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Precise generation of systems biology models from KEGG pathways

机译:从KEGG途径精确生成系统生物学模型

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Background The KEGG PATHWAY database provides a plethora of pathways for a diversity of organisms. All pathway components are directly linked to other KEGG databases, such as KEGG COMPOUND or KEGG REACTION. Therefore, the pathways can be extended with an enormous amount of information and provide a foundation for initial structural modeling approaches. As a drawback, KGML-formatted KEGG pathways are primarily designed for visualization purposes and often omit important details for the sake of a clear arrangement of its entries. Thus, a direct conversion into systems biology models would produce incomplete and erroneous models. Results Here, we present a precise method for processing and converting KEGG pathways into initial metabolic and signaling models encoded in the standardized community pathway formats SBML (Levels 2 and 3) and BioPAX (Levels 2 and 3). This method involves correcting invalid or incomplete KGML content, creating complete and valid stoichiometric reactions, translating relations to signaling models and augmenting the pathway content with various information, such as cross-references to Entrez Gene, OMIM, UniProt ChEBI, and many more. Finally, we compare several existing conversion tools for KEGG pathways and show that the conversion from KEGG to BioPAX does not involve a loss of information, whilst lossless translations to SBML can only be performed using SBML Level 3, including its recently proposed qualitative models and groups extension packages. Conclusions Building correct BioPAX and SBML signaling models from the KEGG database is a unique characteristic of the proposed method. Further, there is no other approach that is able to appropriately construct metabolic models from KEGG pathways, including correct reactions with stoichiometry. The resulting initial models, which contain valid and comprehensive SBML or BioPAX code and a multitude of cross-references, lay the foundation to facilitate further modeling steps.
机译:背景技术KEGG PATHWAY数据库为多种生物提供了多种途径。所有途径成分都直接链接到其他KEGG数据库,例如KEGG COMPOUND或KEGG REACTION。因此,可以用大量信息扩展这些路径,并为初始结构建模方法提供基础。缺点是,KGML格式的KEGG路径主要是为了可视化目的而设计的,并且为了清楚地排列其条目,通常会省略重要的细节。因此,直接转换为系统生物学模型将产生不完整和错误的模型。结果在这里,我们提出了一种精确的方法,用于处理KEGG途径并将其转换为以标准化社区途径格式SBML(2和3级)和BioPAX(2和3级)编码的初始代谢和信号传导模型。此方法涉及校正无效或不完整的KGML含量,创建完整和有效的化学计量反应,将关系转换为信号模型以及使用各种信息来增强途径含量,例如对Entrez基因,OMIM,UniProt ChEBI的交叉引用等等。最后,我们比较了几种用于KEGG途径的现有转换工具,并表明从KEGG到BioPAX的转换不涉及信息丢失,而只能使用SBML Level 3(包括其最近提出的定性模型和组)来进行到SBML的无损转换。扩展程序包。结论从KEGG数据库中建立正确的BioPAX和SBML信号模型是该方法的独特之处。此外,没有其他方法能够从KEGG途径适当构建代谢模型,包括化学计量比正确的反应。最终的初始模型包含有效且全面的SBML或BioPAX代码以及大量的交叉引用,为进一步的建模步骤奠定了基础。

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