Bioinformatics Tools for Kinome Microarrays

用于激酶组微阵列的生物信息学工具

• 批准号: RGPIN-2017-05486
• 负责人: Kusalik, Anthony
• 金额: $ 1.68万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711670
• 关键词: Bioinformatics; Tools; Kinome; Microarrays

Phosphorylation is a fundamental mechanism of cellular signalling. The reaction involves a protein kinase (an enzyme that adds a phosphate group to certain amino acids) and a target (substrate) protein. One way to study protein kinases in a high-throughput manner is with kinome microarrays, which consist of hundreds or thousands of probes affixed to a glass slide. After exposure to a prepared sample, all the probes on the microarray are simultaneously measured for evidence of phosphorylation by kinases in the sample, providing a "snapshot" of (potential) cellular phosphorylation activity. Over the past several years, our group has developed various bioinformatics tools to support this technology. We have devised software to help determine the peptides to be used as probes for species-specific or pathway-specific arrays, and software to filter, adjust, visualize, and interrogate the resulting measurements. We have also developed tools for assisting with the evaluation of software for kinome data analysis. With collaborators, we have demonstrated the utility of the technology and software in organisms ranging from plants to insects to humans, with applications ranging from determining an individual's "kinotype" to studying pathogenic mechanisms of Ebola infection. However, the field is still far from mature, with many open questions remaining. The focus of the proposed research program is to address shortcomings of current software supporting kinome microarray technology, to find solutions to known problems, and to develop new, improved algorithms and software tools. Specifically, we will develop improved data normalization techniques, utilize special calibration probes to extract more and better information from the microarrays, and exploit our unique, wide-ranging collection of data to improve kinome microarray technology and to develop software that leads to the discovery of previously unknown signalling pathways. This research is important to researchers in a broad range of biological sciences, from virology to crop science since cellular signalling is such a fundamental mechanism in cells. Better tools to identify and study signalling networks will facilitate more rapid basic and applied research, and lead to greater biological knowledge. Kinome microarrays are an extremely valuable research tool because they can be employed to study a wide range of biological problems, from human health to agriculture to basic research into cellular physiology. The proposed research will make kinome arrays even more useful for all of these purposes. Another benefit of the proposed program is that it will provide training for undergraduate and graduate students in a highly desirable, inter-disciplinary field (bioinformatics) in which there is a under-supply of HQP (highly-qualified personnel).

磷酸化是细胞信号传导的基本机制。 该反应涉及蛋白激酶（一种将磷酸基团添加到某些氨基酸的酶）和目标（底物）蛋白质。 以高通量方式研究蛋白激酶的一种方法是使用激酶组微阵列，其由固定在载玻片上的数百或数千个探针组成。 暴露于制备好的样本后，同时测量微阵列上的所有探针以寻找样本中激酶磷酸化的证据，提供（潜在）细胞磷酸化活性的“快照”。在过去的几年里，我们的团队开发了各种生物信息学工具来支持这项技术。 我们设计了软件来帮助确定要用作物种特异性或路径特异性阵列的探针的肽，以及软件来过滤、调整、可视化和询问所得到的测量结果。我们还开发了用于协助评估激酶组数据分析软件的工具。与合作者一起，我们已经证明了该技术和软件在从植物到昆虫再到人类的生物体中的实用性，其应用范围从确定个体的“运动型”到研究埃博拉病毒感染的致病机制。然而，这一领域还远未成熟，仍有许多悬而未决的问题。 拟议的研究计划的重点是解决目前的软件支持kinome微阵列技术的缺点，找到解决已知问题的方法，并开发新的，改进的算法和软件工具。 具体来说，我们将开发改进的数据标准化技术，利用特殊的校准探针从微阵列中提取更多更好的信息，并利用我们独特的，广泛的数据收集，以改善激酶组微阵列技术和开发软件，导致发现以前未知的信号通路。 这项研究对从病毒学到作物科学的广泛生物科学研究人员都很重要，因为细胞信号传导是细胞中的一种基本机制。 更好的识别和研究信号网络的工具将促进更快的基础和应用研究，并导致更多的生物学知识。 Kinome微阵列是一种非常有价值的研究工具，因为它们可以用于研究广泛的生物学问题，从人类健康到农业到细胞生理学的基础研究。拟议中的研究将使激酶组阵列对所有这些目的更加有用。 拟议计划的另一个好处是，它将为本科生和研究生提供培训，在一个非常理想的，跨学科的领域（生物信息学），其中有一个供应不足的HQP（高素质的人员）。