asms: finding allele-specific methylation in human genomes without phasing

Abstract Allele-specific methylation (ASM) refers to the differential DNA methylation between two alleles at a specific locus. This phenomenon can be driven by genomic imprinting (where gene expression depends on the parent of origin) or by genetic variants (that may affect DNA–protein binding), both of which play crucial roles in gene regulation and contribute to normal biological variation and disease. ASM can be tissue- or cell-type specific, which adds an extra layer of complexity to its analysis. Detection methods typically rely on phasing using genetic variants, a process that is computationally intensive and can fail in regions with low heterozygosity. To overcome these limitations, we developed asms (Allele-Specific Methylation Scanner), a tool that identifies potential ASM loci from methylation data without requiring prior phasing by looking at heterogeneous methylation across reads. Although we tested it using Oxford Nanopore Technologies (ONT) data, the tool can be used with any platform using MM/ML tags to store methylation in BAM files. asms can examine efficiently thousands of loci (either from a list or through an automatic genomic scan) by segregating reads based on their methylation patterns. When information on variants is available, asms can verify whether distinct alleles correspond to different base modification profiles. asms is available at https://github.com/ecmra/asms.