Bioinformatics, data integration, and knowledge extraction from high throughput proteomics for enabling biomedical applications

项目概要- TR&D 3 该资源的总体目标是通过提供以下能力来广泛影响生物医学研究： 更小样本的高质量蛋白质组学数据， 测量，产生关于低丰度组分的改进的和更广泛的信息， 目前有问题的肽异构体，并使研究更大的样品集比目前 通过提供测量吞吐量的增加而实用。本次更新中TR& D 1和2的预付款 将在蛋白质组的灵敏度、广度、质量和数量（即通量）方面提供大的改进 数据TR&D 3的努力将通过先进的数据处理算法实现这些功能， 整合多种蛋白质组学和其他数据集，以帮助提取生物医学见解。TR&D 3 将开发新的蛋白质识别和定量算法， 在TR&D 2中开发的SLIM离子迁移率（IM）-MS平台的独特功能。高度准确和 非常高的精度和可再现的碰撞截面（CCS）值来自SLIM超高 分辨率IM测量将提供对肽/蛋白质的更可靠和灵敏的鉴定。一 我们的方法的一个关键方面是使用大量稳定同位素标记的肽来校准SLIM 超高分辨率的IM分离，导致更精确的肽碰撞截面信息。这些 相同的稳定同位素标记的肽组也将用作校准物， 它们的未标记的类似物以及用于在稍微降低的浓度下广泛定量所有肽和蛋白质， 精度TR& D 1和2的进展也将使翻译后的更广泛的测量成为可能。 修改，我们将使用它来推断样品中活跃的网络和途径。我们将继续 与这些网络一起开发我们的协作视觉分析工具，以促进探索和 数据的解释。这些努力将建立在以前的资源发展基础上， 在TR&D 2下的关键技术发展。这些努力结合起来，将为快速发展提供基础。 实施和初步评估新的蛋白质组学能力，提供更大和更丰富的数据集 对于具有挑战性的生物医学项目，以及他们有效地传播到研究界。

Project Summary – TR&D 3 The Resource overall has the goal of broadly impacting biomedical research by providing the abilities to: obtain high quality proteomics data from much smaller samples, produce more quantitative and comprehensive measurements, generate improved and more extensive information on low abundance components, distinguish presently problematic peptide isomers, and enable the study of much larger sample sets than presently practical by providing increases in measurement throughput. Advances under TR&Ds 1 and 2 in this renewal will provide large improvements in the sensitivity, breadth, quality, and quantity (i.e. throughput) of proteome data. The efforts of TR&D 3 will enable these capabilities through advanced algorithms for data processing and the integration of multiple proteomics and other data sets to aid the extraction of biomedical insights. TR&D 3 will develop new algorithms for protein identification and quantification that are needed to effectively utilize the unique capabilities of the SLIM ion mobility (IM)-MS platform developed in TR&D 2. Highly accurate and very highly precise and reproducible collision cross section (CCS) values derived from the SLIM ultra-high resolution IM measurements will provide more confident and sensitive identification of peptides/proteins. A key aspect of our approach is the use of large sets of stable isotope labeled peptides for the calibration of SLIM ultra-high resolution IM separations leading to more precise peptide collision cross section information. These same stable isotope labeled peptide sets will also serve as calibrants to enable highly accurate quantification of their unlabeled analogs as well as for broad quantification of all peptides and proteins at somewhat reduced accuracy. Advances under TR&Ds 1 and 2 will also enable a broader measurement of post-translational modifications, which we will use to infer networks and pathways active in the samples. We will continue to develop our collaborative visual analytic tool in conjunction with these networks to facilitate exploration and interpretation of the data. These efforts will build upon previous Resource developments and will be facilitated by key technological developments under TR&D 2. In combination, these efforts will provide a basis for rapid implementation and initial evaluation of new proteomics capabilities providing both larger and richer data sets for challenging biomedical projects, as well as their effective dissemination to the research community.