Software for exploring all forms of genetic variation in any species

用于探索任何物种中所有形式的遗传变异的软件

基本信息

批准号：
9749979
负责人：
Aaron R Quinlan
金额：
$ 45.75万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9749979
关键词：
Address Alleles Animal Model Biology Catalogs Cell physiology ChIP-seq Complex Analysis Computer software Copy Number Polymorphism DNA sequencing Data Set Databases Diploidy Disease Genes Genetic Genetic Research Genetic Variation Genetic study Genome Genotype Haploidy Haplotypes Human Human Genome Inheritance Patterns Investigation Laboratories Livestock Mendelian disorder Methods Microscope Mining Modernization Nucleotides Organism Performance Phenotype Ploidies Polyploidy Publishing Research Research Personnel Research Support Sampling Software Framework Structure System Technology Variant base biological research blind crosslinking and immunoprecipitation sequencing data integration design experience experimental study flexibility foot genome analysis genome annotation genome-wide genome-wide analysis human disease indexing innovation insertion/deletion mutation insight software systems success tool trait transcriptome sequencing web based interface

Address Alleles Animal Model Biology Catalogs Cell physiology ChIP-seq Complex Analysis Computer software Copy Number Polymorphism DNA sequencing Data Set Databases Diploidy Disease Genes Genetic Genetic Research Genetic Variation Genetic study Genome Genotype Haploidy Haplotypes Human Human Genome Inheritance Patterns Investigation Laboratories Livestock Mendelian disorder Methods Microscope Mining Modernization Nucleotides Organism Performance Phenotype Ploidies Polyploidy Publishing Research Research Personnel Research Support Sampling Software Framework Structure System Technology Variant base biological research blind crosslinking and immunoprecipitation sequencing data integration design experience experimental study flexibility foot genome analysis genome annotation genome-wide genome-wide analysis human disease indexing innovation insertion/deletion mutation insight software systems success tool trait transcriptome sequencing web based interface

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项目摘要

Modern DNA sequencing technologies have revolutionized the design of experiments investigating the biology of the genome and the genetic basis of traits. Arguably the most powerful application of these technologies has been the creation of exquisitely detailed catalogs describing the landscape of genetic variation in multiple species. However, discovery of genetic variation is merely the beginning. Exploration and analysis of the resulting catalogs is required to catalyze new insights into the relationship between genotype and phenotype. This proposal is motivated by two fundamental limitations inhibiting discovery from genetic variation datasets. First, existing software for mining variation to understand disease and other traits does not scale to large datasets involving thousands of samples. Second, most existing tools are focused on human studies; consequently, this inhibits the application of modern DNA sequencing to genetic studies of model organisms, livestock genetics, and newly sequenced species. We propose to solve these challenges by building upon our GEMINI framework. Since 2012, we have maintained GEMINI as a powerful software framework for exploring genome variation. GEMINI's strength is that it integrates genetic variation with a diverse set of genome annotations into a database to facilitate variant prioritization. It allows researchers to conduct complex analyses with simple queries based on sample genotypes, phenotypes, inheritance patterns, and genome annotations. GEMINI has quickly become a very popular tool for rare human disease research leading to discoveries by multiple labs, including our own. Despite its power and popularity, GEMINI has three important limitations. It was not designed for studies involving genetic variation from more than a few hundred samples. Furthermore, its focus is the analysis of single-nucleotide (SNP) and insertion-deletion (INDEL); it is blind to structural and copy number variation. Finally, GEMINI can only analyze genetic variation datasets for the human genome; no other species or genome builds are supported. Therefore, this proposal seeks to provide geneticists studying any species with a powerful, flexible and simple to use software system that is fast and scalable enough to support genetic research for many years to come. We will do this but achieving the following Specific Aims: (1) Develop a scalable, high performance genotype and haplotype query engine to empower large scale genome studies. (2) Devise new methods for genotyping, integrating and prioritizing structural variation. (3) Enable scalable, flexible genome analysis in any species and genome build. In summary, by completing these aims, the proposed research will provide geneticists studying any species with a powerful, flexible and simple to use software system that is fast and scalable enough to support genetic research for many years to come.

现代DNA测序技术已彻底改变了研究的实验设计基因组的生物学和特征的遗传基础。可以说是这些最强大的应用技术已经创建了描述遗传景观的精美详细目录多种物种的变化。但是，遗传变异的发现仅仅是开始。探索和需要对所得目录的分析来催化对基因型之间关系的新见解和表型。该提议是由两个基本限制抑制了遗传发现的基本限制的动机变体数据集。首先，现有用于理解疾病和其他特征的采矿变化软件不会扩展到涉及数千个样本的大型数据集。其次，大多数现有工具都集中在人类上研究；因此，这抑制了现代DNA测序在模型的遗传研究中的应用生物，牲畜遗传学和新测序的物种。我们建议通过建立双子座框架来解决这些挑战。自2012年以来，我们有将双子座保留为探索基因组变异的强大软件框架。双子座的力量是它将遗传变异与各种基因组注释集整合到数据库中，以促进变体优先级。它允许研究人员根据样品进行简单查询进行复杂的分析基因型，表型，遗传模式和基因组注释。双子座很快变得非常稀有人类疾病研究的流行工具，导致包括我们自己在内的多个实验室发现。尽管具有其力量和知名度，但双子座仍有三个重要的局限性。它不是为涉及数百多个样本的遗传变异的研究。此外，它的重点是分析单核苷酸（SNP）和插入 - 缺失（Indel）；它对结构和拷贝数视而不见变化。最后，双子座只能分析人类基因组的遗传变异数据集。没有其他物种或支持基因组构建。因此，该提议旨在为研究任何物种的遗传学家提供具有功能强大，灵活且易于使用的软件系统，该软件系统足够快，可扩展以支持遗传未来多年的研究。我们将做到这一点，但要实现以下特定目标：（1）开发可扩展的高性能基因型和单倍型查询引擎以授权大规模基因组研究。（2）设计用于基因分型，整合和确定结构变化的新方法。（3）在任何物种和基因组构建中启用可扩展的，灵活的基因组分析。总而言之，通过完成这些目标，拟议的研究将为研究任何人提供遗传学家具有功能强大，灵活且易于使用的软件系统的物种，足以支持足以支持遗传研究已有很多年了。