March 28, 2024

Leading the Way into the Future: HiFi Whole Genomes as a Replacement for Exome and Short-Read Genome Sequencing

The Promise of HiFi Long-Read Sequencing
– PacBio

For years, exome sequencing has been the go-to method for identifying disease-causing variants due to its cost-effectiveness and practicality. However, its focus on protein-coding regions, which constitute only about 1.5% to 2% of the genome, limits its comprehensiveness. HiFi whole-genome sequencing on the Revio system presents a transformative alternative, offering a more complete genetic picture by capturing both intronic and exonic variations, and detecting variants that short-read technologies often miss.

The Limitations of Exome Sequencing

Exome sequencing, despite its utility, leaves much of the genome unexplored, potentially missing disease-causing variants in non-coding regions. It also struggles with coverage uniformity and detecting large structural variants, especially in high-GC areas. Consequently, only a minority of patients receive a definitive diagnosis from exome sequencing alone.

Read more here about  “The Role of Whole Genome and Exome Sequencing in Uncovering Variants in Rare Diseases “

Challenges with Short-Read Whole-Genome Sequencing

While whole-genome sequencing (WGS) is an improvement over exome sequencing, short-read WGS still faces significant challenges. It often fails to detect complex structural variants and variations in highly repetitive or GC-rich regions, thereby underestimating genomic complexity. This limitation has led to skepticism about the clinical utility differences between short-read WGS and exome sequencing.

The Promise of HiFi Long-Read Sequencing

HiFi long-read sequencing offers a more comprehensive method for capturing genomic complexity. It excels in identifying disease-causing structural variations that short-read technologies miss, making it particularly valuable in rare disease research. Institutions like Children’s Mercy Kansas City and Bioscientia are pioneering the use of HiFi sequencing to replace traditional exome and short-read genome approaches, accelerating diagnostic processes and improving the detection of genetic variations.

Leading the Way with HiFi Sequencing

Children’s Mercy Kansas City and Bioscientia are at the forefront of adopting HiFi sequencing. They leverage this technology to capture multiple variant types in a single run, eliminating the need for sequential exome and whole-genome tests. Dr. Pastinen’s team at Children’s Mercy utilizes 5-base HiFi sequencing, which includes methylation annotation without requiring special preparation, drastically reducing the time to results. Meanwhile, Dr. Hanno Bolz’s team at Bioscientia has launched a clinical whole-genome sequencing test using HiFi long reads, highlighting its advantages in resolving complex exonic regions, repetitive areas, and providing phasing information crucial for rare disease studies.

Expanding Genomic Horizons

HiFi sequencing on the Revio system not only improves genomic data accuracy but also enables the simultaneous generation of multiple ‘omes, including the genome, methylome, epigenome, and transcriptome. This capability reduces the need for multiple experiments, streamlining the research process. The Revio system, supported by comprehensive SNP and SV detection workflows and new analysis tools, simplifies the translation of extensive genomic data into actionable insights.


Cost-Effectiveness of HiFi Whole-Genome Sequencing

HiFi sequencing consolidates multiple tests into a single run, reducing overall costs and time. For approximately $1,000 per 30x human genome, the Revio system can deliver a complete genomic analysis within 24 hours, eliminating the need for batching samples to achieve cost efficiency.


The field of genomics is evolving, with HiFi long-read sequencing emerging as a groundbreaking technology. Recognized for its accuracy and comprehensive variant detection, HiFi sequencing is poised to revolutionize genetic research and clinical diagnostics. Institutions like Children’s Mercy and Bioscientia are leading this change, demonstrating the vast potential of HiFi sequencing on the Revio system. Embrace the future of genomics with HiFi sequencing for more accurate and thorough genetic insights.


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