Informatics resources for liquid biopsy research

摘要 液体活检是外科活组织检查的一种非侵入性替代方法，使医生能够 通过非固体生物组织发现一系列关于肿瘤的信息，主要是 血。人类血液中的无细胞DNA(CfDNA)已成为一种理想的遗传来源 用于癌症检测和监测的信息。死亡的细胞会释放cfDNA片段 进入血流，包括由肿瘤细胞释放的循环中的肿瘤DNA。在……里面 原理上，肿瘤cfdna包含与肿瘤细胞相同的遗传和表观遗传改变。 它们起源于。这些分子变化包括(但不限于)单核苷酸。 变异(SNV)、结构变异、拷贝数变异和DNA甲基化变化。 下一代测序已被广泛应用于靶向或靶向的液体活检 全基因组的cfDNA图谱。鉴于cfDNA作为DNA混合物的固有性质 从体内所有可能的细胞中释放出来的碎片，并考虑到敏感性和 在检测微小的ctDNA片段时，需要特定的生物信息学工具。 然而，目前还没有用户友好和全面的生物信息学工具来促进 从cfDNA测序数据中提取信息。鉴于cfDNA的巨大潜力- 基于液体活检的个性化医疗，这是一个亟待匹配的需求。这项建议 旨在满足这一需求。具体地说，我们将开发用于cfDNA分析的R-工作流 基因组和表观基因组测序数据。我们将广泛记录该软件工具包， 并提供详细的在线手册，以便非专家用户可以轻松地学习和使用其所有 功能。

Abstract A liquid biopsy is a non-invasive alternative to surgical biopsies which enables doctors to discover a range of information about a tumor through non-solid biological tissue, primarily blood. cell-free DNA (cfDNA) in human blood has emerged as an ideal source of genetic information for cancer detection and monitoring. cfDNA fragments are released by dying cells into the blood stream, including circulating tumor DNA that are released by tumor cells. In principle, tumor cfDNA contains genetic and epigenetic alterations identical to the tumor cells they originate from. These molecular alterations include (but not limited to) single nucleotide variations (SNV), structural variations, copy number variations, and DNA methylation changes. Next generation sequencing has been extensively used in “liquid biopsy” for targeted or genome-wide profiling of cfDNA. Given the inherent nature of cfDNA as a mixture of DNA fragments released from all possible cells in the body, and given the demand of sensitivity and specificity in detecting the tiny fraction of the ctDNA, specific bioinformatics tools are needed. However, currently no user-friendly and comprehensive bioinformatics tools exist to facilitate information extraction from cfDNA sequencing data. Given the enormous potential of cfDNA- based liquid biopsy in personalized medicine, this is an urgent demand to match. This proposal aims to match this need. Specifically, we will develop R-workflows for the analysis of cfDNA genomic and epigenomic sequencing data. We will extensively document the software toolkit, and provide detailed online manual so that non-expert users can easily learn and use all its functionalities.