Bioinformatics and Medical Information Technology Laboratory, Federal Clinical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.
Clin Chem Lab Med. 2013 Jun;51(6):1141-54. doi: 10.1515/cclm-2012-0281.
Rapidly developing next-generation sequencing (NGS) technologies produce a large amount of data across the whole human genome and allow a large number of DNA samples to be analyzed simultaneously. Screening cell-free fetal DNA (cffDNA) obtained from maternal blood using NGS technologies has provided new opportunities for non-invasive prenatal diagnosis (NIPD) of fetal aneuploidies. One of the major challenges to the analysis of fetal abnormalities is the development of accurate and reliable algorithms capable of analyzing large numbers of short sequence reads. Several such algorithms have recently been developed. Here, we provide a review of recent NGS-based NIPD methods as well as the available algorithms for short-read sequence analysis. We furthermore introduce the practical application of these algorithms for the detection of different types of fetal aneuploidies, and compare the performance, cost and complexity of each approach for clinical deployment. Our review identifies several main technologies and trends in NGS-based NIPD. The main considerations for clinical development for NIPD and screening tests using DNA sequencing are: accuracy, intellectual property, cost and the ability to screen for a wide range of chromosomal abnormalities and genetic defects. The cost of the diagnostic test depends on the sequencing method, diagnostic algorithm and volume of the tests. If the cost of sequencing equipment and reagents remains at or around current levels, targeted approaches for sequencing-based aneuploidy testing and SNP-based methods are preferred.
快速发展的新一代测序（NGS）技术在整个人类基因组中产生了大量数据，并允许同时分析大量的 DNA 样本。使用 NGS 技术筛选从母体血液中获得的游离胎儿 DNA（cffDNA）为胎儿非整倍体的非侵入性产前诊断（NIPD）提供了新的机会。分析胎儿异常的主要挑战之一是开发能够分析大量短序列读段的准确可靠的算法。最近已经开发了几种这样的算法。在这里，我们回顾了基于 NGS 的 NIPD 方法以及用于短读序列分析的现有算法。我们进一步介绍了这些算法在检测不同类型的胎儿非整倍体中的实际应用，并比较了每种方法用于临床部署的性能、成本和复杂性。我们的综述确定了基于 NGS 的 NIPD 的几种主要技术和趋势。用于 NIPD 临床开发和使用 DNA 测序的筛选测试的主要考虑因素是：准确性、知识产权、成本以及筛查广泛的染色体异常和遗传缺陷的能力。诊断测试的成本取决于测序方法、诊断算法和测试量。如果测序设备和试剂的成本保持在当前水平或接近当前水平，则首选基于测序的非整倍体检测的靶向方法和 SNP 方法。
