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Related Experiment Video

Updated: Jun 1, 2025

Exploring m6A and m5C Epitranscriptomes upon Viral Infection: an Example with HIV
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Decoding the m6A epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing

Chuwei Liu1, Heng Liang2, Arabella H Wan3

  • 1Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.

Nature Communications
|January 17, 2025
PubMed
Summary

We developed pum6a, a new computational tool for detecting N6-methyladenosine (m6A) modifications in RNA. Pum6a improves accuracy, especially with limited data, and offers new insights into gastric cancer.

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Area of Science:

  • Molecular Biology
  • Bioinformatics
  • Genomics

Background:

  • Epitranscriptomic modifications, like N6-methyladenosine (m6A), regulate gene expression through RNA stability, splicing, and translation.
  • Current computational methods for m6A detection in Nanopore direct RNA sequencing (DRS) data are limited by reliance on labeled data, leading to underestimation of modification sites.

Purpose of the Study:

  • To introduce pum6a, an attention-based framework using positive and unlabeled multi-instance learning (MIL) to improve m6A detection from DRS data.
  • To address challenges of incomplete labeling and missing read-level annotations in m6A site identification.

Main Methods:

  • Pum6a integrates electrical signal features with base alignment data.
  • A weighted Noisy-OR probability mechanism is employed for enhanced sensitivity and accuracy.
  • The framework utilizes positive and unlabeled multi-instance learning (MIL) for robust annotation.

Main Results:

  • Pum6a demonstrates superior performance in m6A detection across diverse cell lines and species, particularly in low-coverage regions.
  • The tool outperforms existing methods without requiring extensive parameter tuning.
  • Application to gastric cancer under hypoxia revealed distinct roles of FTO and ALKBH5 in m6A regulation and transcript stability.

Conclusions:

  • Pum6a is a powerful tool for advancing the understanding of epitranscriptomic regulation.
  • The findings provide key insights into m6A-mediated transcript stability in cancer.
  • Pum6a has potential for biotechnological and therapeutic applications in epitranscriptomics.