Mixed-Weight Neural Bagging for Detecting m6A Modifications in SARS-CoV-2 RNA Sequencing

IEEE Trans Biomed Eng. 2022 Aug;69(8):2557-2568. doi: 10.1109/TBME.2022.3150420. Epub 2022 Jul 18.

Abstract

Objective: The m6A modification is the most common ribonucleic acid (RNA) modification, playing a role in prompting the virus's gene mutation and protein structure changes in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Nanopore single-molecule direct RNA sequencing (DRS) provides data support for RNA modification detection, which can preserve the potential m6A signature compared to second-generation sequencing. However, due to insufficient DRS data, there is a lack of methods to find m6A RNA modifications in DRS. Our purpose is to identify m6A modifications in DRS precisely.

Methods: We present a methodology for identifying m6A modifications that incorporated mapping and extracted features from DRS data. To detect m6A modifications, we introduce an ensemble method called mixed-weight neural bagging (MWNB), trained with 5-base RNA synthetic DRS containing modified and unmodified m6A.

Results: Our MWNB model achieved the highest classification accuracy of 97.85% and AUC of 0.9968. Additionally, we applied the MWNB model to the COVID-19 dataset; the experiment results reveal a strong association with biomedical experiments.

Conclusion: Our strategy enables the prediction of m6A modifications using DRS data and completes the identification of m6A modifications on the SARS-CoV-2.

Significance: The Corona Virus Disease 2019 (COVID-19) outbreak has significantly influence, caused by the SARS-CoV-2. An RNA modification called m6A is connected with viral infections. The appearance of m6A modifications related to several essential proteins affects proteins' structure and function. Therefore, finding the location and number of m6A RNA modifications is crucial for subsequent analysis of the protein expression profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19*
  • Humans
  • RNA, Viral / analysis
  • RNA, Viral / genetics
  • SARS-CoV-2* / genetics
  • Sequence Analysis, RNA

Substances

  • RNA, Viral

Grants and funding

This work was supported in part by the National Natural Science Foundation of China under Grants 61872241 and 61572316, in part by Shanghai Municipal Science and Technology Major Project under Grant 2021SHZDZX0102, and in part by Shanghai Science and Technology Commission under Grant 21511101200.