On February 24, 2021 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, reported the launch of the Twist NGS Methylation Detection System, a robust, end-to-end sample preparation and target enrichment solution for identifying methylated regions in the human genome (Press release, Twist Bioscience, FEB 24, 2021, View Source [SID1234575556]).
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DNA methylation plays a key role in many biological processes including cancer. When present on a single nucleotide, a methyl group can alter genetic behavior without changing the DNA sequence. Analyzing these methylation patterns provides unique understanding of disease pathology, including the ability to screen for cancer earlier using blood samples known as "liquid biopsies."
"Methylation is one of the most interesting and informative epigenetic modifications due to its wide-reaching effects, but historically it has been difficult to study efficiently," said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. "In partnership with New England Biolabs, we’ve developed a state-of-the-art system, to identify and accurately evaluate methylation patterns that enable our customers to create better tests and/or conduct research more efficiently. In addition, the superior results produced through this system provide incentive for our customers using SNP microarray technology to switch to using Twist products plus sequencing."
DNA methylation appears in consistent patterns across the genome, making it possible to assess multiple loci for a more specific and sensitive test. In cancer methylation, patterns appear early, providing an attractive approach for screening through revolutionary liquid biopsy tests, which are designed to detect a wide range of tumors from a single blood sample.
HelioHealth, an early access customer, is currently developing simple, accurate liquid biopsy tests for the detection of early-stage liver, colon, breast and lung cancers.
"The complex, very large panels needed to detect circulating tumor DNA early in the disease require expertise in design, robust coverage from minimal sample material, and exceptional sensitivity in detecting the change between differentially methylated regions," said Kenneth Chahine, Ph.D., J.D., CEO of HelioHealth. "After some trial and error with other systems, we found that the Twist NGS Methylation Detection System improved the efficiency and accuracy of all of our tests, providing the best data possible for rapid and early cancer detection."
Despite the promise of methylation detection, the approach presents many challenges, including the preparation of the blood sample and the need for multiple probes for each sequence of interest. For many years, bisulfite sequencing was considered the gold standard in methylation detection. While this method provides a quantitative readout with high throughput and single-base pair resolution, bisulfite treatment can degrade DNA samples substantially and result in specific areas not being detected, particularly for tests with a small relative volume of target DNA for study, as in liquid biopsies. In addition, effective methylation detection requires four different DNA probes for every target sequence of DNA, a substantial undertaking for complex diagnostic tests. In order to overcome these challenges, Twist has partnered with New England Biolabs (NEB), who have developed a novel, enzyme-based alternative to sodium bisulfite treatment, EM-seqTM, for preparation of samples for methylation analysis.
"We developed Enzymatic Methyl-seq, or EM-seq, using a combination of enzymes to achieve highly efficient and gentle conversion of 5mC and 5hmC for downstream identification using next generation sequencing," said Theodore Davis, executive director of Applications and Product Development at NEB. "Application of EM-seq to target enrichment workflows enables efficient analysis of methylation status in defined regions of the genome, with utility across a broad spectrum of areas that can impact human health. We are delighted to partner with Twist to expand the utility of EM-seq."
The Twist NGS Methylation Detection System begins with NEB’s EM-seq for preparation of enzymatically converted libraries, and includes the Twist Methylation Enhancer, Universal Blocker and FastHyb as well as the Twist NGS Custom Methylation Panels. The Custom Panels, a key component of the product, include DNA probes to capture all four potential sequences at a given site: methylated, unmethylated, sense and antisense, and offer the same fidelity, uniformity, and flexibility as Twist Custom Panels. Twist works with customers to create custom content unique to a particular area of focus, allowing flexibility not found using static array designs. This unique feature of the Twist System facilitates exploration of dynamic and cell-specific methylation targets or poorly understood targets found in more elusive noncoding regions at single base pair resolution.
About the Twist NGS Methylation Detection System
The Twist NGS Methylation Detection System offers state-of-the-art end-to-end methylation sequencing workflow for the improved detection of genomic methylation patterns. DNA methylation occurs when DNA methyltransferases add a methyl group to the cytosine residue of cytosine-phosphoguanine (CpG) dinucleotides. This modification contributes to a wide variety of biological processes by promoting genomic instability or transcriptional silencing. Affected processes include normal processes, like cellular differentiation, as well as abnormal ones, like carcinogenesis. Methylation levels vary substantially across the human genome, and differentially methylated regions (DMRs) can be used to identify certain cancers and other diseases.
About New England Biolabs
Established in the mid 1970’s, New England Biolabs, Inc. (NEB) is the industry leader in the discovery and production of enzymes for molecular biology applications and now offers the largest selection of recombinant and native enzymes for genomic research. NEB continues to expand its product offerings into areas related to PCR, gene expression, sample preparation for next generation sequencing, synthetic biology, glycobiology, epigenetics and RNA analysis. Additionally, NEB is focused on strengthening alliances that enable new technologies to reach key market sectors, including molecular diagnostics development. New England Biolabs is a privately held company, headquartered in Ipswich, MA, and has extensive worldwide distribution through a network of exclusive distributors, agents and eight subsidiaries located in Australia, Canada, China, France, Germany, Japan, Singapore and the UK. For more information about New England Biolabs, visit www.neb.com.
NEB and NEW ENGLAND BIOLABS are registered trademarks of New England Biolabs, Inc.