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March 19, 2026

What can HiFi long-read sequencing so that short-read NGS normally can’t?

HiFi sequencing combines long reads (500–20,000 bases) with 99.9% read accuracy, delivering comprehensive, high-confidence genomic and epigenomic insight in a single run. 

Unlike short reads (typically 150–200 bp), HiFi reads can span: 

  • Structural variants 
  • Repetitive and GC-rich regions 
  • Segmental duplications 
  • Medically relevant “dark” genes 

Because HiFi sequences native DNA without PCR, it detects: 

  • All major variant types 
  • Haplotype phasing 
  • DNA methylation (5mC, 5hmC, 6mA) 
  • Genetic and epigenetic information simultaneously 

For RNA applications, HiFi long reads capture full-length isoforms, enabling accurate transcript and splice variant characterization, without assembly guesswork. 

HiFi is the only known sequencing technology delivering the gold standard in native long reads accurate enough to trust, and long lengths that truly span SVs and complex regions. 

Interested in getting a deeper understanding of what the advantages and applications of native long read sequencing? Start reading here.   

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