Functional Annotation of Genomes via Phenotypic Convergence

通过表型趋同对基因组进行功能注释

• 批准号: 9328363
• 负责人: Maria D Chikina
• 金额: $ 37.79万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9328363
• 关键词: Amino Acids; Animal Model; Biochemical; Biological; Biological Process; Biology; Candidate Disease Gene; Cells; Clinical; Code; Codon Nucleotides; Communities; Computational algorithm; Computer software; Custom; DNA Sequence Alteration; Data; Data Set; Dependency; Development; Developmental Gene; Diet; Disease; Elements; Enhancers; Environment; Evolution; Exhibits; Experimental Genetics; Eye Development; Gene Expression; Genes; Genetic Research; Genetic Transcription; Genome; Genome Scan; Genomics; Health; Hearing; Human; Human Development; Imagery; Insecta; Lesion; Longevity; Mammals; Measures; Medical Genetics; Methodology; Methods; Modeling; Morphology; Mutate; Mutation; Nematoda; Nucleic Acid Regulatory Sequences; Pathogenicity; Patients; Pattern; Performance; Phenotype; Phylogenetic Analysis; Physiological; Play; Proteins; Regulatory Element; Research; Research Personnel; Research Project Grants; Role; Statistical Computing; System; Taxonomy; Testing; Time; Tissues; Untranslated RNA; Validation; Variant; Vision; Visualization software; Whole Organism; Work; accurate diagnosis; base; blind; comparative genomics; computerized tools; ear development; environmental change; epigenomics; experimental study; fungus; genetic disorder diagnosis; genetic element; genome annotation; genome browser; genome-wide; genomic data; human disease; innovation; interest; mammalian genome; novel; plant fungi; pressure; programs; promoter; response; tool; trait; user-friendly; web app; web based interface

Project Summary Of the multiple classes of functional elements encoded in the genome, non-coding RNA genes and regulatory elements are some of the least functionally characterized in terms of their specific contributions to the whole organism. While great strides have been made in identifying these elements at the biochemical level, there is still much work to be done. Parsing them into specific functions will greatly enable the biomedical community to use them to accurately diagnose genetic lesions and to treat human disease. This project develops and applies novel computational tools to assign specific biological functions to genes and regulatory elements based on their patterns of evolution among more than 60 mammalian species. The tools will also be applicable to other model taxonomic groups with sequenced genomes, such as insects, nematodes, plants, and fungi. The resulting functional assignments will be invaluable to focus and prioritize experimental efforts and will reveal the pathogenic effects of genetic mutations in patients. The project specifically develops and distributes programs to analyze organismal traits (phenotypes) that show variation over evolutionary time. By exploiting their variation within a large number of species, these programs identify those specific genetic elements whose rates of evolution are associated with the trait. The first aim provides computational tools and algorithms to study continuous trait variables, and applies them to identify genes accommodating long lifespan in mammals. The second aim delivers a computational toolset to determine the functions of regulatory regions and non-coding RNA genes, with specific applications to eye and ear development. The resulting set of enhancers and promoters will be highly valuable for the identification of important mutations in non-coding sequences of hearing- and vision-compromised patients. The final aim distributes these programs to the public as code and through a user-friendly web-based interface. Any biomedical researcher will be able to upload their trait/phenotype of interest across mammalian species and rapidly retrieve genes and regulatory regions associated with their trait along with vital statistical measures and tools for downstream analysis and visualization. To provide access to human and model organism genes, the user will have access to pre-computed genome-wide datasets in mammals, insects, nematodes, and fungi. The culmination of this research program will enable the rapid identification of genes and regulatory elements underlying countless morphological and physiological traits, thereby propelling experimental and medical genetics research with the power of evolutionary biology.

项目概要 在基因组中编码的多类功能元件中，非编码RNA基因和 监管要素是一些就其具体功能而言功能特征最不明显的要素 对整个有机体的贡献。虽然在识别这些要素方面已经取得了很大进展 在生化层面，还有很多工作要做。将它们解析为特定的函数将 极大地使生物医学界能够利用它们来准确诊断遗传病变并 治疗人类疾病。该项目开发并应用新颖的计算工具来分配特定的 基因和调控元件的生物学功能基于其进化模式 超过60种哺乳动物。这些工具也将适用于其他模型分类组 基因组测序，例如昆虫、线虫、植物和真菌。由此产生的函数 作业对于集中和确定实验工作的优先顺序将非常有价值，并将揭示致病因素 基因突变对患者的影响。该项目专门开发和分发程序 分析随进化时间而变化的有机体特征（表型）。通过利用他们的 大量物种内的变异，这些程序识别出那些特定的遗传元素 其进化速度与特征相关。第一个目标提供计算工具和 研究连续性状变量的算法，并应用它们来识别适应长的基因 哺乳动物的寿命。第二个目标提供计算工具集来确定 调控区和非编码 RNA 基因，具体应用于眼睛和耳朵的发育。 由此产生的一组增强子和启动子对于鉴定重要的增强子和启动子将非常有价值 听力和视力受损患者的非编码序列发生突变。最终目标 将这些程序以代码形式并通过用户友好的基于网络的界面分发给公众。任何 生物医学研究人员将能够上传他们感兴趣的跨哺乳动物物种的性状/表型 并快速检索与其性状相关的基因和调控区域以及重要的统计数据 用于下游分析和可视化的措施和工具。提供接触人类和模型的机会 生物体基因，用户将可以访问预先计算的哺乳动物全基因组数据集， 昆虫、线虫和真菌。该研究计划的最终成果将使 鉴定无数形态和生理学背后的基因和调控元件 性状，从而利用进化的力量推动实验和医学遗传学研究 生物学。