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（由适用提供）：癌症基因组表现出了惊人的难题，供基因组学家根据其结构解决。用于尝试组装成完整视图的数据“零件”的大小既非常大（细胞遗传学）和很小的（序列数据），通常会在规模上区分超过一千倍。此外，肿瘤内的基因组分散体和散布重复序列的断点，拼图溶液变得更加困难。因此，本应用的目的是通过层次框架，新算法和计算管道有效地无缝扩展数据“零件”的大小，这些算法将涉及纳米胶化的重大进步构成的远程物理图，并逐步启动序列数据，以创建从核苷酸到核透明的癌症基因组的可扩展性观点。这个多管齐的项目将涉及：DNA标记，非常大的基因组DNA分子的呈现，用于单分子分析仪的扫描仪以及机器视觉 - 所有系统组件，这些组件将由先进的生物信息信息分析技术告知，这些技术将开发用于单分子分析和较大的DNA构图的DATES供DEADES在DESWICES中开发的，并将其构建为DEADECES，是该驱动器的模拟。这个高度集成的系统将针对在四个配对的多个骨髓瘤 /正常样品中发现新的结构变体，以制成以前不可发现的事件作为验证和进一步研究的候选事件。最终的平台完成了新的单分子技术，并与先进的生物信息学技术融合在一起，预示着可扩展的，全面的，快速的基因组分析，用于导航癌症基因组。