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.

项目摘要 在基因组中编码的多种功能元素，非编码RNA基因和 监管元素是根据其特定的功能最低的特征 对整个生物体的贡献。尽管在识别这些元素方面取得了长足的进步 在生化水平上，还有很多工作要做。将它们解析为特定功能 极大地使生物医学界能够使用它们来准确诊断遗传病变和 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 基于基因和调节元素的生物学功能，基于其进化模式 超过60种哺乳动物。这些工具还将适用于其他模型分类学组 测序的基因组，例如昆虫，线虫，植物和真菌。由此产生的功能 分配对于聚焦和确定实验努力将是无价的，并将揭示致病性 遗传突变对患者的影响。该项目专门开发和分发程序 分析显示进化时间变化的生物性状（表型）。通过利用他们的 这些程序在大量物种内的变化，确定了那些特定的遗传元素 其进化速率与特征有关。第一个目的提供了计算工具和 研究连续特征变量的算法，并将其应用于识别可容纳长期基因的算法 哺乳动物的寿命。第二个目标提供了计算工具集来确定 调节区域和非编码RNA基因，具有特定的眼睛和耳朵发育。 由此产生的增强子和启动子将非常有价值 听力和视力强化患者的非编码序列中的突变。最终目标 通过代码和基于用户友好的基于Web的接口将这些程序分发给公众。任何 生物医学研究人员将能够在哺乳动物物种上上传其感兴趣的特质/表型 并快速检索与其性状相关的基因和调节区域以及重要的统计 用于下游分析和可视化的措施和工具。提供人类和模型的访问权限 有机基因，用户将可以访问哺乳动物的预计全基因组数据集， 昆虫，线虫和真菌。该研究计划的高潮将使快速 鉴定基因和无数形态和生理的基因元素 特质，从而推动实验和医学遗传学研究，并具有进化的力量 生物学。