# Injecting structure-aware insights for the learning of RNA sequence representations to identify m6A modification sites

**Authors:** Yue Yu, Shuang Xiang, Minghao Wu

PMC · DOI: 10.7717/peerj.18878 · 2025-02-24

## TL;DR

This paper introduces M6A-SAI, a new method that improves the identification of RNA m6A modification sites by incorporating structural insights into deep learning models.

## Contribution

The novel contribution is integrating structure-aware insights into RNA sequence representation learning using a transformer-based framework and graph optimization techniques.

## Key findings

- M6A-SAI enhances m6A modification site identification by incorporating structural information into sequence representations.
- The method uses a similarity graph and structure-aware optimization block to refine RNA sequence correlations.
- Experimental results show M6A-SAI outperforms traditional methods in identifying m6A modification sites.

## Abstract

N6-methyladenosine (m6A) represents one of the most prevalent methylation modifications in eukaryotes and it is crucial to accurately identify its modification sites on RNA sequences. Traditional machine learning based approaches to m6A modification site identification primarily focus on RNA sequence data but often incorporate additional biological domain knowledge and rely on manually crafted features. These methods typically overlook the structural insights inherent in RNA sequences. To address this limitation, we propose M6A-SAI, an advanced predictor for RNA m6A modifications. M6A-SAI leverages a transformer-based deep learning framework to integrate structure-aware insights into sequence representation learning, thereby enhancing the precision of m6A modification site identification. The core innovation of M6A-SAI lies in its ability to incorporate structural information through a multi-step process: initially, the model utilizes a Transformer encoder to learn RNA sequence representations. It then constructs a similarity graph based on Manhattan distance to capture sequence correlations. To address the limitations of the smooth similarity graph, M6A-SAI integrates a structure-aware optimization block, which refines the graph by defining anchor sets and generating an awareness graph through PageRank. Following this, M6A-SAI employs a self-correlation fusion graph convolution framework to merge information from both the similarity and awareness graphs, thus producing enriched sequence representations. Finally, a support vector machine is utilized for classifying these representations. Experimental results validate that M6A-SAI substantially improves the recognition of m6A modification sites by incorporating structure-aware insights, demonstrating its efficacy as a robust method for identifying RNA m6A modification sites.

## Full-text entities

- **Genes:** GPM6A (glycoprotein M6A) [NCBI Gene 2823] {aka GPM6, M6A}

## Figures

50 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11867033/full.md

---
Source: https://tomesphere.com/paper/PMC11867033