Abstract

Circular RNA (circRNA) is a novel non-coding endogenous RNAs. Evidence has shown that circRNAs are related to many biological processes and play essential roles in different biological functions. Although increasing numbers of circRNAs are discovered using high-throughput sequencing technologies, these techniques are still time-consuming and costly. In this study, we propose a computational method to predict circRNA-disesae associations which is based on metapath2vec++ and matrix factorization with integrated multiple data (called PCD MVMF). To construct more reliable networks, various aspects are considered. Firstly, circRNA annotation, sequence, and functional similarity networks are established, and disease-related genes and semantics are adopted to construct disease functional and semantic similarity networks. Secondly, metapath2vec++ is applied on an integrated heterogeneous network to learn the embedded features and initial prediction score. Finally, we use matrix factorization, take similarity as a constraint, and optimize it to obtain the final prediction results. Leave-one-out cross-validation, five-fold cross-validation, and f-measure are adopted to evaluate the performance of PCD MVMF. These evaluation metrics verify that PCD MVMF has better prediction performance than other methods. To further illustrate the performance of PCD MVMF, case studies of common diseases are conducted. Therefore, PCD MVMF can be regarded as a reliable and useful circRNA-disease association prediction tool.

Highlights

  • Circular RNA, which is a novel biological molecule circRNA[l], has attracted considerable attention

  • The accumulated evidence shows that circRNAs can be divided into four types, namely, exonic circRNAs, which are mainly derived from back-spliced exons[9]; intronic circRNAs, which are predominantly generated by Groups I and II introns, i.e., intron lariats and excised tRNA introns[lO]; exon-intron circRNAs[8], which are exons circularized with introns retained between exons; and intergenic circRNAs[ll], which consist of two intronic circRNA fragments

  • The circRNA-disease associations data used in our paper, which have been verified by experiments, are screened out from the circR2Disease[33] database

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Summary

Introduction

Circular RNA (circRNA), which is a novel biological molecule circRNA[l], has attracted considerable attention. CircRNA plays essential roles in different biological functions and controls the expressions of genes[2]. In contrast to linear RNAs that have the exposed 3' caps and 5' tails, the structure of circRNA is a closed loop with neither 5' to 3' polarity nor polyadenylated tail[3]. Because of its stable loop structure and low expression level[5,6] , circRNAs are always identified as molecular fragments or by-products of transcription. With the development of highthroughput sequencing techniques, increasing numbers of circRNAs are discovered gradually. CircRNA-related biological functions illustrate that circRNAs are endogenous, abundant, conserved, and stable in mammalian cells[2,7,8].

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