M6Allele: a toolkit for detection of allele-specific RNA N6-methyladenosine modifications.

Background: Allelic gene-specific regulatory events are crucial mechanisms in organisms, pivotal to many fundamental biological processes such as embryonic development and chromosome inactivation. Allelic gene imbalance manifests at both RNA expression and epigenetic levels. Recent research has unveiled allelic-specific regulation of RNA N6-methyladenosine (m6A), emphasizing the need for its precise identification. However, prevailing approaches primarily focus on screening allele-specific genetic variations associated with m6A, but not truly identify allelic m6A events. Therefore, the construction of a novel algorithm dedicated to identifying allele-specific m6A (ASm6A) signals is still necessary for comprehensively understanding the regulatory mechanism of ASm6A.

Findings: To address this limitation, we have developed a meta-analysis approach using hierarchical Bayesian models to accurately detect ASm6A events at the peak level from MeRIP-seq data. For user convenience, we introduce a unified analysis pipeline named M6Allele, streamlining the assessment of significant ASm6A across single and paired samples. Applying M6Allele to MeRIP-seq data analysis of pulmonary fibrosis and lung adenocarcinoma reveals enrichment of ASm6A events in key regulatory genes associated with these diseases, suggesting their potential involvement in disease regulation.

Conclusions: Our effort provides a method for precisely identifying ASm6A events at the peak level, elucidates the interplay of m6A with human health and disease genetics, and paves a new visual angle for disease research. The M6Allele software is freely available at https://github.com/RenLabBioinformatics/M6Allele under the MIT license.