Informatics resources for liquid biopsy research

摘要 液体活检是一种非侵入性的替代手术活检，使医生能够 通过非实体生物组织发现有关肿瘤的一系列信息，主要是 血人类血液中的无细胞DNA（cfDNA）已成为遗传学的理想来源。 用于癌症检测和监测的信息。死亡细胞释放cfDNA片段 进入血流，包括肿瘤细胞释放的循环肿瘤DNA。在 原则上，肿瘤cfDNA含有与肿瘤细胞相同的遗传和表观遗传改变 他们来自。这些分子改变包括（但不限于）单核苷酸改变。 变异（SNV）、结构变异、拷贝数变异和DNA甲基化变化。 下一代测序已广泛用于“液体活检”，用于靶向或靶向治疗。 cfDNA的全基因组分析。鉴于cfDNA作为DNA混合物的固有性质， 碎片释放的所有可能的细胞在体内，并考虑到需求的敏感性和 由于在检测ctDNA的微小部分中的特异性，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，这是一个迫切的需求相匹配。这项建议 旨在满足这一需求。具体而言，我们将开发用于cfDNA分析的R-工作流程 基因组和表观基因组测序数据。我们将广泛地记录软件工具包， 并提供详细的在线手册，使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.