Decoding the m6A epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approach
Abstract Epitranscriptomic modifications, particularly N6-methyladenosine (m6A), are crucial regulators of gene expression, influencing processes such as RNA stability, splicing, and translation. Traditional computational methods for detecting m6A from Nanopore direct RNA sequencing (DRS) data are c...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56173-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594549380218880 |
|---|---|
| author | Chuwei Liu Heng Liang Arabella H. Wan Min Xiao Lei Sun Yiling Yu Shijia Yan Yuan Deng Ruonian Liu Juan Fang Zhi Wang Weiling He Guohui Wan |
| author_facet | Chuwei Liu Heng Liang Arabella H. Wan Min Xiao Lei Sun Yiling Yu Shijia Yan Yuan Deng Ruonian Liu Juan Fang Zhi Wang Weiling He Guohui Wan |
| author_sort | Chuwei Liu |
| collection | DOAJ |
| description | Abstract Epitranscriptomic modifications, particularly N6-methyladenosine (m6A), are crucial regulators of gene expression, influencing processes such as RNA stability, splicing, and translation. Traditional computational methods for detecting m6A from Nanopore direct RNA sequencing (DRS) data are constrained by their reliance on experimentally validated labels, often resulting in the underestimation of modification sites. Here, we introduce pum6a, an innovative attention-based framework that integrates positive and unlabeled multi-instance learning (MIL) to address the challenges of incomplete labeling and missing read-level annotations. By combining electrical signal features with base alignment data and employing a weighted Noisy-OR probability mechanism, pum6a achieves enhanced sensitivity and accuracy in m6A detection, particularly in low-coverage loci. Pum6a outperforms existing methods in identifying m6A sites across various cell lines and species, without requiring extensive parameter tuning. We further apply pum6a to study the dynamic regulation of m6A demethylases in gastric cancer under hypoxia, revealing distinct roles for FTO and ALKBH5 in modulating m6A modifications and uncovering key insights into m6A -mediated transcript stability. Our findings highlight the potential of pum6a as a powerful tool for advancing the understanding of epitranscriptomic regulation in health and disease, paving the way for biotechnological and therapeutic applications. |
| format | Article |
| id | doaj-art-5f5d2b16faaf45fcaa37d448a4a8389e |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-5f5d2b16faaf45fcaa37d448a4a8389e2025-01-19T12:31:04ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-025-56173-6Decoding the m6A epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approachChuwei Liu0Heng Liang1Arabella H. Wan2Min Xiao3Lei Sun4Yiling Yu5Shijia Yan6Yuan Deng7Ruonian Liu8Juan Fang9Zhi Wang10Weiling He11Guohui Wan12Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen UniversityNational-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, National Engineering Research Center for New Drug and Druggability (cultivation), Guangdong Province Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen UniversityDepartment of Medicine, Keck School of Medicine, University of Southern CaliforniaNational-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, National Engineering Research Center for New Drug and Druggability (cultivation), Guangdong Province Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen UniversityNational-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, National Engineering Research Center for New Drug and Druggability (cultivation), Guangdong Province Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen UniversitySchool of Public Health, Sun Yat-Sen UniversityNational-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, National Engineering Research Center for New Drug and Druggability (cultivation), Guangdong Province Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen UniversityNational-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, National Engineering Research Center for New Drug and Druggability (cultivation), Guangdong Province Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen UniversityNational-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, National Engineering Research Center for New Drug and Druggability (cultivation), Guangdong Province Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen UniversityHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen UniversityHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen UniversityNational-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, National Engineering Research Center for New Drug and Druggability (cultivation), Guangdong Province Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen UniversityAbstract Epitranscriptomic modifications, particularly N6-methyladenosine (m6A), are crucial regulators of gene expression, influencing processes such as RNA stability, splicing, and translation. Traditional computational methods for detecting m6A from Nanopore direct RNA sequencing (DRS) data are constrained by their reliance on experimentally validated labels, often resulting in the underestimation of modification sites. Here, we introduce pum6a, an innovative attention-based framework that integrates positive and unlabeled multi-instance learning (MIL) to address the challenges of incomplete labeling and missing read-level annotations. By combining electrical signal features with base alignment data and employing a weighted Noisy-OR probability mechanism, pum6a achieves enhanced sensitivity and accuracy in m6A detection, particularly in low-coverage loci. Pum6a outperforms existing methods in identifying m6A sites across various cell lines and species, without requiring extensive parameter tuning. We further apply pum6a to study the dynamic regulation of m6A demethylases in gastric cancer under hypoxia, revealing distinct roles for FTO and ALKBH5 in modulating m6A modifications and uncovering key insights into m6A -mediated transcript stability. Our findings highlight the potential of pum6a as a powerful tool for advancing the understanding of epitranscriptomic regulation in health and disease, paving the way for biotechnological and therapeutic applications.https://doi.org/10.1038/s41467-025-56173-6 |
| spellingShingle | Chuwei Liu Heng Liang Arabella H. Wan Min Xiao Lei Sun Yiling Yu Shijia Yan Yuan Deng Ruonian Liu Juan Fang Zhi Wang Weiling He Guohui Wan Decoding the m6A epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approach Nature Communications |
| title | Decoding the m6A epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approach |
| title_full | Decoding the m6A epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approach |
| title_fullStr | Decoding the m6A epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approach |
| title_full_unstemmed | Decoding the m6A epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approach |
| title_short | Decoding the m6A epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approach |
| title_sort | decoding the m6a epitranscriptomic landscape for biotechnological applications using a direct rna sequencing approach |
| url | https://doi.org/10.1038/s41467-025-56173-6 |
| work_keys_str_mv | AT chuweiliu decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach AT hengliang decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach AT arabellahwan decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach AT minxiao decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach AT leisun decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach AT yilingyu decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach AT shijiayan decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach AT yuandeng decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach AT ruonianliu decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach AT juanfang decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach AT zhiwang decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach AT weilinghe decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach AT guohuiwan decodingthem6aepitranscriptomiclandscapeforbiotechnologicalapplicationsusingadirectrnasequencingapproach |