Moving The Needle In Liquid Biopsy

AsianScientist (Dec. 12, 2024) –Liquid biopsy has been gaining traction as a powerful tool to detect and diagnose cancer. A minimally invasive and easily repeatable procedure, it is used to screen for biomarkers in biofluid samples, which include various forms of freely circulating DNA fragments known as cell-free DNA (cfDNA). Together with next-generation sequencing (NGS), cfDNA-based liquid biopsy marks a promising opportunity for earlier detection and developing more personalized treatments for cancer.

Sequencing cfDNA, however, is challenging as cfDNA is easily degraded and its concentration in fluid samples is often low. This leads to low library yield and low mean target coverage, affecting the detection of variants of low allele frequencies and the identification of low-frequency biomarkers. To address these issues, leading biotechnology and genomics company Twist Bioscience has developed the Twist cfDNA Library Preparation Kit that enables high-yield cfDNA libraries for NGS.

“The latest in our NGS portfolio, the Twist cfDNA Library Preparation Kit overcomes the common challenge of liquid biopsy applications and cancer research workflows where there is low sample input but a need for high performance,” said Emily M. Leproust, PhD, CEO and co-founder of Twist Bioscience.

Compared to other cfDNA library preparation kits available in the market, Twist Bioscience’s offering reports a two-times improvement in conversion rate, which translates to higher yields, better mean target coverage and more sensitive and accurate detection of variants of low allele frequencies, including rare variants. A robust performance is expected even with low cfDNA sample inputs of 1 to 20 ng/ml.

“We have developed a new ligase, along with an optimized protocol and buffer formulation, that allows for increased conversion efficiency and fast reaction times even with low input amounts. Higher conversion generates higher yields which lead to higher sensitivity,” shared Dr Leproust, who stressed the significant improvements in overall performance with the new cfDNA Library Preparation Kit.

A high-yield library is crucial to enabling accurate detection of cfDNA-based biomarkers in NGS. For instance, circulating tumor DNA (ctDNA)—a form of cfDNA derived from tumors and cancerous cells—contains valuable information contributing to cancer prognosis and diagnosis, but its highly fragmented nature makes it hard to detect. With its high conversion rate, the Twist cfDNA Library Preparation Kit helps develop more sensitive ctDNA assays for oncology research.

Since its launch in February 2024, the Twist cfDNA Library Preparation Kit has generated a buzz among clinicians and researchers. One laboratory in Asia-Pacific using the kit to detect low-frequency variants of somatic mutations has observed a 30 percent increase in coverage despite having low sample inputs. This result was also achieved with fewer PCR cycles, reducing both turnaround time and bias.

The solution is designed for workflow efficiency, generating sequence-ready libraries within two hours while minimizing error rates and sequencing reruns. It comes in two configurations: the cfDNA Library Preparation Kit for whole genome sequencing and the Twist cfDNA Library Preparation and Hybridization Mix Kit for target enrichment.

Complementing the kit is the Twist cfDNA Pan-Cancer Reference Standard v2, a set of high-quality standardized controls that can be used to establish the analytical limit of detection (LoD) and limit of blank (LoB) for specific cancer variants. It also serves as a control to track the quality of an NGS assay workflow and assess the fidelity of the assay process during research. The reference standard boasts over 400 variant sites spanning 84 genes, and can be integrated into Twist Bioscience’s range of target enrichment solutions effortlessly.

The company’s latest cfDNA-based offerings elevate the potential of liquid biopsy in various applications, such as the early detection of cancer, tumor profiling and the monitoring of molecular changes in the disease. They also mark the company’s focused commitment to broadening and improving its NGS portfolio as it stands at the forefront of research for precision oncology and personalized therapy.

“The use of cfDNA in an NGS workflow has become a key tool in research and clinical applications. Twist Bioscience leverages its core technology to develop novel solutions and optimize existing ones to push the boundaries of NGS and shape the future of cancer research,” concluded Dr Leproust.

Contact Twist Bioscience here to discover innovative solutions for cfDNA-based liquid biopsy.

Source: Twist Bioscience, Shutterstock

Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

 

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