Over the past few months, we have highlighted the striking versatility of HiFi sequencing in a series of a dozen blogposts, allowing many different research applications to be performed with this one technology.
A quick recap in case you missed any of them:
- Delivering superior data for proteogenomics
- Powering biodiversity genomics
- Resolving the most complex genomic regions
- Enabling the human pangenome reference
- Enabling the era of reference pangenomes
- More precise genomes for precision medicine
- Not all gigabases are created equal
- Getting the right answer
- Haplotype phasing in genome assembly
- Sequencing telomeres
- Full-length RNA sequencing
- True long reads vs. synthetic long reads
And these are just the tip of an iceberg that extends into many other uses, including microbial genomics, metagenomics, metabarcoding, pharmacogenomics, single-cell studies, gene therapy research, viral genome sequencing, genome editing, synthetic biology, chromatin architecture & dynamics, and many more. And then there are entirely new approaches for which HiFi sequencing provides unique and unexpected solutions. For example, check out this new Nature paper by researchers at the John Innes Centre in the UK from a few weeks ago, describing a completely new method for measuring the structural diversity of different RNA isoforms, in vivo and with single-molecule resolution! We continue to be amazed by the brilliance and ingenuity of the scientific community as they apply PacBio HiFi sequencing to an ever-expanding space of research applications.
The consolidation of the many into one has another meaning in HiFi sequencing. In many instances, the combined accuracy, read length, associated kinetic data, and single-molecule nature of HiFi reads allows for multiple questions to be answered with a single assay, whereas previously several different technologies alongside with complex hybrid data analyses were required. This brings about greater simplicities and efficiencies in workflows, easier tracking of samples and datasets, and reduced compute requirements, while at the same time delivering superior results.
A few application examples include:
- Comprehensive detection of all variant types – SNVs, indels and SVs, with long-range allelic phasing, across the entire genome
- Measuring the genome and the epigenome in a single sequencing run
- Simultaneous cell type clustering and full-length transcript isoform detection in single-cell studies
- Targeted assays for clinical research, providing variant calling with long-range phasing and thereby replacing multiple assays like Sanger/NGS sequencing, primer extension assays and/or MLPA
A recent example for the last category is this new paper by researchers from Radboud University Medical Center and the ERN-GENTURIS Lynch-like working group of eight European research hospitals, identifying additional, non-coding aberrations to underlie a substantial part of the missing heritability in Lynch syndrome. By comprehensively sequencing the full genes of interest, including all the intronic regions, the authors find that a substantial proportion (19%) of individuals in their study with colorectal- and endometrial cancers at a young age in life that remained genetically unresolved actually can be diagnosed with Lynch syndrome, as they carried deep-intronic gene aberrations (that result in aberrant splicing), which were resolved by targeted HiFi sequencing.
We look forward to connecting with you as you look to consolidate assays, address and streamline a multitude of sequencing applications demand, or think about creating entirely new uses for HiFi sequencing technology.