Identifying Cancer-Specific circRNA–RBP Binding Sites Based on Deep Learning

Circular RNAs (circRNAs) are extensively expressed in cells and tissues, and play crucial roles in human diseases and biological processes. Recent studies have reported that circRNAs could function as RNA binding protein (RBP) sponges, meanwhile RBPs can also be involved in back-splicing. The intera...

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Main Authors: Zhengfeng Wang, Xiujuan Lei, Fang-Xiang Wu
Format: Article
Language:English
Published: MDPI AG 2019-11-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/24/22/4035
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author Zhengfeng Wang
Xiujuan Lei
Fang-Xiang Wu
author_facet Zhengfeng Wang
Xiujuan Lei
Fang-Xiang Wu
author_sort Zhengfeng Wang
collection DOAJ
description Circular RNAs (circRNAs) are extensively expressed in cells and tissues, and play crucial roles in human diseases and biological processes. Recent studies have reported that circRNAs could function as RNA binding protein (RBP) sponges, meanwhile RBPs can also be involved in back-splicing. The interaction with RBPs is also considered an important factor for investigating the function of circRNAs. Hence, it is necessary to understand the interaction mechanisms of circRNAs and RBPs, especially in human cancers. Here, we present a novel method based on deep learning to identify cancer-specific circRNA−RBP binding sites (CSCRSites), only using the nucleotide sequences as the input. In CSCRSites, an architecture with multiple convolution layers is utilized to detect the features of the raw circRNA sequence fragments, and further identify the binding sites through a fully connected layer with the softmax output. The experimental results show that CSCRSites outperform the conventional machine learning classifiers and some representative deep learning methods on the benchmark data. In addition, the features learnt by CSCRSites are converted to sequence motifs, some of which can match to human known RNA motifs involved in human diseases, especially cancer. Therefore, as a deep learning-based tool, CSCRSites could significantly contribute to the function analysis of cancer-associated circRNAs.
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spelling doaj.art-294f57f3d3384e7da284d7a4da24b3132022-12-21T19:16:52ZengMDPI AGMolecules1420-30492019-11-012422403510.3390/molecules24224035molecules24224035Identifying Cancer-Specific circRNA–RBP Binding Sites Based on Deep LearningZhengfeng Wang0Xiujuan Lei1Fang-Xiang Wu2School of Computer Science, Shaanxi Normal University, Xi’an 710119, ChinaSchool of Computer Science, Shaanxi Normal University, Xi’an 710119, ChinaDepartment of Mechanical Engineering and Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, SK S7N 5A9, CanadaCircular RNAs (circRNAs) are extensively expressed in cells and tissues, and play crucial roles in human diseases and biological processes. Recent studies have reported that circRNAs could function as RNA binding protein (RBP) sponges, meanwhile RBPs can also be involved in back-splicing. The interaction with RBPs is also considered an important factor for investigating the function of circRNAs. Hence, it is necessary to understand the interaction mechanisms of circRNAs and RBPs, especially in human cancers. Here, we present a novel method based on deep learning to identify cancer-specific circRNA−RBP binding sites (CSCRSites), only using the nucleotide sequences as the input. In CSCRSites, an architecture with multiple convolution layers is utilized to detect the features of the raw circRNA sequence fragments, and further identify the binding sites through a fully connected layer with the softmax output. The experimental results show that CSCRSites outperform the conventional machine learning classifiers and some representative deep learning methods on the benchmark data. In addition, the features learnt by CSCRSites are converted to sequence motifs, some of which can match to human known RNA motifs involved in human diseases, especially cancer. Therefore, as a deep learning-based tool, CSCRSites could significantly contribute to the function analysis of cancer-associated circRNAs.https://www.mdpi.com/1420-3049/24/22/4035circrnarna binding proteincancer-specificconvolutional neural network
spellingShingle Zhengfeng Wang
Xiujuan Lei
Fang-Xiang Wu
Identifying Cancer-Specific circRNA–RBP Binding Sites Based on Deep Learning
Molecules
circrna
rna binding protein
cancer-specific
convolutional neural network
title Identifying Cancer-Specific circRNA–RBP Binding Sites Based on Deep Learning
title_full Identifying Cancer-Specific circRNA–RBP Binding Sites Based on Deep Learning
title_fullStr Identifying Cancer-Specific circRNA–RBP Binding Sites Based on Deep Learning
title_full_unstemmed Identifying Cancer-Specific circRNA–RBP Binding Sites Based on Deep Learning
title_short Identifying Cancer-Specific circRNA–RBP Binding Sites Based on Deep Learning
title_sort identifying cancer specific circrna rbp binding sites based on deep learning
topic circrna
rna binding protein
cancer-specific
convolutional neural network
url https://www.mdpi.com/1420-3049/24/22/4035
work_keys_str_mv AT zhengfengwang identifyingcancerspecificcircrnarbpbindingsitesbasedondeeplearning
AT xiujuanlei identifyingcancerspecificcircrnarbpbindingsitesbasedondeeplearning
AT fangxiangwu identifyingcancerspecificcircrnarbpbindingsitesbasedondeeplearning