CAREER: Algorithms for single molecule sequence analysis

职业：单分子序列分析算法

• 批准号: 1350041
• 负责人: Michael Schatz
• 金额: $ 153.43万
• 依托单位: Cold Spring Harbor Laboratory
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1350041&HistoricalAwards=false
• 关键词: CAREER; Algorithms; single; molecule; sequence

The Cold Spring Harbor Laboratory is awarded a CAREER grant for the PI Michael Schatz to develop new computational methods for processing DNA sequencing data from the latest high-throughput sequencing technologies. DNA sequencing costs and throughput have improved by orders of magnitudes over the last three decades, although many questions remain unsolved, especially because of the short sequence lengths currently available. Emerging "third generation" sequencing technology from Pacific Biosciences, Moleculo, Oxford Nanopore, and other companies are poised to revolutionize genomics by enabling the sequencing of long, individual molecules of DNA and RNA. The sequence lengths with these technologies can reach up to tens of thousands of nucleotides, however few or no analysis packages are capable of dealing with these types of genetic sequence data. This project will overcome these limitations by developing several novel analysis algorithms specifically for long read single molecule sequencing and their associated complex error models. The outcomes will help answer biological questions of profound significance to all of society, such as: What were the genetic implications of the domestication of rice? What genes and regulatory elements give rise to the incredible regenerative properties of the flatworm? or, What can be understood from assembling reference genomes of sugarcane and pineapple towards breeding more robust plant crops and biofuels?Specific objectives of the research include working towards assembling entire plant and animal chromosomes into complete, haplotype-phased sequences; identifying fusion genes and complex alternative splicing patterns responsible for diseases or adaptability; and searching for structural variations associated with improved crop yield or human diseases such as cancer or autism. Even if some future technology is capable of directly reading entire transcripts or entire genomes, this research will remain necessary to examine the higher level relationships across populations of genomes or in measuring the dynamics of gene expression and splicing.This project will tightly integrate research and education, promoting opportunities at high school through postdoctoral levels with the development of new course materials, hands-on research opportunities, and one-on-one mentoring experiences. This effort will specifically target the intersection of computer science and biology, promoting interdisciplinary education, and ensuring the next generation of scientists are ready for the complexities of quantitative and digital biology. To engage the widest possible audience, Dr Schatz will also develop novel online teaching materials made available through a yearly bioinformatics contest. The first round of the contest reached nearly 1000 students around the world and at all levels of education, engaging students far beyond our physical limits. The products of the research will be made available as open-source software, and installed into the graphical iPlant Discovery Environment making them easily accessible to the large community of plant researcher around the world.

冷泉港实验室获得了 PI Michael Schatz 的职业资助，用于开发新的计算方法来处理来自最新高通量测序技术的 DNA 测序数据。在过去三十年里，DNA 测序成本和通量已经提高了几个数量级，但许多问题仍未解决，特别是因为目前可用的序列长度很短。 Pacific Biosciences、Moleculo、Oxford Nanopore 和其他公司的新兴“第三代”测序技术有望通过对长的 DNA 和 RNA 单个分子进行测序，从而彻底改变基因组学。这些技术的序列长度可以达到数万个核苷酸，但是很少或没有分析包能够处理这些类型的基因序列数据。该项目将通过开发几种专门针对长读单分子测序及其相关复杂错误模型的新颖分析算法来克服这些限制。研究结果将有助于回答对整个社会具有深远意义的生物学问题，例如：水稻驯化对遗传有何影响？哪些基因和调控元件赋予了扁虫令人难以置信的再生特性？或者，通过组装甘蔗和菠萝的参考基因组来培育更强大的植物作物和生物燃料，可以理解什么？该研究的具体目标包括致力于将整个植物和动物染色体组装成完整的单倍型定相序列；识别导致疾病或适应性的融合基因和复杂的选择性剪接模式；寻找与作物产量提高或癌症或自闭症等人类疾病相关的结构变异。即使未来的某些技术能够直接读取整个转录本或整个基因组，这项研究仍然有必要来检查基因组群体之间的更高层次的关系或测量基因表达和剪接的动态。该项目将研究和教育紧密结合起来，通过开发新的课程材料、实践研究机会和一对一的指导经验，促进从高中到博士后的机会。这项工作将专门针对计算机科学和生物学的交叉点，促进跨学科教育，并确保下一代科学家为应对定量和数字生物学的复杂性做好准备。为了吸引尽可能多的受众，沙茨博士还将开发新颖的在线教材，通过每年一度的生物信息学竞赛提供。第一轮比赛吸引了来自世界各地、各个教育层次的近千名学生，学生的参与度远远超出了我们的身体极限。该研究的产品将作为开源软件提供，并安装到图形化的 iPlant Discovery 环境中，使世界各地的大型植物研究人员社区可以轻松访问它们。

项目成果

Automated assembly scaffolding elevates a new tomato system for high-throughput genome editing

• DOI: 10.1101/2021.11.18.469135
• 发表时间: 2021-11-19
• 期刊: bioRxiv
• 作者: Alonge, M.;Lebeigle, L.;Soyk, S.
• 通讯作者: Soyk, S.

The human origin recognition complex is essential for pre-RC assembly, mitosis, and maintenance of nuclear structure.

• DOI: 10.7554/elife.61797
• 发表时间: 2021-02-01
• 期刊: eLife
• 影响因子: 7.7
• 作者: Chou HC;Bhalla K;Demerdesh OE;Klingbeil O;Hanington K;Aganezov S;Andrews P;Alsudani H;Chang K;Vakoc CR;Schatz MC;McCombie WR;Stillman B
• 通讯作者: Stillman B

Sapling: accelerating suffix array queries with learned data models

• DOI: 10.1093/bioinformatics/btaa911
• 发表时间: 2021-03-15
• 期刊: BIOINFORMATICS
• 影响因子: 5.8
• 作者: Kirsche, Melanie;Das, Arun;Schatz, Michael C.
• 通讯作者: Schatz, Michael C.

Recovering rearranged cancer chromosomes from karyotype graphs

• DOI: 10.1186/s12859-019-3208-4
• 发表时间: 2019-12-17
• 期刊: BMC BIOINFORMATICS
• 影响因子: 3
• 作者: Aganezov, Sergey;Zban, Ilya;Schatz, Michael C.
• 通讯作者: Schatz, Michael C.

Pan-genomic matching statistics for targeted nanopore sequencing.

• DOI: 10.1016/j.isci.2021.102696
• 发表时间: 2021-06-25
• 期刊: iScience
• 影响因子: 5.8
• 作者: Ahmed O;Rossi M;Kovaka S;Schatz MC;Gagie T;Boucher C;Langmead B
• 通讯作者: Langmead B