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: 7500843
• 负责人: BURKHARD ROST
• 金额: $ 31.81万
• 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/7500843
• 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; Class; Collection; Communities; Computational Biology; Computer Simulation; DNA Binding; Daily; Data; Data Set; Databases; Development; Environment; Eukaryota; Eukaryotic Cell; Evolution; Fingerprint; Follow-Up Studies; Generations; Genes; Genome; Goals; Golgi Apparatus; Homo sapiens; Human; Integral Membrane Protein; Internet; Laboratory Organism; Left; Locales; Localized; 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; Today; 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与具有充分研究功能的蛋白质（序列-功能间隙）之间的差异日益增加。功能的一个定义明确的粗粒度方面是在基因本体（GO）层次结构中具有中心作用的蛋白质的原生亚细胞定位。许多详细和高通量的实验注释了定位。在实验不能达到的地方，基于同源性和从头开始的预测方法是成功的。在此，我们建议开发一个综合系统，将实验资源与数据挖掘技术和新颖的预测方法相结合，以前所未有的细节和准确性注释全测序真核生物的定位。首先，我们建议收集所有可用的数据和所有相关的方法，建立一个全面的人类和拟南芥定位图谱。其次，我们计划开发专门用于捕获在完成第一步后没有可靠注释的蛋白质的新方法。我们假设这些方法将集中于预测整合膜蛋白插入的特定类型的膜，以及较小的真核细胞室（内质网，高尔基体，溶酶体）的天然定位。第三，我们建议对目前基于基序的分泌蛋白和核蛋白方法进行具体改进，并扩展对主要隔室的从头预测。一个重要的目标将是保持高水平的性能剪接变体和序列片段。总的来说，该项目将需要分析现有的生物数据库，发展新的方法，并将现有的方法结合起来；它将通过互联网服务器、独立程序和数据库产生新的信息。