RMDisease: a database of genetic variants that affect RNA modifications, with implications for epitranscriptome...

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Single nucleotide variants (SNVs) pose challenges in understanding biological impacts.
• RNA modifications are crucial in biological processes and disease, including cancer.
• Epitranscriptomic alterations are increasingly linked to disease pathogenesis.

Purpose of the Study:

• To build RMDisease, a comprehensive database of genetic variants affecting RNA modifications.
• To investigate the association between disease-associated variants and epitranscriptome disturbance.
• To provide a resource for studying the epitranscriptome impact of genetic variants.

Main Methods:

• Integrated predictions from 18 RNA modification tools and 303,426 validated modification sites.
• Identified 202,307 human SNPs potentially affecting eight types of RNA modifications (m6A, m5C, m1A, m5U, Ψ, m6Am, m7G, Nm).
• Annotated SNPs with post-transcriptional regulatory information (miRNA binding, RNA-binding protein interactions, alternative splicing).

Main Results:

• Discovered 4,289 disease-associated variants potentially linked to epitranscriptomic pathogenesis.
• Cataloged 202,307 SNPs affecting RNA modification sites, including common and rare variants.
• Provided functional annotations for SNPs, revealing potential regulatory circuits.

Conclusions:

• RMDisease offers a valuable resource for exploring the epitranscriptome's role in disease.
• The database facilitates the study of how genetic variants influence RNA modifications and disease.
• RMDisease supports research into epitranscriptomic mechanisms underlying disease pathogenesis.