Interpretable Deep Learning Model Reveals Subsequences of Various Functions for Long Non-Coding RNA Identification

Rattaphon Lin; Duangdao Wichadakul

doi:10.3389/fgene.2022.876721

Interpretable Deep Learning Model Reveals Subsequences of Various Functions for Long Non-Coding RNA Identification

Front Genet. 2022 May 24:13:876721. doi: 10.3389/fgene.2022.876721. eCollection 2022.

Authors

Rattaphon Lin¹, Duangdao Wichadakul^{1

2}

Affiliations

¹ Department of Computer Engineering, Faculty of Engineering, Chulalongkorn University, Pathumwan, Thailand.
² Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Pathumwan, Thailand.

Abstract

Long non-coding RNAs (lncRNAs) play crucial roles in many biological processes and are implicated in several diseases. With the next-generation sequencing technologies, substantial unannotated transcripts have been discovered. Classifying unannotated transcripts using biological experiments are more time-consuming and expensive than computational approaches. Several tools are available for identifying long non-coding RNAs. These tools, however, did not explain the features in their tools that contributed to the prediction results. Here, we present Xlnc1DCNN, a tool for distinguishing long non-coding RNAs (lncRNAs) from protein-coding transcripts (PCTs) using a one-dimensional convolutional neural network with prediction explanations. The evaluation results of the human test set showed that Xlnc1DCNN outperformed other state-of-the-art tools in terms of accuracy and F1-score. The explanation results revealed that lncRNA transcripts were mainly identified as sequences with no conserved regions, short patterns with unknown functions, or only regions of transmembrane helices while protein-coding transcripts were mostly classified by conserved protein domains or families. The explanation results also conveyed the probably inconsistent annotations among the public databases, lncRNA transcripts which contain protein domains, protein families, or intrinsically disordered regions (IDRs). Xlnc1DCNN is freely available at https://github.com/cucpbioinfo/Xlnc1DCNN.

Keywords: SHAP (SHapley additive exPlanations); deep learning; explainable artificial intelligence (XAI); long non-coding RNA (lncRNA); one-dimensional convolutional neural network (1D CNN).