Long-read sequencing technologies have improved the contiguity and, as a result, the quality of genome assemblies by generating reads long enough to span and resolve complex or repetitive regions of the genome. Several groups have shown the power of long reads in detecting thousands of genomic and epigenomic features that were previously missed by short-read sequencing approaches. While these studies demonstrate how long reads can help resolve repetitive and complex regions of the genome, they also highlight the throughput and coverage requirements needed to accurately resolve variant alleles across large populations using these platforms. At the time of this review, whole-genome long-read sequencing is more expensive than short-read sequencing on the highest throughput short-read instruments; thus, achieving sufficient coverage to detect low-frequency variants (such as somatic variation) in heterogenous samples remains challenging. Targeted sequencing, on the other hand, provides the depth necessary to detect these low-frequency variants in heterogeneous populations. Here, we review currently used and recently developed targeted sequencing strategies that leverage existing long-read technologies to increase the resolution with which we can look at nucleic acids in a variety of biological contexts.

中文翻译：

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利用长读长的强大功能进行靶向测序


长读长测序技术通过生成足够长的读长来跨越和解析基因组的复杂或重复区域，从而提高了基因组组装的质量。几个小组已经展示了长读长在检测数千个基因组和表观基因组特征方面的力量，这些特征以前被短读长测序方法遗漏了。虽然这些研究证明了长读长如何帮助解析基因组的重复和复杂区域，但它们也强调了使用这些平台准确解析大量群体中的变异等位基因所需的通量和覆盖度要求。在进行本综述时，全基因组长读长测序比最高通量短读长仪器上的短读长测序更昂贵;因此，实现足够的覆盖率以检测异质性样品中的低频变异（例如体细胞变异）仍然具有挑战性。另一方面，靶向测序提供了在异质性群体中检测这些低频变异所需的深度。在这里，我们回顾了当前使用和最近开发的靶向测序策略，这些策略利用现有的长读长技术来提高分辨率，从而我们可以在各种生物学环境中观察核酸。