Genome-wide cell-free DNA methylation profiling via TAPS for moyamoya disease diagnosis and postoperative collateral formation prediction
9 affiliations
- 1Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
- 2Brain Research Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
- 3State Key Laboratory of Metabolism and Regulation in Complex Organisms, College of Chemistry and Molecular Sciences, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei 430071, China
- 4Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China
- 5Neurosurgical Institute, Nanjing University, Nanjing, Jiangsu 210008, China
- 6Department of Neurosurgery, Guangdong Sanjiu Brain Hospital, Guangzhou, Guangdong 510510, China
- 7Department of Neurosurgery, Hainan Second People’s Hospital, Wuzhishan City, Hainan 572200, China
- 8Medical Research Institute, Wuhan University, Wuhan, Hubei 430071, China
- 9Sino-Italian Ascula Brain Science Joint Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
Abstract
Moyamoya disease (MMD) lacks reliable biomarkers for distinguishing it from atherosclerotic cerebrovascular disease (ACVD) and predicting postoperative collateral formation (PCF). Here, we apply low-input, bisulfite-free TET-assisted pyridine borane sequencing to plasma cell-free DNA (cfDNA) from 39 MMD and 37 ACVD patients in the discovery cohort and 40 MMD and 16 ACVD patients in an external multicenter cohort. The same libraries enable the analysis of methylation, fragmentation, end-nucleotide composition, nucleosome positioning, and tissue-of-origin signals. Although global methylation and tissue-of-origin profiles are broadly similar, differentially methylated regions distinguish MMD from ACVD and associate with PCF. A cfDNA methylation model achieves areas under the curve (AUCs) of 0.923 and 0.822 in the discovery and external cohorts, respectively, while a separate model predicts PCF with AUCs of 0.907 and 0.854. These findings provide proof-of-concept evidence for cfDNA methylation profiling as a minimally invasive approach to MMD diagnosis and preoperative assessment, while establishing an epigenomic resource for future studies.
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BibTeX
@article{chen2026genomewide,
title = {{Genome-wide cell-free DNA methylation profiling via TAPS for moyamoya disease diagnosis and postoperative collateral formation prediction}},
author = {Tongyu Chen and Zetian Jia and Ying Tang and Jianjian Zhang and Yi Zhang and Xiaojian Li and Jiazhi Jiang and Jin Yu and Tingbao Zhang and Dongliang Guo and Da Liu and Hao Peng and Jincao Chen and Wei Wei and Wei Li and Yibin Liu and Xiang Li},
journal = {Cell Reports Medicine},
year = {2026},
month = sep,
doi = {10.1016/j.xcrm.2026.103075},
url = {https://doi.org/10.1016/j.xcrm.2026.103075},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Genome-wide cell-free DNA methylation profiling via TAPS for moyamoya disease diagnosis and postoperative collateral formation prediction
AU - Tongyu Chen
AU - Zetian Jia
AU - Ying Tang
AU - Jianjian Zhang
AU - Yi Zhang
AU - Xiaojian Li
AU - Jiazhi Jiang
AU - Jin Yu
AU - Tingbao Zhang
AU - Dongliang Guo
AU - Da Liu
AU - Hao Peng
AU - Jincao Chen
AU - Wei Wei
AU - Wei Li
AU - Yibin Liu
AU - Xiang Li
PY - 2026
DA - 2026/09/24
JO - Cell Reports Medicine
DO - 10.1016/j.xcrm.2026.103075
UR - https://doi.org/10.1016/j.xcrm.2026.103075
AB - Moyamoya disease (MMD) lacks reliable biomarkers for distinguishing it from atherosclerotic cerebrovascular disease (ACVD) and predicting postoperative collateral formation (PCF). Here, we apply low-input, bisulfite-free TET-assisted pyridine borane sequencing to plasma cell-free DNA (cfDNA) from 39 MMD and 37 ACVD patients in the discovery cohort and 40 MMD and 16 ACVD patients in an external multicenter cohort. The same libraries enable the analysis of methylation, fragmentation, end-nucleotide composition, nucleosome positioning, and tissue-of-origin signals. Although global methylation and tissue-of-origin profiles are broadly similar, differentially methylated regions distinguish MMD from ACVD and associate with PCF. A cfDNA methylation model achieves areas under the curve (AUCs) of 0.923 and 0.822 in the discovery and external cohorts, respectively, while a separate model predicts PCF with AUCs of 0.907 and 0.854. These findings provide proof-of-concept evidence for cfDNA methylation profiling as a minimally invasive approach to MMD diagnosis and preoperative assessment, while establishing an epigenomic resource for future studies.
SN - 2666-3791
ER -