Scalable Cancer Genomics via Nanocoding and Sequencing

通过纳米编码和测序实现可扩展的癌症基因组学

• 批准号: 9318471
• 负责人: Jian Ma
• 金额: $ 37.32万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9318471
• 关键词: Address; Algorithms; Amaze; Beds; Bioinformatics; Biological Assay; Biomedical Research; Catalogs; Charge; Chemistry; Chromosomes; Complement; Computer Simulation; Cytogenetic Analysis; Cytogenetics; DNA; DNA Sequence Rearrangement; Data; Data Analyses; Data Set; Deposition; Development; Devices; Diagnosis; Diagnostic; Event; Fluorochrome; Future; Genetic Materials; Genome; Genomic DNA; Genomics; Glass; Goals; Graph; Hand; Human; Image; Individual; Investments; Label; Link; Malignant Neoplasms; Maps; Methods; Microfluidics; Modeling; Modification; Molecular Conformation; Multiple Myeloma; Nucleotides; Patient risk; Patients; Peripheral Blood Mononuclear Cell; Planet Earth; Planets; Process; Protocols documentation; Research Infrastructure; Research Personnel; Resolution; Risk; Sampling; Scheme; Site; Speed; Stretching; Structure; Surface; System; Techniques; Technology; Temperature; Testing; The Cancer Genome Atlas; Time; Translations; Variant; Vision; base; cancer genome; cancer genomics; candidate validation; computer framework; computer infrastructure; data acquisition; fluorescence microscope; genome analysis; genomic aberrations; high risk; human reference genome; neglect; new technology; next generation sequencing; novel; operation; programs; public health relevance; reference genome; restriction enzyme; single molecule; tool; tumor

 DESCRIPTION (provided by applicant): Cancer genomes present amazing puzzles for genomicists to solve in terms of their structures. The size of the data "pieces" for attempting assembly into a complete view are both very large (cytogenetic) and very small (sequence data), often differing in scale by more than a thousand-fold. Add to this, genomic dispersity within a tumor and breakpoints within interspersed repeats, and the puzzle solution grows much more difficult. As such, the aims of this application are to effectively seamlessly scale data "piece" size by a hierarchical framework, through new algorithms and computational pipelines that will engage both long-range physical maps constructed by significant advancements to Nanocoding, and sequence data to create scalable views of cancer genomes that span from nucleotide-to-chromosome. This multipronged project will involve synergistic advancements to: DNA labeling, presentation of very large genomic DNA molecules, scanners for single molecule analytes, and machine vision-all system components that will be informed by advanced bioinformatic analysis techniques, developed for single molecule analysis, and cutting-edge computer simulations of DNA conformations within the devices that will be the foundry for large datasets. This highly integrated system will be aimed at the discovery of novel structural variants within four paired multiple myeloma / normal samples for tabulation of previously undetectable events as candidates for validation and further study. The resulting platform, comprising new single molecule technologies, melded with advanced bioinformatics techniques, portends scalable, comprehensive, fast genome analysis for navigating cancer genomes.

 描述（由申请人提供）：癌症基因组在其结构方面为基因组学家提供了令人惊奇的难题，用于尝试组装成完整视图的数据“片段”的大小既非常大（细胞遗传学）又非常小（序列数据）。 ），通常规模相差一千倍以上，再加上肿瘤内的基因组分散性和散布的重复序列中的断点，因此，这个难题的解决变得更加困难。应用程序将通过新的算法和计算管道，通过分层框架有效地无缝缩放数据“块”大小，这些算法和计算管道将利用纳米编码的重大进步构建的远程物理图谱和序列数据，以创建跨越癌症基因组的可扩展视图这个多管齐下的项目将涉及以下方面的协同进步：DNA 标记、非常大的基因组 DNA 分子的呈现、单分子分析物扫描仪和机器视觉——所有系统组件都将被告知。通过先进的生物信息分析技术，为单分子分析而开发，以及设备内 DNA 构象的尖端计算机模拟，该设备将成为大型数据集的铸造厂，这个高度集成的系统将旨在发现四对中的新颖结构变异。多发性骨髓瘤/正常样本用于将以前无法检测到的事件制成表格，作为验证和进一步研究的候选者。由此产生的平台包含新的单分子技术，与先进的生物信息学技术相结合，预示着可扩展、全面、快速的基因组分析。导航癌症基因组。