Functional Annotation of Genomes via Phenotypic Convergence

项目摘要 在基因组中编码的多种功能元件中，非编码的RNA基因和 就其特定的功能而言，监管要素是最不具功能性的要素之一 对整个生物体的贡献。虽然在识别这些元素方面取得了很大进展 在生物化学层面，仍有许多工作要做。将它们解析为特定的函数将 极大地使生物医学界能够使用它们来准确诊断遗传损伤并 治疗人类疾病。该项目开发并应用新的计算工具来分配特定的 基因和调控元件的生物功能，基于它们的进化模式 超过60种哺乳动物。这些工具也将适用于其他模式分类组，具有 测序的基因组，如昆虫、线虫、植物和真菌。由此产生的泛函 作业将是非常宝贵的集中和优先的实验工作，并将揭示致病 基因突变对患者的影响。该项目专门开发并分发节目给 分析随进化时间变化的生物特征(表型)。通过利用他们的 在大量物种中的变异，这些程序识别那些特定的遗传元素 其进化速度与该特征有关。第一个目标是提供计算工具和 学习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。第二个目标是提供一个计算工具集来确定 调节区和非编码的RNA基因，对眼睛和耳朵发育有特定的应用。 由此产生的一组增强子和启动子将对鉴定重要的 听力和视力受损患者的非编码序列突变。最终目标 以代码的形式并通过用户友好的基于Web的界面向公众分发这些程序。任何 生物医学研究人员将能够上传他们在哺乳动物物种中感兴趣的特征/表型 并快速检索与其特征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。提供访问人类和模特的途径 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。这一研究计划的高潮将使快速 无数形态和生理基础的基因和调控元件的鉴定 特征，从而以进化的力量推动实验和医学遗传学研究 生物学。

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.