WHISTLE: A Functionally Annotated High-Accuracy Map of Human m⁶A Epitranscriptome.

Area of Science:

• Molecular Biology
• Epigenetics
• Bioinformatics

Background:

• N-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes.
• m6A regulates critical cellular processes including splicing, RNA decay, and RNA-protein interactions.
• Precise identification of m6A sites is crucial for understanding its biological roles.

Purpose of the Study:

• To develop a highly accurate prediction framework for transcriptome-wide m6A RNA methylation sites.
• To functionally annotate identified m6A sites using integrated biological data.
• To provide a user-friendly web server for accessing predicted m6A sites and their functions.

Main Methods:

• Development of the WHISTLE prediction framework utilizing RNA methylation, gene expression, and protein-protein interaction data.
• Validation of WHISTLE's accuracy on independent datasets, achieving high AUC scores.
• Functional annotation of m6A sites based on the 'guilt-by-association' principle.

Main Results:

• WHISTLE achieved the highest accuracy to date in mapping human m6A RNA methylation sites (AUC: 0.948 for full transcript, 0.880 for mature mRNA).
• Generated a comprehensive, functionally annotated map of the human m6A epitranscriptome.
• Established a web server for convenient querying and downloading of predicted m6A sites and their putative biological functions.

Conclusions:

• WHISTLE provides a powerful and accurate tool for m6A site prediction and functional annotation.
• The WHISTLE web server facilitates research into the epitranscriptome and m6A-mediated biological processes.
• This resource enhances the study of m6A's role in eukaryotic gene regulation.