Exonuclease Based Microsatellite Sequencing

项目摘要 电子生物科学(EBS)将研究和开发微卫星区域测序的方法 在人类基因组中，通过真正的单分子、超高精度方法进行癌症基因分型。 微卫星是简单/短重复序列(长度为1-10个核苷酸)，串联出现5-50次， 基因组中变异最大的DNA序列类型。这些微卫星区域的突变，或 所谓的微卫星不稳定性(MSI)包括重复数的扩张或收缩， 单核苷酸多态(SNPs)和/或插入或缺失(Indels)，已有文献记载 所有当前类型的癌症。不幸的是，目前的测序技术，包括下一代 测序(NGS)和第三代测序(TGS)不能对微卫星和 由于所用方法的限制，MSI具有任何种类的临床相关准确度或精密度， 这严重阻碍了对这些类型序列的理解。在此第一阶段SBIR期间 计划，EBS将专注于开发专门针对以下目标的新平台和排序方法 微型卫星。在该计划期间进行的调查将使新的调查方法成为可能 微卫星、微卫星和人类基因组，直接改善基础癌症研究，并最终 使临床诊断和/或预后技术得到极大改进。

Project Summary Electronic BioSciences (EBS) will investigate and develop methodologies to sequence microsatellite regions within the human genome to enable cancer genotyping via a true single-molecule, ultra-high-accuracy approach. Microsatellites are simple/short repeats (1-10 nucleotides in length) that occur in tandem 5-50 times and are among the most variable types of DNA sequence in the genome. Mutations to these microsatellite regions, or what is referred to as microsatellite instability (MSI), includes expansion or contraction of the repeat number, single nucleotide polymorphisms (SNPs), and/or insertions or deletions (indels), which have been documented with all current types of cancer. Unfortunately, current sequencing technologies, including both next generation sequencing (NGS) and third generation sequencing (TGS), are not capable of sequencing microsatellites and MSI with any sort of clinically relevant accuracy or precision due to limitations with the methodology utilized, which has significantly hindered the understanding of these types of sequences. During this Phase I SBIR program, EBS will focus on developing a new platform and sequencing approach specifically aimed at microsatellites. The investigations performed during this program will enable new approaches to probe microsatellites, MSI and the human genome in general, directly improving basic cancer research and ultimately enabling vastly improved clinical diagnostics and/or prognostics technologies.