复杂生物性状局部基因网络构建方法的研究
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摘要
本课题的研究目的是构建出复杂生物性状的局部基因网络模式,并且运用构建的局部基因网络模式作为分析复杂生物性状分子机制的手段。选取高血压、长寿和胚胎干细胞的敏感基因作为研究对象,搜集并整合大量生物信号通路等基因相关信息,使用KEGG数据库提供的KGML图解基因网络编辑器和Osprey软件,对这四种复杂生物性状的敏感基因之间的关联性做了初步分析,得到以下结论:
1构建的高血压局部基因网络模式,包含22条信号通路作为连线,15个基因作为节点,建立了64种连接方式的局部基因网络模式。随机选择其中的一种连接方式,构画出了一张包含47个基因、9条信号转导通路的高血压局部基因网络图,其中,MAPK signaling pathway,Purine metabolism,Calcium signaling pathway和Adipocytokine signaling pathway分别控制多糖代谢、葡萄糖代谢和游离脂肪酸的代谢。
2应用基因芯片技术分析得出,LEPR、PLC、NCX基因表达值上调与GLUT1、VEGF、GPCR、GS、PKG、RAP1A、AKT、PRKAR2B、ADA、AMPK、AGT、GUCY基因的表达值下调。
3构建出人类长寿局部基因网络模式包含2~(23)种连接方式,19条信号通路,8个人类长寿基因,5个连接基因和一个化合物(c00097),以一种连接方式为依据得到人类长寿局部基因网络图,包含17个基因和2个化合物。
4建立了线虫长寿基因网络,包含38个基因,6条信号通路,运用芯片数据分析,发现有六个基因age-1,cyc-1,aak-2,let-363,cst-1/MST和akt-1表达值的下调有助于延长寿命。
5建立了胚胎干细胞基因网络图,包含23个蛋白质和20个基因。利用芯片数据分析,得出SOX2、OCT-4基因表达值上调,IGF-2、OCT-4基因表达值下调。
The purpose of the study was to set up a protocol to construct the local gene network pattern of several complex biological phenotypes,and analyze the molecular mechanism of complex biological phenotypes by using the LGNPs.Hypertension,longevity and maintenance or transformation of embryonic stem cell were selected for studying the molecular mechanism of the three complex biological phenotypes.We collected lots of gene-related information such as signaling pathway from biological databases by the internet in the way of the bioinformatics methods.KGML Editor gene network diagrams from KEGG database and the software Osprey visualizing the network between gene and protein were employed in this study.The Local gene network pattern of the four complex biological traits were successfully constructed through analyzing the relevance among the susceptibility genes.Five conclusions were obtained:
Firstly the local gene network patterns of hypertension included 22 signal transduction pathways,and 15 genes.We set up a hypertension genes network through selecting connections of the 64 kinds of the LGNPs.This network contained 47 genes,9 signal pathways,four of which control the Polysaccharide metabolism、glucose metabolism and fatty acid metabolism.
Secondly there are fifteen genes changed significantly in microarray expression.The gene expression level of LEPR,PLC,NCX increased and the gene expression level of GLUT1,VEGF,GPCR,GS,PKG,RAP1A,AKT,PRKAR2B,ADA,AMPK,AGT,GUCY went down in microarray.The new sensitive gene of complex biological phenotype could be predicted by the application of gene chip technology.
Thirdly the local gene network of human longevity contained 19 signaling pathways, 17 genes and the two compounds.We set up the LGN through selecting connections of the two to the power of twenty-three(2~(23)) kinds of the LGNPs.
Fourthly the LGN of the worm longevity contained 6 signaling pathways,38 genes,of which 24 genes were already reported as nematode longevity genes.The gene expression levels of six genes age-1,cyc-1,aak-2,let-363,cst-1/MST and akt-1 went down in the consumption of low-fat and low-protein culture medium.
Fifthly the LGN of embryonic stem cell contained 23 proteins and 20 genes.The gene expression levels of the two genes SOX2 and OCT-4 increased and the gene expression levels of IGF-2 and OCT-4 decreased in the microarray data.
1构建的高血压局部基因网络模式,包含22条信号通路作为连线,15个基因作为节点,建立了64种连接方式的局部基因网络模式。随机选择其中的一种连接方式,构画出了一张包含47个基因、9条信号转导通路的高血压局部基因网络图,其中,MAPK signaling pathway,Purine metabolism,Calcium signaling pathway和Adipocytokine signaling pathway分别控制多糖代谢、葡萄糖代谢和游离脂肪酸的代谢。
2应用基因芯片技术分析得出,LEPR、PLC、NCX基因表达值上调与GLUT1、VEGF、GPCR、GS、PKG、RAP1A、AKT、PRKAR2B、ADA、AMPK、AGT、GUCY基因的表达值下调。
3构建出人类长寿局部基因网络模式包含2~(23)种连接方式,19条信号通路,8个人类长寿基因,5个连接基因和一个化合物(c00097),以一种连接方式为依据得到人类长寿局部基因网络图,包含17个基因和2个化合物。
4建立了线虫长寿基因网络,包含38个基因,6条信号通路,运用芯片数据分析,发现有六个基因age-1,cyc-1,aak-2,let-363,cst-1/MST和akt-1表达值的下调有助于延长寿命。
5建立了胚胎干细胞基因网络图,包含23个蛋白质和20个基因。利用芯片数据分析,得出SOX2、OCT-4基因表达值上调,IGF-2、OCT-4基因表达值下调。
The purpose of the study was to set up a protocol to construct the local gene network pattern of several complex biological phenotypes,and analyze the molecular mechanism of complex biological phenotypes by using the LGNPs.Hypertension,longevity and maintenance or transformation of embryonic stem cell were selected for studying the molecular mechanism of the three complex biological phenotypes.We collected lots of gene-related information such as signaling pathway from biological databases by the internet in the way of the bioinformatics methods.KGML Editor gene network diagrams from KEGG database and the software Osprey visualizing the network between gene and protein were employed in this study.The Local gene network pattern of the four complex biological traits were successfully constructed through analyzing the relevance among the susceptibility genes.Five conclusions were obtained:
Firstly the local gene network patterns of hypertension included 22 signal transduction pathways,and 15 genes.We set up a hypertension genes network through selecting connections of the 64 kinds of the LGNPs.This network contained 47 genes,9 signal pathways,four of which control the Polysaccharide metabolism、glucose metabolism and fatty acid metabolism.
Secondly there are fifteen genes changed significantly in microarray expression.The gene expression level of LEPR,PLC,NCX increased and the gene expression level of GLUT1,VEGF,GPCR,GS,PKG,RAP1A,AKT,PRKAR2B,ADA,AMPK,AGT,GUCY went down in microarray.The new sensitive gene of complex biological phenotype could be predicted by the application of gene chip technology.
Thirdly the local gene network of human longevity contained 19 signaling pathways, 17 genes and the two compounds.We set up the LGN through selecting connections of the two to the power of twenty-three(2~(23)) kinds of the LGNPs.
Fourthly the LGN of the worm longevity contained 6 signaling pathways,38 genes,of which 24 genes were already reported as nematode longevity genes.The gene expression levels of six genes age-1,cyc-1,aak-2,let-363,cst-1/MST and akt-1 went down in the consumption of low-fat and low-protein culture medium.
Fifthly the LGN of embryonic stem cell contained 23 proteins and 20 genes.The gene expression levels of the two genes SOX2 and OCT-4 increased and the gene expression levels of IGF-2 and OCT-4 decreased in the microarray data.
引文
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