TY - JOUR
T1 - Multiplexed, single-molecule, epigenetic analysis of plasma-isolated nucleosomes for cancer diagnostics
AU - Fedyuk, Vadim
AU - Erez, Nir
AU - Furth, Noa
AU - Beresh, Olga
AU - Andreishcheva, Ekaterina
AU - Shinde, Abhijeet
AU - Jones, Daniel
AU - Zakai, Barak Bar
AU - Mavor, Yael
AU - Peretz, Tamar
AU - Hubert, Ayala
AU - Cohen, Jonathan E.
AU - Salah, Azzam
AU - Temper, Mark
AU - Grinshpun, Albert
AU - Maoz, Myriam
AU - Zick, Aviad
AU - Ron, Guy
AU - Shema, Efrat
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023/2
Y1 - 2023/2
N2 - The analysis of cell-free DNA (cfDNA) in plasma provides information on pathological processes in the body. Blood cfDNA is in the form of nucleosomes, which maintain their tissue- and cancer-specific epigenetic state. We developed a single-molecule multiparametric assay to comprehensively profile the epigenetics of plasma-isolated nucleosomes (EPINUC), DNA methylation and cancer-specific protein biomarkers. Our system allows for high-resolution detection of six active and repressive histone modifications and their ratios and combinatorial patterns on millions of individual nucleosomes by single-molecule imaging. In addition, our system provides sensitive and quantitative data on plasma proteins, including detection of non-secreted tumor-specific proteins, such as mutant p53. EPINUC analysis of a cohort of 63 colorectal cancer, 10 pancreatic cancer and 33 healthy plasma samples detected cancer with high accuracy and sensitivity, even at early stages. Finally, combining EPINUC with direct single-molecule DNA sequencing revealed the tissue of origin of colorectal, pancreatic, lung and breast tumors. EPINUC provides multilayered information of potential clinical relevance from limited (<1 ml) liquid biopsy material.
AB - The analysis of cell-free DNA (cfDNA) in plasma provides information on pathological processes in the body. Blood cfDNA is in the form of nucleosomes, which maintain their tissue- and cancer-specific epigenetic state. We developed a single-molecule multiparametric assay to comprehensively profile the epigenetics of plasma-isolated nucleosomes (EPINUC), DNA methylation and cancer-specific protein biomarkers. Our system allows for high-resolution detection of six active and repressive histone modifications and their ratios and combinatorial patterns on millions of individual nucleosomes by single-molecule imaging. In addition, our system provides sensitive and quantitative data on plasma proteins, including detection of non-secreted tumor-specific proteins, such as mutant p53. EPINUC analysis of a cohort of 63 colorectal cancer, 10 pancreatic cancer and 33 healthy plasma samples detected cancer with high accuracy and sensitivity, even at early stages. Finally, combining EPINUC with direct single-molecule DNA sequencing revealed the tissue of origin of colorectal, pancreatic, lung and breast tumors. EPINUC provides multilayered information of potential clinical relevance from limited (<1 ml) liquid biopsy material.
UR - http://www.scopus.com/inward/record.url?scp=85137566688&partnerID=8YFLogxK
U2 - 10.1038/s41587-022-01447-3
DO - 10.1038/s41587-022-01447-3
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C2 - 36076083
AN - SCOPUS:85137566688
SN - 1087-0156
VL - 41
SP - 212
EP - 221
JO - Nature Biotechnology
JF - Nature Biotechnology
IS - 2
ER -
