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首页> 外文期刊>Lipids in Health Disease >Mining literature for a comprehensive pathway analysis: A case study for retrieval of homocysteine related genes for genetic and epigenetic studies
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Mining literature for a comprehensive pathway analysis: A case study for retrieval of homocysteine related genes for genetic and epigenetic studies

机译：全面路径分析的挖掘文献：为基因和表观遗传学研究检索同型半胱氨酸相关基因的案例研究

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Homocysteine is an independent risk factor for cardiovascular diseases. It is also known to be associated with a variety of complex disorders. While there are a large number of independent studies implicating homocysteine in isolated pathways, the mechanism of homocysteine induced adverse effects are not clear. Homocysteine-induced modulation of gene expression through alteration of methylation status or by hitherto unknown mechanisms is predicted to lead to several pathological conditions either directly or indirectly. In the present manuscript, using literature mining approach, we have identified the genes that are modulated directly or indirectly by an elevated level of homocysteine. These genes were then placed in appropriate pathways in an attempt to understand the molecular basis of homocysteine induced complex disorders and to provide a resource for selection of genes for polymorphism screening and analysis of mutations as well as epigenetic modifications in relation to hyperhomocysteinemia. We have identified 135 genes in 1137 abstracts that either modulate the levels of homocysteine or are modulated by elevated levels of homocysteine. Mapping the genes to their respective pathways revealed that an elevated level of homocysteine leads to the atherosclerosis either by directly affecting lipid metabolism and transport or via oxidative stress and/or Endoplasmic Reticulum (ER) stress. Elevated levels of homocysteine also decreases the bioavailability of nitric oxide and modulates the levels of other metabolites including S-adenosyl methionine and S-adenosyl homocysteine which may result in cardiovascular or neurological disorders. The ER stress emerges as the common pathway that relates to apoptosis, atherosclerosis and neurological disorders and is modulated by levels of homocysteine. The comprehensive network collated has lead to the identification of genes that are modulated by homocysteine indicating that homocysteine exerts its effect not only through modulating the substrate levels for various catalytic processes but also through regulation of expression of genes involved in complex diseases.
机译：同型半胱氨酸是心血管疾病的独立危险因素。还已知与多种复杂疾病有关。尽管有大量独立研究涉及高半胱氨酸在孤立的途径中，但高半胱氨酸引起的不良反应的机制尚不清楚。据预测，同型半胱氨酸通过甲基化状态的改变或迄今为止未知的机制引起的基因表达调节直接或间接导致多种病理状况。在本手稿中，我们采用文献挖掘的方法，鉴定了高半胱氨酸水平直接或间接调节的基因。然后将这些基因置于适当的途径中，以试图了解高半胱氨酸诱导的复杂疾病的分子基础，并为选择基因进行多态性筛选和突变分析以及与高同型半胱氨酸血症相关的表观遗传修饰提供资源。我们已经在1137个摘要中鉴定了135个基因，这些基因要么调节同型半胱氨酸的水平，要么被同型半胱氨酸水平的升高调节。将基因定位到它们各自的途径表明，高半胱氨酸水平升高通过直接影响脂质代谢和运输或通过氧化应激和/或内质网（ER）应激而导致动脉粥样硬化。高半胱氨酸水平的升高还会降低一氧化氮的生物利用度，并调节其他代谢物（包括S-腺苷甲硫氨酸和S-腺苷高半胱氨酸）的水平，这可能会导致心血管疾病或神经疾病。内质网应激是与凋亡，动脉粥样硬化和神经系统疾病有关的常见途径，并受同型半胱氨酸水平的调节。整理的综合网络已导致鉴定出由同型半胱氨酸调节的基因，这表明同型半胱氨酸不仅通过调节各种催化过程的底物水平，而且通过调节与复杂疾病有关的基因的表达来发挥其作用。

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