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Assignment of novel functions to Helicobacter pylori 26695’s genome and reconstruction of a genome-scale metabolic model

机译:赋予幽门螺杆菌26695基因组新功能并重建基因组规模的代谢模型

摘要

Helicobacter pylori is a pathogenic organism associated with human gastric diseases. The development of mathematical models of metabolism is now considered a fundamental part of the study of the cell. For the particular case of microorganisms associated with human diseases, information on metabolic and regulatory networks can be used to understand the molecular factors of the microorganism that are likely to interact with the host and cause diseases. The availability of the genome sequence of H. pylori 26695 and its annotation has allowed in the past the construction of a metabolic model for this organism. The first genome-scale metabolic model for H. pylori 26695 was published in 2002 (iCS291) and a corrected reconstruction was published in 2005 (iIT341 GSM/GPR). The main goal of the present work was to update H. pylori’s genome-scale metabolic model based on the new information made available. For that purposes, using new annotation methodologies and data available in databases, an assignment of novel functions to H. pylori 26695’s genome was performed. For a total of 510 “hypothetical proteins” (almost 1/3 of the genes) identified in the last re-annotation, 137 new functions were attributed. A total of 581 E.C. numbers were assigned to CDS, being 528 complete E.C. numbers. This new information was used as the basis of the model reconstruction. In addition, transport reactions in the model were updated. The biomass equation was reviewed and H. pylori biomass coefficients and composition were adjusted. The obtained model successfully predicted the nutritional requirements and amino acids essentialities, which were experimentally validated. As a result, the present work presents a new H. pylori 26695 genome-scale metabolic model with more accurate and reliable predictions and can be used to identify potential targets for designing more effective drugs for H. pylori inactivation.
机译:幽门螺杆菌是与人类胃部疾病相关的致病生物。现在,代谢数学模型的开发被认为是细胞研究的基础部分。对于与人类疾病有关的微生物的特殊情况,可以使用有关代谢和调节网络的信息来了解可能与宿主相互作用并引起疾病的微生物分子因素。幽门螺杆菌26695的基因组序列的可用性及其注释在过去已经允许建立该生物的代谢模型。幽门螺杆菌26695的第一个基因组规模的代谢模型于2002年发布(iCS291),2005年发布了经过校正的重建模型(iIT341 GSM / GPR)。目前工作的主要目的是根据可获得的新信息更新幽门螺杆菌的基因组规模代谢模型。为此,使用新的注释方法和数据库中可用的数据,对幽门螺杆菌26695的基因组进行了新功能的分配。在上一次重新注释中,总共鉴定出510个“假设蛋白质”(几乎占基因的1/3),其中137个新功能被赋予。总共581个E.C.编号分配给CDS,即528个完整的E.C.编号。此新信息用作模型重建的基础。此外,更新了模型中的运输反应。审查了生物量方程,并调整了幽门螺杆菌的生物量系数和组成。获得的模型成功地预测了营养需求和氨基酸必需性,并通过实验进行了验证。因此,本工作提出了一种新的幽门螺杆菌26695基因组规模的代谢模型,具有更准确和可靠的预测,可用于确定潜在的靶点,以设计用于幽门螺杆菌灭活的更有效药物。

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