Achyut Saroj, Founder, Consultant, and Author at AwareOnc, KOL Engagement and Medical Affairs Liaison at Tatva Health, shared a post on LinkedIn:
“The Future of Liquid Biopsy is Holistic
For years, the field of cell-free DNA (cfDNA) fragmentomics has been primarily focused on the 5′ ends of DNA fragments. But what if we’re only looking at half the picture?
I am excited to share a groundbreaking study recently published in Cell Genomics by Peiyong Jiang, Dennis Lo, and their team at The Chinese University of Hong Kong: ‘Holistic determination of ends of cfDNA molecules’.
The Innovation: Holistic Fragmentomics
Conventional sequencing library preparations often “repair” DNA ends, which, unfortunately, alters or destroys the native 3′ end information. This study introduces two powerful new approaches to capture the full molecular signature:
- 2-End Sequencing: Using single-stranded library preparation to preserve and measure both the native 5′ (EM5) and 3′ (EM3) ends, along with their flanking pre-end (PREM) and post-end (POEM) motifs.
- 4-End Sequencing: A novel protocol using stem-loop adapters and long-read SMRT-seq to simultaneously interrogate all four ends of a single double-stranded cfDNA molecule for the first time.
Why This Matters for CancerDetection?
The results are a significant leap forward for non-invasive diagnostics, particularly for Hepatocellular Carcinoma (HCC).
- Enhanced Accuracy: Integrating these new ‘constellation’ markers achieved an AUC of 0.95 for HCC detection.
- 3′ FRAGMA: By applying fragmentomics-based methylation analysis to the 3′ ends, the team reached an impressive AUC of 0.97.
- Synergistic Power: The holistic 4-end analysis outperformed conventional 5′ methods, reaching an AUC of 0.98.
Beyond the Screen: BiologicalInsights
This isn’t just about better tests; it’s about better science. This holistic view enabled the researchers to dissect how nucleases such as DNASE1L3, DNASE1, and DFFB coordinate to fragment DNA, providing a much deeper understanding of cfDNA biology.
This work opens a new dimension in liquid biopsy, moving us closer to high-fidelity, multi-dimensional cancerscreening.”
Title: Holistic determination of ends of cfDNA molecules
Authors: Peiyong Jiang, Mary-Jane Ma, Rong Qiao, Yuwei Shi, Jing Liu, Qing Zhou, Wenlei Peng, Jacky Lam, Jinyue Bai, Lois Choy, Adrian Tsui, Yasine Malki, Guannan Kang, Stephanie Yu, Dongyan Xiong, Grace Wong, Landon Chan, John Wong, Stephen Chan, Vincent Wong, Allen Chan, Dennis Lo
Read the Full Article.
Other articles featuring Achyut Saroj on OncoDaily.