The Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Nat Biotechnol. 2021 May;39(5):586-598. doi: 10.1038/s41587-020-00775-6. Epub 2021 Jan 11.
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.
血浆中的无细胞游离 DNA（cfDNA）提供了关于其起源的器官或肿瘤中病理过程的分子信息。这些 DNA 片段来源于死亡细胞中碎片化的染色质，保留了一些起源细胞的组蛋白修饰。在这项研究中，我们应用了携带活性染色质修饰的无细胞核小体的染色质免疫沉淀 followed by sequencing（cfChIP-seq）技术，对 268 个人类样本进行了分析。在健康供体中，我们发现骨髓巨核细胞而非红细胞是 cfDNA 池的主要来源。在患有一系列肝脏疾病的患者中，我们表明我们可以识别与肝转录程序相关的病理变化。在转移性结直肠癌患者中，我们检测到了具有临床意义和患者特异性的信息，包括转录激活的人类表皮生长因子受体 2（HER2）扩增。总之，cfChIP-seq 技术使用低测序深度提供了系统和全基因组信息，可以为血液样本的诊断和生理及病理过程的研究提供信息。
