jeroen de Ridder from Cyclomics and the University Medical Center Utrecht in the Netherlands presented “CyclomicsSeq: targeted and genome-wide detection of circulating tumor DNA using nanopore consensus sequencing” at London Calling 2022. They spoke about monitoring of treatment response and disease recurrence and avoiding invasive procedures. For this, they focused on cell-free tumor DNA: cfDNA molecules are small (~150 bp) and only a fraction carry a specific mutation of interest. Thus, highly sensitive detection systems are needed. CyclomicsSeq begins with cfDNA extraction. Molecules are circularized and rolling circle amplification is used. Sequencing and data processing results is rapid and flexible: amplicons can be sequenced. Ridder shared example data and explained that CyclomicsSeq detects low abundance variant allele frequencies (VAF). Ridder explained they have used this approach for head and neck cancer samples. Their first study subject results they shared is corroborated by ddPCR results. The second study subject Ridder described highlighted the speed of the process. Importantly, their studies indicated that “cfDNA levels correlate with outcomes.” Genome-wide CyclomicsSeq allows for detection of sSNVs. Ridder concluded that:
- CyclomicsSeq allows for accurate detection of cell free tumor DNA
- Genome-wide CyclomicsSeq allows multi-modal interrogation of the cell free DNA
This work is led by Ridder’s lab and colleagues who started a spinout company called Cyclomics. This session helped me understand the advantage of “liquid” biopsies and monitoring. The use of rolling circle amplification helps increase accuracy through high-quality concatemers and consensus accuracy.
