HiFi sequencing detects methylation directly from native DNA, automatically, in every run—no extra assays required.
It works by measuring subtle changes in polymerase kinetics as modified bases (such as 5mC) are incorporated during sequencing.
This enables:
- Direct, nucleotide-level methylation detection
- Simultaneous variant + methylation analysis
- 5-base multiomic sequencing in a single assay
In contrast, short-read platforms typically require separate methods such as bisulfite sequencing (which can damage DNA) or arrays (which sample only a fraction of CpG sites).
With HiFi—and advanced assays like Fiber-seq—researchers can link genetic variation, methylation, and chromatin accessibility at single-molecule resolution.