Massively Parallel Contiguity Mapping

大规模并行连续性映射

• 批准号: 9064787
• 负责人: Jay Ashok Shendure
• 金额: $ 55.24万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9064787
• 关键词: Advanced Development; Algorithms; Award; Cancer cell line; Chromatin; Chromosome Mapping; Chromosomes; Clinical; Collaborations; Coupled; DNA; DNA Resequencing; DNA Sequence; Data; Data Set; Development; Diagnostic; Drops; Funding; Genetic; Genetic Polymorphism; Genetic Variation; Genome; Genomic DNA; Genomics; Goals; Haploidy; Haplotypes; Hela Cells; Human Genome; Human Genome Project; In Situ; In Vitro; Individual; Length; Libraries; Maps; Methods; Molecular Weight; Nucleotides; Optics; Organism; Performance; Phase; Probability; Public Health; Reading; Recovery; Resolution; Role; Shotguns; Source; Technology; base; cancer genome; combinatorial; comparative; cost; cost effective; density; epigenome; fetal; genome-wide; human disease; human reference genome; improved; indexing; mammalian genome; nanopore; new technology; novel strategies; personalized medicine; programs; public health relevance; tumorigenesis; virtual

DESCRIPTION (provided by applicant): Even as new technologies continue to drive down the cost of DNA sequencing, we are in critical need of equivalently powerful methods informing long-range contiguity to support both de novo genome assembly and haplotype-resolved genome resequencing. With funding through this program, we have explored diverse approaches for low-cost, massively parallel capture of contiguity information. Our progress is substantial, and includes the development of a method for in situ library construction and optical sequencing, a method in which we exploit 'contact probability maps' to produce the first chromosome-scale de novo mammalian genome assemblies based exclusively on short reads, and a method that combines contiguity preserving transposition and combinatorial indexing for accurate, megabase-scale haplotype-resolved human genome resequencing. We have also demonstrated the remarkable value of contiguity information through signature projects, including the first accurate, non-invasive prediction of a fetal genome, and the first haplotype-resolved sequencing of a cancer genome and epigenome. In this renewal application, we propose to narrow our focus to the advanced development of our two most promising approaches, namely contact probability mapping (Aim 1) and contiguity preserving transposition (Aim 2). We will then formally evaluate these methods for cost, performance and scalability, while also seeking to integrate them with one another and with emerging sequencing paradigms (Aim 3). Coupled with a modest drop in the per-base cost of short read DNA sequencing, these methods will enable chromosome-scale de novo assembly of large genomes as well as chromosome-scale haplotype-resolved human genome resequencing for about $1,000.

描述（由申请人提供）：即使新技术继续降低DNA测序的成本，我们仍需要等效强大的方法来告知长期连续性，以支持从头基因组组装和单倍型分辨的基因组重新陈述。通过该计划的资金，我们探索了低成本，大规模平行捕获连续性信息的多种方法。 Our progress is substantial, and includes the development of a method for in situ library construction and optical sequencing, a method in which we exploit 'contact probability maps' to produce the first chromosome-scale de novo mammalian genome assemblies based exclusively on short reads, and a method that combines contiguity preserving transposition and combinatorial indexing for accurate, megabase-scale haplotype-resolved human genome重新陈述。我们还通过签名项目证明了连续性信息的显着价值，包括对胎儿基因组的第一个准确，非侵入性预测，以及对癌症基因组和表观基因组的首次单倍型分辨测序。在此续订应用中，我们建议将重点缩小到我们两种最有前途的方法的高级发展，即接触概率映射（AIM 1）和保持连续性保存转位（AIM 2）。然后，我们将正式评估这些方法的成本，性能和可伸缩性，同时也试图将它们相互整合并与新兴的测序范式（AIM 3）。加上短读DNA测序的每碱基成本的适度下降，这些方法将使大型基因组的染色体规模从头组装以及染色体规模的单倍型分辨人基因组重新陈述约1,000美元。

项目成果

Primate evolution of the recombination regulator PRDM9.

• DOI: 10.1038/ncomms5370
• 发表时间: 2014-07-08
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Schwartz, Jerrod J.;Roach, David J.;Thomas, James H.;Shendure, Jay
• 通讯作者: Shendure, Jay

Multiplex single cell profiling of chromatin accessibility by combinatorial cellular indexing.

• DOI: 10.1126/science.aab1601
• 发表时间: 2015-05-22
• 期刊: Science (New York, N.Y.)
• 作者: Cusanovich DA;Daza R;Adey A;Pliner HA;Christiansen L;Gunderson KL;Steemers FJ;Trapnell C;Shendure J
• 通讯作者: Shendure J

Haplotype-resolved whole-genome sequencing by contiguity-preserving transposition and combinatorial indexing.

• DOI: 10.1038/ng.3119
• 发表时间: 2014-12
• 期刊: NATURE GENETICS
• 影响因子: 30.8
• 作者: Amini, Sasan;Pushkarev, Dmitry;Christiansen, Lena;Kostem, Emrah;Royce, Tom;Turk, Casey;Pignatelli, Natasha;Adey, Andrew;Kitzman, Jacob O.;Vijayan, Kandaswamy;Ronaghi, Mostafa;Shendure, Jay;Gunderson, Kevin L.;Steemers, Frank J.
• 通讯作者: Steemers, Frank J.