Objective:To identify promising biomarkers for the pathogenesis of major depressive disorder(MDD).Methods:Microarray chips of MDD patients,including the GSE98793,GSE52790,and GSE39653 datasets,were obtained from the G...Objective:To identify promising biomarkers for the pathogenesis of major depressive disorder(MDD).Methods:Microarray chips of MDD patients,including the GSE98793,GSE52790,and GSE39653 datasets,were obtained from the Gene Expression Omnibus database.The biological processes and pathways related to MDD were investigated using the GO and KEGG pathway tools.Weighted gene coexpression network analysis was conducted to identify modules related to MDD.The hub genes associated with MDD were obtained via protein-protein interaction analysis.Finally,the expression of hub genes in the hippocampal tissues of depression-like rats was detected by reverse transcription-polymerase chain reaction and Western blotting.Results:A total of 658 differentially expressed genes were identified from the Gene Expression Omnibus datasets;thus,these genes and the GSE98793 dataset were used to conduct weighted gene coexpression network analysis.A total of 244 module-related genes were identified and these genes were highly correlated with MDD.These genes were involved in the Ras signaling pathway,regulation of the actin cytoskeleton,and axon guidance according to the KEGG analysis.Hub genes,including MAPK14,SOCS1,TLR2,PTK2B,and GRB2,were obtained via protein-protein interaction analysis.All these hub genes showed better diagnostic efficiency in the GSE52790,GSE39653,and GSE98793 datasets.In vivo experiments revealed that compared with those in control rats,SOCS1 and MAPK14 expression was significantly decreased;while GRB2,TLR2,and PTK2B expression was increased in the hippocampi of depression-like rats.Conclusions:Our study demonstrates that GRB2,TLR2,SOCS1,PTK2B,and MAPK14 are promising hub genes,and targeting these five genes may be an effective treatment strategy for MDD.展开更多
Seed weight is a component of seed yield in rapeseed(Brassica napus L.).Although quantitative trait loci(QTL)for seed weight have been reported in rapeseed,only a few causal quantitative trait genes(QTGs)have been ide...Seed weight is a component of seed yield in rapeseed(Brassica napus L.).Although quantitative trait loci(QTL)for seed weight have been reported in rapeseed,only a few causal quantitative trait genes(QTGs)have been identified,resulting in a limitation in understanding of seed weight regulation.We constructed a gene coexpression network at the early seed developmental stage using transcripts of 20,408 genes in QTL intervals and 1017 rapeseed homologs of known genes from other species.Among the 10 modules in this gene coexpression network,modules 1 and 2 were core modules and contained genes involved in source–flow–sink processes such as synthesis and transportation of fatty acid and protein,and photosynthesis.A hub gene SERINE CARBOXYPEPTIDASE-LIKE 19(SCPL19)was identified by candidate gene association analysis in rapeseed and functionally investigated using Arabidopsis T-DNA mutant and overexpression lines.Our study demonstrates the power of gene coexpression analysis to prioritize candidate genes from large candidate QTG sets and enhances the understanding of molecular mechanism for seed weight at the early developmental stage in rapeseed.展开更多
BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers a...BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS Saliva samples from 31 DILI patients and 35 healthy controls(HCs)were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry.Subsequent analyses,including partial least squares-discriminant analysis modeling,t tests and weighted metabolite coexpression network analysis(WMCNA),were conducted to identify key differentially expressed metabolites(DEMs)and metabolite sets.Furthermore we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction.The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS We found 247 differentially expressed salivary metabolites between the DILI group and the HC group.Using WMCNA,we identified a set of 8 DEMs closely related to liver injury for further prediction testing.Interestingly,the distinct separation of DILI patients and HCs was achieved with five metabolites,namely,12-hydroxydodecanoic acid,3-hydroxydecanoic acid,tetradecanedioic acid,hypoxanthine,and inosine(area under the curve:0.733-1).CONCLUSION Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients.Our study may provide a potentially feasible and noninvasive diagnostic method for DILI,but further validation is needed.展开更多
BACKGROUND The development and progression of hepatocellular carcinoma(HCC)have been reported to be associated with immune-related genes and the tumor microenvir-onment.Nevertheless,there are not enough prognostic bio...BACKGROUND The development and progression of hepatocellular carcinoma(HCC)have been reported to be associated with immune-related genes and the tumor microenvir-onment.Nevertheless,there are not enough prognostic biomarkers and models available for clinical use.Based on seven prognostic genes,this study calculated overall survival in patients with HCC using a prognostic survival model and revealed the immune status of the tumor microenvironment(TME).AIM To develop a novel immune cell-related prognostic model of HCC and depict the basic profile of the immune response in HCC.METHODS We obtained clinical information and gene expression data of HCC from The Cancer Genome Atlas(TCGA)and International Cancer Genome Consortium(ICGC)datasets.TCGA and ICGC datasets were used for screening prognostic genes along with developing and validating a seven-gene prognostic survival model by weighted gene coexpression network analysis and least absolute shrinkage and selection operator regression with Cox regression.The relative analysis of tumor mutation burden(TMB),TME cell infiltration,immune check-points,immune therapy,and functional pathways was also performed based on prognostic genes.RESULTS Seven prognostic genes were identified for signature construction.Survival receiver operating characteristic curve analysis showed the good performance of survival prediction.TMB could be regarded as an independent factor in HCC survival prediction.There was a significant difference in stromal score,immune score,and estimate score between the high-risk and low-risk groups stratified based on the risk score derived from the seven-gene prognostic model.Several immune checkpoints,including VTCN1 and TNFSF9,were found to be associated with the seven prognostic genes and risk score.Different combinations of checkpoint blockade targeting inhibitory CTLA4 and PD1 receptors and potential chemotherapy drugs hold great promise for specific HCC therapies.Potential pathways,such as cell cycle regulation and metabolism of some amino acids,were also identified and analyzed.CONCLUSION The novel seven-gene(CYTH3,ENG,HTRA3,PDZD4,SAMD14,PGF,and PLN)prognostic model showed high predictive efficiency.The TMB analysis based on the seven genes could depict the basic profile of the immune response in HCC,which might be worthy of clinical application.展开更多
BACKGROUND Self-renewal of gastric cancer stem cells(GCSCs)is considered to be the underlying cause of the metastasis,drug resistance,and recurrence of gastric cancer(GC).AIM To characterize the expression of stem cel...BACKGROUND Self-renewal of gastric cancer stem cells(GCSCs)is considered to be the underlying cause of the metastasis,drug resistance,and recurrence of gastric cancer(GC).AIM To characterize the expression of stem cell-related genes in GC.METHODS RNA sequencing results and clinical data for gastric adenoma and adenocarcinoma samples were obtained from The Cancer Genome Atlas database,and the results of the GC mRNA expression-based stemness index(mRNAsi)were analyzed.Weighted gene coexpression network analysis was then used to find modules of interest and their key genes.Survival analysis of key genes was performed using the online tool Kaplan-Meier Plotter,and the online database Oncomine was used to assess the expression of key genes in GC.RESULTS mRNAsi was significantly upregulated in GC tissues compared to normal gastric tissues(P<0.0001).A total of 16 modules were obtained from the gene coexpression network;the brown module was most positively correlated with mRNAsi.Sixteen key genes(BUB1,BUB1 B,NCAPH,KIF14,RACGAP1,RAD54 L,TPX2,KIF15,KIF18 B,CENPF,TTK,KIF4 A,SGOL2,PLK4,XRCC2,a n d C1 orf112)were identified in the brown module.The functional and pathway enrichment analyses showed that the key genes were significantly enriched in the spindle cellular component,the sister chromatid segregation biological process,the motor activity molecular function,and the cell cycle and homologous recombination pathways.Survival analysis and Oncomine analysis revealed that the prognosis of patients with GC and the expression of three genes(RAD54 L,TPX2,and XRCC2)were consistently related.CONCLUSION Sixteen key genes are primarily associated with stem cell self-renewal and cell proliferation characteristics.RAD54 L,TPX2,and XRCC2 are the most likely therapeutic targets for inhibiting the stemness characteristics of GC cells.展开更多
The study of yield traits can reveal the genetic architecture of grain yield for improving maize production.In this study, an association panel comprising 362 inbred lines and a recombinant inbred line population deri...The study of yield traits can reveal the genetic architecture of grain yield for improving maize production.In this study, an association panel comprising 362 inbred lines and a recombinant inbred line population derived from X178 × 9782 were used to identify candidate genes for nine yield traits. High-priority overlap(HPO) genes, which are genes prioritized in a genome-wide association study(GWAS), were investigated using coexpression networks. The GWAS identified 51 environmentally stable SNPs in two environments and 36 pleiotropic SNPs, including three SNPs with both attributes. Seven hotspots containing 41 trait-associated SNPs were identified on six chromosomes by permutation. Pyramiding of superior alleles showed a highly positive effect on all traits, and the phenotypic values of ear diameter and ear weight consistently corresponded with the number of superior alleles in tropical and temperate germplasm. A total of 61 HPO genes were detected after trait-associated SNPs were combined with the coexpression networks. Linkage mapping identified 16 environmentally stable and 16 pleiotropic QTL.Seven SNPs that were located in QTL intervals were assigned as consensus SNPs for the yield traits.Among the candidate genes predicted by our study, some genes were confirmed to function in seed development. The gene Zm00001 d016656 encoding a serine/threonine protein kinase was associated with five different traits across multiple environments. Some genes were uniquely expressed in specific tissues and at certain stages of seed development. These findings will provide genetic information and resources for molecular breeding of maize grain yield.展开更多
The pathogenesis of hypertrophic cardiomyopathy(HCM)is very complicated,particularly regarding the role of circular RNA(circRNA).This research pays special attention to the relationships of the circRNA-mediated networ...The pathogenesis of hypertrophic cardiomyopathy(HCM)is very complicated,particularly regarding the role of circular RNA(circRNA).This research pays special attention to the relationships of the circRNA-mediated network,including RNA-RNA relationships and RNA-RNA binding protein(RNA-RBP)relationships.We use the parameter framework technology proposed in this paper to screen differentially expressed circRNA,messenger RNA(mRNA),and microRNA(miRNA)from the expression profile of samples related to HCM.And 31 pairs of circRNA and mRNA relationship pairs were extracted,combined with the miRNA targeting database;145 miRNA-mRNA relationship pairs were extracted;268 circRNA-mRNA-miRNA triads were established through the common mRNA in the 2 types of relationship pairs.Thus,268 circRNA-miRNA regulatory relationships were deduced and 30 circRNARBP relationship pairs were analyzed at the protein level.On this basis,a circRNA-mediated regulatory network corresponding to the two levels of RNA-RNA and RNA-RBP was established.And then the roles of circRNA in HCM were analyzed through circRNA-mRNA,circRNA-miRNA,and circRNA-RBP,and the possible role in disease development mas inferred.展开更多
Linoleic acid is an essential polyunsaturated fatty acid that cannot be synthesized by humans or animals themselves and can only be obtained externally.The amount of linoleic acid present has an impact on the quality ...Linoleic acid is an essential polyunsaturated fatty acid that cannot be synthesized by humans or animals themselves and can only be obtained externally.The amount of linoleic acid present has an impact on the quality and flavour of meat and indirectly affects consumer preference.However,the molecular mechanisms influencing the deposition of linoleic acid in organisms are not clear.As the molecular mechanisms of linoleic acid deposition are not well understood,to investigate the main effector genes affecting the linoleic acid content,this study aimed to screen for hub genes in slow-type yellow-feathered chickens by transcriptome sequencing(RNA-Seq)and weighted gene coexpression network analysis(WGCNA).We screened for candidate genes associated with the linoleic acid content in slow-type yellow-feathered broilers.A total of 399 Tiannong partridge chickens were slaughtered at 126 days of age,fatty acid levels were measured in pectoral muscle,and pectoral muscle tissue was collected for transcriptome sequencing.Transcriptome sequencing results were combined with phenotypes for WGCNA to screen for candidate genes.KEGG enrichment analysis was also performed on the genes that were significantly enriched in the modules with the highest correlation.A total of 13310 genes were identified after quality control of transcriptomic data from 399 pectoral muscle tissues.WGCNA was performed,and a total of 26 modules were obtained,eight of which were highly correlated with the linoleic acid content.Four key genes,namely,MDH2,ATP5B,RPL7A and PDGFRA,were screened according to the criteria|GS|>0.2 and|MM|>0.8.The functional enrichment results showed that the genes within the target modules were mainly enriched in metabolic pathways.In this study,a large-sample-size transcriptome analysis revealed that metabolic pathways play an important role in the regulation of the linoleic acid content in Tiannong partridge chickens,and MDH2,ATP5B,RPL7A and PDGFRA were screened as important candidate genes affecting the linoleic acid content.The results of this study provide a theoretical basis for selecting molecular markers and comprehensively understanding the molecular mechanism affecting the linoleic acid content in muscle,providing an important reference for the breeding of slow-type yellowfeathered broiler chickens.展开更多
BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patie...BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patients with bladder cancer,meanwhile,predict the sensitivity of patients to chemotherapy and immunotherapy.METHODS Bladder cancer information data was obtained from The Cancer Genome Atlas and GSE32894.The CIBERSORT was used to calculate the immune score of each sample.Weighted gene co-expression network analysis was used to find genes that will have the same or similar expression patterns.Subsequently,multivariate cox regression and lasso regression was used to further screen prognosis-related genes.The prrophetic package was used to predict phenotype from gene expression data,drug sensitivity of external cell line and predict clinical data.RESULTS The stage and risk scores are independent prognostic factors in patients with BUC.Mutations in FGFR3 lead to an increase in Tregs percolation and affect the prognosis of the tumor,and additionally,EMP1,TCHH and CNTNAP3B in the model are mainly positively correlated with the expression of immune checkpoints,while CMTM8,SORT1 and IQSEC1 are negatively correlated with immune checkpoints and the high-risk group had higher sensitivity to chemotherapy drugs.CONCLUSION Prognosis-related models of bladder tumor patients,based on Treg and NK cell percolation in tumor tissue.In addition to judging the prognosis of patients with bladder cancer,it can also predict the sensitivity of patients to chemotherapy and immunotherapy.At the same time,patients were divided into high and low risk groups based on this model,and differences in genetic mutations were found between the high and low risk groups.展开更多
Maize(Zea mays),a major food crop worldwide,is susceptible to infection by the saprophytic fungus Aspergillus flavus that can produce the carcinogenic metabolite aflatoxin(AF)especially under climate change induced ab...Maize(Zea mays),a major food crop worldwide,is susceptible to infection by the saprophytic fungus Aspergillus flavus that can produce the carcinogenic metabolite aflatoxin(AF)especially under climate change induced abiotic stressors that favor mold growth.Several studies have used“-omics”approaches to identify genetic elements with potential roles in AF resistance,but there is a lack of research identifying the involvement of small RNAs such as microRNAs(miRNAs)in maize-A.flavus interaction.In this study,we compared the miRNA profiles of three maize lines(resistant TZAR102,moderately resistant MI82,and susceptible Va35)at 8 h,3 d,and 7 d after A.flavus infection to investigate possible regulatory antifungal role of miRNAs.A total of 316 miRNAs(275 known and 41 putative novel)belonging to 115 miRNA families were identified in response to the fungal infection across all three maize lines.Eighty-two unique miRNAs were significantly differentially expressed with 39 miRNAs exhibiting temporal differential regulation irrespective of the maize genotype,which targeted 544 genes(mRNAs)involved in diverse molecular functions.The two most notable biological processes involved in plant immunity,namely cellular responses to oxidative stress(GO:00345990)and reactive oxygen species(GO:0034614)were significantly enriched in the resistant line TZAR102.Coexpression network analysis identified 34 hubs of miRNA-mRNA pairs where nine hubs had a node in the module connected to their target gene with potentially important roles in resistance/susceptible response of maize to A.flavus.The miRNA hubs in resistance modules(TZAR102 and MI82)were mostly connected to transcription factors and protein kinases.Specifically,the module of miRNA zma-miR156b-nb-squamosa promoter binding protein(SBP),zma-miR398a-3p-SKIP5,and zma-miR394a-5p-F-box protein 6 combinations in the resistance-associated modules were considered important candidates for future functional studies.展开更多
Starch is the major component in maize kernels,providing a stable carbohydrate source for humans and livestock as well as raw material for the biofuel industry.Increasing maize kernel starch content will help meet ind...Starch is the major component in maize kernels,providing a stable carbohydrate source for humans and livestock as well as raw material for the biofuel industry.Increasing maize kernel starch content will help meet industry demands and has the potential to increase overall yields.We developed a pair of maize near-isogenic lines（NILs） with different alleles for a starch quantitative trait locus on chromosome 3（q HS3）, resulting in different kernel starch content. To investigate the candidate genes for q HS3 and elucidate their effects on starch metabolism, RNA-Seq was performed for the developing kernels of the NILs at 14 and 21 d after pollination（DAP）. Analysis of genomic and transcriptomic data identified 76 genes with nonsynonymous single nucleotide polymorphisms and 384 differentially expressed genes（DEGs） in the in trogressed fragment, including a hexokinase gene, Zm HXK3 a, which catalyzes the conversion of glucose to glucose-6-phosphate and may play a key role instarch metabolism. The expression pattern of all DEGs in starch metabolism shows that altered expression of the candidate genes for q HS3 promoted starch synthesis,with positive consequences for kernel starch content. These results expand the current understanding of starch biosynthesis and accumulation in maize kernels and provide potential candidate genes to increase starch content.展开更多
The initiation of B-cell ligand recognition is a critical step for the generation of an immune response against foreign bodies. We sought to identify the biochemical pathways involved in the B-cell ligand recognition ...The initiation of B-cell ligand recognition is a critical step for the generation of an immune response against foreign bodies. We sought to identify the biochemical pathways involved in the B-cell ligand recognition cascade and sets of ligands that trigger similar immunological responses. We utilized several comparative approaches to analyze the gene coexpression networks generated from a set of microarray experiments spanning 33 different ligands. First, we compared the degree distributions of the generated networks. Second, we utilized a pairwise network alignment algorithm, BiNA, to align the networks based on the hubs in the networks. Third, we aligned the networks based on a set of KEGG pathways. We summarized our results by constructing a consensus hierarchy of pathways that are involved in B cell ligand recognition. The resulting pathways were further validated through literature for their common physiological responses. Col- lectively, the results based on our comparative analyses of degree distributions, alignment of hubs, and alignment based on KEGG path- ways provide a basis for molecular characterization of the immune response states of B-cells and demonstrate the power of comparative approaches （e.g., gene coexpression network alignment algorithms） in elucidating biochemical pathways involved in complex signaling events in ceils.展开更多
Background and Aims:Great efforts have been made towards increasing our understanding of the pathogenesis involved in hepatocellular carcinoma(HCC),but the rapid growth inherent to such tumor development remains to be...Background and Aims:Great efforts have been made towards increasing our understanding of the pathogenesis involved in hepatocellular carcinoma(HCC),but the rapid growth inherent to such tumor development remains to be explored.Methods:We identified distinct gene coexpression modes upon liver tumor growth using weighted gene coexpression network analysis.Modeling of tumor growth as signaling activity was employed to understand the main cascades responsible for the growth.Hub genes in the modules were determined,examined in vitro,and further assembled into the growth signature.Results:We revealed modules related to the different growth states in HCC,especially the fastest growth module,which is preserved among different HCC cohorts.Moreover,signaling flux in the cell cycle pathway was found to act as a driving force for rapid growth.Twenty hub genes in the module were identified and assembled into the growth signature,and two genes(NCAPH,and RAD54L)were tested for their growth potential in vitro.Genetic alteration of the growth signature affected the global gene expression.The activity of the signature was associated with tumor metabolism and immunity in HCC.Finally,the prognosis effect of the growth signature was reproduced in nine cancers.Conclusions:These results collectively demonstrate the molecule organization of rapid tumor growth in HCC,which is a highly synergistic process,with implications for the future management of patients.展开更多
基金supported by the National Natural Science Foundation of China(No.81774281 and No.82474303)the Natural Science Foundation of Hunan Province(2023JJ30888)the leading national joint discipline of Chinese and Western medicines to the Chinese Medicine Department,Xiangya Hospital,CSU.
文摘Objective:To identify promising biomarkers for the pathogenesis of major depressive disorder(MDD).Methods:Microarray chips of MDD patients,including the GSE98793,GSE52790,and GSE39653 datasets,were obtained from the Gene Expression Omnibus database.The biological processes and pathways related to MDD were investigated using the GO and KEGG pathway tools.Weighted gene coexpression network analysis was conducted to identify modules related to MDD.The hub genes associated with MDD were obtained via protein-protein interaction analysis.Finally,the expression of hub genes in the hippocampal tissues of depression-like rats was detected by reverse transcription-polymerase chain reaction and Western blotting.Results:A total of 658 differentially expressed genes were identified from the Gene Expression Omnibus datasets;thus,these genes and the GSE98793 dataset were used to conduct weighted gene coexpression network analysis.A total of 244 module-related genes were identified and these genes were highly correlated with MDD.These genes were involved in the Ras signaling pathway,regulation of the actin cytoskeleton,and axon guidance according to the KEGG analysis.Hub genes,including MAPK14,SOCS1,TLR2,PTK2B,and GRB2,were obtained via protein-protein interaction analysis.All these hub genes showed better diagnostic efficiency in the GSE52790,GSE39653,and GSE98793 datasets.In vivo experiments revealed that compared with those in control rats,SOCS1 and MAPK14 expression was significantly decreased;while GRB2,TLR2,and PTK2B expression was increased in the hippocampi of depression-like rats.Conclusions:Our study demonstrates that GRB2,TLR2,SOCS1,PTK2B,and MAPK14 are promising hub genes,and targeting these five genes may be an effective treatment strategy for MDD.
基金provided by the National Natural Science Foundation of China(32201776)the Natural Science Foundation of Chongqing(cstc2019jcyj-bsh X0055,cstc2019jcyj-zdxm X0012)。
文摘Seed weight is a component of seed yield in rapeseed(Brassica napus L.).Although quantitative trait loci(QTL)for seed weight have been reported in rapeseed,only a few causal quantitative trait genes(QTGs)have been identified,resulting in a limitation in understanding of seed weight regulation.We constructed a gene coexpression network at the early seed developmental stage using transcripts of 20,408 genes in QTL intervals and 1017 rapeseed homologs of known genes from other species.Among the 10 modules in this gene coexpression network,modules 1 and 2 were core modules and contained genes involved in source–flow–sink processes such as synthesis and transportation of fatty acid and protein,and photosynthesis.A hub gene SERINE CARBOXYPEPTIDASE-LIKE 19(SCPL19)was identified by candidate gene association analysis in rapeseed and functionally investigated using Arabidopsis T-DNA mutant and overexpression lines.Our study demonstrates the power of gene coexpression analysis to prioritize candidate genes from large candidate QTG sets and enhances the understanding of molecular mechanism for seed weight at the early developmental stage in rapeseed.
基金Supported by Medical Education Association Foundation of China,No.2020KTY001National Natural Science Foundation of China,No.81673806National Natural Science Foundation Youth Fund,No.82104702.
文摘BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS Saliva samples from 31 DILI patients and 35 healthy controls(HCs)were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry.Subsequent analyses,including partial least squares-discriminant analysis modeling,t tests and weighted metabolite coexpression network analysis(WMCNA),were conducted to identify key differentially expressed metabolites(DEMs)and metabolite sets.Furthermore we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction.The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS We found 247 differentially expressed salivary metabolites between the DILI group and the HC group.Using WMCNA,we identified a set of 8 DEMs closely related to liver injury for further prediction testing.Interestingly,the distinct separation of DILI patients and HCs was achieved with five metabolites,namely,12-hydroxydodecanoic acid,3-hydroxydecanoic acid,tetradecanedioic acid,hypoxanthine,and inosine(area under the curve:0.733-1).CONCLUSION Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients.Our study may provide a potentially feasible and noninvasive diagnostic method for DILI,but further validation is needed.
文摘BACKGROUND The development and progression of hepatocellular carcinoma(HCC)have been reported to be associated with immune-related genes and the tumor microenvir-onment.Nevertheless,there are not enough prognostic biomarkers and models available for clinical use.Based on seven prognostic genes,this study calculated overall survival in patients with HCC using a prognostic survival model and revealed the immune status of the tumor microenvironment(TME).AIM To develop a novel immune cell-related prognostic model of HCC and depict the basic profile of the immune response in HCC.METHODS We obtained clinical information and gene expression data of HCC from The Cancer Genome Atlas(TCGA)and International Cancer Genome Consortium(ICGC)datasets.TCGA and ICGC datasets were used for screening prognostic genes along with developing and validating a seven-gene prognostic survival model by weighted gene coexpression network analysis and least absolute shrinkage and selection operator regression with Cox regression.The relative analysis of tumor mutation burden(TMB),TME cell infiltration,immune check-points,immune therapy,and functional pathways was also performed based on prognostic genes.RESULTS Seven prognostic genes were identified for signature construction.Survival receiver operating characteristic curve analysis showed the good performance of survival prediction.TMB could be regarded as an independent factor in HCC survival prediction.There was a significant difference in stromal score,immune score,and estimate score between the high-risk and low-risk groups stratified based on the risk score derived from the seven-gene prognostic model.Several immune checkpoints,including VTCN1 and TNFSF9,were found to be associated with the seven prognostic genes and risk score.Different combinations of checkpoint blockade targeting inhibitory CTLA4 and PD1 receptors and potential chemotherapy drugs hold great promise for specific HCC therapies.Potential pathways,such as cell cycle regulation and metabolism of some amino acids,were also identified and analyzed.CONCLUSION The novel seven-gene(CYTH3,ENG,HTRA3,PDZD4,SAMD14,PGF,and PLN)prognostic model showed high predictive efficiency.The TMB analysis based on the seven genes could depict the basic profile of the immune response in HCC,which might be worthy of clinical application.
基金the National Natural Science Foundation of China,No.81560389Key Research and Development Program of Jiangxi Province,No.20181BBG70015。
文摘BACKGROUND Self-renewal of gastric cancer stem cells(GCSCs)is considered to be the underlying cause of the metastasis,drug resistance,and recurrence of gastric cancer(GC).AIM To characterize the expression of stem cell-related genes in GC.METHODS RNA sequencing results and clinical data for gastric adenoma and adenocarcinoma samples were obtained from The Cancer Genome Atlas database,and the results of the GC mRNA expression-based stemness index(mRNAsi)were analyzed.Weighted gene coexpression network analysis was then used to find modules of interest and their key genes.Survival analysis of key genes was performed using the online tool Kaplan-Meier Plotter,and the online database Oncomine was used to assess the expression of key genes in GC.RESULTS mRNAsi was significantly upregulated in GC tissues compared to normal gastric tissues(P<0.0001).A total of 16 modules were obtained from the gene coexpression network;the brown module was most positively correlated with mRNAsi.Sixteen key genes(BUB1,BUB1 B,NCAPH,KIF14,RACGAP1,RAD54 L,TPX2,KIF15,KIF18 B,CENPF,TTK,KIF4 A,SGOL2,PLK4,XRCC2,a n d C1 orf112)were identified in the brown module.The functional and pathway enrichment analyses showed that the key genes were significantly enriched in the spindle cellular component,the sister chromatid segregation biological process,the motor activity molecular function,and the cell cycle and homologous recombination pathways.Survival analysis and Oncomine analysis revealed that the prognosis of patients with GC and the expression of three genes(RAD54 L,TPX2,and XRCC2)were consistently related.CONCLUSION Sixteen key genes are primarily associated with stem cell self-renewal and cell proliferation characteristics.RAD54 L,TPX2,and XRCC2 are the most likely therapeutic targets for inhibiting the stemness characteristics of GC cells.
基金funded and supported by China Agriculture Research System of MOF and MARA,Sichuan Science and Technology Support Project(2021YFYZ0020,2021YFYZ0027,2021YFFZ0017)National Natural Science Foundation of China(31971955)Sichuan Science and Technology Program(2019YJ0418,2020YJ0138)。
文摘The study of yield traits can reveal the genetic architecture of grain yield for improving maize production.In this study, an association panel comprising 362 inbred lines and a recombinant inbred line population derived from X178 × 9782 were used to identify candidate genes for nine yield traits. High-priority overlap(HPO) genes, which are genes prioritized in a genome-wide association study(GWAS), were investigated using coexpression networks. The GWAS identified 51 environmentally stable SNPs in two environments and 36 pleiotropic SNPs, including three SNPs with both attributes. Seven hotspots containing 41 trait-associated SNPs were identified on six chromosomes by permutation. Pyramiding of superior alleles showed a highly positive effect on all traits, and the phenotypic values of ear diameter and ear weight consistently corresponded with the number of superior alleles in tropical and temperate germplasm. A total of 61 HPO genes were detected after trait-associated SNPs were combined with the coexpression networks. Linkage mapping identified 16 environmentally stable and 16 pleiotropic QTL.Seven SNPs that were located in QTL intervals were assigned as consensus SNPs for the yield traits.Among the candidate genes predicted by our study, some genes were confirmed to function in seed development. The gene Zm00001 d016656 encoding a serine/threonine protein kinase was associated with five different traits across multiple environments. Some genes were uniquely expressed in specific tissues and at certain stages of seed development. These findings will provide genetic information and resources for molecular breeding of maize grain yield.
基金the National Natural Science Foundation of China under Grant No.61872405the Key R&D program of Sichuan Province under Grant No.2020YFS0243the Key Project of Natural Science Foundation of Guangdong Province under Grant No.2016A030311040.
文摘The pathogenesis of hypertrophic cardiomyopathy(HCM)is very complicated,particularly regarding the role of circular RNA(circRNA).This research pays special attention to the relationships of the circRNA-mediated network,including RNA-RNA relationships and RNA-RNA binding protein(RNA-RBP)relationships.We use the parameter framework technology proposed in this paper to screen differentially expressed circRNA,messenger RNA(mRNA),and microRNA(miRNA)from the expression profile of samples related to HCM.And 31 pairs of circRNA and mRNA relationship pairs were extracted,combined with the miRNA targeting database;145 miRNA-mRNA relationship pairs were extracted;268 circRNA-mRNA-miRNA triads were established through the common mRNA in the 2 types of relationship pairs.Thus,268 circRNA-miRNA regulatory relationships were deduced and 30 circRNARBP relationship pairs were analyzed at the protein level.On this basis,a circRNA-mediated regulatory network corresponding to the two levels of RNA-RNA and RNA-RBP was established.And then the roles of circRNA in HCM were analyzed through circRNA-mRNA,circRNA-miRNA,and circRNA-RBP,and the possible role in disease development mas inferred.
基金This study was supported by the China Agriculture Research System of MOF and MARA(CARS-41)the Key-Area Research and Development Program of Guangdong Province,China(2020B020222002)+3 种基金the Foshan University High-level Talent Program,China(CGZ07243)the Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding,China(2019B030301010)the Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes,China(2019KSYS011)the Foshan Institute of Science and Technology Postgraduate Free Exploration Fund,China(2021ZYTS36).
文摘Linoleic acid is an essential polyunsaturated fatty acid that cannot be synthesized by humans or animals themselves and can only be obtained externally.The amount of linoleic acid present has an impact on the quality and flavour of meat and indirectly affects consumer preference.However,the molecular mechanisms influencing the deposition of linoleic acid in organisms are not clear.As the molecular mechanisms of linoleic acid deposition are not well understood,to investigate the main effector genes affecting the linoleic acid content,this study aimed to screen for hub genes in slow-type yellow-feathered chickens by transcriptome sequencing(RNA-Seq)and weighted gene coexpression network analysis(WGCNA).We screened for candidate genes associated with the linoleic acid content in slow-type yellow-feathered broilers.A total of 399 Tiannong partridge chickens were slaughtered at 126 days of age,fatty acid levels were measured in pectoral muscle,and pectoral muscle tissue was collected for transcriptome sequencing.Transcriptome sequencing results were combined with phenotypes for WGCNA to screen for candidate genes.KEGG enrichment analysis was also performed on the genes that were significantly enriched in the modules with the highest correlation.A total of 13310 genes were identified after quality control of transcriptomic data from 399 pectoral muscle tissues.WGCNA was performed,and a total of 26 modules were obtained,eight of which were highly correlated with the linoleic acid content.Four key genes,namely,MDH2,ATP5B,RPL7A and PDGFRA,were screened according to the criteria|GS|>0.2 and|MM|>0.8.The functional enrichment results showed that the genes within the target modules were mainly enriched in metabolic pathways.In this study,a large-sample-size transcriptome analysis revealed that metabolic pathways play an important role in the regulation of the linoleic acid content in Tiannong partridge chickens,and MDH2,ATP5B,RPL7A and PDGFRA were screened as important candidate genes affecting the linoleic acid content.The results of this study provide a theoretical basis for selecting molecular markers and comprehensively understanding the molecular mechanism affecting the linoleic acid content in muscle,providing an important reference for the breeding of slow-type yellowfeathered broiler chickens.
文摘BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patients with bladder cancer,meanwhile,predict the sensitivity of patients to chemotherapy and immunotherapy.METHODS Bladder cancer information data was obtained from The Cancer Genome Atlas and GSE32894.The CIBERSORT was used to calculate the immune score of each sample.Weighted gene co-expression network analysis was used to find genes that will have the same or similar expression patterns.Subsequently,multivariate cox regression and lasso regression was used to further screen prognosis-related genes.The prrophetic package was used to predict phenotype from gene expression data,drug sensitivity of external cell line and predict clinical data.RESULTS The stage and risk scores are independent prognostic factors in patients with BUC.Mutations in FGFR3 lead to an increase in Tregs percolation and affect the prognosis of the tumor,and additionally,EMP1,TCHH and CNTNAP3B in the model are mainly positively correlated with the expression of immune checkpoints,while CMTM8,SORT1 and IQSEC1 are negatively correlated with immune checkpoints and the high-risk group had higher sensitivity to chemotherapy drugs.CONCLUSION Prognosis-related models of bladder tumor patients,based on Treg and NK cell percolation in tumor tissue.In addition to judging the prognosis of patients with bladder cancer,it can also predict the sensitivity of patients to chemotherapy and immunotherapy.At the same time,patients were divided into high and low risk groups based on this model,and differences in genetic mutations were found between the high and low risk groups.
基金funded by a USDA-ARS grant in the form of a Non-Assistance Cooperative Agreement#58-6054-0-010approved for publication by the Louisiana Agricultural Experiment Station as MS#2024-306-39132.
文摘Maize(Zea mays),a major food crop worldwide,is susceptible to infection by the saprophytic fungus Aspergillus flavus that can produce the carcinogenic metabolite aflatoxin(AF)especially under climate change induced abiotic stressors that favor mold growth.Several studies have used“-omics”approaches to identify genetic elements with potential roles in AF resistance,but there is a lack of research identifying the involvement of small RNAs such as microRNAs(miRNAs)in maize-A.flavus interaction.In this study,we compared the miRNA profiles of three maize lines(resistant TZAR102,moderately resistant MI82,and susceptible Va35)at 8 h,3 d,and 7 d after A.flavus infection to investigate possible regulatory antifungal role of miRNAs.A total of 316 miRNAs(275 known and 41 putative novel)belonging to 115 miRNA families were identified in response to the fungal infection across all three maize lines.Eighty-two unique miRNAs were significantly differentially expressed with 39 miRNAs exhibiting temporal differential regulation irrespective of the maize genotype,which targeted 544 genes(mRNAs)involved in diverse molecular functions.The two most notable biological processes involved in plant immunity,namely cellular responses to oxidative stress(GO:00345990)and reactive oxygen species(GO:0034614)were significantly enriched in the resistant line TZAR102.Coexpression network analysis identified 34 hubs of miRNA-mRNA pairs where nine hubs had a node in the module connected to their target gene with potentially important roles in resistance/susceptible response of maize to A.flavus.The miRNA hubs in resistance modules(TZAR102 and MI82)were mostly connected to transcription factors and protein kinases.Specifically,the module of miRNA zma-miR156b-nb-squamosa promoter binding protein(SBP),zma-miR398a-3p-SKIP5,and zma-miR394a-5p-F-box protein 6 combinations in the resistance-associated modules were considered important candidates for future functional studies.
基金supported by the National Natural Science Foundation of China (31421005)International Cooperation in Science and Technology Project in China (2014DFG31690)DuPont Pioneer
文摘Starch is the major component in maize kernels,providing a stable carbohydrate source for humans and livestock as well as raw material for the biofuel industry.Increasing maize kernel starch content will help meet industry demands and has the potential to increase overall yields.We developed a pair of maize near-isogenic lines（NILs） with different alleles for a starch quantitative trait locus on chromosome 3（q HS3）, resulting in different kernel starch content. To investigate the candidate genes for q HS3 and elucidate their effects on starch metabolism, RNA-Seq was performed for the developing kernels of the NILs at 14 and 21 d after pollination（DAP）. Analysis of genomic and transcriptomic data identified 76 genes with nonsynonymous single nucleotide polymorphisms and 384 differentially expressed genes（DEGs） in the in trogressed fragment, including a hexokinase gene, Zm HXK3 a, which catalyzes the conversion of glucose to glucose-6-phosphate and may play a key role instarch metabolism. The expression pattern of all DEGs in starch metabolism shows that altered expression of the candidate genes for q HS3 promoted starch synthesis,with positive consequences for kernel starch content. These results expand the current understanding of starch biosynthesis and accumulation in maize kernels and provide potential candidate genes to increase starch content.
基金funded by the National Science Foundation (NSF) Grant (DGE0504304) to Iowa State University and NSF Grants 0939370,0835541 and 0641037 awarded to SS
文摘The initiation of B-cell ligand recognition is a critical step for the generation of an immune response against foreign bodies. We sought to identify the biochemical pathways involved in the B-cell ligand recognition cascade and sets of ligands that trigger similar immunological responses. We utilized several comparative approaches to analyze the gene coexpression networks generated from a set of microarray experiments spanning 33 different ligands. First, we compared the degree distributions of the generated networks. Second, we utilized a pairwise network alignment algorithm, BiNA, to align the networks based on the hubs in the networks. Third, we aligned the networks based on a set of KEGG pathways. We summarized our results by constructing a consensus hierarchy of pathways that are involved in B cell ligand recognition. The resulting pathways were further validated through literature for their common physiological responses. Col- lectively, the results based on our comparative analyses of degree distributions, alignment of hubs, and alignment based on KEGG path- ways provide a basis for molecular characterization of the immune response states of B-cells and demonstrate the power of comparative approaches （e.g., gene coexpression network alignment algorithms） in elucidating biochemical pathways involved in complex signaling events in ceils.
基金supported by the National Natural Science Foundation of China(No.81772520)Zhejiang Provincial Natural Science Foundation(No.LGF19H030004)+1 种基金Zhejiang Medical and Health Technology Project(No.2018PY039)and Hangzhou Science and Technology Project(No.2017A36,20180533B46).
文摘Background and Aims:Great efforts have been made towards increasing our understanding of the pathogenesis involved in hepatocellular carcinoma(HCC),but the rapid growth inherent to such tumor development remains to be explored.Methods:We identified distinct gene coexpression modes upon liver tumor growth using weighted gene coexpression network analysis.Modeling of tumor growth as signaling activity was employed to understand the main cascades responsible for the growth.Hub genes in the modules were determined,examined in vitro,and further assembled into the growth signature.Results:We revealed modules related to the different growth states in HCC,especially the fastest growth module,which is preserved among different HCC cohorts.Moreover,signaling flux in the cell cycle pathway was found to act as a driving force for rapid growth.Twenty hub genes in the module were identified and assembled into the growth signature,and two genes(NCAPH,and RAD54L)were tested for their growth potential in vitro.Genetic alteration of the growth signature affected the global gene expression.The activity of the signature was associated with tumor metabolism and immunity in HCC.Finally,the prognosis effect of the growth signature was reproduced in nine cancers.Conclusions:These results collectively demonstrate the molecule organization of rapid tumor growth in HCC,which is a highly synergistic process,with implications for the future management of patients.
