Genome Biology (Jun 2024)
LABS: linear amplification-based bisulfite sequencing for ultrasensitive cancer detection from cell-free DNA
- Xiao-Long Cui,
- Ji Nie,
- Houxiang Zhu,
- Krissana Kowitwanich,
- Alana V. Beadell,
- Diana C. West-Szymanski,
- Zhou Zhang,
- Urszula Dougherty,
- Akushika Kwesi,
- Zifeng Deng,
- Yan Li,
- Danqing Meng,
- Kevin Roggin,
- Teresa Barry,
- Ryan Owyang,
- Ben Fefferman,
- Chang Zeng,
- Lu Gao,
- Carolyn W. T. Zhao,
- Yuri Malina,
- Jiangbo Wei,
- Melanie Weigert,
- Wenjun Kang,
- Ajay Goel,
- Brian C.-H. Chiu,
- Marc Bissonnette,
- Wei Zhang,
- Mengjie Chen,
- Chuan He
Affiliations
- Xiao-Long Cui
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago
- Ji Nie
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago
- Houxiang Zhu
- Department of Medicine, The University of Chicago
- Krissana Kowitwanich
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago
- Alana V. Beadell
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago
- Diana C. West-Szymanski
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago
- Zhou Zhang
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine
- Urszula Dougherty
- Department of Medicine, The University of Chicago
- Akushika Kwesi
- Department of Medicine, The University of Chicago
- Zifeng Deng
- Department of Medicine, The University of Chicago
- Yan Li
- Department of Medicine, The University of Chicago
- Danqing Meng
- Department of Molecular Biosciences, Northwestern University
- Kevin Roggin
- Department of Surgery, The University of Chicago
- Teresa Barry
- Department of Medicine, The University of Chicago
- Ryan Owyang
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago
- Ben Fefferman
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago
- Chang Zeng
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine
- Lu Gao
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago
- Carolyn W. T. Zhao
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago
- Yuri Malina
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago
- Jiangbo Wei
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago
- Melanie Weigert
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago
- Wenjun Kang
- Department of Medicine, The University of Chicago
- Ajay Goel
- City of Hope Comprehensive Cancer Center
- Brian C.-H. Chiu
- Department of Public Health Sciences, The University of Chicago
- Marc Bissonnette
- Department of Medicine, The University of Chicago
- Wei Zhang
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine
- Mengjie Chen
- Department of Medicine, The University of Chicago
- Chuan He
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago
- DOI
- https://doi.org/10.1186/s13059-024-03262-2
- Journal volume & issue
-
Vol. 25,
no. 1
pp. 1 – 18
Abstract
Abstract Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here, we report linear amplification-based bisulfite sequencing (LABS), enabling linear amplification of bisulfite-treated DNA fragments in a genome-wide, unbiased fashion, detecting cancer abnormalities with sub-nanogram inputs. Applying LABS to 100 patient samples revealed cancer-specific patterns, copy number alterations, and enhanced cancer detection accuracy by identifying tissue-of-origin and immune cell composition.
Keywords