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: 10305480
• 负责人: Vineet Bafna
• 金额: $ 74.91万
• 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/10305480
• 关键词: Address; Adoption; Algorithmic Software; Algorithms; Architecture; Biology; Capers; Cations; Centromere; Cloud Service; Collaborations; Communities; Community Outreach; Computer software; Computing Methodologies; DNA Damage; DNA analysis; Data; Development; Diagnostic; 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; Patients; Pharmaceutical Preparations; Prognosis; Research; Resources; Running; Sampling; Stains; Structure; Technology; Visualization; Work; algorithmic methodologies; anticancer research; cloud platform; computational platform; computer infrastructure; deep neural network; design; extrachromosomal DNA; genome sequencing; nanopore; novel; novel therapeutics; outreach; 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.

项目总结