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

用于阐明染色体外 DNA 的结构、功能和进化的软件和算法

• 批准号: 10477356
• 负责人: Vineet Bafna
• 金额: $ 72.84万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10477356
• 关键词: Address; Adoption; Algorithmic Software; Algorithms; Architecture; Biology; Capers; Cations; Centromere; Cloud Service; Collaborations; Communities; Community Outreach; Computer software; Computing Methodologies; DNA Repair; DNA analysis; Data; Development; Diagnostic; Drug resistance; Ecosystem; Education and Outreach; Environment; Evolution; Feedback; Genes; Genetic Heterogeneity; Genomics; Goals; Heterogeneity; High Performance Computing; Hour; Lead; Letters; Libraries; Malignant Neoplasms; Maps; Mediating; Memory; Metaphase; Methods; Nature; Normal Cell; Oncogenes; Optics; Pathogenicity; Research; Resources; Running; Sampling; Stains; Structure; Technology; Visualization; Work; algorithmic methodologies; anticancer research; chromothripsis; cloud platform; computational platform; computer infrastructure; deep neural network; design; extrachromosomal DNA; genome sequencing; nanopore; novel; novel therapeutics; outreach; patient prognosis; reconstruction; single molecule; supercomputer; tool; tumor; user-friendly; whole genome

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.

项目概要 促癌基因的体细胞拷贝数扩增（SCNA）和局灶拷贝数扩增- 具体而言，阳离子是癌症致病性的主要驱动因素。 癌基因扩增在很大程度上是由染色体外 DNA (ecDNA) 介导的，即大 (1.3 Mb 平均而言），高度扩增、含有癌基因的环状分子存在于近 25% 的癌症中 跨所有亚型，但在正常细胞中很少有关于形成、进化、异质性的未解决的问题。 ecDNA 的异源性和致病性正成为发现可针对的漏洞的核心 拟议的项目将增强和传播“软件和算法”。 为了阐明染色体外 DNA 的结构、功能和进化，我们将 (1) 解- 利用 GenePattern 开发 CAPER（社区可访问的 EcDNA 重建管道） 生态系统提供一个简单的点击界面来运行CPU、内存和存储重型软件 (2) 设计并实施 CAPER 工作流程的新颖算法改进，包括支持 用于组学数据的长读取和集成；(3) 通过战略性实现 CAPER 的广泛采用； 合作、外展和教育。