Attention-Based Deep Multiple-Instance Learning for Classifying Circular RNA and Other Long Non-Coding RNA

Yunhe Liu,Xueqing Peng,Lei Liu,Gang Liu,Qiqing Fu,Chaoyu Zhu

doi:10.3390/genes12122018

Abstract

Circular RNA (circRNA) is a distinguishable circular formed long non-coding RNA (lncRNA), which has specific roles in transcriptional regulation, multiple biological processes. The identification of circRNA from other lncRNA is necessary for relevant research. In this study, we designed attention-based multi-instance learning (MIL) network architecture fed with a raw sequence, to learn the sparse features of RNA sequences and to accomplish the circRNAs identification task. The model outperformed the state-of-art models. Moreover, following the validation of the attention mechanism effectiveness by the handwritten digit dataset, the key sequence loci underlying circRNA’s recognition were obtained based on the corresponding attention score. Then, motif enrichment analysis identified some of the key motifs for circRNA formation. In conclusion, we designed deep learning network architecture suitable for learning gene sequences with sparse features and implemented it for the circRNA identification task, and the model has strong representation capability in the indication of some key loci.

Highlights

Non-coding RNAs, referring to RNAs without protein-coding potential, account for the majority of RNAs
It is generally recognized that long non-coding RNA (lncRNA) is a kind of ncRNAs longer than 200 nucleotides, which distinguishes itself from other smaller ncRNA species such as miRNAs and siRNAs. lncRNA has complex biological functions such as transcriptional regulation and post-transcriptional control [1,2,3]
CircRNAs are relevant to the development of multiple diseases [3,4,5], and can be used for disease biomarkers [6,7]

Summary

Introduction

Non-coding RNAs (ncRNAs), referring to RNAs without protein-coding potential, account for the majority of RNAs. It is generally recognized that lncRNA (long noncoding RNA) is a kind of ncRNAs longer than 200 nucleotides, which distinguishes itself from other smaller ncRNA species such as miRNAs and siRNAs. lncRNA has complex biological functions such as transcriptional regulation and post-transcriptional control [1,2,3]. Circular RNA (circRNA) is a closed formed lncRNA by covalently closed loops. CircRNAs are more stable than mRNAs and play a major role as a microRNA activity modulator. CircRNAs are relevant to the development of multiple diseases [3,4,5], and can be used for disease biomarkers [6,7]. It is vital to detect circular RNAs

Methods

Results

Conclusion