AsianScientist (Jul. 14, 2023)–The human genome has provided insight into our understanding of diseases, particularly when sequencing technology was developed in the 1970s and refined after the turn of the century. Genomics became an important field and sequencing techniques continued to evolve, with one of the latest breakthroughs being next-generation sequencing (NGS).
Whole exome sequencing (WES) is an NGS technique that specifically examines the complete exonic regions of the genome, also known as the human exome. The exome contains the protein-coding regions of the genome and makes up only 1 to 2 percent of the whole genome, but is estimated to account for 85 percent of disease-related mutations.
Studying exomes has become an ideal approach to identifying and understanding diseases, particularly rare and inherited diseases. The advent of WES has also significantly reduced sequencing costs by targeting only the region of interest, making it practical for several applications and changing the way laboratories approach genomic and translational research.
In October 2021, Twist Bioscience, a global leading synthetic biology and genomics company, launched the Twist Exome 2.0, its latest panel iteration for WES. Twist Exome 2.0 is part of the company’s suite of NGS tools that enable end-to-end workflows. In fact, the panel was launched shortly after the release of the Enzymatic Fragmentation 2.0 Kit for NGS library preparation.
The Twist Exome 2.0 panel contains biotinylated oligonucleotide probes, also known as baits, that are hybridized to a fragmented genome sample and then pulled down by magnetic streptavidin beads. These enable clinicians and researchers to isolate and enrich only the regions of interest from the genome for sequencing.
“Being able to sequence only the regions you’re interested in dramatically lowers the amount of sequencing required per genome and, therefore, the total cost of sequencing. It becomes much more feasible to run larger studies to elucidate the causes of disease or understand the genome,” explained Dr Emily Leproust, CEO and co-founder of Twist Bioscience.
Twist Bioscience’s Exome 2.0 target enrichment panel is designed based on the latest models of the genome and includes disease-causing variants from key genetic databases, such as ACMG73, ClinVar, GenCode and RefSeq. The probes used in the panel, which are uniquely double-stranded, are also optimized to improve capture efficiency and sequencing performance.
“Our understanding of the genome continues to evolve, and regular updates are made to the genome assembly. As we gather more data, we have the opportunity to continually improve the design performance and efficiency of our target enrichment products,” added Dr Leproust.
Twist Exome 2.0 has been demonstrated to outperform other available WES solutions in terms of coverage uniformity and sequencing efficiency. In a published technical note, the panel reportedly has the most uniform coverage with fold-80 scores of 1.3 compared to four competing panels. Featuring high uniformity combined with a low duplicate rate and high on-target rate, it covers 97 percent of the target bases in at least 30x sequencing depth with only 6Gb sequencing. In other words, compared to other panels, Twist Bioscience’s solution offers higher quality data and efficiency yield. These comparisons were conducted by a third-party laboratory.
In addition, Twist Exome 2.0 has a low GC bias, enabling detection of target regions across varying GC levels. The robustness of the panel is further illustrated by its capability to cover 36.5Mb of human exonic regions as well as non-protein-coding regions and telomerase reverse transcriptase (TERT) promoters. The panel sets a new industry benchmark in terms of coverage breadth, depth and uniformity in WES.
“With the Exome 2.0, we’re delivering best-in-class sequencing efficiency. It comes down to having the best balance between uniform coverage across the genome and low off-target rates compared to other commercially available exome panels. With highly uniform coverage, we want to ensure we don’t over-sequence or under-sequence any region for the greatest efficiency,” described Dr Leproust.
Similar to other products in Twist Bioscience’s target enriched NGS portfolio, Twist Exome 2.0 is customizable to suit the different content and workflow requirements of clinicians and researchers. Additional probe content can be easily spiked in, and the panel supports sample multiplexing, whereby multiple samples can be enriched and sequenced together in a single run.
Since its introduction to the market, Twist Exome 2.0 has been used across various areas of research, from screening for copy-number variants in rare diseases to narrowing down the genetic risk factors of epilepsy. In a more recent study, the panel was used to determine genetic variants in glioblastoma, a type of aggressive brain cancer.
According to Dr Leproust, “We have dozens of publications on our website that highlight how this panel has been used to understand the human genome. Its applications span different research areas in oncology, developmental diseases, congenital abnormalities, neurological disorders—it can be used to study almost any condition with a genetic component.”
With best-in-class properties, Twist Exome 2.0 emphasizes unparalleled coverage and optimized performance in WES. It enables high-throughput sequencing to study the mutational profiles, genetic variations and clinical phenotypes of various diseases, including germline cancers. It also reflects Twist Bioscience’s track record of continuously and impactfully pushing the envelope in NGS technology.
“At Twist, we create solutions that allow our customers to maximize their data during sequencing in the most efficient way. Exome 2.0 is a game-changer because it represents the next iteration of what genomics researchers are looking for: probes designed based on updated content from recent genome assemblies, low GC bias and coverage uniformity,” concluded Dr Leproust.
Reach out to Twist Bioscience to learn more about Twist Exome 2.0 here.
Source: Twist Bioscience; Yurchanka Siarhei/Shutterstock
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