NGS for oncology research: how workflow specificity drives sensitivity in liquid biopsy

Twist Bioscience products featured in this article and the accompanying webinar including the Twist cfDNA Library Preparation Kit, RNA Exome, and Custom Enrichment Panels are marketed and sold strictly for Research Use Only (RUO). They are not cleared, approved, or intended for the diagnosis, prevention, monitoring, prognosis, or treatment of any disease or clinical condition, nor should they be utilized as a standalone baseline for clinical decision-making. Case studies and institutional experiences presented by external speakers reflect specific research parameters and should not be interpreted as indicative of performance in standard clinical diagnostic protocols.

Detecting rare variants, profiling fragmented samples, and scaling targeted sequencing workflows are all important goals for studies incorporating next generation sequencing (NGS). These goals can make it difficult to achieve sufficient sensitivity and coverage uniformity when working with low-input or difficult samples. To boost success rates, the library prep and target enrichment chosen can make the difference between usable, publication-ready data and noise.

In this webinar, “Oncology in Practice: Liquid Biopsy Research for Clinical Decision-Making,” [Note: The featured workflows and data are intended strictly for research purposes] scientists from Twist Bioscience, OncoDNA, and Hospital del Mar focus on how successful sequencing supports liquid biopsy research. Dr. Fer Tornos, Ph.D., NGS Field Application Support Manager for Twist Bioscience in Europe, and Dr. Gerald Martin, Ph.D., Commercial Applications Scientist for OncoDNA in Belgium, provide details about the sequencing technology. Dr. Beatriz Bellosillo is the Head of Molecular Diagnostics in the Pathology Department at Hospital del Mar in Spain. She relays her experience evaluating the tools presented by Drs. Tornos and Martin to study solid tumors and hematological neoplasms.

The presenters demonstrate how sequencing and workflow choices (library prep, target enrichment, sequencing depth) directly affect research outcomes. Twist’s synthesis platform underpins a portfolio of NGS products covering liquid biopsy, cancer genomics, methylation profiling, and custom panel design. Twist designs these products for the sensitivity demands of oncology research. 

Sequencing uniformity impacts coverage and sensitivity

In the past, cancer researchers have avoided target enrichment due to a lack of uniformity in sequencing coverage. If one region of the genome is sequenced more than another, the researcher would have to pay for additional sequencing to cover the area with low coverage. The amount of Gs and Cs in the sequencing, a metric known as GC%, influences this type of bias. Twist’s proprietary oligo synthesis method drives very uniform target capture, alleviating this problem. 

Sequencing difficult samples with greater confidence

One of the reasons cancer samples tend to lack uniformity in sequencing the quality of the samples. Biological samples used in cancer research often come in the form of liquid biopsies: blood containing cell-free DNA (cfDNA) or circulating tumor DNA (ctDNA). Liquid biopsies contain less DNA than other sample types, so NGS assays must be very sensitive to generate usable data. Higher uniformity translates directly to sensitivity gains, more usable data per run, fewer reruns, and more samples covered within a fixed sequencing budget. 

From methylation to RNA sequencing

Cancer genomics workflows increasingly extend beyond DNA variant detection. RNA sequencing and methylation profiling are now integral to biomarker discovery, tumor characterization, and epigenomic research.

Twist’s NGS portfolio spans these modalities, from cfDNA library prep through EM-seq v2 for enzymatic methylation detection¹ and RNA Exome for targeted transcriptomic profiling. Recent webinars demonstrate applications including RNA exome enrichment and methylation analysis across oncology and complex disease research.

Watch the webinar

If your research involves liquid biopsy workflows, cfDNA or ctDNA detection, or cancer genomics panel development, this webinar offers a concrete look at how researchers are improving sensitivity and on-target performance, using real workflow data from teams working with FFPE, cfDNA, and low-input samples.  

Watch the full webinar here: Oncology in Practice: Liquid Biopsy Research for Clinical Decision-Making

Twist Bioscience products featured in this article and the accompanying webinar—including the Twist cfDNA Library Preparation Kit, RNA Exome, and Custom Enrichment Panels—are marketed and sold strictly for Research Use Only (RUO). They are not cleared, approved, or intended for the diagnosis, prevention, monitoring, prognosis, or treatment of any disease or clinical condition, nor should they be utilized as a standalone baseline for clinical decision-making. Case studies and institutional experiences presented by external speakers reflect specific research parameters and should not be interpreted as indicative of performance in standard clinical diagnostic protocols.

References

1. Romualdas Vaisvila, V.K. Chaithanya Ponnaluri, Zhiyi Sun, Bradley W. Langhorst, Lana Saleh, Shengxi Guan, Nan Dai, Matthew A. Campbell, Brittany S. Sexton, Katherine Marks, Mala Samaranayake, James C. Samuelson, Heidi E. Church, Esta Tamanaha, Ivan R. Corrêa, Sriharsa Pradhan, Eileen T. Dimalanta, Thomas C. Evans, Louise Williams, and Theodore B. Davis. 2021, Enzymatic methyl sequencing detects DNA methylation at single-base resolution from picograms of DNA. Cold Spring Harbor Laboratory Press. https://genome.cshlp.org/content/31/7/1280