Using Multilayer Heterogeneous Networks to Infer Functions of Phosphorylated Sites.
Using Multilayer Heterogeneous Networks to Infer Functions of Phosphorylated Sites.
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DOI：
10.1021/acs.jproteome.1c00150
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发表时间：
2021-07-02
影响因子：
4.4
通讯作者：
Francavilla C
中科院分区：
文献类型：
--
作者：
Watson J;Schwartz JM;Francavilla C
Mass spectrometry-based quantitative phosphoproteomics has become an essential approach in the study of cellular processes such as signaling.分析磷酸化蛋白质组数据集的常用方法依赖于通用的、以基因为中心的注释，例如基因本体术语，这些注释不考虑特定磷酸化状态下蛋白质的功能。 Analysis of phosphoproteomics data is hampered by a lack of phosphorylated site-specific annotations.我们提出了一种将鸟枪法磷酸化蛋白质组学数据、蛋白质-蛋白质相互作用和功能注释结合到异质多层网络中的方法。 Phosphorylation sites are associated to potential functions using a random walk on the heterogeneous network (RWHN) algorithm.我们根据 MAPK/ERK 通路模型和 PhosphoSitePlus 的功能注释验证了我们的方法，并能够将相同蛋白质上的差异调节位点与其先前描述的特定功能相关联。我们在三个先前发布的数据集上进一步测试了该算法，并能够重现其经过实验验证的结论，并根据其调控模式将磷酸化位点与已知功能相关联。我们的方法提供了常用分析方法的改进，并准确预测具有相似磷酸化谱的位点的特定功能。
Mass spectrometry-based quantitative phosphoproteomics has become an essential approach in the study of cellular processes such as signaling. Commonly used methods to analyze phosphoproteomics datasets depend on generic, gene-centric annotations such as Gene Ontology terms, which do not account for the function of a protein in a particular phosphorylation state. Analysis of phosphoproteomics data is hampered by a lack of phosphorylated site-specific annotations. We propose a method that combines shotgun phosphoproteomics data, protein–protein interactions, and functional annotations into a heterogeneous multilayer network. Phosphorylation sites are associated to potential functions using a random walk on the heterogeneous network (RWHN) algorithm. We validated our approach against a model of the MAPK/ERK pathway and functional annotations from PhosphoSitePlus and were able to associate differentially regulated sites on the same proteins to their previously described specific functions. We further tested the algorithm on three previously published datasets and were able to reproduce their experimentally validated conclusions and to associate phosphorylation sites with known functions based on their regulatory patterns. Our approach provides a refinement of commonly used analysis methods and accurately predicts context-specific functions for sites with similar phosphorylation profiles.
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