Thanks to Illumina’s (ILMN) short-read next-generation sequencing (NGS) instruments, the cost to sequence a whole human genome has dropped from $3 billion in 2003 to $600. As a result, against all expectations 15-20 years ago, NGS has subsumed the role of microarrays in the molecular diagnostics space.
NGS skeptics argued that short-read sequencing would be too expensive, too error-prone, and produce superfluous data. Now, skeptics of long-read sequencing are making the same arguments in support of short-read sequencing.
Pacific Biosciences (PACB) pioneered long-read sequencing with its HiFi sequencing method. Unlike short-read NGS, long-reads can detect difficult-to-sequence mutations known as structural variants (SVs). SVs are critical to understanding and diagnosing conditions within oncology, rare disease, hereditary disease predisposition, and neurology. In our view, Illumina’s recent decision to repurchase GRAIL and focus on multi-cancer screening, effectively competing with its customers, will galvanize PacBio’s acceptance in the clinical market.
In line with Wright’s Law, for every cumulative doubling in the data produced on PacBio’s instruments, unit costs have declined consistently at a 28% rate. According to our research, during the next two to three years, as PacBio continues to optimize its HiFi chemistry, the cost of long-read sequencing could approach that of short-read sequencing, causing an inflection in clinical demand for PacBio’s technology.
Unlike other NGS vendors, PacBio designed its Sequel II system to be field-upgradable, enabling increased access to state-of-the-art sequencing. With its Sequel IIe system, PacBio has cut the time for downstream analysis by 70% and the cost of data storage by 90%, making it easier for diagnostic providers to integrate it into their sequencing clusters.
Recently, in the PrecisionFDA 2.0 challenge, PacBio HiFi reads, aided by Google’s (GOOGL) DeepVariant interpretation pipeline, produced more accurate data than either Illumina or Oxford Nanopore, suggesting that PacBio now is the industry leader in complete, highly accurate sequencing. This success already is bearing fruit. For certain clinical workflows, genomic innovators like Invitae (NVTA) and Children’s Mercy Hospital are migrating from short-read to long-read sequencing. In our view, as costs continue to fall, more diagnostic providers will follow suit, ushering in the age of third-generation sequencing.
