Long-read sequencing is a DNA sequencing technique that enables the sequencing of much longer DNA fragments than traditional short-read sequencing methods. While short reads can capture the majority of genetic variation, long-read sequencing allows the detection of complex structural variants that may be difficult to detect with short reads. These include large inversions, deletions, or translocations, some of which have been implicated in areas like genetic disease.
Long-read technology can help resolve challenging regions of the genome by sequencing thousands of bases to:
Tagmentation is used to normalize long fragment sizes. Long fragments are “land-marked” to capture single-molecule, long-read information and amplified. Marked fragments are tagmented to standard libraries for sequencing. Marked and unmarked data from standard short-read genome are combined to generate highly accurate long reads.
It can be advantageous to combine long-read data with complementary short-read information. Many long-read solutions have laborious workflows and highly variable results.1-4 Short reads (typically 50–600 bp) offer high data quality and sequence depth at low cost. With advanced data analysis, short-read sequencing can generate whole-genome variant calls with outstanding accuracy. In addition, a small fraction of genic regions can benefit from long-read information to improve resolution of the most difficult-to-map genes.
Long-read sequencing technology has the potential to improve the efficiency and accuracy of some existing DNA sequencing applications while increasing the resolution of clinically important genes.
These advantages allow for the phased re‐sequencing of human genomes and rapid de novo sequencing of plant and animal genomes.
The long reads produced typically span more than one heterozygous SNP in the phasing application. The technology simplifies de novo sequencing because large repeat regions in the DNA fragments can easily be spanned.
Linked reads are an alternative technology that generates non-contiguous, long-range data to inform de novo assembly or ultra-long distance (> 1 Mb) phasing. This alternative sequencing data type can be used to complement standard short reads for novel or complex genomes.
TELL-Seq technology generates ultra-long phasing blocks, providing an accessible solution to perform genome phasing studies.
TELL-Seq demonstrates exceptional performance for microbial WGS, even for challenging samples or regions with high GC content.
Whole-genome sequencing is the most comprehensive test for rare disease, with the potential for superior diagnostics and outcomes.
Human whole-genome sequencing provides the most detailed view into the complex genetic variants that make us unique.
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