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和具有充分研究的功能的蛋白质数量之间的差异（序列-功能差距）每天都在增加。功能的一个明确定义的粗粒度方面是在基因本体（GO）层次结构中发挥核心作用的蛋白质的天然亚细胞定位。许多详细和高通量的实验注释了定位。在实验无法达到的地方，基于同源性和从头预测的方法会成功。在这里，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，目标是以前所未有的细节和准确性注释完全测序的真核生物的定位。首先，我们建议收集所有可用数据和所有相关方法来构建人类和拟南芥的综合定位图集。其次，我们计划开发专门用于捕获蛋白质的新方法，在完成第一步后，我们没有留下可靠的注释。我们假设这些方法将侧重于预测插入完整膜蛋白的特定类型的膜，以及小真核区室（内质网、高尔基体、溶酶体）的天然定位。第三，我们建议对当今基于基序的分泌蛋白和核蛋白方法进行具体改进，以及扩展主要区室的从头预测。一个重要的目标是保持剪接变体和序列片段的高水平性能。总体而言，该项目将需要分析现有的生物数据库，开发新方法，以及现有方法的结合；它将生成可通过互联网服务器、独立程序和数据库获取的新颖信息。 相关性：我们的系统生成的注释将有助于详细和高通量实验研究的设计。特别是，定位作为用于推断交互网络的基本特征之一，其相关性可能会增加。我们项目的最终目标是生成绘制细胞中所有蛋白质图谱。最终，这个地图集将构成一张4D地图；它将在 3D 细胞环境中定位蛋白质并解析系统的粗粒度动力学，例如“在核糖体上表达，结合输入蛋白，转运到细胞核，结合DNA，结合输出蛋白，从细胞核输出；下一个细胞周期”。这里提出的组件构成了这种细胞 4D 地图的关键构建模块。