Dataset Information

Predicting Microbe-Disease Association by Learning Graph Representations and Rule-Based Inference on the Heterogeneous Network.

ABSTRACT: More and more clinical observations have implied that microbes have great effects on human diseases. Understanding the relations between microbes and diseases are of profound significance for disease prevention and therapy. In this paper, we propose a predictive model based on the known microbe-disease associations to discover potential microbe-disease associations through integrating Learning Graph Representations and a modified Scoring mechanism on the Heterogeneous network (called LGRSH). Firstly, the similarity networks for microbe and disease are obtained based on the similarity of Gaussian interaction profile kernel. Then, we construct a heterogeneous network including these two similarity networks and microbe-disease associations' network. After that, the embedding algorithm Node2vec is implemented to learn representations of nodes in the heterogeneous network. Finally, according to these low-dimensional vector representations, we calculate the relevance between each microbe and disease by utilizing a modified rule-based inference method. By comparison with three other methods including LRLSHMDA, KATZHMDA and BiRWHMDA, LGRSH performs better than others. Moreover, in case studies of asthma, Chronic Obstructive Pulmonary Disease and Inflammatory Bowel Disease, there are 8, 8, and 10 out of the top-10 discovered disease-related microbes were validated respectively, demonstrating that LGRSH performs well in predicting potential microbe-disease associations.

SUBMITTER: Lei X

PROVIDER: S-EPMC7174569 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Predicting Microbe-Disease Association by Learning Graph Representations and Rule-Based Inference on the Heterogeneous Network.

Lei Xiujuan X Wang Yueyue Y

Frontiers in microbiology 20200415

More and more clinical observations have implied that microbes have great effects on human diseases. Understanding the relations between microbes and diseases are of profound significance for disease prevention and therapy. In this paper, we propose a predictive model based on the known microbe-disease associations to discover potential microbe-disease associations through integrating Learning Graph Representations and a modified Scoring mechanism on the Heterogeneous network (called LGRSH). Fir ...[more]

PMID: 32351464

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Project description:BackgroundAn increasing number of biological and clinical evidences have indicated that the microorganisms significantly get involved in the pathological mechanism of extensive varieties of complex human diseases. Inferring potential related microbes for diseases can not only promote disease prevention, diagnosis and treatment, but also provide valuable information for drug development. Considering that experimental methods are expensive and time-consuming, developing computational methods is an alternative choice. However, most of existing methods are biased towards well-characterized diseases and microbes. Furthermore, existing computational methods are limited in predicting potential microbes for new diseases.ResultsHere, we developed a novel computational model to predict potential human microbe-disease associations (MDAs) based on Weighted Meta-Graph (WMGHMDA). We first constructed a heterogeneous information network (HIN) by combining the integrated microbe similarity network, the integrated disease similarity network and the known microbe-disease bipartite network. And then, we implemented iteratively pre-designed Weighted Meta-Graph search algorithm on the HIN to uncover possible microbe-disease pairs by cumulating the contribution values of weighted meta-graphs to the pairs as their probability scores. Depending on contribution potential, we described the contribution degree of different types of meta-graphs to a microbe-disease pair with bias rating. Meta-graph with higher bias rating will be assigned greater weight value when calculating probability scores.ConclusionsThe experimental results showed that WMGHMDA outperformed some state-of-the-art methods with average AUCs of 0.9288, 0.9068 ±0.0031 in global leave-one-out cross validation (LOOCV) and 5-fold cross validation (5-fold CV), respectively. In the case studies, 9, 19, 37 and 10, 20, 45 out of top-10, 20, 50 candidate microbes were manually verified by previous reports for asthma and inflammatory bowel disease (IBD), respectively. Furthermore, three common human diseases (Crohn's disease, Liver cirrhosis, Type 1 diabetes) were adopted to demonstrate that WMGHMDA could be efficiently applied to make predictions for new diseases. In summary, WMGHMDA has a high potential in predicting microbe-disease associations.

Project description:MOTIVATION:Human microbes play critical roles in drug development and precision medicine. How to systematically understand the complex interaction mechanism between human microbes and drugs remains a challenge nowadays. Identifying microbe-drug associations can not only provide great insights into understanding the mechanism, but also boost the development of drug discovery and repurposing. Considering the high cost and risk of biological experiments, the computational approach is an alternative choice. However, at present, few computational approaches have been developed to tackle this task. RESULTS:In this work, we leveraged rich biological information to construct a heterogeneous network for drugs and microbes, including a microbe similarity network, a drug similarity network, and a microbe-drug interaction network. We then proposed a novel Graph Convolutional Network (GCN) based framework for predicting human Microbe-Drug Associations, named GCNMDA. In the hidden layer of GCN, we further exploited the Conditional Random Field (CRF), which can ensure that similar nodes (i.e., microbes or drugs) have similar representations. To more accurately aggregate representations of neighborhoods, an attention mechanism was designed in the CRF layer. Moreover, we performed a random walk with restart (RWR) based scheme on both drug and microbe similarity networks to learn valuable features for drugs and microbes respectively. Experimental results on three different datasets showed that our GCNMDA model consistently achieved better performance than seven state-of-the-art methods. Case studies for three microbes including SARS-CoV-2 and two antimicrobial drugs (i.e., Ciprofloxacin and Moxifloxacin) further confirmed the effectiveness of GCNMDA in identifying potential microbe-drug associations. AVAILABILITY:Python codes and dataset are available at: https://github.com/longyahui/GCNMDA. SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.

Project description:Background The existing studies show that circRNAs can be used as a biomarker of diseases and play a prominent role in the treatment and diagnosis of diseases. However, the relationships between the vast majority of circRNAs and diseases are still unclear, and more experiments are needed to study the mechanism of circRNAs. Nowadays, some scholars use the attributes between circRNAs and diseases to study and predict their associations. Nonetheless, most of the existing experimental methods use less information about the attributes of circRNAs, which has a certain impact on the accuracy of the final prediction results. On the other hand, some scholars also apply experimental methods to predict the associations between circRNAs and diseases. But such methods are usually expensive and time-consuming. Based on the above shortcomings, follow-up research is needed to propose a more efficient calculation-based method to predict the associations between circRNAs and diseases. Results In this study, a novel algorithm (method) is proposed, which is based on the Graph Convolutional Network (GCN) constructed with Random Walk with Restart (RWR) and Principal Component Analysis (PCA) to predict the associations between circRNAs and diseases (CRPGCN). In the construction of CRPGCN, the RWR algorithm is used to improve the similarity associations of the computed nodes with their neighbours. After that, the PCA method is used to dimensionality reduction and extract features, it makes the connection between circRNAs with higher similarity and diseases closer. Finally, The GCN algorithm is used to learn the features between circRNAs and diseases and calculate the final similarity scores, and the learning datas are constructed from the adjacency matrix, similarity matrix and feature matrix as a heterogeneous adjacency matrix and a heterogeneous feature matrix. Conclusions After 2-fold cross-validation, 5-fold cross-validation and 10-fold cross-validation, the area under the ROC curve of the CRPGCN is 0.9490, 0.9720 and 0.9722, respectively. The CRPGCN method has a valuable effect in predict the associations between circRNAs and diseases.

Project description:Recently, a growing number of biological research and scientific experiments have demonstrated that microRNA (miRNA) affects the development of human complex diseases. Discovering miRNA-disease associations plays an increasingly vital role in devising diagnostic and therapeutic tools for diseases. However, since uncovering associations via experimental methods is expensive and time-consuming, novel and effective computational methods for association prediction are in demand. In this study, we developed a computational model of Matrix Decomposition and Heterogeneous Graph Inference for miRNA-disease association prediction (MDHGI) to discover new miRNA-disease associations by integrating the predicted association probability obtained from matrix decomposition through sparse learning method, the miRNA functional similarity, the disease semantic similarity, and the Gaussian interaction profile kernel similarity for diseases and miRNAs into a heterogeneous network. Compared with previous computational models based on heterogeneous networks, our model took full advantage of matrix decomposition before the construction of heterogeneous network, thereby improving the prediction accuracy. MDHGI obtained AUCs of 0.8945 and 0.8240 in the global and the local leave-one-out cross validation, respectively. Moreover, the AUC of 0.8794+/-0.0021 in 5-fold cross validation confirmed its stability of predictive performance. In addition, to further evaluate the model's accuracy, we applied MDHGI to four important human cancers in three different kinds of case studies. In the first type, 98% (Esophageal Neoplasms) and 98% (Lymphoma) of top 50 predicted miRNAs have been confirmed by at least one of the two databases (dbDEMC and miR2Disease) or at least one experimental literature in PubMed. In the second type of case study, what made a difference was that we removed all known associations between the miRNAs and Lung Neoplasms before implementing MDHGI on Lung Neoplasms. As a result, 100% (Lung Neoplasms) of top 50 related miRNAs have been indexed by at least one of the three databases (dbDEMC, miR2Disease and HMDD V2.0) or at least one experimental literature in PubMed. Furthermore, we also tested our prediction method on the HMDD V1.0 database to prove the applicability of MDHGI to different datasets. The results showed that 50 out of top 50 miRNAs related with the breast neoplasms were validated by at least one of the three databases (HMDD V2.0, dbDEMC, and miR2Disease) or at least one experimental literature.

Dataset Information

Predicting Microbe-Disease Association by Learning Graph Representations and Rule-Based Inference on the Heterogeneous Network.

Publications

Predicting Microbe-Disease Association by Learning Graph Representations and Rule-Based Inference on the Heterogeneous Network.

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