Dataset Information

Predicting disease associations via biological network analysis.

ABSTRACT: BACKGROUND: Understanding the relationship between diseases based on the underlying biological mechanisms is one of the greatest challenges in modern biology and medicine. Exploring disease-disease associations by using system-level biological data is expected to improve our current knowledge of disease relationships, which may lead to further improvements in disease diagnosis, prognosis and treatment. RESULTS: We took advantage of diverse biological data including disease-gene associations and a large-scale molecular network to gain novel insights into disease relationships. We analysed and compared four publicly available disease-gene association datasets, then applied three disease similarity measures, namely annotation-based measure, function-based measure and topology-based measure, to estimate the similarity scores between diseases. We systematically evaluated disease associations obtained by these measures against a statistical measure of comorbidity which was derived from a large number of medical patient records. Our results show that the correlation between our similarity measures and comorbidity scores is substantially higher than expected at random, confirming that our similarity measures are able to recover comorbidity associations. We also demonstrated that our predicted disease associations correlated with disease associations generated from genome-wide association studies significantly higher than expected at random. Furthermore, we evaluated our predicted disease associations via mining the literature on PubMed, and presented case studies to demonstrate how these novel disease associations can be used to enhance our current knowledge of disease relationships. CONCLUSIONS: We present three similarity measures for predicting disease associations. The strong correlation between our predictions and known disease associations demonstrates the ability of our measures to provide novel insights into disease relationships.

SUBMITTER: Sun K

PROVIDER: S-EPMC4174675 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Predicting disease associations via biological network analysis.

Sun Kai K Gonçalves Joana P JP Larminie Chris C Przulj Nataša N

BMC bioinformatics 20140917

<h4>Background</h4>Understanding the relationship between diseases based on the underlying biological mechanisms is one of the greatest challenges in modern biology and medicine. Exploring disease-disease associations by using system-level biological data is expected to improve our current knowledge of disease relationships, which may lead to further improvements in disease diagnosis, prognosis and treatment.<h4>Results</h4>We took advantage of diverse biological data including disease-gene asso ...[more]

PMID: 25228247

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Project description:BackgroundThe 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.ResultsIn 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.ConclusionsAfter 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: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.

Dataset Information

Predicting disease associations via biological network analysis.

Publications

Predicting disease associations via biological network analysis.

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