Approaches to Multiorganismal Comparative Proteomics

多生物体比较蛋白质组学方法

• 批准号: 7579012
• 负责人: SHAMIL SUNYAEV
• 金额: $ 24.94万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7579012
• 关键词: Amino Acid Sequence; Cells; Complex; Computing Methodologies; Data; Data Analyses; Databases; Doctor of Philosophy; Event; Functional RNA; Gene Duplication; Genes; Genetic Polymorphism; Genomics; Graph; Individual; Mass Spectrum Analysis; Methods; Molecular Machines; Organism; Pattern; Peptide Sequence Determination; Protein Isoforms; Proteins; Proteomics; RNA Splicing; Role; Structure; base; comparative; design; genome sequencing; improved; programs; protein complex; protein protein interaction; success

DESCRIPTION (provided by applicant): Comparative genomics has had great success in revealing evolutionary mechanisms and in predicting the functionality of proteins and non-coding functional regions. Mass spectrometry-based proteomics generates new types of data on the composition and localization of protein complexes and the interactions between complexes and individual proteins. The comparative analysis of these data has great potential as a useful approach to the characterization of the organization of the cell protein machinery. We propose to develop computational and experimental strategies for cross-species proteomic analysis. In Aim 1, we will improve existing, and develop new, computational methods for the homology-based identification of proteins and protein complexes using mass spectrometry data. These methods will not rely on the availability of protein sequences in the current database and, thus, will enable the analysis of multiple organisms currently out of the scope of proteomics. They will also increase the sensitivity of protein complex identifications in organisms with sequenced genomes because of the robustness with respect to incorrect gene predictions, sequencing errors, splicing isoforms and polymorphisms. In Aim 2, we will compare the protein interaction data for available and de novo generated examples of "molecular machines" from different organisms. We will further derive common patterns of evolutionary events in terms of the changes in protein interaction graphs. The observed changes in the composition of protein complexes, the interactions between complexes and in the individual proteins will be correlated with changes at the level of protein's sequence and structure. Gene duplication events will be characterized in terms of the interaction pattern, such that we will seek to design approaches that generate meaningful functional predictions for the specific "molecular machines." In Aim 3, we will develop automated computational methods for the comparative analysis of protein-protein interaction networks from different organisms. The application of these methods to emerging large-scale data on protein-protein interaction networks from multiple species will enable the identification of conserved interaction sets, the understanding of functionality and robustness of "molecular machines" and the characterization of the functional role of individual proteins.

描述（由申请人提供）：比较基因组学在揭示进化机制以及预测蛋白质和非编码功能区域的功能方面取得了巨大成功。基于质谱的蛋白质组学生成了有关蛋白质复合物组成和定位以及复合物与单个蛋白质之间相互作用的新类型数据。对这些数据的比较分析具有巨大的潜力，是对细胞蛋白机械组织的表征的有用方法。我们建议开发用于跨物种蛋白质组学分析的计算和实验策略。在AIM 1中，我们将改善现有的现有计算方法，用于使用质谱数据基于同源的蛋白质和蛋白质复合物的鉴定。这些方法将不依赖于当前数据库中蛋白质序列的可用性，因此，将能够从蛋白质组学范围内分析当前的多种生物体。它们还将增加具有测序基因组生物体蛋白复合物鉴定的敏感性，因为相对于不正确的基因预测，测序误差，剪接同工型和多态性的鲁棒性。在AIM 2中，我们将比较不同生物体的“分子机器”示例的蛋白质相互作用数据。我们将根据蛋白质相互作用图的变化来进一步得出进化事件的共同模式。观察到的蛋白质复合物组成的变化，复合物与单个蛋白质之间的相互作用将与蛋白质序列和结构水平的变化相关。基因复制事件将以相互作用模式来表征，以便我们试图设计为特定“分子机器”产生有意义的功能预测的方法。在AIM 3中，我们将开发自动计算方法，用于对来自不同生物体的蛋白质 - 蛋白质相互作用网络进行比较分析。这些方法在多种物种的蛋白质 - 蛋白质相互作用网络上的新大规模数据中的应用将使保守相互作用集，对功能的理解和“分子机器”的鲁棒性以及单个蛋白质功能作用的表征。

项目成果

Comparative proteomic studies of root-microbe interactions.

根-微生物相互作用的比较蛋白质组学研究。

• DOI: 10.1016/j.jprot.2008.12.006
• 发表时间: 2009
• 期刊: Journal of proteomics
• 影响因子: 3.3
• 作者: Mathesius,Ulrike

Xenopus meiotic microtubule-associated interactome.

• DOI: 10.1371/journal.pone.0009248
• 发表时间: 2010-02-17
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Gache V;Waridel P;Winter C;Juhem A;Schroeder M;Shevchenko A;Popov AV
• 通讯作者: Popov AV

Chromatin Central: towards the comparative proteome by accurate mapping of the yeast proteomic environment.

• DOI: 10.1186/gb-2008-9-11-r167
• 发表时间: 2008
• 期刊: Genome biology
• 影响因子: 12.3
• 作者: Shevchenko A;Roguev A;Schaft D;Buchanan L;Habermann B;Sakalar C;Thomas H;Krogan NJ;Shevchenko A;Stewart AF
• 通讯作者: Stewart AF

Protein identification pipeline for the homology-driven proteomics.

• DOI: 10.1016/j.jprot.2008.07.003
• 发表时间: 2008-08-21
• 期刊: JOURNAL OF PROTEOMICS
• 影响因子: 3.3
• 作者: Junqueira, Magno;Spirin, Victor;Balbuena, Tiago Santana;Thomas, Henrik;Adzhubei, Ivan;Sunyaev, Shamil;Shevchenko, Andrej
• 通讯作者: Shevchenko, Andrej

Purification and mass spectrometry identification of microtubule-binding proteins from Xenopus egg extracts.

• DOI: 10.1007/978-1-59745-442-1_3
• 发表时间: 2007-01-01
• 期刊: Methods in molecular medicine
• 作者: Gache, Vincent;Waridel, Patrice;Popov, Andrei V
• 通讯作者: Popov, Andrei V