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]