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

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.

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NCMCMDA: miRNA–disease association prediction through neighborhood constraint matrix completion

Briefings in Bioinformatics ◽

10.1093/bib/bbz159 ◽

2020 ◽

Cited By ~ 6

Author(s):

Xing Chen ◽

Lian-Gang Sun ◽

Yan Zhao

Keyword(s):

Computational Models ◽

Cross Validation ◽

Matrix Completion ◽

Critical Role ◽

Disease Association ◽

Human Diseases ◽

Superior Performance ◽

Main Task ◽

Constraint Matrix ◽

Disease Associations

Abstract Emerging evidence shows that microRNAs (miRNAs) play a critical role in diverse fundamental and important biological processes associated with human diseases. Inferring potential disease related miRNAs and employing them as the biomarkers or drug targets could contribute to the prevention, diagnosis and treatment of complex human diseases. In view of that traditional biological experiments cost much time and resources, computational models would serve as complementary means to uncover potential miRNA–disease associations. In this study, we proposed a new computational model named Neighborhood Constraint Matrix Completion for MiRNA–Disease Association prediction (NCMCMDA) to predict potential miRNA–disease associations. The main task of NCMCMDA was to recover the missing miRNA–disease associations based on the known miRNA–disease associations and integrated disease (miRNA) similarity. In this model, we innovatively integrated neighborhood constraint with matrix completion, which provided a novel idea of utilizing similarity information to assist the prediction. After the recovery task was transformed into an optimization problem, we solved it with a fast iterative shrinkage-thresholding algorithm. As a result, the AUCs of NCMCMDA in global and local leave-one-out cross validation were 0.9086 and 0.8453, respectively. In 5-fold cross validation, NCMCMDA achieved an average AUC of 0.8942 and standard deviation of 0.0015, which demonstrated NCMCMDA’s superior performance than many previous computational methods. Furthermore, NCMCMDA was applied to three different types of case studies to further evaluate its prediction reliability and accuracy. As a result, 84% (colon neoplasms), 98% (esophageal neoplasms) and 98% (breast neoplasms) of the top 50 predicted miRNAs were verified by recent literature.

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LE-MDCAP: A Computational Model to Prioritize Causal miRNA–Disease Associations

International Journal of Molecular Sciences ◽

10.3390/ijms222413607 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13607

Author(s):

Zhou Huang ◽

Yu Han ◽

Leibo Liu ◽

Qinghua Cui ◽

Yuan Zhou

Keyword(s):

Computational Models ◽

Operating Characteristic ◽

Cross Validation ◽

Characteristic Curve ◽

Levenshtein Distance ◽

Similarity Matrix ◽

Disease Treatment ◽

Independent Test ◽

Disease Associations ◽

Fold Cross Validation

MicroRNAs (miRNAs) are associated with various complex human diseases and some miRNAs can be directly involved in the mechanisms of disease. Identifying disease-causative miRNAs can provide novel insight in disease pathogenesis from a miRNA perspective and facilitate disease treatment. To date, various computational models have been developed to predict general miRNA–disease associations, but few models are available to further prioritize causal miRNA–disease associations from non-causal associations. Therefore, in this study, we constructed a Levenshtein-Distance-Enhanced miRNA–Disease Causal Association Predictor (LE-MDCAP), to predict potential causal miRNA–disease associations. Specifically, Levenshtein distance matrixes covering the sequence, expression and functional miRNA similarities were introduced to enhance the previous Gaussian interaction profile kernel-based similarity matrix. LE-MDCAP integrated miRNA similarity matrices, disease semantic similarity matrix and known causal miRNA–disease associations to make predictions. For regular causal vs. non-disease association discrimination task, LF-MDCAP achieved area under the receiver operating characteristic curve (AUROC) of 0.911 and 0.906 in 10-fold cross-validation and independent test, respectively. More importantly, LE-MDCAP prominently outperformed the previous MDCAP model in distinguishing causal versus non-causal miRNA–disease associations (AUROC 0.820 vs. 0.695). Case studies performed on diabetic retinopathy and hsa-mir-361 also validated the accuracy of our model. In summary, LE-MDCAP could be useful for screening causal miRNA–disease associations from general miRNA–disease associations.

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Adaptive multi-source multi-view latent feature learning for inferring potential disease-associated miRNAs

Briefings in Bioinformatics ◽

10.1093/bib/bbaa028 ◽

2020 ◽

Cited By ~ 2

Author(s):

Qiu Xiao ◽

Ning Zhang ◽

Jiawei Luo ◽

Jianhua Dai ◽

Xiwei Tang

Keyword(s):

Computational Models ◽

Geometric Characteristic ◽

Feature Learning ◽

Cost Effective ◽

Disease Diagnosis ◽

Computational Method ◽

Data Sources ◽

Superior Performance ◽

Graph Regularization ◽

Latent Features

Abstract Accumulating evidence has shown that microRNAs (miRNAs) play crucial roles in different biological processes, and their mutations and dysregulations have been proved to contribute to tumorigenesis. In silico identification of disease-associated miRNAs is a cost-effective strategy to discover those most promising biomarkers for disease diagnosis and treatment. The increasing available omics data sources provide unprecedented opportunities to decipher the underlying relationships between miRNAs and diseases by computational models. However, most existing methods are biased towards a single representation of miRNAs or diseases and are also not capable of discovering unobserved associations for new miRNAs or diseases without association information. In this study, we present a novel computational method with adaptive multi-source multi-view latent feature learning (M2LFL) to infer potential disease-associated miRNAs. First, we adopt multiple data sources to obtain similarity profiles and capture different latent features according to the geometric characteristic of miRNA and disease spaces. Then, the multi-modal latent features are projected to a common subspace to discover unobserved miRNA-disease associations in both miRNA and disease views, and an adaptive joint graph regularization term is developed to preserve the intrinsic manifold structures of multiple similarity profiles. Meanwhile, the Lp,q-norms are imposed into the projection matrices to ensure the sparsity and improve interpretability. The experimental results confirm the superior performance of our proposed method in screening reliable candidate disease miRNAs, which suggests that M2LFL could be an efficient tool to discover diagnostic biomarkers for guiding laborious clinical trials.

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A novel computational model for predicting potential LncRNA-disease associations based on both direct and indirect features of LncRNA-disease pairs

BMC Bioinformatics ◽

10.1186/s12859-020-03906-7 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Yubin Xiao ◽

Zheng Xiao ◽

Xiang Feng ◽

Zhiping Chen ◽

Linai Kuang ◽

...

Keyword(s):

Computational Model ◽

Cross Validation ◽

State Of The Art ◽

Prediction Methods ◽

Good Prediction ◽

Average Case ◽

Comparison Results ◽

Disease Associations ◽

Fold Cross Validation

Abstract Background Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are closely associated with human diseases, and it is useful for the diagnosis and treatment of diseases to get the relationships between lncRNAs and diseases. Due to the high costs and time complexity of traditional bio-experiments, in recent years, more and more computational methods have been proposed by researchers to infer potential lncRNA-disease associations. However, there exist all kinds of limitations in these state-of-the-art prediction methods as well. Results In this manuscript, a novel computational model named FVTLDA is proposed to infer potential lncRNA-disease associations. In FVTLDA, its major novelty lies in the integration of direct and indirect features related to lncRNA-disease associations such as the feature vectors of lncRNA-disease pairs and their corresponding association probability fractions, which guarantees that FVTLDA can be utilized to predict diseases without known related-lncRNAs and lncRNAs without known related-diseases. Moreover, FVTLDA neither relies solely on known lncRNA-disease nor requires any negative samples, which guarantee that it can infer potential lncRNA-disease associations more equitably and effectively than traditional state-of-the-art prediction methods. Additionally, to avoid the limitations of single model prediction techniques, we combine FVTLDA with the Multiple Linear Regression (MLR) and the Artificial Neural Network (ANN) for data analysis respectively. Simulation experiment results show that FVTLDA with MLR can achieve reliable AUCs of 0.8909, 0.8936 and 0.8970 in 5-Fold Cross Validation (fivefold CV), 10-Fold Cross Validation (tenfold CV) and Leave-One-Out Cross Validation (LOOCV), separately, while FVTLDA with ANN can achieve reliable AUCs of 0.8766, 0.8830 and 0.8807 in fivefold CV, tenfold CV, and LOOCV respectively. Furthermore, in case studies of gastric cancer, leukemia and lung cancer, experiment results show that there are 8, 8 and 8 out of top 10 candidate lncRNAs predicted by FVTLDA with MLR, and 8, 7 and 8 out of top 10 candidate lncRNAs predicted by FVTLDA with ANN, having been verified by recent literature. Comparing with the representative prediction model of KATZLDA, comparison results illustrate that FVTLDA with MLR and FVTLDA with ANN can achieve the average case study contrast scores of 0.8429 and 0.8515 respectively, which are both notably higher than the average case study contrast score of 0.6375 achieved by KATZLDA. Conclusion The simulation results show that FVTLDA has good prediction performance, which is a good supplement to future bioinformatics research.

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PMDFI: Predicting miRNA–Disease Associations Based on High-Order Feature Interaction

Frontiers in Genetics ◽

10.3389/fgene.2021.656107 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mingyan Tang ◽

Chenzhe Liu ◽

Dayun Liu ◽

Junyi Liu ◽

Jiaqi Liu ◽

...

Keyword(s):

Computational Models ◽

Treatment Method ◽

High Order ◽

Computational Method ◽

Feature Interaction ◽

Rna Molecules ◽

Feature Interactions ◽

Non Coding Rna ◽

Disease Associations ◽

Fold Cross Validation

MicroRNAs (miRNAs) are non-coding RNA molecules that make a significant contribution to diverse biological processes, and their mutations and dysregulations are closely related to the occurrence, development, and treatment of human diseases. Therefore, identification of potential miRNA–disease associations contributes to elucidating the pathogenesis of tumorigenesis and seeking the effective treatment method for diseases. Due to the expensive cost of traditional biological experiments of determining associations between miRNAs and diseases, increasing numbers of effective computational models are being used to compensate for this limitation. In this study, we propose a novel computational method, named PMDFI, which is an ensemble learning method to predict potential miRNA–disease associations based on high-order feature interactions. We initially use a stacked autoencoder to extract meaningful high-order features from the original similarity matrix, and then perform feature interactive learning, and finally utilize an integrated model composed of multiple random forests and logistic regression to make comprehensive predictions. The experimental results illustrate that PMDFI achieves excellent performance in predicting potential miRNA–disease associations, with the average area under the ROC curve scores of 0.9404 and 0.9415 in 5-fold and 10-fold cross-validation, respectively.

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A Novel Computational Model for Predicting Potential LncRNA-Disease Associations based on Both Direct and Indirect Features of LncRNA-Disease Pairs

10.21203/rs.2.18937/v3 ◽

2020 ◽

Author(s):

Yubin Xiao ◽

Zheng Xiao ◽

Xiang Feng ◽

Zhiping Chen ◽

Linai Kuang ◽

...

Keyword(s):

Computational Model ◽

Cross Validation ◽

State Of The Art ◽

Prediction Methods ◽

Good Prediction ◽

Average Case ◽

Comparison Results ◽

Disease Associations ◽

Fold Cross Validation

Abstract Background: Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are closely associated with human diseases, and it is useful for the diagnosis and treatment of diseases to get the relationships between lncRNAs and diseases. Due to the high costs and time complexity of traditional bio-experiments, in recent years, more and more computational methods have been proposed by researchers to infer potential lncRNA-disease associations. However, there exist all kinds of limitations in these state-of-the-art prediction methods as well.Results: In this manuscript, a novel computational model named FVTLDA is proposed to infer potential lncRNA-disease associations. In FVTLDA, its major novelty lies in the integration of direct and indirect features related to lncRNA-disease associations such as the feature vectors of lncRNA-disease pairs and their corresponding association probability fractions, which guarantees that FVTLDA can be utilized to predict diseases without known related-lncRNAs and lncRNAs without known related-diseases. Moreover, FVTLDA neither relies solely on known lncRNA-disease nor requires any negative samples, which guarantee that it can infer potential lncRNA-disease associations more equitably and effectively than traditional state-of-the-art prediction methods. Additionally, to avoid the limitations of single model prediction techniques, we combine FVTLDA with the Multiple Linear Regression (MLR) and the Artificial Neural Network (ANN) for data analysis respectively. Simulation experiment results show that FVTLDA with MLR can achieve reliable AUCs of 0.8909, 0.8936 and 0.8970 in 5-Fold Cross Validation (5-fold CV), 10-Fold Cross Validation (10-fold CV) and Leave-One-Out Cross Validation (LOOCV), separately, while FVTLDA with ANN can achieve reliable AUCs of 0.8766, 0.8830 and 0.8807 in 5-fold CV, 10-fold CV, and LOOCV respectively. Furthermore, in case studies of gastric cancer, leukemia and lung cancer, experiment results show that there are 8, 8 and 8 out of top 10 candidate lncRNAs predicted by FVTLDA with MLR, and 8, 7 and 8 out of top 10 candidate lncRNAs predicted by FVTLDA with ANN, having been verified by recent literature. Comparing with the representative prediction model of KATZLDA, comparison results illustrate that FVTLDA with MLR and FVTLDA with ANN can achieve the average case study contrast scores of 0.8429 and 0.8515 respectively, which are both notably higher than the average case study contrast score of 0.6375 achieved by KATZLDA.Conclusion: The simulation results show that FVTLDA has good prediction performance, which is a good supplement to future bioinformatics research.

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IPCARF: improving lncRNA-disease association prediction using incremental principal component analysis feature selection and a random forest classifier

BMC Bioinformatics ◽

10.1186/s12859-021-04104-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Rong Zhu ◽

Yong Wang ◽

Jin-Xing Liu ◽

Ling-Yun Dai

Keyword(s):

Principal Component Analysis ◽

Random Forest ◽

Cross Validation ◽

Search Algorithm ◽

Principal Component ◽

Component Analysis ◽

Biological Data ◽

Learning Technology ◽

Disease Associations ◽

Fold Cross Validation

Abstract Background Identifying lncRNA-disease associations not only helps to better comprehend the underlying mechanisms of various human diseases at the lncRNA level but also speeds up the identification of potential biomarkers for disease diagnoses, treatments, prognoses, and drug response predictions. However, as the amount of archived biological data continues to grow, it has become increasingly difficult to detect potential human lncRNA-disease associations from these enormous biological datasets using traditional biological experimental methods. Consequently, developing new and effective computational methods to predict potential human lncRNA diseases is essential. Results Using a combination of incremental principal component analysis (IPCA) and random forest (RF) algorithms and by integrating multiple similarity matrices, we propose a new algorithm (IPCARF) based on integrated machine learning technology for predicting lncRNA-disease associations. First, we used two different models to compute a semantic similarity matrix of diseases from a directed acyclic graph of diseases. Second, a characteristic vector for each lncRNA-disease pair is obtained by integrating disease similarity, lncRNA similarity, and Gaussian nuclear similarity. Then, the best feature subspace is obtained by applying IPCA to decrease the dimension of the original feature set. Finally, we train an RF model to predict potential lncRNA-disease associations. The experimental results show that the IPCARF algorithm effectively improves the AUC metric when predicting potential lncRNA-disease associations. Before the parameter optimization procedure, the AUC value predicted by the IPCARF algorithm under 10-fold cross-validation reached 0.8529; after selecting the optimal parameters using the grid search algorithm, the predicted AUC of the IPCARF algorithm reached 0.8611. Conclusions We compared IPCARF with the existing LRLSLDA, LRLSLDA-LNCSIM, TPGLDA, NPCMF, and ncPred prediction methods, which have shown excellent performance in predicting lncRNA-disease associations. The compared results of 10-fold cross-validation procedures show that the predictions of the IPCARF method are better than those of the other compared methods.

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Bipartite graph-based collaborative matrix factorization method for predicting miRNA-disease associations

BMC Bioinformatics ◽

10.1186/s12859-021-04486-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Feng Zhou ◽

Meng-Meng Yin ◽

Cui-Na Jiao ◽

Zhen Cui ◽

Jing-Xiu Zhao ◽

...

Keyword(s):

Bipartite Graph ◽

Matrix Factorization ◽

Cross Validation ◽

Rapid Development ◽

Factorization Method ◽

Computational Method ◽

Human Diseases ◽

Simulation Experiments ◽

Disease Associations ◽

Fold Cross Validation

Abstract Background With the rapid development of various advanced biotechnologies, researchers in related fields have realized that microRNAs (miRNAs) play critical roles in many serious human diseases. However, experimental identification of new miRNA–disease associations (MDAs) is expensive and time-consuming. Practitioners have shown growing interest in methods for predicting potential MDAs. In recent years, an increasing number of computational methods for predicting novel MDAs have been developed, making a huge contribution to the research of human diseases and saving considerable time. In this paper, we proposed an efficient computational method, named bipartite graph-based collaborative matrix factorization (BGCMF), which is highly advantageous for predicting novel MDAs. Results By combining two improved recommendation methods, a new model for predicting MDAs is generated. Based on the idea that some new miRNAs and diseases do not have any associations, we adopt the bipartite graph based on the collaborative matrix factorization method to complete the prediction. The BGCMF achieves a desirable result, with AUC of up to 0.9514 ± (0.0007) in the five-fold cross-validation experiments. Conclusions Five-fold cross-validation is used to evaluate the capabilities of our method. Simulation experiments are implemented to predict new MDAs. More importantly, the AUC value of our method is higher than those of some state-of-the-art methods. Finally, many associations between new miRNAs and new diseases are successfully predicted by performing simulation experiments, indicating that BGCMF is a useful method to predict more potential miRNAs with roles in various diseases.

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Drug repositioning by prediction of drug’s anatomical therapeutic chemical code via network-based inference approaches

Briefings in Bioinformatics ◽

10.1093/bib/bbaa027 ◽

2020 ◽

Cited By ~ 4

Author(s):

Yayuan Peng ◽

Manjiong Wang ◽

Yixiang Xu ◽

Zengrui Wu ◽

Jiye Wang ◽

...

Keyword(s):

Cross Validation ◽

Drug Repositioning ◽

Anatomical Therapeutic Chemical ◽

External Validation ◽

Chemical Properties ◽

Glucose Deprivation ◽

Target Drug ◽

Validation Set ◽

Fold Cross Validation

Abstract Drug discovery and development is a time-consuming and costly process. Therefore, drug repositioning has become an effective approach to address the issues by identifying new therapeutic or pharmacological actions for existing drugs. The drug’s anatomical therapeutic chemical (ATC) code is a hierarchical classification system categorized as five levels according to the organs or systems that drugs act and the pharmacology, therapeutic and chemical properties of drugs. The 2nd-, 3rd- and 4th-level ATC codes reserved the therapeutic and pharmacological information of drugs. With the hypothesis that drugs with similar structures or targets would possess similar ATC codes, we exploited a network-based approach to predict the 2nd-, 3rd- and 4th-level ATC codes by constructing substructure drug-ATC (SD-ATC), target drug-ATC (TD-ATC) and Substructure&Target drug-ATC (STD-ATC) networks. After 10-fold cross validation and two external validations, the STD-ATC models outperformed the SD-ATC and TD-ATC ones. Furthermore, with KR as fingerprint, the STD-ATC model was identified as the optimal model with AUC values at 0.899 ± 0.015, 0.916 and 0.893 for 10-fold cross validation, external validation set 1 and external validation set 2, respectively. To illustrate the predictive capability of the STD-ATC model with KR fingerprint, as a case study, we predicted 25 FDA-approved drugs (22 drugs were actually purchased) to have potential activities on heart failure using that model. Experiments in vitro confirmed that 8 of the 22 old drugs have shown mild to potent cardioprotective activities on both hypoxia model and oxygen–glucose deprivation model, which demonstrated that our STD-ATC prediction model would be an effective tool for drug repositioning.

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Deep-belief network for predicting potential miRNA-disease associations

Briefings in Bioinformatics ◽

10.1093/bib/bbaa186 ◽

2020 ◽

Author(s):

Xing Chen ◽

Tian-Hao Li ◽

Yan Zhao ◽

Chun-Chun Wang ◽

Chi-Chi Zhu

Keyword(s):

Computational Models ◽

Cross Validation ◽

Biological Data ◽

Deep Belief Network ◽

Computational Method ◽

Restricted Boltzmann Machines ◽

Belief Network ◽

Disease Associations ◽

Leave One Out ◽

The Impact

Abstract MicroRNA (miRNA) plays an important role in the occurrence, development, diagnosis and treatment of diseases. More and more researchers begin to pay attention to the relationship between miRNA and disease. Compared with traditional biological experiments, computational method of integrating heterogeneous biological data to predict potential associations can effectively save time and cost. Considering the limitations of the previous computational models, we developed the model of deep-belief network for miRNA-disease association prediction (DBNMDA). We constructed feature vectors to pre-train restricted Boltzmann machines for all miRNA-disease pairs and applied positive samples and the same number of selected negative samples to fine-tune DBN to obtain the final predicted scores. Compared with the previous supervised models that only use pairs with known label for training, DBNMDA innovatively utilizes the information of all miRNA-disease pairs during the pre-training process. This step could reduce the impact of too few known associations on prediction accuracy to some extent. DBNMDA achieves the AUC of 0.9104 based on global leave-one-out cross validation (LOOCV), the AUC of 0.8232 based on local LOOCV and the average AUC of 0.9048 ± 0.0026 based on 5-fold cross validation. These AUCs are better than other previous models. In addition, three different types of case studies for three diseases were implemented to demonstrate the accuracy of DBNMDA. As a result, 84% (breast neoplasms), 100% (lung neoplasms) and 88% (esophageal neoplasms) of the top 50 predicted miRNAs were verified by recent literature. Therefore, we could conclude that DBNMDA is an effective method to predict potential miRNA-disease associations.

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