#WritingtheFuture

CEO
Emily Leproust, Ph.D.
Founded
2013

Problem Tech Solves

Marketed

Tech Brief

Among the most studied epigenetic modifications, 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. Oncologists have considered a number of candidates in their search for diagnostic biomarkers, but few are as compelling as DNA methylation. For one, aberrant DNA methylation occurs very early during cancer progression. DNA methylation also manifests inconsistent patterns across the genome, making it possible to assay multiple loci for a more specific and sensitive test. For these reasons, detecting DNA methylation is an attractive approach for early cancer screening, particularly when it can be done non-invasively, as in liquid biopsies of circulating tumor DNA (ctDNA). Detecting methylation by sequencing is not without its share of challenges. The methyl-seq procedure can be difficult to apply to the whole genome without starting with a substantial amount of sample DNA. Methyl-seq also complicates efforts to reduce cost by target enrichment because libraries converted for methylation detection are inherently more difficult to capture. The Twist methyl-seq workflow clears these hurdles to provide a cost-effective, yet highly efficient, alternative to existing methyl-seq workflows.

Tech Differentiators

The Twist NGS Methylation Detection System offers the most efficient targeted methyl-seq solution yet — and all in one box. By reducing sample loss during library prep and hybrid capture, the system enables even the most sensitive applications.

Validation

Helio Health adopted the system into their liquid biopsy: “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.” Several other customers have as well, but have not been public with their adoption at this time.

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