Phasing DNA Methylation.

Area of Science:

• Genomics
• Epigenetics
• Bioinformatics

Background:

• Haplotyping is crucial for studying allele-specific genetic and epigenetic events.
• Heterozygous variants, such as single nucleotide variants (SNVs), are key for assigning parental chromosome origin and phasing sequencing reads.
• Long-read sequencing technologies offer the unique capability to detect both DNA sequence and epigenetic modifications, like DNA methylation.

Purpose of the Study:

• To present a comprehensive workflow for simultaneous genome-wide haplotyping and allele-specific DNA methylation analysis.
• To demonstrate the utility of long-read nanopore sequencing for integrated genomic and epigenomic phasing.
• To enable the study of allele-specific methylation patterns in conjunction with haplotype information.

Main Methods:

• Utilizing long-read nanopore sequencing to generate reads containing both DNA sequence and methylation data.
• Developing and applying a bioinformatics workflow to phase sequencing reads based on heterozygous variants.
• Integrating methylation information with phased reads to perform allele-specific DNA methylation analysis.

Main Results:

• Successful phasing of sequencing reads to their respective haplotypes (paternal and maternal).
• Simultaneous detection and analysis of DNA methylation patterns on an allele-specific basis.
• Demonstration of a unified approach for analyzing both sequence variation and epigenetic modifications.

Conclusions:

• Long-read nanopore sequencing provides a powerful platform for combined haplotyping and allele-specific methylation analysis.
• The described workflow facilitates a deeper understanding of genome regulation at the haplotype level.
• This approach opens new avenues for investigating the interplay between genetic variation and epigenetic modifications across the genome.