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方法 在人类基因组中，通过真正的单分子，超高精度的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，并且 是基因组中变异最大的DNA序列之一。这些微卫星区域的突变，或 所谓的微卫星不稳定性（MSI），包括重复数的扩大或缩小， 单核苷酸多态性（SNP）和/或插入或缺失（indels），这些已被记录 所有癌症类型的癌症。不幸的是，目前的测序技术，包括下一代测序技术， 测序（NGS）和第三代测序（TGS）不能对微卫星进行测序， 由于所用方法的限制，MSI具有任何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。在本阶段I SBIR期间 EBS将专注于开发一个新的平台和测序方法，专门针对 微型卫星在该计划期间进行的调查将使新的方法来探测 微卫星、MSI和人类基因组，直接改善了基础癌症研究， 从而能够极大地改进临床诊断和/或诊断学技术。

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.