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GIMDA: Graphlet interaction-based MiRNA-disease association prediction
Xing Chen1, Na-Na Guan2, Jian-Qiang Li2
1School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, China.
Abstract:
MicroRNAs (miRNAs) have been confirmed to be closely related to various human complex diseases by many experimental studies. It is necessary and valuable to develop powerful and effective computational models to predict potential associations between miRNAs and diseases. In this work, we presented a prediction model of Graphlet Interaction for MiRNA-Disease Association prediction (GIMDA) by integrating the disease semantic similarity, miRNA functional similarity, Gaussian interaction profile kernel similarity and the experimentally confirmed miRNA-disease associations. The related score of a miRNA to a disease was calculated by measuring the graphlet interactions between two miRNAs or two diseases. The novelty of GIMDA lies in that we used graphlet interaction to analyse the complex relationships between two nodes in a graph. The AUCs of GIMDA in global and local leave-one-out cross-validation (LOOCV) turned out to be 0.9006 and 0.8455, respectively. The average result of five-fold cross-validation reached to 0.8927 ± 0.0012. In case study for colon neoplasms, kidney neoplasms and prostate neoplasms based on the database of HMDD V2.0, 45, 45, 41 of the top 50 potential miRNAs predicted by GIMDA were validated by dbDEMC and miR2Disease. Additionally, in the case study of new diseases without any known associated miRNAs and the case study of predicting potential miRNA-disease associations using HMDD V1.0, there were also high percentages of top 50 miRNAs verified by the experimental literatures.
Insights
This study introduces GIMDA, a novel computational model for predicting microRNA-disease associations. GIMDA effectively identifies potential links between microRNAs and complex human diseases using graphlet interactions.
Area of Science:
- Computational Biology
- Genomics
- Bioinformatics
Background:
- MicroRNAs (miRNAs) are implicated in numerous human complex diseases.
- Accurate prediction of miRNA-disease associations is crucial for understanding disease mechanisms.
- Existing computational models require enhancement for improved prediction accuracy.
Purpose of the Study:
- To develop and validate a novel computational model, GIMDA, for predicting miRNA-disease associations.
- To leverage graphlet interaction analysis for uncovering complex relationships between miRNAs and diseases.
- To assess the predictive performance and clinical relevance of the proposed model.
Main Methods:
- Integrated disease semantic similarity, miRNA functional similarity, and Gaussian interaction profile kernel similarity.
- Employed graphlet interaction analysis to quantify relationships between miRNAs and diseases.
- Utilized experimentally confirmed miRNA-disease associations for model training and validation.
Main Results:
- GIMDA achieved high performance in cross-validation, with AUCs of 0.9006 (global) and 0.8455 (local).
- The average five-fold cross-validation AUC reached 0.8927 ± 0.0012.
- Case studies demonstrated high validation rates for predicted miRNA-disease associations, with up to 90% accuracy for top predictions.
Conclusions:
- GIMDA is a powerful and effective computational model for predicting miRNA-disease associations.
- The graphlet interaction approach offers a novel way to analyze complex biological networks.
- The model shows significant potential for identifying novel diagnostic and therapeutic biomarkers for complex diseases.
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