Software and algorithms for elucidating the structure, function, and evolution of extrachromosomal DNA

项目摘要 促癌基因的体细胞拷贝数扩增(SCNA)和焦点拷贝数扩增。 具体地说，阳离子是癌症致病性的主要驱动力。最近的结果显示，这个焦点 癌基因扩增在很大程度上是由染色体外DNA(EcDNA)介导的，即大(1.3Mb 平均而言)，高度放大的、含有癌基因的环状分子，出现在近25%的癌症中 在所有亚型中，但在正常细胞中很少。尚未解决的问题，关于形成，进化，她- EcDNA的异质性和致病性正在成为发现可针对的漏洞的核心 用于诊断和治疗。拟议的项目将增强和传播“软件和算法” 以阐明染色体外DNA的结构、功能和进化.具体地说，我们将(1)取消- 利用GenePattern构建社区可访问的EcDNA重建管道--VEFET CAPER 生态系统提供了一个简单的点击式界面来运行CPU、内存和存储等繁重的软件 软件；(2)设计和实施对CAPER工作流程的新颖算法改进，包括支持 用于OMICS数据的长时间读取和集成；以及，(3)通过战略支持广泛采用CAPER 合作、外展和教育。

Project Summary Somatic copy number amplification (SCNA) of tumor promoting oncogenes, and focal copy number amplifi- cations specifically, are a major driver of cancer pathogenicity. Recent results have revealed that that focal oncogene amplification is mediated to a large extent by extrachromosomal DNA (ecDNA) i.e., large (1.3 Mb on average), highly amplified, oncogene-containing circular molecules that occur in nearly 25% of cancers across all sub-types, but rarely in normal cells. Unresolved questions regarding the formation, evolution, het- erogeneity, and pathogenicity of ecDNA are becoming central to uncovering vulnerabilities that can be targeted for diagnostics and therapy. The proposed project will enhance and disseminate “Software and algorithms for elucidating the structure, function, and evolution of extrachromosomal DNA.” Specifically, we will (1) de- velop CAPER (a Community Accessible Pipeline for EcDNA Reconstruction) by leveraging the GenePattern ecosystem to provide an easy point and click interface to running the CPU, memory and storage heavy soft- ware; (2) design and implement novel algorithmic improvements to the CAPER work flow, including support for long-reads and integration of Omics data; and, (3) enable the broad adoption of CAPER through strategic collaborations, outreach and education.