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首页> 外文期刊>BMC Genomics >Systems analysis of gene ontology and biological pathways involved in post-myocardial infarction responses
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Systems analysis of gene ontology and biological pathways involved in post-myocardial infarction responses

机译：心肌梗死后反应涉及的基因本体和生物途径的系统分析

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Background Pathway analysis has been widely used to gain insight into essential mechanisms of the response to myocardial infarction (MI). Currently, there exist multiple pathway databases that organize molecular datasets and manually curate pathway maps for biological interpretation at varying forms of organization. However, inconsistencies among different databases in pathway descriptions, frequently due to conflicting results in the literature, can generate incorrect interpretations. Furthermore, although pathway analysis software provides detailed images of interactions among molecules, it does not exhibit how pathways interact with one another or with other biological processes under specific conditions. Methods We propose a novel method to standardize descriptions of enriched pathways for a set of genes/proteins using Gene Ontology terms. We used this method to examine the relationships among pathways and biological processes for a set of condition-specific genes/proteins, represented as a functional biological pathway-process network. We applied this algorithm to a set of 613 MI-specific proteins we previously identified. Results A total of 96 pathways from Biocarta, KEGG, and Reactome, and 448 Gene Ontology Biological Processes were enriched with these 613 proteins. The pathways were represented as Boolean functions of biological processes, delivering an interactive scheme to organize enriched information with an emphasis on involvement of biological processes in pathways. We extracted a network focusing on MI to demonstrate that tyrosine phosphorylation of Signal Transducer and Activator of Transcription (STAT) protein, positive regulation of collagen metabolic process, coagulation, and positiveegative regulation of blood coagulation have immediate impacts on the MI response. Conclusions Our method organized biological processes and pathways in an unbiased approach to provide an intuitive way to identify biological properties of pathways under specific conditions. Pathways from different databases have similar descriptions yet diverse biological processes, indicating variation in their ability to share similar functional characteristics. The coverages of pathways can be expanded with the incorporation of more biological processes, predicting involvement of protein members in pathways. Further, detailed analyses of the functional biological pathway-process network will allow researchers and scientists to explore critical routes in biological systems in the progression of disease.
机译：背景途径分析已被广泛用于深入了解心肌梗塞（MI）反应的基本机制。当前，存在多个途径数据库，其组织分子数据集并手动编制途径图以用于在不同组织形式下进行生物学解释。但是，通常由于文献中的结果冲突，导致路径描述中不同数据库之间的不一致会产生错误的解释。此外，尽管途径分析软件提供了分子之间相互作用的详细图像，但它并未显示途径在特定条件下如何彼此相互作用或与其他生物学过程相互作用。方法我们提出了一种新颖的方法，可以使用基因本体论术语标准化一组基因/蛋白质的富集途径的描述。我们使用这种方法来检查一组条件特定的基因/蛋白质的通路与生物学过程之间的关系，这些基因/蛋白质表示为功能性生物学通路-过程网络。我们将此算法应用于我们先前确定的一组613种MI特异性蛋白。结果613种蛋白质丰富了来自Biocarta，KEGG和Reactome的96种途径，以及448种基因本体生物学过程。这些途径被表示为生物过程的布尔函数，提供了一种交互方案来组织丰富的信息，并着重于途径中生物过程的参与。我们提取了一个以MI为中心的网络，以证明信号转导和转录激活（STAT）蛋白的酪氨酸磷酸化，胶原蛋白代谢过程的正调节，凝血以及血液凝固的正/负调节对MI响应具有直接影响。结论我们的方法以无偏见的方式组织了生物学过程和途径，从而提供了一种直观的方法来鉴定特定条件下途径的生物学特性。来自不同数据库的途径具有相似的描述，但生物学过程多种多样，表明它们共享相似功能特征的能力存在差异。整合更多的生物过程可以扩大途径的覆盖面，从而预测蛋白质成员参与途径。此外，对功能性生物途径-过程网络的详细分析将使研究人员和科学家能够探索疾病进展中生物系统中的关键途径。

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