Sampling the live brain is difficult and dangerous, and withdrawing cerebrospinal fluid is uncomfortable and frightening to the subject, so new sources of real-time analysis are constantly sought. Cell-free DNA (cfDNA) derived from glia and neurons offers the potential for wide-ranging neurological disease diagnosis and monitoring. However, new laboratory and bioinformatic strategies are needed. DNA methylation patterns on individual cfDNA fragments can be used to ascribe their cell-of-origin. Here we describe bisulfite sequencing assays and bioinformatic processing methods to identify cfDNA derived from glia and neurons. In proof-of-concept experiments we describe the presence of both glia- and neuron-cfDNA in the blood plasma of human subjects following mild trauma. These detection of glia- and neuron-cfDNA represents a significant step forward in the translation of liquid biopsies for neurological diseases.

中文翻译：

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亚硫酸氢盐扩增子测序可检测血浆中的 Glia 和 Neuron 游离 DNA

对活体大脑进行采样既困难又危险，提取脑脊液对受试者来说既不舒服又害怕，因此不断寻找新的实时分析来源。源自神经胶质和神经元的无细胞 DNA (cfDNA) 为广泛的神经系统疾病诊断和监测提供了潜力。然而，需要新的实验室和生物信息学策略。单个 cfDNA 片段上的 DNA 甲基化模式可用于确定其细胞来源。在这里，我们描述了亚硫酸氢盐测序分析和生物信息学处理方法，以识别源自神经胶质和神经元的 cfDNA。在概念验证实验中，我们描述了轻度创伤后人类受试者血浆中神经胶质和神经元 cfDNA 的存在。