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      Integrating random walk with restart and k-Nearest Neighbor to identify novel circRNA-disease association

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          Abstract

          CircRNA is a special type of non-coding RNA, which is closely related to the occurrence and development of many complex human diseases. However, it is time-consuming and expensive to determine the circRNA-disease associations through experimental methods. Therefore, based on the existing databases, we propose a method named RWRKNN, which integrates the random walk with restart (RWR) and k-nearest neighbors (KNN) to predict the associations between circRNAs and diseases. Specifically, we apply RWR algorithm on weighting features with global network topology information, and employ KNN to classify based on features. Finally, the prediction scores of each circRNA-disease pair are obtained. As demonstrated by leave-one-out, 5-fold cross-validation and 10-fold cross-validation, RWRKNN achieves AUC values of 0.9297, 0.9333 and 0.9261, respectively. And case studies show that the circRNA-disease associations predicted by RWRKNN can be successfully demonstrated. In conclusion, RWRKNN is a useful method for predicting circRNA-disease associations.

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          Most cited references18

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          Transcriptome-wide discovery of circular RNAs in Archaea

          Circular RNA forms had been described in all domains of life. Such RNAs were shown to have diverse biological functions, including roles in the life cycle of viral and viroid genomes, and in maturation of permuted tRNA genes. Despite their potentially important biological roles, discovery of circular RNAs has so far been mostly serendipitous. We have developed circRNA-seq, a combined experimental/computational approach that enriches for circular RNAs and allows profiling their prevalence in a whole-genome, unbiased manner. Application of this approach to the archaeon Sulfolobus solfataricus P2 revealed multiple circular transcripts, a subset of which was further validated independently. The identified circular RNAs included expected forms, such as excised tRNA introns and rRNA processing intermediates, but were also enriched with non-coding RNAs, including C/D box RNAs and RNase P, as well as circular RNAs of unknown function. Many of the identified circles were conserved in Sulfolobus acidocaldarius, further supporting their functional significance. Our results suggest that circular RNAs, and particularly circular non-coding RNAs, are more prevalent in archaea than previously recognized, and might have yet unidentified biological roles. Our study establishes a specific and sensitive approach for identification of circular RNAs using RNA-seq, and can readily be applied to other organisms.
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            The Circular RNA circPRKCI Promotes Tumor Growth in Lung Adenocarcinoma

            Somatic copy number variations (CNV) may drive cancer progression through both coding and noncoding transcripts. However, noncoding transcripts resulting from CNV are largely unknown, especially for circular RNAs. By integrating bioinformatics analyses of alerted circRNAs and focal CNV in lung adenocarcinoma, we identify a proto-oncogenic circular RNA (circPRKCI) from the 3q26.2 amplicon, one of the most frequent genomic aberrations in multiple cancers. circPRKCI was overexpressed in lung adenocarcinoma tissues, in part due to amplification of the 3q26.2 locus, and promoted proliferation and tumorigenesis of lung adenocarcinoma. circPRKCI functioned as a sponge for both miR-545 and miR-589 and abrogated their suppression of the protumorigenic transcription factor E2F7 Intratumor injection of cholesterol-conjugated siRNA specifically targeting circPRKCI inhibited tumor growth in a patient-derived lung adenocarcinoma xenograft model. In summary, circPRKCI is crucial for tumorigenesis and may serve as a potential therapeutic target in patients with lung adenocarcinoma.Significance: These findings reveal high expression of the circular RNA circPRKCI drives lung adenocarcinoma tumorigenesis. Cancer Res; 78(11); 2839-51. ©2018 AACR.
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              Circular RNAs in Cardiovascular Disease: An Overview

              Circular RNA (circRNA), a novel type of endogenous noncoding RNA (ncRNA), has become a research hotspot in recent years. CircRNAs are abundant and stably exist in creatures, and they are found with covalently closed loop structures in which they are quite different from linear RNAs. Nowadays, an increasing number of scientists have demonstrated that circRNAs may have played an essential role in the regulation of gene expression, especially acting as miRNA sponges, and have described the potential mechanisms of several circRNAs in diseases, hinting at their clinical therapeutic values. In this review, the authors summarized the current understandings of the biogenesis and properties of circRNAs and their functions and role as biomarkers in cardiovascular diseases.
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                Author and article information

                Contributors
                xjlei@snnu.edu.cn
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                6 February 2020
                6 February 2020
                2020
                : 10
                : 1943
                Affiliations
                ISNI 0000 0004 1759 8395, GRID grid.412498.2, School of Computer Science, , Shaanxi Normal University, ; Xi’an, 710119 China
                Article
                59040
                10.1038/s41598-020-59040-0
                7005057
                32029856
                87a73bab-d98b-48e4-bc92-d79e55856611
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 7 October 2019
                : 23 January 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 61672334
                Award ID: 61972451
                Award ID: 61902230
                Award Recipient :
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                © The Author(s) 2020

                Uncategorized
                computational models,data processing
                Uncategorized
                computational models, data processing

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