Biomedical big data,characterized by its massive scale,multi-dimensionality,and heterogeneity,offers novel perspectives for disease research,elucidates biological principles,and simultaneously prompts changes in relat...Biomedical big data,characterized by its massive scale,multi-dimensionality,and heterogeneity,offers novel perspectives for disease research,elucidates biological principles,and simultaneously prompts changes in related research methodologies.Biomedical ontology,as a shared formal conceptual system,not only offers standardized terms for multi-source biomedical data but also provides a solid data foundation and framework for biomedical research.In this review,we summarize enrichment analysis and deep learning for biomedical ontology based on its structure and semantic annotation properties,highlighting how technological advancements are enabling the more comprehensive use of ontology information.Enrichment analysis represents an important application of ontology to elucidate the potential biological significance for a particular molecular list.Deep learning,on the other hand,represents an increasingly powerful analytical tool that can be more widely combined with ontology for analysis and prediction.With the continuous evolution of big data technologies,the integration of these technologies with biomedical ontologies is opening up exciting new possibilities for advancing biomedical research.展开更多
Enrichment analysis methods, e.g., gene set enrichment analysis, represent one class of important bio- informatical resources for mining patterns in biomedical datasets. However, tools for inferring patterns and rules...Enrichment analysis methods, e.g., gene set enrichment analysis, represent one class of important bio- informatical resources for mining patterns in biomedical datasets. However, tools for inferring patterns and rules of a list of drugs are limited. In this study, we developed a web-based tool, DrugPattern, for drug set enrichment analysis. We first collected and curated 7019 drug sets, including indications, adverse reactions, targets, pathways, etc. from public databases. For a list of interested drugs, DrugPat- tern then evaluates the significance of the enrichment of these drugs in each of the 7019 drug sets. To validate DrugPattern, we employed it for the prediction of the effects of oxidized low-density lipoprotein （oxLDL）, a factor expected to be deleterious. We predicted that oxLDL has beneficial effects on some diseases, most of which were supported by evidence in the literature. Because DrugPattern predicted the potential beneficial effects of oxLDL in type 2 diabetes （T2D）, animal experiments were then performed to further verify this prediction. As a result, the experimental evidences validated the DrugPattern prediction that oxLDL indeed has beneficial effects on T2D in the case of energy restriction. These data confirmed the prediction accuracy of our approach and revealed unexpected protective roles for oxLDL in various diseases. This study provides a tool to infer patterns and rules in biomedical datasets based on drug set enrichment analysis.展开更多
Alzheimer's disease(AD) is a serious neurodegenerative disorder and its cause remains largely elusive.In past years,genome-wide association(GWA) studies have provided an effective means for AD research.However,the...Alzheimer's disease(AD) is a serious neurodegenerative disorder and its cause remains largely elusive.In past years,genome-wide association(GWA) studies have provided an effective means for AD research.However,the univariate method that is commonly used in GWA studies cannot effectively detect the biological mechanisms associated with this disease.In this study,we propose a new strategy for the GWA analysis of AD that combines random forests with enrichment analysis.First,backward feature selection using random forests was performed on a GWA dataset of AD patients carrying the apolipoprotein gene(APOEε4) and 1058 susceptible single nucleotide polymorphisms(SNPs) were detected,including several known AD-associated SNPs.Next,the susceptible SNPs were investigated by enrichment analysis and significantly-associated gene functional annotations,such as 'alternative splicing','glycoprotein',and 'neuron development',were successfully discovered,indicating that these biological mechanisms play important roles in the development of AD in APOEε4 carriers.These findings may provide insights into the pathogenesis of AD and helpful guidance for further studies.Furthermore,this strategy can easily be modified and applied to GWA studies of other complex diseases.展开更多
The first step in the analysis of high-throughput experiment results is often to identify genes orproteins with certain characteristics, such as genes being differentially expressed (DE). To gainmore insights into the...The first step in the analysis of high-throughput experiment results is often to identify genes orproteins with certain characteristics, such as genes being differentially expressed (DE). To gainmore insights into the underlying biology, functional enrichment analysis is then conductedto provide functional interpretation for the identified genes or proteins. The hypergeometricP value has been widely used to investigate whether genes from predefined functional terms,e.g., Reactome, are enriched in the DE genes. The hypergeometric P value has several limitations: (1) computed independently for each term, thus neglecting biological dependence;(2) subject to a size constraint that leads to the tendency of selecting less-specific terms. In this paper,a Bayesian approach is proposed to overcome these limitations by incorporating the interconnected dependence structure of biological functions in the Reactome database through a CARprior in a Bayesian hierarchical logistic model. The inference on functional enrichment is thenbased on posterior probabilities that are immune to the size constraint. This method can detectmoderate but consistent enrichment signals and identify sets of closely related and biologicallymeaningful functional terms rather than isolated terms. The performance of the Bayesian methodis demonstrated via a simulation study and a real data application.展开更多
Objective:Based on bioinformatics,gene set enrichment analysis(GSEA)and immune infiltration analysis were carried out on the microarray data of psoriasis expression profile to further understand the pathogenesis of ps...Objective:Based on bioinformatics,gene set enrichment analysis(GSEA)and immune infiltration analysis were carried out on the microarray data of psoriasis expression profile to further understand the pathogenesis of psoriasis.Methods:GSE6710 chip data were obtained from gene expression database(GEO),and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed using GSEA software.22 kinds of immune cell gene expression matrices and R packages were downloaded from CIBERSOFT official website,and the immune cell infiltration matrix was obtained by R software and related graphs were drawn.Results:The pathways related to cell proliferation and innate immunity were highly expressed in psoriatic lesions,and some cancer-related pathways were highly expressed in psoriatic lesions.Immunized cell infiltration analysis showed that activated memory T cells,follicular helper T cells,M0 macrophages and activated dendritic cells were up-regulated in psoriatic skin lesion group,and inactive mast cells were down-regulated in psoriatic skin lesion group.Activated dendritic cells are positively correlated with follicular helper T cells,activated mast cells are positively correlated with M0 macrophages.Inactivated mast cells are negatively correlated with activated memory T cells,M1 macrophages are negatively correlated with regulatory T cells,M0 macrophages are negatively correlated with inactive mast cells.Conclusion:Cell proliferation and innate immunity are of great significance in the pathogenesis of psoriasis.Immune cell infiltration analysis is generally consistent with the current psoriasis pathogenesis model.Macrophages and mast cells also play a certain role in psoriasis.展开更多
Background:NDC80 is pivotal in cell division,particularly in regulating the G2/M transition and mitotic progression.Recent studies have demonstrated that NDC80 is significantly overexpressed in multiple solid tumors.F...Background:NDC80 is pivotal in cell division,particularly in regulating the G2/M transition and mitotic progression.Recent studies have demonstrated that NDC80 is significantly overexpressed in multiple solid tumors.Further analysis has suggested that its high expression is significantly associated with an elevated pathological grade,increased metastatic risk,and shortened overall survival in patients with cancer.However,its precise role in pan-cancer development,progression,and prognosis remains unclear.Methods:We conducted a multi-omics analysis of NDC80 using genomic,transcriptomic,and proteomic data from 33 cancer types in The Cancer Genome Atlas,Clinical Proteomic Tumor Analysis Consortium,Genotype-Tissue Expression,and Human Protein Atlas.Results:The results demonstrated frequent NDC80 mutations across multiple malignancies and significantly elevated expression in tumor tissues compared with that in their normal counterparts,correlating with worse overall and disease-free survival.Moreover,NDC80 expression was strongly associated with oncogenic pathways,key protein regulators,cellular components,myeloid-derived suppressor cell infiltration,ESTIMATE scores,and cancer-related signaling networks.Conclusions:These findings underscore the potential of NDC80 as a prognostic biomarker and therapeutic target for cancer treatment.展开更多
Inbreeding usually reduces the mean phenotypic value of various traits.In Crassostrea gigas,inbreeding depression at the early life stage might be particularly remarkable because of a high mutational load that is diff...Inbreeding usually reduces the mean phenotypic value of various traits.In Crassostrea gigas,inbreeding depression at the early life stage might be particularly remarkable because of a high mutational load that is difficult to purge.In this study,the ef-fects of inbreeding on the survival rate and gene expression at the early life stage were investigated.Two inbred groups containing five F1 families and five F2 families with a theoretically higher degree of inbreeding were constructed based on an inbred strain.Meanwhile,5 families were established as the control group(CF)based on the wild population.The results showed that the survival rate of the CF group was significantly higher than those of the two inbred groups.Differential gene analysis showed 1616 common differentially expressed genes(DEGs)in the two inbred groups,which were significantly enriched in pathways associated with im-mune response,nutrient restriction,and virus infection.By weighted gene co-expression network analysis(WGCNA),19 common DEGs were enriched in M21,the functional module most closely related to inbreeding,and 6 of them were related to immunity.No-tably,the survival rate of F2 was higher than that of F1.A total of 643 DEGs between F1 and CF were screened out,which did not show differential expression between F2 and CF,and these genes were significantly enriched in pathways associated with protein syn-thesis.These results contribute to a more comprehensive understanding of the genetic mechanism behind the effect of inbreeding on the early survival rate of oyster larvae.展开更多
In this paper,a standardized analysis method is established for identifying meat quality-related genes in Ordos finewool sheep using transcriptome sequencing data.A meticulously standardized approach is utilized to in...In this paper,a standardized analysis method is established for identifying meat quality-related genes in Ordos finewool sheep using transcriptome sequencing data.A meticulously standardized approach is utilized to investigate the genetic determinants of meat quality in Ordos fine-wool sheep through transcriptome sequencing analysis.Muscle samples from the longissimus dorsi of one-year-old sheep are collected under controlled conditions,and key texture properties—hardness,elasticity,and chewiness—are measured to categorize samples into high-and low-textural-value groups.Genes significantly associated with meat quality traits are identified through standardized RNA extraction,high-throughput sequencing,and differential gene expression analysis.Functional enrichment analysis reveals their involvement in biological processes such as extracellular matrix organization and metabolic pathways.The findings underscore the pivotal role of standardization in meat quality research,laying a solid scientific foundation for future research on meat quality improvement and molecular breeding.展开更多
Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containin...Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2(ZMIZ2)and minichromosome maintenance complex component 3(MCM3)in TNBC progression.Methods:The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated.In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors.The regulatory relationship between ZMIZ2 and MCM3 was also explored.Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.Results:High ZMIZ2 expression levels were associated with the malignant degree of TNBC.ZMIZ2 overexpression promoted TNBC cell proliferation,migration,and invasion;inhibited apoptosis;and induced G1 phase cell cycle arrest,whereas knockdown of ZMIZ2 had the opposite effect.ZMIZ2 directly targeted and positively regulated MCM3 expression.MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo.High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC.The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways,such as the mitogen-activated protein kinase(MAPK),mechanistic target of rapamycin(mTOR),Wnt,and Ras signaling pathways,as verified by The Cancer Genome Atlas data.Conclusions:ZMIZ2 and MCM3 were highly expressed in TNBC.ZMIZ2 promoted the development by positively regulating MCM3 expression.Key pathways,such as the Ras/MAPK,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR,and Wnt signaling pathways,may be key downstreammechanisms.展开更多
Ferroptosis plays a key role in aggravating the progression of spinal cord injury(SCI),but the specific mechanism remains unknown.In this study,we constructed a rat model of T10 SCI using a modified Allen method.We id...Ferroptosis plays a key role in aggravating the progression of spinal cord injury(SCI),but the specific mechanism remains unknown.In this study,we constructed a rat model of T10 SCI using a modified Allen method.We identified 48,44,and 27 ferroptosis genes that were differentially expressed at 1,3,and 7 days after SCI induction.Compared with the sham group and other SCI subgroups,the subgroup at 1 day after SCI showed increased expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 and the oxidative stress marker malondialdehyde in the injured spinal cord while glutathione in the injured spinal cord was lower.These findings with our bioinformatics results suggested that 1 day after SCI was the important period of ferroptosis progression.Bioinformatics analysis identified the following top ten hub ferroptosis genes in the subgroup at 1 day after SCI:STAT3,JUN,TLR4,ATF3,HMOX1,MAPK1,MAPK9,PTGS2,VEGFA,and RELA.Real-time polymerase chain reaction on rat spinal cord tissue confirmed that STAT3,JUN,TLR4,ATF3,HMOX1,PTGS2,and RELA mRNA levels were up-regulated and VEGFA,MAPK1 and MAPK9 mRNA levels were down-regulated.Ten potential compounds were predicted using the DSigDB database as potential drugs or molecules targeting ferroptosis to repair SCI.We also constructed a ferroptosis-related mRNA-miRNA-lncRNA network in SCI that included 66 lncRNAs,10 miRNAs,and 12 genes.Our results help further the understanding of the mechanism underlying ferroptosis in SCI.展开更多
The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative st...The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative strategy to combat debilitating TBI.In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact.The RNA sequencing data from the mouse model of TBI were downloaded from the Gene Expression Omnibus(ID: GSE79441) at the National Center for Biotechnology Information.For the rat data, peri-injury cerebral cortex samples were collected for transcriptomic analysis 24 hours after TBI.Differentially expressed gene-based functional analysis revealed that common features between the two species were mainly involved in the regulation and activation of the innate immune response, including complement cascades as well as Toll-like and nucleotide oligomerization domain-like receptor pathways.These findings were further corroborated by gene set enrichment analysis.Moreover, transcription factor analysis revealed that the families of signal transducers and activators of transcription(STAT), basic leucine zipper(BZIP), Rel homology domain(RHD), and interferon regulatory factor(IRF) transcription factors play vital regulatory roles in the pathophysiological processes of TBI, and are also largely associated with inflammation.These findings suggest that targeting the common innate immune response might be a promising therapeutic approach for TBI.The animal experimental procedures were approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No.201802001) on June 6, 2018.展开更多
BACKGROUND Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world.Although a series of studies on esophageal cancer have been reported,the molecular pathogenesis of the disease remains el...BACKGROUND Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world.Although a series of studies on esophageal cancer have been reported,the molecular pathogenesis of the disease remains elusive.AIM To investigate comprehensively the molecular process of esophageal cancer.METHODS Differential expression analysis was performed to identify differentially expressed genes(DEGs)in different stages of esophageal cancer from The Cancer Genome Atlas data.Exacting gene interaction modules were generated,and hub genes in the module interaction network were found.Further,through survival analysis,methylation analysis,pivot analysis,and enrichment analysis,some important molecules and related functions/pathways were identified to elucidate potential mechanisms in esophageal cancer.RESULTS A total of 7457 DEGs and 14 gene interaction modules were identified.These module genes were significantly involved in the positive regulation of protein transport,gastric acid secretion,insulin-like growth factor receptor binding,and other biological processes as well as p53 signaling pathway,epidermal growth factor signaling pathway,and epidermal growth factor receptor signaling pathway.Transcription factors(including hypoxia inducible factor 1A)and noncoding RNAs(including colorectal differentially expressed and hsa-miR-330-3p)that significantly regulate dysfunction modules were identified.Survival analysis showed that G protein subunit gamma transducin 2(GNGT2)was closely related to survival of esophageal cancer.DEGs with strong methylation regulation ability were identified,including SST and SH3GL2.Furthermore,the expression of GNGT2 was evaluated by quantitative real time polymerase chain reaction,and the results showed that GNGT2 expression was significantly upregulated in esophageal cancer patient samples and cell lines.Moreover,cell counting kit-8 assay revealed that GNGT2 could promote the proliferation of esophageal cancer cell lines.CONCLUSION This study not only revealed the potential regulatory factors involved in the development of esophageal cancer but also deepens our understanding of its underlying mechanism.展开更多
Esophageal cancer is a common malignant tumor, whose pathogenesis and prognosis factors are not fully understood. This study aimed to discover the gene clusters that have similar functions and can be used to predict t...Esophageal cancer is a common malignant tumor, whose pathogenesis and prognosis factors are not fully understood. This study aimed to discover the gene clusters that have similar functions and can be used to predict the prognosis of esophageal cancer. The matched microarray and RNA sequencing data of 185 patients with esophageal cancer were downloaded from The Cancer Genome Atlas(TCGA), and gene co-expression networks were built without distinguishing between squamous carcinoma and adenocarcinoma. The result showed that 12 modules were associated with one or more survival data such as recurrence status, recurrence time, vital status or vital time. Furthermore, survival analysis showed that 5 out of the 12 modules were related to progression-free survival(PFS) or overall survival(OS). As the most important module, the midnight blue module with 82 genes was related to PFS, apart from the patient age, tumor grade, primary treatment success, and duration of smoking and tumor histological type. Gene ontology enrichment analysis revealed that 'glycoprotein binding' was the top enriched function of midnight blue module genes. Additionally, the blue module was the exclusive gene clusters related to OS. Platelet activating factor receptor(PTAFR) and feline Gardner-Rasheed(FGR) were the top hub genes in both modeling datasets and the STRING protein interaction database. In conclusion, our study provides novel insights into the prognosis-associated genes and screens out candidate biomarkers for esophageal cancer.展开更多
Renal ischemia-reperfusion injury(IRI)is a major cause of acute kidney injury(AKI),which could induce the poor prognosis.The purpose of this study was to characterize the molecular mechanism of the functional changes ...Renal ischemia-reperfusion injury(IRI)is a major cause of acute kidney injury(AKI),which could induce the poor prognosis.The purpose of this study was to characterize the molecular mechanism of the functional changes of CD11 b^(+)/Ly6 C^(intermediate)macrophages after renal IRI.The gene expression profiles of CD11 b^(+)/Ly6 C^(intermediate)macrophages of the sham surgery mice,and the mice 4 h,24 h and 9 days after renal IRI were downloaded from the Gene Expression Omnibus database.Analysis of m RNA expression profiles was conducted to identify differentially expressed genes(DEGs),biological processes and pathways by the series test of cluster.Protein-protein interaction network was constructed and analysed to discover the key genes.A total of 6738 DEGs were identified and assigned to 20 model profiles.DEGs in profile 13 were one of the predominant expression profiles,which are involved in immune cell chemotaxis and proliferation.Signet analysis showed that Atp5 a1,Atp5 o,Cox4 i,Cdc42,Rac2 and Nhp2 were the key genes involved in oxidation-reduction,apoptosis,migration,M1-M2 differentiation,and proliferation of macrophages.RPS18 may be an appreciate reference gene as it was stable in macrophages.The identified DEGs and their enriched pathways investigate factors that may participate in the functional changes of CD11 b^(+)/Ly6 C^(intermediate)macrophages after renal IRI.Moreover,the vital gene Nhp2 may involve the polarization of macrophages,which may be a new target to affect the process of AKI.展开更多
Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes,and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichm...Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes,and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichment analysis,protein-protein interaction(PPI)network,and survival analysis based on the Gene Expression Omnibus(GEO)database.Methods By screening with highly expressed genes,we mainly analyzed proteins MUC13 and EPCAM with transmembrane domain and antigen epitope from TMHMM and IEDB websites.Significant genes and pathways associated with the pathogenesis of esophageal cancer were identified using enrichment analysis,PPI network,and survival analysis.Several software and platforms including Prism 8,R language,Cytoscape,DAVID,STRING,and GEPIA platform were used in the search and/or figure creation.Results Genes MUC13 and EPCAM were over-expressed with several antigen epitopes in esophageal squamous cell carcinoma(ESCC)tissue.Enrichment analysis revealed that the process of keratinization was focused and a series of genes were related with the development of esophageal cancer.Four genes including ALDH3A1,C2,SLC6A1,and ZBTB7C were screened with significant P value of survival curve.Conclusions Genes MUC13 and EPCAM may be promising antigen targets or biomarkers for esophageal cancer.Keratinization may greatly impact the pathogenesis of esophageal cancer.Genes ALDH3A1,C2,SLC6A1,and ZBTB7C may play important roles in the development of esophageal cancer.展开更多
Pathway analysis,also known as gene-set enrichment analysis,is a multilocus analytic strategy that integrates a priori,biological knowledge into the statistical analysis of high-throughput genetics data.Originally dev...Pathway analysis,also known as gene-set enrichment analysis,is a multilocus analytic strategy that integrates a priori,biological knowledge into the statistical analysis of high-throughput genetics data.Originally developed for the studies of gene expression data,it has become a powerful analytic procedure for indepth mining of genome-wide genetic variation data.Astonishing discoveries were made in the past years,uncovering genes and biological mechanisms underlying common and complex disorders.However,as massive amounts of diverse functional genomics data accrue,there is a pressing need for newer generations of pathway analysis methods that can utilize multiple layers of high-throughput genomics data.In this review,we provide an intellectual foundation of this powerful analytic strategy,as well as an update of the state-of-the-art in recent method developments.The goal of this review is threefold:(1)introduce the motivation and basic steps of pathway analysis for genome-wide genetic variation data;(2)review the merits and the shortcomings of classic and newly emerging integrative pathway analysis tools;and(3)discuss remaining challenges and future directions for further method developments.展开更多
Copy number variations have been found in patients with neural tube abnormalities.In this study,we performed genome-wide screening using high-resolution array-based comparative genomic hybridization in three children ...Copy number variations have been found in patients with neural tube abnormalities.In this study,we performed genome-wide screening using high-resolution array-based comparative genomic hybridization in three children with tethered spinal cord syndrome and two healthy parents.Of eight copy number variations,four were non-polymorphic.These non-polymorphic copy number variations were associated with Angelman and Prader-Willi syndromes,and microcephaly.Gene function enrichment analysis revealed that COX8 C,a gene associated with metabolic disorders of the nervous system,was located in the copy number variation region of Patient 1.Our results indicate that array-based comparative genomic hybridization can be used to diagnose tethered spinal cord syndrome.Our results may help determine the pathogenesis of tethered spinal cord syndrome and prevent occurrence of this disease.展开更多
The current study aimed to evaluate the susceptibility to regional brain atrophy and its biological mechanism in Alzheimer’s disease(AD).We conducted data-driven meta-analyses to combine 3,118 structural magnetic res...The current study aimed to evaluate the susceptibility to regional brain atrophy and its biological mechanism in Alzheimer’s disease(AD).We conducted data-driven meta-analyses to combine 3,118 structural magnetic resonance images from three datasets to obtain robust atrophy patterns.Then we introduced a set of radiogenomic analyses to investigate the biological basis of the atrophy patterns in AD.Our results showed that the hippocampus and amygdala exhibit the most severe atrophy,followed by the temporal,frontal,and occipital lobes in mild cognitive impairment(MCI)and AD.The extent of atrophy in MCI was less severe than that in AD.A series of biological processes related to the glutamate signaling pathway,cellular stress response,and synapse structure and function were investigated through gene set enrichment analysis.Our study contributes to understanding the manifestations of atrophy and a deeper understanding of the pathophysiological processes that contribute to atrophy,providing new insight for further clinical research on AD.展开更多
Anaplastic thyroid carcinoma(ATC)is a rare but extremely lethal malignancy.However,little is known about the pathogenesis of ATC.Given its high mortality,it is critical to improve our understanding of ATC pathogenesis...Anaplastic thyroid carcinoma(ATC)is a rare but extremely lethal malignancy.However,little is known about the pathogenesis of ATC.Given its high mortality,it is critical to improve our understanding of ATC pathogenesis and to find new diagnostic biomarkers.In the present study,two gene microarray profiles(GSE53072 and GSE65144),which included 17 ATC and 17 adjacent non-tumorous tissues,were obtained.Bioinformatic analyses were then performed.Immunohistochemistry(IHC)and receiver operating characteristic(ROC)curves were then used to detect transmembrane protein 158(TMEM158)expression and to assess diagnostic sensitivity.A total of 372 differentially expressed genes(DEGs)were identified.Through protein-protein interaction(PPI)analysis,we identified a significant module with 37 upregulated genes.Most of the genes in this module were related to cell-cycle processes.After co-expression analysis,132 hub genes were selected for further study.Nine genes were identified as both DEGs and genes of interest in the weighted gene co-expression network analysis(WGCNA).IHC and ROC curves confirmed that TMEM158 was overexpressed in ATC tissue as compared with other types of thyroid cancer and normal tissue samples.We identified 8 KEGG pathways that were associated with high expression of TMEM158,including aminoacyl-tRNA biosynthesis and DNA replication.Our results suggest that TMEM158 may be a potential oncogene and serve as a diagnostic indicator for ATC.展开更多
BACKGROUND The incidence rate of cerebral infarction in young people is increasing day by day,the age of onset tends to be younger,and its internal pathogenesis and mechanism are very complicated,which leads to greate...BACKGROUND The incidence rate of cerebral infarction in young people is increasing day by day,the age of onset tends to be younger,and its internal pathogenesis and mechanism are very complicated,which leads to greater difficulties in treatment.Therefore,it is essential to analyze the key pathway that affects the onset of cerebral infarction in young people from the perspective of genetics.AIM To compare the differentially expressed genes in the brain tissue of young and aged rats with middle cerebral artery occlusion and to analyse their effect on the key signalling pathway involved in the development of cerebral ischaemia in young rats.METHODS The Gene Expression Omnibus 2R online analysis tool was used to analyse the differentially expressed genes in the GSE166162 dataset regarding the development of cerebral ischaemia in young and aged groups of rats.DAVID 6.8 software was further used to filter the differentially expressed genes.These genes were subjected to Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to determine the key gene pathway that affects the occurrence of cerebral ischaemia in young rats.RESULTS Thirty-five differentially expressed genes(such as Igf2,Col1a2,and Sfrp1)were obtained;73 GO enrichment analysis pathways are mainly involved in biological processes such as drug response,amino acid stimulation response,blood vessel development,various signalling pathways,and enzyme regulation.They are involved in molecular functions such as drug binding,protein binding,dopamine binding,metal ion binding,and dopamine neurotransmitter receptor activity.KEGG pathway enrichment analysis showed a significantly enriched pathway:The cyclic adenosine monophosphate(c-AMP)signalling pathway.CONCLUSION The c-AMP signalling pathway might be the key pathway in the intervention of cerebral infarction in young people.展开更多
基金supported by the National Natural Science Foundation of China(61902095).
文摘Biomedical big data,characterized by its massive scale,multi-dimensionality,and heterogeneity,offers novel perspectives for disease research,elucidates biological principles,and simultaneously prompts changes in related research methodologies.Biomedical ontology,as a shared formal conceptual system,not only offers standardized terms for multi-source biomedical data but also provides a solid data foundation and framework for biomedical research.In this review,we summarize enrichment analysis and deep learning for biomedical ontology based on its structure and semantic annotation properties,highlighting how technological advancements are enabling the more comprehensive use of ontology information.Enrichment analysis represents an important application of ontology to elucidate the potential biological significance for a particular molecular list.Deep learning,on the other hand,represents an increasingly powerful analytical tool that can be more widely combined with ontology for analysis and prediction.With the continuous evolution of big data technologies,the integration of these technologies with biomedical ontologies is opening up exciting new possibilities for advancing biomedical research.
基金supported by the Special Project on Precision Medicine under the National Key R&D Program (2016YFC0903003 and 2017YFC0909600)the National Natural Science Foundation of China (Nos. 81670462 and 81422006 to Q.C.+1 种基金 81670748 and 81471035 to J.Y.)Beijing Natural Science Foundation (No.7171006 to J.Y.)
文摘Enrichment analysis methods, e.g., gene set enrichment analysis, represent one class of important bio- informatical resources for mining patterns in biomedical datasets. However, tools for inferring patterns and rules of a list of drugs are limited. In this study, we developed a web-based tool, DrugPattern, for drug set enrichment analysis. We first collected and curated 7019 drug sets, including indications, adverse reactions, targets, pathways, etc. from public databases. For a list of interested drugs, DrugPat- tern then evaluates the significance of the enrichment of these drugs in each of the 7019 drug sets. To validate DrugPattern, we employed it for the prediction of the effects of oxidized low-density lipoprotein （oxLDL）, a factor expected to be deleterious. We predicted that oxLDL has beneficial effects on some diseases, most of which were supported by evidence in the literature. Because DrugPattern predicted the potential beneficial effects of oxLDL in type 2 diabetes （T2D）, animal experiments were then performed to further verify this prediction. As a result, the experimental evidences validated the DrugPattern prediction that oxLDL indeed has beneficial effects on T2D in the case of energy restriction. These data confirmed the prediction accuracy of our approach and revealed unexpected protective roles for oxLDL in various diseases. This study provides a tool to infer patterns and rules in biomedical datasets based on drug set enrichment analysis.
基金supported by the National Natural Science Foundation of China (Nos. 2100230024 and 2100230023)
文摘Alzheimer's disease(AD) is a serious neurodegenerative disorder and its cause remains largely elusive.In past years,genome-wide association(GWA) studies have provided an effective means for AD research.However,the univariate method that is commonly used in GWA studies cannot effectively detect the biological mechanisms associated with this disease.In this study,we propose a new strategy for the GWA analysis of AD that combines random forests with enrichment analysis.First,backward feature selection using random forests was performed on a GWA dataset of AD patients carrying the apolipoprotein gene(APOEε4) and 1058 susceptible single nucleotide polymorphisms(SNPs) were detected,including several known AD-associated SNPs.Next,the susceptible SNPs were investigated by enrichment analysis and significantly-associated gene functional annotations,such as 'alternative splicing','glycoprotein',and 'neuron development',were successfully discovered,indicating that these biological mechanisms play important roles in the development of AD in APOEε4 carriers.These findings may provide insights into the pathogenesis of AD and helpful guidance for further studies.Furthermore,this strategy can easily be modified and applied to GWA studies of other complex diseases.
基金This work has been supported in part by National Institutes of Health(NIH)[grant number 1R15HG006365-01]National Science Foundation(NSF)[grant number IIS-1302564].
文摘The first step in the analysis of high-throughput experiment results is often to identify genes orproteins with certain characteristics, such as genes being differentially expressed (DE). To gainmore insights into the underlying biology, functional enrichment analysis is then conductedto provide functional interpretation for the identified genes or proteins. The hypergeometricP value has been widely used to investigate whether genes from predefined functional terms,e.g., Reactome, are enriched in the DE genes. The hypergeometric P value has several limitations: (1) computed independently for each term, thus neglecting biological dependence;(2) subject to a size constraint that leads to the tendency of selecting less-specific terms. In this paper,a Bayesian approach is proposed to overcome these limitations by incorporating the interconnected dependence structure of biological functions in the Reactome database through a CARprior in a Bayesian hierarchical logistic model. The inference on functional enrichment is thenbased on posterior probabilities that are immune to the size constraint. This method can detectmoderate but consistent enrichment signals and identify sets of closely related and biologicallymeaningful functional terms rather than isolated terms. The performance of the Bayesian methodis demonstrated via a simulation study and a real data application.
基金Beijing Key Laboratory of Clinical Basic Research on Psoriasis of Traditional Chinese Medicine(No.BZ0375-KF201602)。
文摘Objective:Based on bioinformatics,gene set enrichment analysis(GSEA)and immune infiltration analysis were carried out on the microarray data of psoriasis expression profile to further understand the pathogenesis of psoriasis.Methods:GSE6710 chip data were obtained from gene expression database(GEO),and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed using GSEA software.22 kinds of immune cell gene expression matrices and R packages were downloaded from CIBERSOFT official website,and the immune cell infiltration matrix was obtained by R software and related graphs were drawn.Results:The pathways related to cell proliferation and innate immunity were highly expressed in psoriatic lesions,and some cancer-related pathways were highly expressed in psoriatic lesions.Immunized cell infiltration analysis showed that activated memory T cells,follicular helper T cells,M0 macrophages and activated dendritic cells were up-regulated in psoriatic skin lesion group,and inactive mast cells were down-regulated in psoriatic skin lesion group.Activated dendritic cells are positively correlated with follicular helper T cells,activated mast cells are positively correlated with M0 macrophages.Inactivated mast cells are negatively correlated with activated memory T cells,M1 macrophages are negatively correlated with regulatory T cells,M0 macrophages are negatively correlated with inactive mast cells.Conclusion:Cell proliferation and innate immunity are of great significance in the pathogenesis of psoriasis.Immune cell infiltration analysis is generally consistent with the current psoriasis pathogenesis model.Macrophages and mast cells also play a certain role in psoriasis.
基金supported by grants from the Weifang Municipal Health Commission Research Programme Project(No.WFWSJK-2023-032)the Weifang Science and Technology Development Project(No.2023YX053)the Weifang Young Medical Talent Support Program Funding。
文摘Background:NDC80 is pivotal in cell division,particularly in regulating the G2/M transition and mitotic progression.Recent studies have demonstrated that NDC80 is significantly overexpressed in multiple solid tumors.Further analysis has suggested that its high expression is significantly associated with an elevated pathological grade,increased metastatic risk,and shortened overall survival in patients with cancer.However,its precise role in pan-cancer development,progression,and prognosis remains unclear.Methods:We conducted a multi-omics analysis of NDC80 using genomic,transcriptomic,and proteomic data from 33 cancer types in The Cancer Genome Atlas,Clinical Proteomic Tumor Analysis Consortium,Genotype-Tissue Expression,and Human Protein Atlas.Results:The results demonstrated frequent NDC80 mutations across multiple malignancies and significantly elevated expression in tumor tissues compared with that in their normal counterparts,correlating with worse overall and disease-free survival.Moreover,NDC80 expression was strongly associated with oncogenic pathways,key protein regulators,cellular components,myeloid-derived suppressor cell infiltration,ESTIMATE scores,and cancer-related signaling networks.Conclusions:These findings underscore the potential of NDC80 as a prognostic biomarker and therapeutic target for cancer treatment.
基金supported by grants from the National Natural Science Foundation of China(Nos.W2411019 and 32373115)the China Agriculture Research System Project(No.CARS-49)the Laoshan Laboratory.
文摘Inbreeding usually reduces the mean phenotypic value of various traits.In Crassostrea gigas,inbreeding depression at the early life stage might be particularly remarkable because of a high mutational load that is difficult to purge.In this study,the ef-fects of inbreeding on the survival rate and gene expression at the early life stage were investigated.Two inbred groups containing five F1 families and five F2 families with a theoretically higher degree of inbreeding were constructed based on an inbred strain.Meanwhile,5 families were established as the control group(CF)based on the wild population.The results showed that the survival rate of the CF group was significantly higher than those of the two inbred groups.Differential gene analysis showed 1616 common differentially expressed genes(DEGs)in the two inbred groups,which were significantly enriched in pathways associated with im-mune response,nutrient restriction,and virus infection.By weighted gene co-expression network analysis(WGCNA),19 common DEGs were enriched in M21,the functional module most closely related to inbreeding,and 6 of them were related to immunity.No-tably,the survival rate of F2 was higher than that of F1.A total of 643 DEGs between F1 and CF were screened out,which did not show differential expression between F2 and CF,and these genes were significantly enriched in pathways associated with protein syn-thesis.These results contribute to a more comprehensive understanding of the genetic mechanism behind the effect of inbreeding on the early survival rate of oyster larvae.
基金funded by the 2023 Inner Mongolia Public Institution High-Level Talent Introduction Scientific Research Support Project,and the Ordos Municipal Science and Technology Major Special Project(Grant No.2022EEDSKJZDZX021).
文摘In this paper,a standardized analysis method is established for identifying meat quality-related genes in Ordos finewool sheep using transcriptome sequencing data.A meticulously standardized approach is utilized to investigate the genetic determinants of meat quality in Ordos fine-wool sheep through transcriptome sequencing analysis.Muscle samples from the longissimus dorsi of one-year-old sheep are collected under controlled conditions,and key texture properties—hardness,elasticity,and chewiness—are measured to categorize samples into high-and low-textural-value groups.Genes significantly associated with meat quality traits are identified through standardized RNA extraction,high-throughput sequencing,and differential gene expression analysis.Functional enrichment analysis reveals their involvement in biological processes such as extracellular matrix organization and metabolic pathways.The findings underscore the pivotal role of standardization in meat quality research,laying a solid scientific foundation for future research on meat quality improvement and molecular breeding.
基金supported by the Jilin Province Health Science and Technology Ability Improvement Project(2023JL057).
文摘Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2(ZMIZ2)and minichromosome maintenance complex component 3(MCM3)in TNBC progression.Methods:The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated.In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors.The regulatory relationship between ZMIZ2 and MCM3 was also explored.Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.Results:High ZMIZ2 expression levels were associated with the malignant degree of TNBC.ZMIZ2 overexpression promoted TNBC cell proliferation,migration,and invasion;inhibited apoptosis;and induced G1 phase cell cycle arrest,whereas knockdown of ZMIZ2 had the opposite effect.ZMIZ2 directly targeted and positively regulated MCM3 expression.MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo.High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC.The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways,such as the mitogen-activated protein kinase(MAPK),mechanistic target of rapamycin(mTOR),Wnt,and Ras signaling pathways,as verified by The Cancer Genome Atlas data.Conclusions:ZMIZ2 and MCM3 were highly expressed in TNBC.ZMIZ2 promoted the development by positively regulating MCM3 expression.Key pathways,such as the Ras/MAPK,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR,and Wnt signaling pathways,may be key downstreammechanisms.
基金supported by National Key Research and Development Project of Stem Cell and Transformation Research,No.2019YFA0112100Tianjin Key Research and Development Plan,Key Projects for Science and Technology Support,No.19YFZCSY00660(both to SQF)。
文摘Ferroptosis plays a key role in aggravating the progression of spinal cord injury(SCI),but the specific mechanism remains unknown.In this study,we constructed a rat model of T10 SCI using a modified Allen method.We identified 48,44,and 27 ferroptosis genes that were differentially expressed at 1,3,and 7 days after SCI induction.Compared with the sham group and other SCI subgroups,the subgroup at 1 day after SCI showed increased expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 and the oxidative stress marker malondialdehyde in the injured spinal cord while glutathione in the injured spinal cord was lower.These findings with our bioinformatics results suggested that 1 day after SCI was the important period of ferroptosis progression.Bioinformatics analysis identified the following top ten hub ferroptosis genes in the subgroup at 1 day after SCI:STAT3,JUN,TLR4,ATF3,HMOX1,MAPK1,MAPK9,PTGS2,VEGFA,and RELA.Real-time polymerase chain reaction on rat spinal cord tissue confirmed that STAT3,JUN,TLR4,ATF3,HMOX1,PTGS2,and RELA mRNA levels were up-regulated and VEGFA,MAPK1 and MAPK9 mRNA levels were down-regulated.Ten potential compounds were predicted using the DSigDB database as potential drugs or molecules targeting ferroptosis to repair SCI.We also constructed a ferroptosis-related mRNA-miRNA-lncRNA network in SCI that included 66 lncRNAs,10 miRNAs,and 12 genes.Our results help further the understanding of the mechanism underlying ferroptosis in SCI.
基金supported by the National Natural Science Foundation of China, Nos.81471238, 81771327(both to BYL)Construction of Central Nervous System Injury Basic Science and Clinical Translational Research Platform, Budget of Beijing Municipal Health Commission 2020, No.PXM2020_026280_000002(to BYL)。
文摘The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative strategy to combat debilitating TBI.In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact.The RNA sequencing data from the mouse model of TBI were downloaded from the Gene Expression Omnibus(ID: GSE79441) at the National Center for Biotechnology Information.For the rat data, peri-injury cerebral cortex samples were collected for transcriptomic analysis 24 hours after TBI.Differentially expressed gene-based functional analysis revealed that common features between the two species were mainly involved in the regulation and activation of the innate immune response, including complement cascades as well as Toll-like and nucleotide oligomerization domain-like receptor pathways.These findings were further corroborated by gene set enrichment analysis.Moreover, transcription factor analysis revealed that the families of signal transducers and activators of transcription(STAT), basic leucine zipper(BZIP), Rel homology domain(RHD), and interferon regulatory factor(IRF) transcription factors play vital regulatory roles in the pathophysiological processes of TBI, and are also largely associated with inflammation.These findings suggest that targeting the common innate immune response might be a promising therapeutic approach for TBI.The animal experimental procedures were approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No.201802001) on June 6, 2018.
基金Supported by Construction of Engineering Laboratory of Jilin Development and Reform Commission(grant no.3J115AK93429)Jilin Provincial Science and Technology Department Medical Health Project(grant no.3D5195001429)
文摘BACKGROUND Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world.Although a series of studies on esophageal cancer have been reported,the molecular pathogenesis of the disease remains elusive.AIM To investigate comprehensively the molecular process of esophageal cancer.METHODS Differential expression analysis was performed to identify differentially expressed genes(DEGs)in different stages of esophageal cancer from The Cancer Genome Atlas data.Exacting gene interaction modules were generated,and hub genes in the module interaction network were found.Further,through survival analysis,methylation analysis,pivot analysis,and enrichment analysis,some important molecules and related functions/pathways were identified to elucidate potential mechanisms in esophageal cancer.RESULTS A total of 7457 DEGs and 14 gene interaction modules were identified.These module genes were significantly involved in the positive regulation of protein transport,gastric acid secretion,insulin-like growth factor receptor binding,and other biological processes as well as p53 signaling pathway,epidermal growth factor signaling pathway,and epidermal growth factor receptor signaling pathway.Transcription factors(including hypoxia inducible factor 1A)and noncoding RNAs(including colorectal differentially expressed and hsa-miR-330-3p)that significantly regulate dysfunction modules were identified.Survival analysis showed that G protein subunit gamma transducin 2(GNGT2)was closely related to survival of esophageal cancer.DEGs with strong methylation regulation ability were identified,including SST and SH3GL2.Furthermore,the expression of GNGT2 was evaluated by quantitative real time polymerase chain reaction,and the results showed that GNGT2 expression was significantly upregulated in esophageal cancer patient samples and cell lines.Moreover,cell counting kit-8 assay revealed that GNGT2 could promote the proliferation of esophageal cancer cell lines.CONCLUSION This study not only revealed the potential regulatory factors involved in the development of esophageal cancer but also deepens our understanding of its underlying mechanism.
文摘Esophageal cancer is a common malignant tumor, whose pathogenesis and prognosis factors are not fully understood. This study aimed to discover the gene clusters that have similar functions and can be used to predict the prognosis of esophageal cancer. The matched microarray and RNA sequencing data of 185 patients with esophageal cancer were downloaded from The Cancer Genome Atlas(TCGA), and gene co-expression networks were built without distinguishing between squamous carcinoma and adenocarcinoma. The result showed that 12 modules were associated with one or more survival data such as recurrence status, recurrence time, vital status or vital time. Furthermore, survival analysis showed that 5 out of the 12 modules were related to progression-free survival(PFS) or overall survival(OS). As the most important module, the midnight blue module with 82 genes was related to PFS, apart from the patient age, tumor grade, primary treatment success, and duration of smoking and tumor histological type. Gene ontology enrichment analysis revealed that 'glycoprotein binding' was the top enriched function of midnight blue module genes. Additionally, the blue module was the exclusive gene clusters related to OS. Platelet activating factor receptor(PTAFR) and feline Gardner-Rasheed(FGR) were the top hub genes in both modeling datasets and the STRING protein interaction database. In conclusion, our study provides novel insights into the prognosis-associated genes and screens out candidate biomarkers for esophageal cancer.
基金supported by grants from the National Natural Science Foundation of China(No.81670634)Graduate student scientific research innovation projects in Jiangsu province(No.KYLX15_0981)Nanjing Medical University Science and Technology Development Fund(No.2016NJMU065)
文摘Renal ischemia-reperfusion injury(IRI)is a major cause of acute kidney injury(AKI),which could induce the poor prognosis.The purpose of this study was to characterize the molecular mechanism of the functional changes of CD11 b^(+)/Ly6 C^(intermediate)macrophages after renal IRI.The gene expression profiles of CD11 b^(+)/Ly6 C^(intermediate)macrophages of the sham surgery mice,and the mice 4 h,24 h and 9 days after renal IRI were downloaded from the Gene Expression Omnibus database.Analysis of m RNA expression profiles was conducted to identify differentially expressed genes(DEGs),biological processes and pathways by the series test of cluster.Protein-protein interaction network was constructed and analysed to discover the key genes.A total of 6738 DEGs were identified and assigned to 20 model profiles.DEGs in profile 13 were one of the predominant expression profiles,which are involved in immune cell chemotaxis and proliferation.Signet analysis showed that Atp5 a1,Atp5 o,Cox4 i,Cdc42,Rac2 and Nhp2 were the key genes involved in oxidation-reduction,apoptosis,migration,M1-M2 differentiation,and proliferation of macrophages.RPS18 may be an appreciate reference gene as it was stable in macrophages.The identified DEGs and their enriched pathways investigate factors that may participate in the functional changes of CD11 b^(+)/Ly6 C^(intermediate)macrophages after renal IRI.Moreover,the vital gene Nhp2 may involve the polarization of macrophages,which may be a new target to affect the process of AKI.
文摘Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes,and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichment analysis,protein-protein interaction(PPI)network,and survival analysis based on the Gene Expression Omnibus(GEO)database.Methods By screening with highly expressed genes,we mainly analyzed proteins MUC13 and EPCAM with transmembrane domain and antigen epitope from TMHMM and IEDB websites.Significant genes and pathways associated with the pathogenesis of esophageal cancer were identified using enrichment analysis,PPI network,and survival analysis.Several software and platforms including Prism 8,R language,Cytoscape,DAVID,STRING,and GEPIA platform were used in the search and/or figure creation.Results Genes MUC13 and EPCAM were over-expressed with several antigen epitopes in esophageal squamous cell carcinoma(ESCC)tissue.Enrichment analysis revealed that the process of keratinization was focused and a series of genes were related with the development of esophageal cancer.Four genes including ALDH3A1,C2,SLC6A1,and ZBTB7C were screened with significant P value of survival curve.Conclusions Genes MUC13 and EPCAM may be promising antigen targets or biomarkers for esophageal cancer.Keratinization may greatly impact the pathogenesis of esophageal cancer.Genes ALDH3A1,C2,SLC6A1,and ZBTB7C may play important roles in the development of esophageal cancer.
基金supported by National Institutes of Health R00 MH101367 and R01 MH119243(to P.H.Lee)。
文摘Pathway analysis,also known as gene-set enrichment analysis,is a multilocus analytic strategy that integrates a priori,biological knowledge into the statistical analysis of high-throughput genetics data.Originally developed for the studies of gene expression data,it has become a powerful analytic procedure for indepth mining of genome-wide genetic variation data.Astonishing discoveries were made in the past years,uncovering genes and biological mechanisms underlying common and complex disorders.However,as massive amounts of diverse functional genomics data accrue,there is a pressing need for newer generations of pathway analysis methods that can utilize multiple layers of high-throughput genomics data.In this review,we provide an intellectual foundation of this powerful analytic strategy,as well as an update of the state-of-the-art in recent method developments.The goal of this review is threefold:(1)introduce the motivation and basic steps of pathway analysis for genome-wide genetic variation data;(2)review the merits and the shortcomings of classic and newly emerging integrative pathway analysis tools;and(3)discuss remaining challenges and future directions for further method developments.
文摘Copy number variations have been found in patients with neural tube abnormalities.In this study,we performed genome-wide screening using high-resolution array-based comparative genomic hybridization in three children with tethered spinal cord syndrome and two healthy parents.Of eight copy number variations,four were non-polymorphic.These non-polymorphic copy number variations were associated with Angelman and Prader-Willi syndromes,and microcephaly.Gene function enrichment analysis revealed that COX8 C,a gene associated with metabolic disorders of the nervous system,was located in the copy number variation region of Patient 1.Our results indicate that array-based comparative genomic hybridization can be used to diagnose tethered spinal cord syndrome.Our results may help determine the pathogenesis of tethered spinal cord syndrome and prevent occurrence of this disease.
基金Science and Technology Innovation 2030 Major Projects(2022ZD0211600)Fundamental Research Funds for the Central Universities(2021XD-A03)+3 种基金National Natural Science Foundation of China(81871438 and 82102018)Data collection and sharing for this project were supported by the National Natural Science Foundation of China(61633018,81571062,81400890,81471120,81701781,and 81901101)Data collection and sharing for this project were funded by the Alzheimer’s Disease Neuroimaging Initiative(ADNI)(National Institutes of Health Grant U01 AG024904)DOD ADNI(Department of Defense award number W81XWH-12-2-0012)。
文摘The current study aimed to evaluate the susceptibility to regional brain atrophy and its biological mechanism in Alzheimer’s disease(AD).We conducted data-driven meta-analyses to combine 3,118 structural magnetic resonance images from three datasets to obtain robust atrophy patterns.Then we introduced a set of radiogenomic analyses to investigate the biological basis of the atrophy patterns in AD.Our results showed that the hippocampus and amygdala exhibit the most severe atrophy,followed by the temporal,frontal,and occipital lobes in mild cognitive impairment(MCI)and AD.The extent of atrophy in MCI was less severe than that in AD.A series of biological processes related to the glutamate signaling pathway,cellular stress response,and synapse structure and function were investigated through gene set enrichment analysis.Our study contributes to understanding the manifestations of atrophy and a deeper understanding of the pathophysiological processes that contribute to atrophy,providing new insight for further clinical research on AD.
基金This study was supported by grants from Tongji Medical College,Huazhong University of Science and Technology(CN)(No.5001540018)Young Scientists Fund(No.81802676).
文摘Anaplastic thyroid carcinoma(ATC)is a rare but extremely lethal malignancy.However,little is known about the pathogenesis of ATC.Given its high mortality,it is critical to improve our understanding of ATC pathogenesis and to find new diagnostic biomarkers.In the present study,two gene microarray profiles(GSE53072 and GSE65144),which included 17 ATC and 17 adjacent non-tumorous tissues,were obtained.Bioinformatic analyses were then performed.Immunohistochemistry(IHC)and receiver operating characteristic(ROC)curves were then used to detect transmembrane protein 158(TMEM158)expression and to assess diagnostic sensitivity.A total of 372 differentially expressed genes(DEGs)were identified.Through protein-protein interaction(PPI)analysis,we identified a significant module with 37 upregulated genes.Most of the genes in this module were related to cell-cycle processes.After co-expression analysis,132 hub genes were selected for further study.Nine genes were identified as both DEGs and genes of interest in the weighted gene co-expression network analysis(WGCNA).IHC and ROC curves confirmed that TMEM158 was overexpressed in ATC tissue as compared with other types of thyroid cancer and normal tissue samples.We identified 8 KEGG pathways that were associated with high expression of TMEM158,including aminoacyl-tRNA biosynthesis and DNA replication.Our results suggest that TMEM158 may be a potential oncogene and serve as a diagnostic indicator for ATC.
文摘BACKGROUND The incidence rate of cerebral infarction in young people is increasing day by day,the age of onset tends to be younger,and its internal pathogenesis and mechanism are very complicated,which leads to greater difficulties in treatment.Therefore,it is essential to analyze the key pathway that affects the onset of cerebral infarction in young people from the perspective of genetics.AIM To compare the differentially expressed genes in the brain tissue of young and aged rats with middle cerebral artery occlusion and to analyse their effect on the key signalling pathway involved in the development of cerebral ischaemia in young rats.METHODS The Gene Expression Omnibus 2R online analysis tool was used to analyse the differentially expressed genes in the GSE166162 dataset regarding the development of cerebral ischaemia in young and aged groups of rats.DAVID 6.8 software was further used to filter the differentially expressed genes.These genes were subjected to Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to determine the key gene pathway that affects the occurrence of cerebral ischaemia in young rats.RESULTS Thirty-five differentially expressed genes(such as Igf2,Col1a2,and Sfrp1)were obtained;73 GO enrichment analysis pathways are mainly involved in biological processes such as drug response,amino acid stimulation response,blood vessel development,various signalling pathways,and enzyme regulation.They are involved in molecular functions such as drug binding,protein binding,dopamine binding,metal ion binding,and dopamine neurotransmitter receptor activity.KEGG pathway enrichment analysis showed a significantly enriched pathway:The cyclic adenosine monophosphate(c-AMP)signalling pathway.CONCLUSION The c-AMP signalling pathway might be the key pathway in the intervention of cerebral infarction in young people.
