标题： 稀有等位基因检测使用压缩测序 显示英文标题

标题： Rare-Allele Detection Using Compressed Se(que)nsing

摘要： 通过重新测序检测稀有变异对于识别携带疾病变异的个体非常重要。 新型技术的快速测序使得目标区域的低成本重新测序成为可能，尽管测试超过几个个体仍然成本过高。 为了改善成本权衡，最近建议应用池化设计，这可以检测个体群体中稀有等位基因的携带者。 然而，这仅在池中个体数量相对较少时成立，并且需要为特定情况设计池化方案。 我们提出了一种新的池化设计，基于压缩感知方法，该方法既通用、简单又高效。 我们对实验过程进行了建模，并通过计算机模拟表明，它能够从比以前更大的群体中恢复稀有等位基因携带者，尤其是在每个个体获得高覆盖度的情况下。 我们的方法还可以与条形码技术结合，以提高性能并提供基于当前重新测序成本的可行解决方案。 例如，当针对足够小的基因组区域（约100个碱基对）并仅使用约10个测序通道和约10个不同的条形码时，可以从超过4000个个体的群体中恢复出4个稀有等位基因携带者的身份。 显示英文摘要

摘要： Detection of rare variants by resequencing is important for the identification of individuals carrying disease variants. Rapid sequencing by new technologies enables low-cost resequencing of target regions, although it is still prohibitive to test more than a few individuals. In order to improve cost trade-offs, it has recently been suggested to apply pooling designs which enable the detection of carriers of rare alleles in groups of individuals. However, this was shown to hold only for a relatively low number of individuals in a pool, and requires the design of pooling schemes for particular cases. We propose a novel pooling design, based on a compressed sensing approach, which is both general, simple and efficient. We model the experimental procedure and show via computer simulations that it enables the recovery of rare allele carriers out of larger groups than were possible before, especially in situations where high coverage is obtained for each individual. Our approach can also be combined with barcoding techniques to enhance performance and provide a feasible solution based on current resequencing costs. For example, when targeting a small enough genomic region (~100 base-pairs) and using only ~10 sequencing lanes and ~10 distinct barcodes, one can recover the identity of 4 rare allele carriers out of a population of over 4000 individuals.