scholarly journals Multi-Similarities Bilinear Matrix Factorization-Based Method for Predicting Human Microbe–Disease Associations

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoyu Yang ◽  
Linai Kuang ◽  
Zhiping Chen ◽  
Lei Wang

Accumulating studies have shown that microbes are closely related to human diseases. In this paper, a novel method called MSBMFHMDA was designed to predict potential microbe–disease associations by adopting multi-similarities bilinear matrix factorization. In MSBMFHMDA, a microbe multiple similarities matrix was constructed first based on the Gaussian interaction profile kernel similarity and cosine similarity for microbes. Then, we use the Gaussian interaction profile kernel similarity, cosine similarity, and symptom similarity for diseases to compose the disease multiple similarities matrix. Finally, we integrate these two similarity matrices and the microbe-disease association matrix into our model to predict potential associations. The results indicate that our method can achieve reliable AUCs of 0.9186 and 0.9043 ± 0.0048 in the framework of leave-one-out cross validation (LOOCV) and fivefold cross validation, respectively. What is more, experimental results indicated that there are 10, 10, and 8 out of the top 10 related microbes for asthma, inflammatory bowel disease, and type 2 diabetes mellitus, respectively, which were confirmed by experiments and literatures. Therefore, our model has favorable performance in predicting potential microbe–disease associations.

Author(s):  
Mengyun Yang ◽  
Gaoyan Wu ◽  
Qichang Zhao ◽  
Yaohang Li ◽  
Jianxin Wang

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.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Da Xu ◽  
Hanxiao Xu ◽  
Yusen Zhang ◽  
Mingyi Wang ◽  
Wei Chen ◽  
...  

Abstract Background Microbes are closely related to human health and diseases. Identification of disease-related microbes is of great significance for revealing the pathological mechanism of human diseases and understanding the interaction mechanisms between microbes and humans, which is also useful for the prevention, diagnosis and treatment of human diseases. Considering the known disease-related microbes are still insufficient, it is necessary to develop effective computational methods and reduce the time and cost of biological experiments. Methods In this work, we developed a novel computational method called MDAKRLS to discover potential microbe-disease associations (MDAs) based on the Kronecker regularized least squares. Specifically, we introduced the Hamming interaction profile similarity to measure the similarities of microbes and diseases besides Gaussian interaction profile kernel similarity. In addition, we introduced the Kronecker product to construct two kinds of Kronecker similarities between microbe-disease pairs. Then, we designed the Kronecker regularized least squares with different Kronecker similarities to obtain prediction scores, respectively, and calculated the final prediction scores by integrating the contributions of different similarities. Results The AUCs value of global leave-one-out cross-validation and 5-fold cross-validation achieved by MDAKRLS were 0.9327 and 0.9023 ± 0.0015, which were significantly higher than five state-of-the-art methods used for comparison. Comparison results demonstrate that MDAKRLS has faster computing speed under two kinds of frameworks. In addition, case studies of inflammatory bowel disease (IBD) and asthma further showed 19 (IBD), 19 (asthma) of the top 20 prediction disease-related microbes could be verified by previously published biological or medical literature. Conclusions All the evaluation results adequately demonstrated that MDAKRLS has an effective and reliable prediction performance. It may be a useful tool to seek disease-related new microbes and help biomedical researchers to carry out follow-up studies.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Tian-Ru Wu ◽  
Meng-Meng Yin ◽  
Cui-Na Jiao ◽  
Ying-Lian Gao ◽  
Xiang-Zhen Kong ◽  
...  

Abstract Background MicroRNAs (miRNAs) are non-coding RNAs with regulatory functions. Many studies have shown that miRNAs are closely associated with human diseases. Among the methods to explore the relationship between the miRNA and the disease, traditional methods are time-consuming and the accuracy needs to be improved. In view of the shortcoming of previous models, a method, collaborative matrix factorization based on matrix completion (MCCMF) is proposed to predict the unknown miRNA-disease associations. Results The complete matrix of the miRNA and the disease is obtained by matrix completion. Moreover, Gaussian Interaction Profile kernel is added to the miRNA functional similarity matrix and the disease semantic similarity matrix. Then the Weight K Nearest Known Neighbors method is used to pretreat the association matrix, so the model is close to the reality. Finally, collaborative matrix factorization method is applied to obtain the prediction results. Therefore, the MCCMF obtains a satisfactory result in the fivefold cross-validation, with an AUC of 0.9569 (0.0005). Conclusions The AUC value of MCCMF is higher than other advanced methods in the fivefold cross validation experiment. In order to comprehensively evaluate the performance of MCCMF, accuracy, precision, recall and f-measure are also added. The final experimental results demonstrate that MCCMF outperforms other methods in predicting miRNA-disease associations. In the end, the effectiveness and practicability of MCCMF are further verified by researching three specific diseases.


2020 ◽  
Author(s):  
Tian-Ru Wu ◽  
Meng-Meng Yin ◽  
Cui-Na Jiao ◽  
Ying-Lian Gao ◽  
Xiang-Zhen Kong ◽  
...  

Abstract Background: microRNAs (miRNAs) are non-coding RNAs with regulatory functions. Many studies have shown that miRNAs are closely associated with human diseases. Among the methods to explore the relationship between the miRNA and the disease, traditional methods are time-consuming and the accuracy needs to be improved. In view of the shortcoming of previous models, a collaborative matrix factorization based on matrix completion (MCCMF) is proposed to predict the unknown miRNA-disease associations.Results: The complete matrix of the miRNA and the disease is obtained by matrix completion. Moreover, Gaussian Interaction Profile (GIP) kernel is added to the miRNA functional similarity matrix and the disease semantic similarity matrix to form the GIP kernel similarity matrix. Then the Weight K Nearest Known Neighbors (WKNKN) method is used to pretreat the association matrix, so the model is close to the reality. Finally, collaborative matrix factorization (CMF) method is applied to obtain the prediction results. Therefore, the MCCMF obtains a satisfactory result in the five-fold cross-validation, with an AUC of 0.9569(0.0005).Conclusions: The AUC value of MCCMF is higher than other advanced methods in the 5-fold cross validation experiment. In order to comprehensively evaluate the performance of MCCMF, accuracy, precision, recall and f-measure are also added. The final experimental results demonstrate that MCCMF outperforms other methods in predicting miRNA-disease associations. In the end, the effectiveness and practicability of MCCMF are further verified by researching three specific diseases.


2021 ◽  
Vol 17 (7) ◽  
pp. e1009165
Author(s):  
Lei Li ◽  
Zhen Gao ◽  
Yu-Tian Wang ◽  
Ming-Wen Zhang ◽  
Jian-Cheng Ni ◽  
...  

miRNAs belong to small non-coding RNAs that are related to a number of complicated biological processes. Considerable studies have suggested that miRNAs are closely associated with many human diseases. In this study, we proposed a computational model based on Similarity Constrained Matrix Factorization for miRNA-Disease Association Prediction (SCMFMDA). In order to effectively combine different disease and miRNA similarity data, we applied similarity network fusion algorithm to obtain integrated disease similarity (composed of disease functional similarity, disease semantic similarity and disease Gaussian interaction profile kernel similarity) and integrated miRNA similarity (composed of miRNA functional similarity, miRNA sequence similarity and miRNA Gaussian interaction profile kernel similarity). In addition, the L2 regularization terms and similarity constraint terms were added to traditional Nonnegative Matrix Factorization algorithm to predict disease-related miRNAs. SCMFMDA achieved AUCs of 0.9675 and 0.9447 based on global Leave-one-out cross validation and five-fold cross validation, respectively. Furthermore, the case studies on two common human diseases were also implemented to demonstrate the prediction accuracy of SCMFMDA. The out of top 50 predicted miRNAs confirmed by experimental reports that indicated SCMFMDA was effective for prediction of relationship between miRNAs and diseases.


2020 ◽  
Author(s):  
Tian-Ru Wu ◽  
Meng-Meng Yin ◽  
Cui-Na Jiao ◽  
Ying-Lian Gao ◽  
Xiang-Zhen Kong ◽  
...  

Abstract Background: MicroRNAs (MiRNAs) are non-coding RNAs with regulatory functions. Many studies have shown that miRNAs are closely associated with human diseases. Among the methods to explore the relationship between the miRNA and the disease, traditional methods are time-consuming and the accuracy needs to be improved. In view of the shortcoming of previous models, a collaborative matrix factorization based on matrix completion (MCCMF) is proposed to predict the unknown miRNA-disease associations.Results: The complete matrix of the miRNA and the disease is obtained by matrix completion. Moreover, Gaussian Interaction Profile (GIP) kernel is added to the miRNA functional similarity matrix and the disease semantic similarity matrix to form the GIP kernel similarity matrix. Then the Weight K Nearest Known Neighbors (WKNKN) method is used to pretreat the association matrix, so the model is close to the reality. Finally, collaborative matrix factorization (CMF) method is applied to obtain the prediction results. Therefore, the MCCMF obtains a satisfactory result in the five-fold cross-validation, with an AUC of 0.9569(0.0005). Conclusions: The AUC value of MCCMF is higher than other advanced methods in the 5-fold cross validation experiment. In order to comprehensively evaluate the performance of MCCMF, f-measure and other evaluation indexes are also added. The final experimental results demonstrate that MCCMF outperforms other methods in prediction miRNA-disease associations. In the end, the effectiveness and practicability of MCCMF are further verified by researching three specific diseases.


2020 ◽  
Author(s):  
Tian-Ru Wu ◽  
Meng-Meng Yin ◽  
Cui-Na Jiao ◽  
Jin-Xing Liu ◽  
Ying-Lian Gao ◽  
...  

Abstract Background: MicroRNAs (MiRNAs) are non-coding RNAs with regulatory functions. Many studies have shown that miRNAs are closely associated with human diseases. Among the methods to explore the relationship between the miRNA and the disease, traditional methods are time-consuming and the accuracy needs to be improved. In view of the shortcoming of previous models, a collaborative matrix factorization based on matrix completion (MCCMF) is proposed to predict the unknown miRNA-disease associations. Results: The complete matrix of the miRNA and the disease is obtained by matrix completion. Moreover, Gaussian Interaction Profile (GIP) kernel is added to the miRNA functional similarity matrix and the disease semantic similarity matrix to form the GIP kernel similarity matrix. Then the Weight K Nearest Known Neighbors (WKNKN) method is used to pretreat the association matrix, so the model is close to the reality. Finally, collaborative matrix factorization (CMF) method is applied to obtain the prediction results. Therefore, the MCCMF obtains a satisfactory result in the five-fold cross-validation, with an AUC of 0.9569(0.0005). Conclusions: The AUC value of MCCMF is higher than other advanced methods in the 5-fold cross validation experiment. In order to comprehensively evaluate the performance of MCCMF, f-measure and other evaluation indexes are also added. The final experimental results demonstrate that MCCMF outperforms other methods in prediction miRNA-disease associations. In the end, the effectiveness and practicability of MCCMF are further verified by researching three specific diseases.


2020 ◽  
Author(s):  
Tian-Ru Wu ◽  
Meng-Meng Yin ◽  
Cui-Na Jiao ◽  
Ying-Lian Gao ◽  
Xiang-Zhen Kong ◽  
...  

Abstract Background: microRNAs (miRNAs) are non-coding RNAs with regulatory functions. Many studies have shown that miRNAs are closely associated with human diseases. Among the methods to explore the relationship between the miRNA and the disease, traditional methods are time-consuming and the accuracy needs to be improved. In view of the shortcoming of previous models, a method, collaborative matrix factorization based on matrix completion (MCCMF) is proposed to predict the unknown miRNA-disease associations.Results: The complete matrix of the miRNA and the disease is obtained by matrix completion. Moreover, Gaussian Interaction Profile (GIP) kernel is added to the miRNA functional similarity matrix and the disease semantic similarity matrix. Then the Weight K Nearest Known Neighbors (WKNKN) method is used to pretreat the association matrix, so the model is close to the reality. Finally, collaborative matrix factorization (CMF) method is applied to obtain the prediction results. Therefore, the MCCMF obtains a satisfactory result in the five-fold cross-validation, with an AUC of 0.9569(0.0005).Conclusions: The AUC value of MCCMF is higher than other advanced methods in the 5-fold cross validation experiment. In order to comprehensively evaluate the performance of MCCMF, accuracy, precision, recall and f-measure are also added. The final experimental results demonstrate that MCCMF outperforms other methods in predicting miRNA-disease associations. In the end, the effectiveness and practicability of MCCMF are further verified by researching three specific diseases.


2021 ◽  
Vol 12 ◽  
Author(s):  
Haixiu Yang ◽  
Fan Tong ◽  
Changlu Qi ◽  
Ping Wang ◽  
Jiangyu Li ◽  
...  

Many microbes are parasitic within the human body, engaging in various physiological processes and playing an important role in human diseases. The discovery of new microbe–disease associations aids our understanding of disease pathogenesis. Computational methods can be applied in such investigations, thereby avoiding the time-consuming and laborious nature of experimental methods. In this study, we constructed a comprehensive microbe–disease network by integrating known microbe–disease associations from three large-scale databases (Peryton, Disbiome, and gutMDisorder), and extended the random walk with restart to the network for prioritizing unknown microbe–disease associations. The area under the curve values of the leave-one-out cross-validation and the fivefold cross-validation exceeded 0.9370 and 0.9366, respectively, indicating the high performance of this method. Despite being widely studied diseases, in case studies of inflammatory bowel disease, asthma, and obesity, some prioritized disease-related microbes were validated by recent literature. This suggested that our method is effective at prioritizing novel disease-related microbes and may offer further insight into disease pathogenesis.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Guobo Xie ◽  
Zhiliang Fan ◽  
Yuping Sun ◽  
Cuiming Wu ◽  
Lei Ma

Abstract Background Recently, numerous biological experiments have indicated that microRNAs (miRNAs) play critical roles in exploring the pathogenesis of various human diseases. Since traditional experimental methods for miRNA-disease associations detection are costly and time-consuming, it becomes urgent to design efficient and robust computational techniques for identifying undiscovered interactions. Methods In this paper, we proposed a computation framework named weighted bipartite network projection for miRNA-disease association prediction (WBNPMD). In this method, transfer weights were constructed by combining the known miRNA and disease similarities, and the initial information was properly configured. Then the two-step bipartite network algorithm was implemented to infer potential miRNA-disease associations. Results The proposed WBNPMD was applied to the known miRNA-disease association data, and leave-one-out cross-validation (LOOCV) and fivefold cross-validation were implemented to evaluate the performance of WBNPMD. As a result, our method achieved the AUCs of 0.9321 and $$0.9173 \pm 0.0005$$ 0.9173 ± 0.0005 in LOOCV and fivefold cross-validation, and outperformed other four state-of-the-art methods. We also carried out two kinds of case studies on prostate neoplasm, colorectal neoplasm, and lung neoplasm, and most of the top 50 predicted miRNAs were confirmed to have an association with the corresponding diseases based on dbDeMC, miR2Disease, and HMDD V3.0 databases. Conclusions The experimental results demonstrate that WBNPMD can accurately infer potential miRNA-disease associations. We anticipated that the proposed WBNPMD could serve as a powerful tool for potential miRNA-disease associations excavation.


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