TY - JOUR
T1 - ChIP-seq of plasma cell-free nucleosomes identifies gene expression programs of the cells of origin
AU - Sadeh, Ronen
AU - Sharkia, Israa
AU - Fialkoff, Gavriel
AU - Rahat, Ayelet
AU - Gutin, Jenia
AU - Chappleboim, Alon
AU - Nitzan, Mor
AU - Fox-Fisher, Ilana
AU - Neiman, Daniel
AU - Meler, Guy
AU - Kamari, Zahala
AU - Yaish, Dayana
AU - Peretz, Tamar
AU - Hubert, Ayala
AU - Cohen, Jonathan E.
AU - Salah, Azzam
AU - Temper, Mark
AU - Grinshpun, Albert
AU - Maoz, Myriam
AU - Abu-Gazala, Samir
AU - Ben Ya’acov, Ami
AU - Shteyer, Eyal
AU - Safadi, Rifaat
AU - Kaplan, Tommy
AU - Shemer, Ruth
AU - Planer, David
AU - Galun, Eithan
AU - Glaser, Benjamin
AU - Zick, Aviad
AU - Dor, Yuval
AU - Friedman, Nir
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/5
Y1 - 2021/5
N2 - Cell-free DNA (cfDNA) in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells and retain some of the cell-of-origin histone modifications. In this study, we applied chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) to 268 human samples. In healthy donors, we identified bone marrow megakaryocytes, but not erythroblasts, as major contributors to the cfDNA pool. In patients with a range of liver diseases, we showed that we can identify pathology-related changes in hepatocyte transcriptional programs. In patients with metastatic colorectal carcinoma, we detected clinically relevant and patient-specific information, including transcriptionally active human epidermal growth factor receptor 2 (HER2) amplifications. Altogether, cfChIP-seq, using low sequencing depth, provides systemic and genome-wide information and can inform diagnosis and facilitate interrogation of physiological and pathological processes using blood samples.
AB - Cell-free DNA (cfDNA) in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells and retain some of the cell-of-origin histone modifications. In this study, we applied chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) to 268 human samples. In healthy donors, we identified bone marrow megakaryocytes, but not erythroblasts, as major contributors to the cfDNA pool. In patients with a range of liver diseases, we showed that we can identify pathology-related changes in hepatocyte transcriptional programs. In patients with metastatic colorectal carcinoma, we detected clinically relevant and patient-specific information, including transcriptionally active human epidermal growth factor receptor 2 (HER2) amplifications. Altogether, cfChIP-seq, using low sequencing depth, provides systemic and genome-wide information and can inform diagnosis and facilitate interrogation of physiological and pathological processes using blood samples.
UR - http://www.scopus.com/inward/record.url?scp=85099286111&partnerID=8YFLogxK
U2 - 10.1038/s41587-020-00775-6
DO - 10.1038/s41587-020-00775-6
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 33432199
AN - SCOPUS:85099286111
SN - 1087-0156
VL - 39
SP - 586
EP - 598
JO - Nature Biotechnology
JF - Nature Biotechnology
IS - 5
ER -