Department of Medicine and Radiology, Stanford University School of Medicine, Stanford, CA 94305-5454, USA.
Circ Res. 2013 Jun 7;112(12):1613-23. doi: 10.1161/CIRCRESAHA.113.300939.
High throughput sequencing technologies have become essential in studies on genomics, epigenomics, and transcriptomics. Although sequencing information has traditionally been elucidated using a low throughput technique called Sanger sequencing, high throughput sequencing technologies are capable of sequencing multiple DNA molecules in parallel, enabling hundreds of millions of DNA molecules to be sequenced at a time. This advantage allows high throughput sequencing to be used to create large data sets, generating more comprehensive insights into the cellular genomic and transcriptomic signatures of various diseases and developmental stages. Within high throughput sequencing technologies, whole exome sequencing can be used to identify novel variants and other mutations that may underlie many genetic cardiac disorders, whereas RNA sequencing can be used to analyze how the transcriptome changes. Chromatin immunoprecipitation sequencing and methylation sequencing can be used to identify epigenetic changes, whereas ribosome sequencing can be used to determine which mRNA transcripts are actively being translated. In this review, we will outline the differences in various sequencing modalities and examine the main sequencing platforms on the market in terms of their relative read depths, speeds, and costs. Finally, we will discuss the development of future sequencing platforms and how these new technologies may improve on current sequencing platforms. Ultimately, these sequencing technologies will be instrumental in further delineating how the cardiovascular system develops and how perturbations in DNA and RNA can lead to cardiovascular disease.
高通量测序技术已成为基因组学、表观基因组学和转录组学研究的重要手段。尽管测序信息传统上是通过一种称为 Sanger 测序的低通量技术来阐明的，但高通量测序技术能够并行测序多个 DNA 分子，一次能够测序数亿个 DNA 分子。这一优势使得高通量测序能够用于创建大型数据集，从而更全面地了解各种疾病和发育阶段的细胞基因组和转录组特征。在高通量测序技术中，全外显子组测序可用于识别可能导致许多遗传性心脏疾病的新型变体和其他突变，而 RNA 测序可用于分析转录组的变化。染色质免疫沉淀测序和甲基化测序可用于识别表观遗传变化，而核糖体测序可用于确定哪些 mRNA 转录本正在被积极翻译。在这篇综述中，我们将概述各种测序方式的差异，并根据相对读取深度、速度和成本来考察市场上的主要测序平台。最后，我们将讨论未来测序平台的发展以及这些新技术如何改进现有测序平台。最终，这些测序技术将有助于进一步阐明心血管系统的发育方式，以及 DNA 和 RNA 的干扰如何导致心血管疾病。
