Multiplexed, single-molecule, epigenetic analysis of plasma-isolated nucleosomes for cancer diagnostics

Vadim Fedyuk; Nir Erez; Noa Furth; Olga Beresh; Ekaterina N Andreishcheva; Abhijeet Shinde; Daniel Jones; Barak Bar Zakai; Yael Mavor; Tamar Peretz; Ayala Hubert; Jonathan Cohen; Azzam Salah; Mark Temper; Albert Grinshpun; Myriam Maoz; Aviad Zick; Guy Ron; Efrat Shema

doi:10.1038/s41587-022-01447-3

Multiplexed, single-molecule, epigenetic analysis of plasma-isolated nucleosomes for cancer diagnostics

Vadim Fedyuk, Nir Erez, Noa Furth, Olga Beresh, Ekaterina N Andreishcheva, Abhijeet Shinde, Daniel Jones, Barak Bar Zakai, Yael Mavor, Tamar Peretz, Ayala Hubert, Jonathan Cohen, Azzam Salah, Mark Temper, Albert Grinshpun, Myriam Maoz, Aviad Zick, Guy Ron, Efrat Shema

Weizmann Institute of Science, The Hebrew University of Jerusalem

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	212-221
Number of pages	10
Journal	Nature biotechnology
Volume	41
Issue number	2
DOIs	https://doi.org/10.1038/s41587-022-01447-3
State	Published - Feb 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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10.1038/s41587-022-01447-3

es_Nature biotechnology_MultiplexedSingle-Molecule_AM2022.pdfAccepted author manuscript, 1.98 MBLicense: CC BY-NC

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Fedyuk, V., Erez, N., Furth, N., Beresh, O., Andreishcheva, E. N., Shinde, A., Jones, D., Bar Zakai, B., Mavor, Y., Peretz, T., Hubert, A., Cohen, J., Salah, A., Temper, M., Grinshpun, A., Maoz, M., Zick, A., Ron, G., & Shema, E. (2023). Multiplexed, single-molecule, epigenetic analysis of plasma-isolated nucleosomes for cancer diagnostics. Nature biotechnology, 41(2), 212-221. https://doi.org/10.1038/s41587-022-01447-3

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title = "Multiplexed, single-molecule, epigenetic analysis of plasma-isolated nucleosomes for cancer diagnostics",

abstract = "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.",

author = "Vadim Fedyuk and Nir Erez and Noa Furth and Olga Beresh and Andreishcheva, \{Ekaterina N\} and Abhijeet Shinde and Daniel Jones and \{Bar Zakai\}, Barak and Yael Mavor and Tamar Peretz and Ayala Hubert and Jonathan Cohen and Azzam Salah and Mark Temper and Albert Grinshpun and Myriam Maoz and Aviad Zick and Guy Ron and Efrat Shema",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2023",

month = feb,

doi = "10.1038/s41587-022-01447-3",

language = "الإنجليزيّة",

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Fedyuk, V, Erez, N, Furth, N, Beresh, O, Andreishcheva, EN, Shinde, A, Jones, D, Bar Zakai, B, Mavor, Y, Peretz, T, Hubert, A, Cohen, J, Salah, A, Temper, M, Grinshpun, A, Maoz, M, Zick, A, Ron, G & Shema, E 2023, 'Multiplexed, single-molecule, epigenetic analysis of plasma-isolated nucleosomes for cancer diagnostics', Nature biotechnology, vol. 41, no. 2, pp. 212-221. https://doi.org/10.1038/s41587-022-01447-3

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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 N

AU - Shinde, Abhijeet

AU - Jones, Daniel

AU - Bar Zakai, Barak

AU - Mavor, Yael

AU - Peretz, Tamar

AU - Hubert, Ayala

AU - Cohen, Jonathan

AU - Salah, Azzam

AU - Temper, Mark

AU - Grinshpun, Albert

AU - Maoz, Myriam

AU - Zick, Aviad

AU - Ron, Guy

AU - Shema, Efrat

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.

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U2 - 10.1038/s41587-022-01447-3

DO - 10.1038/s41587-022-01447-3

M3 - مقالة

C2 - 36076083

SN - 1087-0156

VL - 41

SP - 212

EP - 221

JO - Nature biotechnology

JF - Nature biotechnology

IS - 2

ER -

Multiplexed, single-molecule, epigenetic analysis of plasma-isolated nucleosomes for cancer diagnostics

Abstract

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