Comprehensive annotation of subcellular localization of entire organisms

整个生物体亚细胞定位的综合注释

• 批准号: 7681626
• 负责人: BURKHARD ROST
• 金额: $ 30.61万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-24 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7681626
• 关键词: Accounting; Affect; Algorithms; Animal Model; Arabidopsis; Arts; Atlases; Benchmarking; Binding; Bioinformatics; Biological Transport; Biological databases; Biology; Categories; Cell Cycle; Cell Nucleus; Cells; Cereals; Chloroplasts; Collection; Communities; Computational Biology; Computer Simulation; DNA Binding; Data; Data Set; Databases; Development; Environment; Eukaryota; Evolution; Fingerprint; Follow-Up Studies; Generations; Genes; Genome; Goals; Golgi Apparatus; Homo sapiens; Human; Integral Membrane Protein; Internet; Laboratory Organism; Left; Locales; Lysosomes; Machine Learning; Mammals; Maps; Membrane; Methods; Mining; Minor; Mitochondria; Mouse-ear Cress; Nuclear; Nuclear Localization Signal; Nuclear Matrix-Associated Proteins; Nuclear Protein; Nuclear Proteins; Ontology; Organism; Outcome; Peptide Signal Sequences; Performance; Plants; Plasma; Play; Property; Proteins; Proteome; Protocols documentation; PubMed; Quality Control; RNA Splicing; Research; Resources; Ribosomes; Role; Sequence Alignment; Sequence Analysis; Signal Transduction; Software Tools; Sorting - Cell Movement; Structure; SwissProt; System; Techniques; Training; Translating; Variant; base; data mining; design; improved; insight; novel; numb protein; programs; protein function; research study; software systems; structural genomics; success; tool

DESCRIPTION (provided by applicant): The difference between the number of proteins with known sequence and those with well- studied function (sequence-function gap) is growing daily. One well-defined coarse-grained aspect of function is the native subcellular localization of a protein that has a central role in the Gene Ontology (GO) hierarchy. Many detailed and high-throughput experiments annotate localization. Where experiments do not reach, homology-based and de novo prediction methods succeed. Here, we propose the development of a comprehensive system that combines experimental resources with data mining techniques and novel prediction methods with the objective to annotate localization for entirely sequenced eukaryotes at an unprecedented detail and accuracy. Firstly, we propose to gather all available data and all relevant methods to build a comprehensive localization atlas for human and Arabidopsis. Secondly, we plan to develop novel methods tailored specifically to capture proteins for which we are left with no reliable annotations after completing the first step. We assume that these methods will focus on the prediction of the particular type of membrane into which an integral membrane protein is inserted, and of the native localization for minor eukaryotic compartments (ER, Golgi, lysosome). Thirdly, we propose the implementation of specific improvements over today's motif-based methods for secreted and nuclear proteins, as well as the extension of de novo predictions for the major compartments. An important objective will be to maintain high levels of performance for splice variants and for sequence fragments. Overall, the project will require the analysis of existing biological databases, the development of novel methods, and the combination of existing ones; it will generate novel information available through internet servers, standalone programs and databases. RELEVANCE: The annotations generated by our system will aid the design of detailed and high-throughput experimental studies. In particular, localization may increase in its relevance as one essential feature used to infer networks of interactions. The ultimate goal of our project is the generation of an atlas that maps all proteins in a cell. Eventually, this atlas will constitute a 4D map; it will localize proteins in their 3D cellular environments and resolve the coarse-grained dynamics of the system, e.g. "expression on ribosomes, bind importin, transport into nucleus, bind DNA, bind exportin, export out of nucleus; next cell cycle". The components proposed here constitute one crucial building block toward such a 4D map of a cell.

描述（由申请人提供）：具有已知序列的蛋白质数量与具有良好研究功能的蛋白质数量（序列功能间隙）每天都在增长。功能的一个定义明确的粗粒度方面是蛋白质的天然亚细胞定位，该蛋白质在基因本体论（GO）层次结构中具有中心作用。许多详细且高通量实验注释了本地化。在没有实验的情况下，基于同源的和从头的预测方法成功。在这里，我们提出了一个综合系统的开发，该系统将实验资源与数据挖掘技术和新型预测方法结合在一起，并以空前的细节和准确性注释完全测序的真核生物的本地化。首先，我们建议收集所有可用的数据和所有相关方法，以建立人类和拟南芥的全面本地化地图集。其次，我们计划开发专门量身定制的新方法，以捕获蛋白质，在完成第一步后，我们没有可靠的注释。我们假设这些方法将集中于插入整体膜蛋白的特定类型的膜的预测，以及用于次要真核室的天然定位（ER，Golgi，溶酶体）。第三，我们提出了针对当今基于图案的分泌蛋白和核蛋白的方法的具体改进，以及对主要隔室的从头预测的扩展。一个重要的目标是维持剪接变体和序列片段的高表现。总体而言，该项目将需要分析现有的生物数据库，新方法的发展以及现有方法的组合；它将通过Internet服务器，独立程序和数据库生成新的信息。 相关性：我们系统产生的注释将有助于设计详细和高通量实验研究。特别是，本地化可能会增加与推断交互网络的重要功能相关性。我们项目的最终目标是生成一个地图集，该地图集映射细胞中的所有蛋白质。最终，该地图集将构成4D地图。它将将蛋白质定位在其3D细胞环境中，并解决系统的粗粒动力学，例如“核糖体上的表达，结合进口素，转运到核中，结合DNA，结合导出，从核中出口；下一个细胞周期”。此处提出的组件构成了一个至关重要的构建块，朝着这样的4D贴图。