DirectASRM: uncovering allele-specific post-transcriptional RNA modifications through direct RNA sequencing

Area of Science:

• Bioinformatics
• Genomics
• Molecular Biology

Background:

• Direct RNA sequencing enables direct detection of RNA modifications.
• Understanding allele-specific RNA modifications (ASRMs) is crucial for epitranscriptomics.
• Existing resources lack comprehensive integration of ASRMs from direct RNA sequencing data.

Purpose of the Study:

• To develop a comprehensive database for identifying, integrating, and annotating ASRMs.
• To enable single-base, transcript-level detection of ASRMs across various conditions and organisms.
• To provide functional annotations for ASRMs and their associated variants.

Main Methods:

• Developed DirectASRM, a database integrating ASRM data from direct RNA sequencing.
• Implemented a pipeline for single-base, transcript-level detection and annotation of ASRMs.
• Evaluated ASRM-SNP association confidence using statistical evidence and external NGS resources.

Main Results:

• DirectASRM enables detection of ASRMs across diverse RNA modification types, organisms, and conditions.
• The database provides confidence scores for ASRM-SNP associations within isoform context.
• Functional annotations include allele-specific expression, splicing, miRNA binding, and disease relevance.

Conclusions:

• DirectASRM is a comprehensive resource for systematic investigation of ASRMs.
• It supports the study of functional impacts of genetic variants on epitranscriptomic regulation.
• The database facilitates research into allele-specific epitranscriptomic mechanisms.