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

项目摘要 肿瘤促进癌基因的体细胞拷贝数扩增（SCNA）和局灶性拷贝数扩增（SCNA）， 特别是阳离子是癌症致病性的主要驱动因素。最近的研究结果表明， 致癌基因扩增在很大程度上由染色体外DNA（ecDNA）介导，大型（1.3 Mb 平均而言），高度扩增，含有致癌基因的环状分子，发生在近25%的癌症中 在所有亚型中，但很少在正常细胞中。关于形成、演变、het- ecDNA的雌激素性和致病性正成为揭示可作为目标的脆弱性的核心 用于诊断和治疗。拟议的项目将加强和传播“软件和算法 用于阐明染色体外DNA的结构、功能和进化。”具体而言，我们将（1）- velop CAPER（一个用于EcDNA重建的社区可扩展管道）通过利用GenePattern 生态系统提供了一个简单的点击界面，运行CPU，内存和存储沉重的软， 软件;（2）设计和实施新的算法改进CAPER的工作流程，包括支持 用于组学数据的长时间读取和集成;以及（3）通过战略性的 协作、外联和教育。

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.