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Research: Analysis of a cell-free DNA–based cancer screening cohort links fragmentomic profiles, nuclease levels, and plasma DNA concentrations
- Yasine Malki,
- Guannan Kang,
- W.K. Jacky Lam,
- Qing Zhou,
- Suk Hang Cheng,
- Peter P.H. Cheung,
- Jinyue Bai,
- Ming Lok Chan,
- Chui Ting Lee,
- Wenlei Peng,
- Yiqiong Zhang,
- Wanxia Gai,
- Winsome W.S. Wong,
- Mary-Jane L. Ma,
- Wenshuo Li,
- Xinzhou Xu,
- Zhuoran Gao,
- Irene O.L. Tse,
- Huimin Shang,
- L.Y. Lois Choy,
- Peiyong Jiang,
- K.C. Allen Chan,
- and Y.M. Dennis Lo
Genome Res. January 2025 35: 31-42; Published in Advance November 27, 2024, doi:10.1101/gr.279667.124
...Analysis of a cell-free DNA–based cancer screening cohort links fragmentomic profiles, nuclease levels, and plasma DNA concentrations Yasine Malki1,2,3,5, Guannan Kang1,2,3,5, W.K. Jacky Lam1,2,3,4,5, Qing Zhou1,2,3, Suk Hang Cheng1,2,3, Peter P.H. Cheung2,3, Jinyue Bai1,2,3, Ming Lok Chan2,3, Chui...
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Method: Nanopore-based consensus sequencing enables accurate multimodal tumor cell-free DNA profiling
- Li-Ting Chen,
- Myrthe Jager,
- Dàmi Rebergen,
- Geertruid J. Brink,
- Tom van den Ende,
- Willem Vanderlinden,
- Pauline Kolbeck,
- Marc Pagès-Gallego,
- Ymke van der Pol,
- Nicolle Besselink,
- Norbert Moldovan,
- Nizar Hami,
- Wigard P. Kloosterman,
- Hanneke van Laarhoven,
- Florent Mouliere,
- Ronald Zweemer,
- Jan Lipfert,
- Sarah Derks,
- Alessio Marcozzi,
- and Jeroen de Ridder
Genome Res. April 2025 35: 886-899; Published in Advance January 13, 2025, doi:10.1101/gr.279144.124
...DNA fraction can be derived based on all three modalities. (E) cfDNA from plasma of healthy controls, EAC and granulosa cell tumor (GCT) patients, and cfDNA from ascites of ovarian carcinoma (OVCA) patients is subjected to -wide NanoRCS. We also sequenced the same patient samples with Illumina NovaSeq. Created...
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Method: A novel approach for in vivo DNA footprinting using short double-stranded cell-free DNA from plasma
- Jan Müller,
- Christina Hartwig,
- Mirko Sonntag,
- Lisa Bitzer,
- Christopher Adelmann,
- Yevhen Vainshtein,
- Karolina Glanz,
- Sebastian O. Decker,
- Thorsten Brenner,
- Georg F. Weber,
- Arndt von Haeseler,
- and Kai Sohn
Genome Res. August 2024 34: 1185-1195; Published in Advance September 13, 2024, doi:10.1101/gr.279326.124
...3 histone modifications and gene transcription. The diagnostic potential of short double-stranded cell-free DNA (cfDNA) in blood plasma has not yet been recognized. When comparing short double-stranded cfDNA from patient samples of pancreatic ductal adenocarcinoma with colorectal carcinoma or septic...
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Review: Artificial intelligence and machine learning in cell-free-DNA-based diagnostics
- W.H. Adrian Tsui,
- Spencer C. Ding,
- Peiyong Jiang,
- and Y.M. Dennis Lo
Genome Res. January 2025 35: 1-19; doi:10.1101/gr.278413.123
...@cuhk.edu.hkAbstractThe discovery of circulating fetal and tumor cell-free DNA (cfDNA) molecules in plasma has opened up tremendous opportunities in noninvasive diagnostics such as the detection of fetal chromosomal aneuploidies and cancers and in posttransplantation monitoring. The advent of high-throughput sequencing...
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Research: Genomic origin, fragmentomics, and transcriptional properties of long cell-free DNA molecules in human plasma
- Huiwen Che,
- Peiyong Jiang,
- L.Y. Lois Choy,
- Suk Hang Cheng,
- Wenlei Peng,
- Rebecca W.Y. Chan,
- Jing Liu,
- Qing Zhou,
- W.K. Jacky Lam,
- Stephanie C.Y. Yu,
- So Ling Lau,
- Tak Y. Leung,
- John Wong,
- Vincent Wai-Sun Wong,
- Grace L.H. Wong,
- Stephen L. Chan,
- K.C. Allen Chan,
- and Y.M. Dennis Lo
Genome Res. February 2024 34: 189-200; Published in Advance February 26, 2024, doi:10.1101/gr.278556.123
...nuclease activities (Serpas et al. 2019; Han et al. 2020), DNA methylation (Zhou et al. 2022), nucleosome structures (Ivanov et al. 2015; Snyder et al. 2016; Sun et al. 2019), mRNA expression levels (Ulz et al. 2016), and DNA-binding transcription factor activity (Ulz et al. 2019). These characteristics...
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Research: Characteristics, origin, and potential for cancer diagnostics of ultrashort plasma cell-free DNA
- Irena Hudecova,
- Christopher G. Smith,
- Robert Hänsel-Hertsch,
- Chandra S. Chilamakuri,
- James A. Morris,
- Aadhitthya Vijayaraghavan,
- Katrin Heider,
- Dineika Chandrananda,
- Wendy N. Cooper,
- Davina Gale,
- Javier Garcia-Corbacho,
- Simon Pacey,
- Richard D. Baird,
- Nitzan Rosenfeld,
- and Florent Mouliere
Genome Res. February 2022 32: 215-227; Published in Advance December 20, 2021, doi:10.1101/gr.275691.121
..., Victoria 3010, Australia Corresponding authors: f.mouliere@amsterdamumc.nl, nitzan.rosenfeld@cruk.cam.ac.ukAbstractCurrent evidence suggests that plasma cell-free DNA (cfDNA) is fragmented around a mode of 166 bp. Data supporting this view has been mainly acquired through the analysis of double-stranded cf...
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Research: Nuclease deficiencies alter plasma cell-free DNA methylation profiles
- Diana S.C. Han,
- Meng Ni,
- Rebecca W.Y. Chan,
- Danny K.L. Wong,
- Linda T. Hiraki,
- Stefano Volpi,
- Peiyong Jiang,
- Kathy O. Lui,
- K.C. Allen Chan,
- Rossa W.K. Chiu,
- and Y.M. Dennis Lo
Genome Res. November 2021 31: 2008-2021; Published in Advance September 1, 2021, doi:10.1101/gr.275426.121
...Genova, Italy ↵6 These authors contributed equally to this work. Corresponding author: loym@cuhk.edu.hkAbstractThe effects of DNASE1L3 or DNASE1 deficiency on cell-free DNA (cfDNA) methylation were explored in plasma of mice deficient in these nucleases and in DNASE1L3-deficient humans. Compared to wild...
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Research: A transcriptome-wide systematic search does not detect A-to-I RNA editing in cis-antisense RNA duplexes
- Zohar Rosenwasser,
- Roni Cohen-Fultheim,
- Ofir Shliefer,
- Erez Y. Levanon,
- and Eli Eisenberg
Genome Res. March 12, 2026 ; Published in Advance March 12, 2026, doi:10.1101/gr.280820.125
...A-to-I RNA editing Genome Research 5 www..org Discussion In this study, we examined the possible role of cis-NATs in mediating editing, seeking to understand their prevalence, characteristics, and potential implications for RNA editing. NAT regions were considered a prime candidate for RNA editing...
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Method: Orientation-aware plasma cell-free DNA fragmentation analysis in open chromatin regions informs tissue of origin
- Kun Sun,
- Peiyong Jiang,
- Suk Hang Cheng,
- Timothy H.T. Cheng,
- John Wong,
- Vincent W.S. Wong,
- Simon S.M. Ng,
- Brigette B.Y. Ma,
- Tak Y. Leung,
- Stephen L. Chan,
- Tony S.K. Mok,
- Paul B.S. Lai,
- Henry L.Y. Chan,
- Hao Sun,
- K.C. Allen Chan,
- Rossa W.K. Chiu,
- and Y.M. Dennis Lo
Genome Res. March 2019 29: 418-427; Published in Advance February 26, 2019, doi:10.1101/gr.242719.118
..., 999077, China Corresponding authors: sunkun@cuhk.edu.hk, loym@cuhk.edu.hkAbstractCell-free DNA (cfDNA) in human plasma is a class of biomarkers with many current and potential future diagnostic applications. Recent studies have shown that cfDNA molecules are not randomly fragmented and possess...
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Research: Nanopore direct RNA sequencing reveals METTL2A-mediated m³C sites in poly(A) RNA
- Shuhei Mitsutomi,
- Anzu Sugawara,
- Masahide Seki,
- Yutaka Suzuki,
- Sotaro Miyao,
- Haozhe Du,
- Kenji Takahashi,
- Yusuke Mizukami,
- Kenzui Taniue,
- and Nobuyoshi Akimitsu
Genome Res. November 2025 35: 2406-2417; Published in Advance October 30, 2025, doi:10.1101/gr.280269.124
...is enriched in these sites. We further elucidated that METTL2A downregulates these m3C RNAs. Our approach may contribute to uncovering the functions and characteristics of unknown RNA modifications regulated by diverse factors.MethodsCell cultureAsPC-1 cells (American Type Culture Collection [ATCC]) were...

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