Augmenting TOPMed WGS studies across the comprehensive spectrum of short tandem repeats (STRs).

总结 NHLBI TOPM全基因组测序（WGS）研究正在产生前所未有的规模， 序列读段，总计>2个四倍体碱基和> 3亿个变体，跨越> 20，000个个体。 虽然>97%的可接近的基因组区域通过现有的变体被详尽地询问， 调用方法中，由于能力有限，约3%重复序列丰富的基因组区域未得到充分询问 短串联重复序列（STR）。因为约50%的短插入和缺失（indels）被发现在 重复序列丰富的基因组区域，重要的是要全面调用STR，以达到接近完整的 从TOPMed WGS研究中识别致病变异的敏感性。 在这个应用程序中，我们建立在我们开发创新方法和分析PB的记录上。 TOPMed WGS读取以产生全面和准确的短变体调用，利用STR， 来自TOPMed WGS研究。我们利用相关和重复的样本来提高可疑交易报告的质量。 我们还建议估计线粒体DNA拷贝数和端粒长度的序列 数据，并进行全基因组关联研究，以证明新的STR增强的力量 callset。

SUMMARY The NHLBI TOPMed whole genome sequencing (WGS) studies are generating unprecedented scale of sequence reads, totaling >2 quadrillion bases and >300 million variants across >20,000 individuals. While >97% of accessible genomic regions are be exhaustively interrogated through existing variant calling methods, ~3% repeat-rich genomic regions are insufficiently interrogated due to limited ability to call short tandem repeats (STRs). Because ~50% short insertions and deletions (indels) are found in repeat-rich regions of genome, it is important to comprehensively call STRs to reach near-complete sensitivity to identify disease-causing variants from TOPMed WGS studies. In this application, we build on our record of developing innovative methods and analyzing petabytes of TOPMed WGS reads to generate comprehensive and accurate short variant calls, capitalizing on STRs, from TOPMed WGS studies. We leverage related and duplicated samples to improve the quality of STRs. We also propose to estimate mitochondrial DNA copy numbers and telomere lengths from the sequence data, and perform genome-wide association studies to demonstrate the power of the new STR-augmented callset.