kernel and autoencoder (GIPAE) is proposed for drug-disease association. In order to further reduce the computation cost, both batch normalization layer and the full-connected layer are introduced to reduce training complexity. The experimental results of 10-fold cross validation indicate that the proposed method achieves superior performance on Fdataset and Cdataset with the AUCs of 93.30% and 96.03%, respectively, which were higher than many previous computational models. To further assess the accuracy of GIPAE, we conducted case studies on two complex human diseases. The top 20 drugs predicted, 14 obesity-related drugs, and 11 drugs related to Alzheimer's disease were validated in the CTD database. The results of cross validation and case studies indicated that GIPAE is a reliable model for predicting drug-disease associations.

DRIMC: an improved drug repositioning approach using Bayesian inductive matrix completion

2020 ◽  
Vol 36 (9) ◽  
pp. 2839-2847 ◽  
Author(s):  
Wenjuan Zhang ◽  
Hunan Xu ◽  
Xiaozhong Li ◽  
Qiang Gao ◽  
Lin Wang
Keyword(s):  
Drug Repositioning ◽  
Matrix Completion ◽  
Disease Association ◽  
Data Sources ◽  
Supplementary Information ◽  
Similarity Matrix ◽  
Latent Factors ◽  
Discovery Research ◽  
Disease Associations ◽  
Novel Drug

Abstract Motivation One of the most important problems in drug discovery research is to precisely predict a new indication for an existing drug, i.e. drug repositioning. Recent recommendation system-based methods have tackled this problem using matrix completion models. The models identify latent factors contributing to known drug-disease associations, and then infer novel drug-disease associations by the correlations between latent factors. However, these models have not fully considered the various drug data sources and the sparsity of the drug-disease association matrix. In addition, using the global structure of the drug-disease association data may introduce noise, and consequently limit the prediction power. Results In this work, we propose a novel drug repositioning approach by using Bayesian inductive matrix completion (DRIMC). First, we embed four drug data sources into a drug similarity matrix and two disease data sources in a disease similarity matrix. Then, for each drug or disease, its feature is described by similarity values between it and its nearest neighbors, and these features for drugs and diseases are mapped onto a shared latent space. We model the association probability for each drug-disease pair by inductive matrix completion, where the properties of drugs and diseases are represented by projections of drugs and diseases, respectively. As the known drug-disease associations have been manually verified, they are more trustworthy and important than the unknown pairs. We assign higher confidence levels to known association pairs compared with unknown pairs. We perform comprehensive experiments on three benchmark datasets, and DRIMC improves prediction accuracy compared with six stat-of-the-art approaches. Availability and implementation Source code and datasets are available at https://github.com/linwang1982/DRIMC. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Drug repositioning based on bounded nuclear norm regularization

2019 ◽  
Vol 35 (14) ◽  
pp. i455-i463 ◽  
Author(s):  
Mengyun Yang ◽  
Huimin Luo ◽  
Yaohang Li ◽  
Jianxin Wang
Keyword(s):  
Recommendation System ◽  
Drug Repositioning ◽  
Matrix Completion ◽  
Approximation Error ◽  
Disease Association ◽  
Nuclear Norm ◽  
Low Rank ◽  
Supplementary Information ◽  
Disease Associations ◽  
Nuclear Norm Regularization

Abstract Motivation Computational drug repositioning is a cost-effective strategy to identify novel indications for existing drugs. Drug repositioning is often modeled as a recommendation system problem. Taking advantage of the known drug–disease associations, the objective of the recommendation system is to identify new treatments by filling out the unknown entries in the drug–disease association matrix, which is known as matrix completion. Underpinned by the fact that common molecular pathways contribute to many different diseases, the recommendation system assumes that the underlying latent factors determining drug–disease associations are highly correlated. In other words, the drug–disease matrix to be completed is low-rank. Accordingly, matrix completion algorithms efficiently constructing low-rank drug–disease matrix approximations consistent with known associations can be of immense help in discovering the novel drug–disease associations. Results In this article, we propose to use a bounded nuclear norm regularization (BNNR) method to complete the drug–disease matrix under the low-rank assumption. Instead of strictly fitting the known elements, BNNR is designed to tolerate the noisy drug–drug and disease–disease similarities by incorporating a regularization term to balance the approximation error and the rank properties. Moreover, additional constraints are incorporated into BNNR to ensure that all predicted matrix entry values are within the specific interval. BNNR is carried out on an adjacency matrix of a heterogeneous drug–disease network, which integrates the drug–drug, drug–disease and disease–disease networks. It not only makes full use of available drugs, diseases and their association information, but also is capable of dealing with cold start naturally. Our computational results show that BNNR yields higher drug–disease association prediction accuracy than the current state-of-the-art methods. The most significant gain is in prediction precision measured as the fraction of the positive predictions that are truly positive, which is particularly useful in drug design practice. Cases studies also confirm the accuracy and reliability of BNNR. Availability and implementation The code of BNNR is freely available at https://github.com/BioinformaticsCSU/BNNR. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals A Drug Repositioning Algorithm Based on Deep Auto-Encoder and Adaptive Fusion

2020 ◽  
Author(s):  
Peng Chen ◽  
Tianjiazhi Bao ◽  
Xiaosheng Yu ◽  
Zhongtu Liu
Keyword(s):  
Drug Target ◽  
Chemical Structure ◽  
Drug Repositioning ◽  
Disease Association ◽  
Target Protein ◽  
New Drugs ◽  
Data Set ◽  
Fusion Methods ◽  
Disease Associations ◽  
Adaptive Fusion

Abstract Background: Drug repositioning has aroused extensive attention by scholars at home and abroad due to its effective reduction in development cost and time of new drugs. However, the current drug repositioning based on computational analysis methods is still limited by the problems of data sparse and fusion methods, so we use autoencoders and adaptive fusion methods to calculate drug repositioning.Results: In this paper, a drug repositioning algorithm based on deep auto-encoder and adaptive fusion has been proposed against the problems of declined precision and low-efficiency multi-source data fusion caused by data sparseness. Specifically, the drug is repositioned through fusing drug-disease association, drug target protein, drug chemical structure and drug side effects. To begin with, drug feature data integrated by drug target protein and chemical structure were processed with dimension reduction via a deep auto-encoder, to obtain feature representation more densely and abstractly. On this basis, disease similarity was computed by the drug-disease association data, while drug similarity was calculated by drug feature and drug-side effect data. Besides, the predictions of drug-disease associations were calculated using a Top-k neighbor method that is more suitable for drug repositioning. Finally, a predicted matrix for drug-disease associations has been acquired upon fusing a wide variety of data via adaptive fusion. According to the experimental results, the proposed algorithm has higher precision and recall rate in comparison to DRCFFS, SLAMS and BADR algorithms that use the same data set for computation.Conclusion: our proposed algorithm contributes to studying novel uses of drugs, as can be seen from the case analysis of Alzheimer's disease. Therefore, it can provide a certain auxiliary effect for clinical trials of drug repositioning

EHAI: Enhanced Human Microbe-Disease Association Identification

2020 ◽  
Vol 21 (11) ◽  
pp. 1078-1084
Author(s):  
Ruizhi Fan ◽  
Chenhua Dong ◽  
Hu Song ◽  
Yixin Xu ◽  
Linsen Shi ◽  
...  
Keyword(s):  
Microbial Community ◽  
Human Health ◽  
Complex Diseases ◽  
Disease Association ◽  
Computational Results ◽  
Computational Approaches ◽  
Disease Diagnostics ◽  
Disease Associations ◽  
Association Discovery ◽  
Biological Tool

: Recently, an increasing number of biological and clinical reports have demonstrated that imbalance of microbial community has the ability to play important roles among several complex diseases concerning human health. Having a good knowledge of discovering potential of microbe-disease relationships, which provides the ability to having a better understanding of some issues, including disease pathology, further boosts disease diagnostics and prognostics, has been taken into account. Nevertheless, a few computational approaches can meet the need of huge scale of microbe-disease association discovery. In this work, we proposed the EHAI model, which is Enhanced Human microbe- disease Association Identification. EHAI employed the microbe-disease associations, and then Gaussian interaction profile kernel similarity has been utilized to enhance the basic microbe-disease association. Actually, some known microbe-disease associations and a large amount of associations are still unavailable among the datasets. The ‘super-microbe’ and ‘super-disease’ were employed to enhance the model. Computational results demonstrated that such super-classes have the ability to be helpful to the performance of EHAI. Therefore, it is anticipated that EHAI can be treated as an important biological tool in this field.

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