Interpretable Multi-Scale Deep Learning for RNA Methylation Analysis across Multiple Species

Author:

Wang Rulan1,Chung Chia-Ru2ORCID,Lee Tzong-Yi3

Affiliation:

1. Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China

2. Department of Computer Science and Information Engineering, National Central University, Taoyuan 320317, Taiwan

3. Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan

Abstract

RNA modification plays a crucial role in cellular regulation. However, traditional high-throughput sequencing methods for elucidating their functional mechanisms are time-consuming and labor-intensive, despite extensive research. Moreover, existing methods often limit their focus to specific species, neglecting the simultaneous exploration of RNA modifications across diverse species. Therefore, a versatile computational approach is necessary for interpretable analysis of RNA modifications across species. A multi-scale biological language-based deep learning model is proposed for interpretable, sequential-level prediction of diverse RNA modifications. Benchmark comparisons across species demonstrate the model’s superiority in predicting various RNA methylation types over current state-of-the-art methods. The cross-species validation and attention weight visualization also highlight the model’s capability to capture sequential and functional semantics from genomic backgrounds. Our analysis of RNA modifications helps us find the potential existence of “biological grammars” in each modification type, which could be effective for mapping methylation-related sequential patterns and understanding the underlying biological mechanisms of RNA modifications.

Funder

Ganghong Young Scholar Development Fund

Guangdong Province Basic and Applied Basic Research Fund

National Natural Science Foundation of China

Science, Technology, and Innovation Commission of Shenzhen Municipality

Shenzhen–Hong Kong Cooperation Zone for Technology and Innovation

The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project and Yushan Young Fellow Program

Ministry of Education (MOE), National Science and Technology Council

National Health Research Institutes

Publisher

MDPI AG

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