首页|基于加权基因共表达网络分析法筛选调控奶牛酮病的关键基因和代谢物

基于加权基因共表达网络分析法筛选调控奶牛酮病的关键基因和代谢物

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本试验旨在筛选调控奶牛酮病的关键基因和代谢物.采集酮病奶牛(n=6)和健康奶牛(n=6)的干奶期、围产前期和围产后期的血液进行代谢组和转录组测序,利用加权共表达网络分析(WGNCA)法分析干奶期、围产前期和围产后期酮病奶牛和健康奶牛代谢物和基因的变化,并对关键代谢物和基因分别进行GO和KEGG富集分析.结果表明:1)干奶期棕色模块代谢物与奶牛酮病性状显著相关,主要富集在维生素的消化和吸收、泛醌和其他萜类-醌类生物合成物通路上,模块代谢物与差异代谢物有28种共同代谢物.2)围产前期的绿松石模块与奶牛酮病性状显著相关,主要富集在抗叶酸抗性、嗅觉传导和环磷酸鸟苷-蛋白激酶G信号等通路上,模块代谢物与差异代谢物共有18种共同代谢物.3)围产后期绿松石模块与奶牛酮病性状显著相关,主要富集在初级胆汁酸生物合成等通路上,模块代谢物与差异代谢物有6种共同代谢物.4)1-脱氧甲基鞘氨醇、特非司他辛、11A-乙酰氧基黄体酮和3-β-羟基-23,24-双去甲胆-5-nic酸可能是调控奶牛酮病的关键代谢物.5)WGCNA法分析转录组结果表明,淡青色模块与4种关键代谢物均呈正相关,GO分析富集生物过程部分主要在防御反应、免疫反应和炎性反应等条目上,分子功能部分主要富集信号受体结合、转移酶活性、含磷基团转移和细胞因子受体结合条目上.6)KEGG分析该部分基因显著富集在细胞因子-细胞因子受体相互作用、细胞因子信号传导途径和病毒蛋白与细胞因子和细胞因子受体的相互作用等信号通路.7)绘制淡青色模块基因与干奶期、围产前期及围产后期酮病奶牛差异基因韦恩图发现,淡青色模块、干奶期和围产前期酮病奶牛糖皮质激素诱导激酶1(SGK1)和肿瘤坏死因子α诱导蛋白3(TNFAIP3)为共同基因,淡青色模块、围产前期和围产后期酮病奶牛趋化因子(C-X-C矩阵)配体1(GRO1)为共同基因,淡青色模块、干奶期和围产后期酮病奶牛白细胞介素12β(IL12B)和染色体浓缩调节因子1(RCC1)为共同基因.综上所述,1-脱氧甲基鞘氨醇、特非司他辛、11A-乙酰氧基黄体酮和3-β-羟基-23,24-双去甲胆-5-nic酸可能是调控奶牛酮病的关键代谢物,SGK1、TNFAIP3、GRO1和RCC1可能是调控奶牛酮病的关键基因.
Screening of Key Genes and Metabolites Regulating Ketosis in Dairy Cows Based on Weighted Gene Co-Expression Network Analysis Method
The aim of this experiment was to screen key genes and metabolites regulating ketosis in dairy cows.The blood was collected from ketosis cows(n=6)and healthy cows(n=6)during dry milk period,pre-peri-natal period and post-perinatal period for metabolome and transcriptome sequencing,the metabolite and gene changes in ketosis and healthy cows during dry milk period,pre-perinatal period and post-perinatal period were analyzed by using weighted co-expression network analysis(WGNCA)method,and analyzed the key metabo-lites and genes by GO and KEGG enrichment,respectively.The results showed as follows:1)the brown mod-ule metabolites in dry milk period were significantly associated with ketosis traits in dairy cows,mainly en-riched in the pathways of vitamin digestion and absorption,ubiquinone and other terpene-quinone biosynthesi-zers,and there were 28 common metabolites between the module metabolites and the differential metabolites.2)The turquoise module in pre-perinatal period was significantly associated with ketosis traits in dairy cows,and mainly enriched in the pathways of antifolate resistance,olfactory transduction and cyclic guanosine mono-phosphate-protein kinase G(cGMP-PKG)signaling,and there were 18 common metabolites between the mod-ule metabolites and the differential metabolites.3)The turquoise module in post-perinatal period was signifi-cantly correlated with ketosis traits in dairy cows,mainly enriched on pathways such as primary bile acid bio-synthesis,and there were 6 common metabolites between the module metabolites and the differential metabo-lites.4)The 1-desoxymethylsphinganine,terpestacin,11A-acetoxyprogesterone and 3-beta-hydroxy-23,24-bisdemethoxychol-5-nic acid might be key metabolites regulating ketosis in dairy cows.5)The WGCNA meth-od analysis the transcriptome showed that the light cyan module was positively correlated with four key metabo-lites,and the GO analysis enriched the bioprocess portion mainly on entries such as defense response,immune response and inflammatory response entries,and the molecular function part was mainly enriched on signaling receptor binding,transferase activity,phosphorus-containing group transfer and cytokine receptor binding en-tries.6)The KEGG analysis of this fraction of genes was significantly enriched in signaling pathways such as cytokine-cytokine receptor interactions,cytokine signaling pathways,and interactions of viral proteins with cy-tokines and cytokine receptors.7)Plotting of the light cyan module genes with differential genes of dairy cows during dry milk period,pre-perinatal period and post-perinatal period found that the glucocorticoid-induced ki-nase 1(SGK1)and tumor necrosis factor alpha inducible protein 3(TNFAIP3)as common genes in light cyan module,dry milk period and pre-perinatal period ketosis cows,the chemokine(C-X-C motif)ligand 1(GRO1)as common genes in light cyan module,pre-perinatal period and post-perinatal period ketosis cows,and the interleukin 1 beta(IL12B)and regulator of chromosome condensation 1(RCC1)as common genes in light cyan module,dry milk period and post-perinatal ketosis cows.In summary,1-desoxymethylsphinganine,terpestacin,11A-acetoxyprogesterone and 3-beta-hydroxy-23,24-bisdesmethylchol-5-nic acid may be the key metabolites,and SGK1,TNFAIP3,GRO1 and RCC1 may be the key genes in the regulation of ketosis in dairy cows.[Chinese Journal of Animal Nutrition,2024,36(12):8072-8087]

dairy cowsketosisWGCNAmetabolitesgenesnutrition metabolism

户春丽、曹佩佩、冀国尚、沙萍、马敏、马燕芬

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宁夏大学动物科技学院,银川 750021

奶牛 酮病 WGCNA 代谢物 基因 营养代谢

2024

动物营养学报
中国畜牧兽医学会

动物营养学报

CSTPCD北大核心
影响因子:1.297
ISSN:1006-267X
年,卷(期):2024.36(12)