ProKinO: an ontology for integrative analysis of protein kinases in cancer.

ProKinO: an ontology for integrative analysis of protein kinases in cancer.
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Prokino:癌症蛋白激酶综合分析的本体。

DOI:
10.1371/journal.pone.0028782
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Kannan N
Kannan N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gosal G;Kochut KJ;Kannan N

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蛋白激酶是一个庞大而多样的酶家族,在许多人类癌症中发生基因组改变。靶向癌症基因组测序工作已经揭示了许多不同癌症类型的蛋白激酶基因的突变谱。虽然蛋白激酶的突变数据目前在各种数据库中编目,但突变数据与其他形式的蛋白激酶数据(如序列、结构、功能和途径)的整合对于鉴定和表征关键的致癌突变是必要的。然而,由于蛋白激酶数据源和数据格式的不同性质,蛋白激酶数据的综合分析是一个挑战。在这里,我们描述ProKinO,蛋白激酶的特定本体,它提供了一个控制词汇的术语,它们的层次结构,和关系统一的序列,结构,功能,突变和蛋白激酶的途径信息。这种不同形式的信息在一个地方的概念表示不仅允许快速发现与特定蛋白激酶相关的重要信息,而且还能够以通过其他激酶特异性资源不可能的方式对蛋白激酶数据进行大规模综合分析。我们已经对ProKinO数据进行了几次综合分析,并且作为一个例子,发现与造血肿瘤癌症类型相关的大量体细胞突变(约288个不同的突变)仅映射到人类激酶组中的8种激酶。这与神经胶质瘤相反,神经胶质瘤的突变分布在82种不同的激酶上。我们还提供了基于本体的数据分析如何用于生成关于癌症突变的可验证假设的例子。我们提出了一个大规模的蛋白激酶数据的综合分析的综合框架。本体数据的导航和分析可以使用可在http://vulcan.cs.uga.edu/prokino获得的本体浏览器来执行。
Protein kinases are a large and diverse family of enzymes that are genomically altered in many human cancers. Targeted cancer genome sequencing efforts have unveiled the mutational profiles of protein kinase genes from many different cancer types. While mutational data on protein kinases is currently catalogued in various databases, integration of mutation data with other forms of data on protein kinases such as sequence, structure, function and pathway is necessary to identify and characterize key cancer causing mutations. Integrative analysis of protein kinase data, however, is a challenge because of the disparate nature of protein kinase data sources and data formats. Here, we describe ProKinO, a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on protein kinases. The conceptual representation of such diverse forms of information in one place not only allows rapid discovery of significant information related to a specific protein kinase, but also enables large-scale integrative analysis of protein kinase data in ways not possible through other kinase-specific resources. We have performed several integrative analyses of ProKinO data and, as an example, found that a large number of somatic mutations (∼288 distinct mutations) associated with the haematopoietic neoplasm cancer type map to only 8 kinases in the human kinome. This is in contrast to glioma, where the mutations are spread over 82 distinct kinases. We also provide examples of how ontology-based data analysis can be used to generate testable hypotheses regarding cancer mutations. We present an integrated framework for large-scale integrative analysis of protein kinase data. Navigation and analysis of ontology data can be performed using the ontology browser available at: http://vulcan.cs.uga.edu/prokino.
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