小柯机器人

以色列魏茨曼科学研究所Efrat Shema小组在研究中取得进展。他们对用于癌症诊断的血浆分离核小体进行了多路、单分子、表观遗传分析。该项研究成果发表在2022年9月8日出版的《自然-生物技术》上。

研究人员研发了一种单分子多参数测定法，以全面分析血浆中分离核小体(EPINUC)、DNA甲基化和癌症特异性蛋白质生物标志物的表观遗传学。该系统允许通过单分子成像对数百万个单核小体上的六种活性，和抑制性组蛋白修饰及其比率和组合模式进行高分辨率检测。

此外，该系统提供有关血浆蛋白的敏感和定量数据，包括非分泌型肿瘤特异性蛋白的检测，例如p53突变。EPINUC对一组包含63例结肠直肠癌、10例胰腺癌和33例健康血浆样本进行分析，即使在早期阶段该系统也能以高准确度和灵敏度检测出癌症。最后，将EPINUC与直接单分子DNA测序相结合，可揭示结直肠、胰腺、肺和乳腺肿瘤的组织起源。EPINUC可从有限的（<1 ml）液体活检样本中获得潜在的与临床相关的多层信息。

研究人员表示，对血浆中游离DNA(cfDNA)进行分析可以获得有关身体病理过程的信息。血液cfDNA以核小体的形式存在，可维持其组织和癌症特异性的表观遗传状态。

附：英文原文

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

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

Issue&Volume: 2022-09-08

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 (<1ml) liquid biopsy material.

DOI: 10.1038/s41587-022-01447-3

Source: https://www.nature.com/articles/s41587-022-01447-3

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
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