NEW YORK – Dovetail Genomics, a unit of Cantata Bio, is gearing up for the launch of a structural variant detection kit and service based on the firm's LinkPrep chromatin conformation technology.
The new offering will feature a kit and data analysis service for detecting structural variants and will be launched at the American Society of Human Genetics annual meeting in November.
The LinkPrep technology builds on the Hi-C method, in which chromatin is cross-linked with formaldehyde, digested, and religated such that only DNA fragments that are covalently linked form ligation products. These contain information on where the DNA resided in the genome's three-dimensional organization. Despite small differences in library preparation methods, such as sample processing and quality control, all LinkPrep applications consist largely of the same steps, differing mainly in how data analysis is done.
While broadly similar to Hi-C, LinkPrep is a single-day assay, compared to the standard two to three days needed for most Hi-C assays. This largely results from the use of Tn5 tagmentation, in which Tn5 transposase breaks DNA double strands and ligates sequencing adapters in a rapid reaction that eliminates bias from traditional restriction enzymes used in most Hi-C workflows and combines two components of the assay into a single step.
Lisa Munding, VP of research and development at Dovetail, said that replacing endonucleases such as MNase and DNase with transposase in the Hi-C workflow simplifies the assay by eliminating the need to manage and optimize digestion kinetics.
She explained that the use of Tn5 provides whole-genome sequencing (WGS)-like coverage while maintaining haplotype-aware long-range interactions, a hallmark of Hi-C data. It also enables robust single nucleotide variant (SNV) detection.
"This allows phasing across low-complexity regions, through variants occurring hundreds of kilobases apart on the same haplotype," she said. "Tn5-based workflows, such as LinkPrep, can detect and phase variants from the same data."
LinkPrep has potential applications in human leukocyte antigen (HLA) genotyping and in oncology, Munding said.
In fact, Dovetail is positioning its upcoming LinkPrep for SV detection product for cancer research, since SVs frequently drive oncogenesis. "We're really focused on being able to leverage this tool as a way to help cancer researchers better detect structural variants at higher resolution and much more cheaply than what you can do with today's technology," said Naissan Hussainzada, Dovetail’s VP of commercial operations, adding that the company sees future potential for LinkPrep in a clinical assay.
Likewise, Munding described the HLA region as a "hyper-focused region of structural variation," ideal for Hi-C and Hi-C adjacent methods such as LinkPrep.
Transposase-based library prep featuring Tn5 has been around since at least 2010. NGS platform developer SeqWell recently launched a portfolio of transposase reagents, which includes its Tagify i5 Unique Molecular Identifier (UMI) adapter-loaded Tn5 transposase.
Similarly, German researchers earlier this year published a high-throughput chromatin accessibility and gene expression assay called SHARE-seq that utilizes the Tn5 transposase to mark regions of open chromatin during sequencing library assembly.
Scotts Valley, California-based Dovetail validated LinkPrep last year and has been launching related applications throughout 2024.
Earlier this week, the company announced a partnership with CareDx on HLA genotyping for organ and stem cell matching that will combine Dovetail's LinkPrep NGS chromatin conformation assay with CareDx's next-generation sequencing-based AlloSeq Tx 17 HLA typing test.
"It's intended to really highlight the kind of data that can come from the combination of [CareDx's] extensive panel for genotyping [and] our technology, which can extend that genotyping into fully phased, haplotype-resolved results," Hussainzada said.
This combined service is offered through CareDx under early access and is currently for research use only. While Dovetail does not see itself as a diagnostics developer, Hussainzada said that the company is "very excited about this being a potential tool in the clinical toolbox."
A spokesperson for CareDx said in an email that the partnership with Dovetail Genomics "is aimed at driving [the] next wave of innovation by delivering haplotyping without the need for family studies."