使用磁性纳米平台的高分辨率 DNA 大小富集及其在非侵入性产前检测中的应用。,Analyst

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使用磁性纳米平台的高分辨率 DNA 大小富集及其在非侵入性产前检测中的应用。
Analyst ( IF 3.6 ) Pub Date : 2020-07-17 , DOI: 10.1039/d0an00813c
Bo Zhang ₁ , Shuting Zhao , Hao Wan , Ying Liu , Fei Zhang , Xin Guo , Wenqi Zeng , Haiyan Zhang , Linghua Zeng , Jiale Qu , Ben-Qing Wu , Xinhong Wan , Charles R Cantor , Dongliang Ge

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精确的 DNA 大小可以提高测序效率、降低成本、提高数据质量，甚至允许对低输入样本进行测序，而目前普遍的 DNA 大小方法无法以高分辨率（<20 bp）区分 200 bp 以下的 DNA 片段。在无创产前检测 (NIPT) 中，母体血浆中胎儿游离 DNA 的大小分布（主峰 143 bp）与母体游离 DNA 的大小分布（主峰 166 bp）有显着差异。当前普遍存在的 NIPT 和 DNA 大小测定工作流程无法利用这种 20 bp 差异，从而导致样本拒绝、测试不准确和临床应用受限。在这里，我们报告了一个简单、可自动化、高分辨率的 DNA 大小富集工作流程，名为 MiniEnrich，在磁性纳米平台上利用这种 20 bp 大小差异并从母血中富集胎儿 DNA 片段。开发了两种类型的磁性纳米粒子，一种能够以高分辨率过滤高分子量 DNA，另一种能够以 >95% 的收率回收目标尺寸阈值下的剩余 DNA 片段。使用这种方法，通过血浆 DNA 测序测量，富集后平均胎儿分数从 13% 增加到 20%。这种方法为 200 bp 以下的高分辨率 DNA 大小富集提供了一种新工具，它可以通过挽救被拒绝的不可报告的临床样本来提高 NIPT 的准确性，并在怀孕早期启用 NIPT。它还具有改善胎儿单基因疾病的非侵入性筛查的潜力，

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High-resolution DNA size enrichment using a magnetic nano-platform and application in non-invasive prenatal testing.

Precise DNA sizing can boost sequencing efficiency, reduce cost, improve data quality, and even allow sequencing of low-input samples, while current pervasive DNA sizing approaches are incapable of differentiating DNA fragments under 200 bp with high resolution (<20 bp). In non-invasive prenatal testing (NIPT), the size distribution of cell-free fetal DNA in maternal plasma (main peak at 143 bp) is significantly different from that of maternal cell-free DNA (main peak at 166 bp). The current pervasive workflow of NIPT and DNA sizing is unable to take advantage of this 20 bp difference, resulting in sample rejection, test inaccuracy, and restricted clinical utility. Here we report a simple, automatable, high-resolution DNA size enrichment workflow, named MiniEnrich, on a magnetic nano-platform to exploit this 20 bp size difference and to enrich fetal DNA fragments from maternal blood. Two types of magnetic nanoparticles were developed, with one able to filter high-molecular-weight DNA with high resolution and the other able to recover the remaining DNA fragments under the size threshold of interest with >95% yield. Using this method, the average fetal fraction was increased from 13% to 20% after the enrichment, as measured by plasma DNA sequencing. This approach provides a new tool for high-resolution DNA size enrichment under 200 bp, which may improve NIPT accuracy by rescuing rejected non-reportable clinical samples, and enable NIPT earlier in pregnancy. It also has the potential to improve non-invasive screening for fetal monogenic disorders, differentiate tumor-related DNA in liquid biopsy and find more applications in autoimmune disease diagnosis.

更新日期：2020-08-24

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