Weighted Gene Co-expression Analysis Research Articles

Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies

BackgroundDisulfidptosis and the disulfidptosis-related gene SLC7A11 have recently attracted significant attention for their role in tumorigenesis and tumour management. However, its association with adrenocortical carcinoma (ACC) is rarely discussed.MethodsDifferential analysis, Cox regression analysis, and survival analysis were used to screen for the hub gene SLC7A11 in the TCGA and GTEx databases and disulfidptosis-related gene sets. Then, we performed an association analysis between SLC7A11 and clinically relevant factors in ACC patients. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic value of SLC7A11 and clinically relevant factors. Weighted gene coexpression analysis was used to find genes associated with SLC7A11. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and the LinkedOmics database were used to analyse the functions of SLC7A11-associated genes. The CIBERSORT and Xcell algorithms were used to analyse the relationship between SLC7A11 and immune cell infiltration in ACC. The TISIDB database was applied to search for the correlation between SLC7A11 expression and immune chemokines. In addition, we performed a correlation analysis for SLC7A11 expression and tumour mutational burden and immune checkpoint-related genes and assessed drug sensitivity based on SLC7A11 expression. Immunohistochemistry and RT‒qPCR were used to validate the upregulation of SLC7A11 in the ACC.ResultsSLC7A11 is highly expressed in multiple urological tumours, including ACC. SLC7A11 expression is strongly associated with clinically relevant factors (M-stage and MYL6 expression) in ACC. SLC7A11 and the constructed nomogram can accurately predict ACC patient outcomes. The functions of SLC7A11 and its closely related genes are tightly associated with the occurrence of disulfidptosis in ACC. SLC7A11 expression was tightly associated with various immune cell infiltration disorders in the ACC tumour microenvironment (TME). It was positively correlated with the expression of immune chemokines (CXCL8, CXCL3, and CCL20) and negatively correlated with the expression of immune chemokines (CXCL17 and CCL14). SLC7A11 expression was positively associated with the expression of immune checkpoint genes (NRP1, TNFSF4, TNFRSF9, and CD276) and tumour mutation burden. The expression level of SLC7A11 in ACC patients is closely associated withcthe drug sensitivity.ConclusionIn ACC, high expression of SLC7A11 is associated with migration, invasion, drug sensitivity, immune infiltration disorders, and poor prognosis, and its induction of disulfidptosis is a promising target for the treatment of ACC.

Metabolome and Transcriptome Analyses Provide Insights into Glucosinolate Accumulation in the Novel Vegetable Crop Cardamine violifolia

Cardamine violifolia, a species belonging to the Brassicaceae family, is a novel vegetable crop that is rich in glucosinolates. However, the specific glucosinolate profiles in this species remain unknown. In the present study, four parts of C. violifolia were collected including central leaves (CLs), outer leaves (OLs), petiole (P), and root (R). The highest level of total glucosinolate was observed in the R. A total of 19 glucosinolates were found in C. violifolia. The predominant glucosinolate compounds were 3-methylbutyl glucosinolate, 6-methylsulfinylhexyl glucosinolate, Indol-3-ylmethyl glucosinolate, 4-methoxyglucobrassicin, and neoglucobrassicin. A transcriptome analysis showed that 16 genes, including BCAT1, BCAT3-6, CYP79A2, CYP79B2-3, CYP83A1, CYP83B1, and SOT17-18, and nine metabolites, such as valine, tryptophan, and 1-methylpropyl glucosinolate, were enriched in the glucosinolate biosynthesis pathway. These genes may be involved in the regulation of glucosinolate accumulation among the four parts. A weighted gene co-expression analysis showed that five genes were predicted to regulate glucosinolate accumulation, including ABC transporter G family member 19, 3-ketoacyl-CoA synthase 19, and pyruvate decarboxylase 1. This study deepens our understanding of the nutrient quality of C. violifolia and provides insights into the regulatory mechanism of glucosinolate accumulation in C. violifolia.

Epigenetic responses to rhinovirus exposure in airway epithelial cells are correlated with key transcriptional pathways in chronic rhinosinusitis.

Viruses may drive immune mechanisms responsible for chronic rhinosinusitis with nasal polyposis (CRSwNP), but little is known about the underlying molecular mechanisms. To identify epigenetic and transcriptional responses to a common upper respiratory pathogen, rhinovirus (RV), that are specific to patients with CRSwNP using a primary sinonasal epithelial cell culture model. Airway epithelial cells were collected at surgery from patients with CRSwNP (cases) and from controls without sinus disease, cultured, and then exposed to RV or vehicle for 48 h. Differential gene expression and DNA methylation (DNAm) between cases and controls in response to RV were determined using linear mixed models. Weighted gene co-expression analysis (WGCNA) was used to identify (a) co-regulated gene expression and DNAm signatures, and (b) genes, pathways, and regulatory mechanisms specific to CRSwNP. We identified 5585 differential transcriptional and 261 DNAm responses (FDR <0.10) to RV between CRSwNP cases and controls. These differential responses formed three co-expression/co-methylation modules that were related to CRSwNP and three that were related to RV (Bonferroni corrected p < .01). Most (95%) of the differentially methylated CpGs (DMCs) were in modules related to CRSwNP, whereas the differentially expressed genes (DEGs) were more equally distributed between the CRSwNP- and RV-related modules. Genes in the CRSwNP-related modules were enriched in known CRS and/or viral response immune pathways. RV activates specific epigenetic programs and correlated transcriptional networks in the sinonasal epithelium of individuals with CRSwNP. These novel observations suggest epigenetic signatures specific to patients with CRSwNP modulate response to viral pathogens at the mucosal environmental interface. Determining how viral response pathways are involved in epithelial inflammation in CRSwNP could lead to therapeutic targets for this burdensome airway disorder.

Reprogramming astrocytic NDRG2/NF-κB/C3 signaling restores the diabetes-associated cognitive dysfunction.

Dementia is a serious complication in patients with diabetes-associated cognitive dysfunction (DACD). In this study, we aim to explore the protective effect of exercise on DACD in diabetic mice, and the role of NDRG2 as a potential guarder for reversing the pathological structure of neuronal synapses. Seven weeks of standardized exercise at moderate intensity was carried out using an animal treadmill in the vehicle+Run and STZ+Run groups. Based on quantitative transcriptome and tandem mass tag (TMT) proteome sequencing, weighted gene co-expression analysis (WGCNA) and gene set enrichment analysis (GSEA) were used to investigate the activation of complement cascades to injury neuronal synaptic plasticity. Golgi staining, Western blotting, immunofluorescence staining, and electrophysiology were used to verify the reliability of sequencing data. The role of NDRG2 was assessed by overexpressing or inhibiting the NDRG2 gene invivo. Moreover, we estimated the cognitive function in diabetic or normal patients using DSST scores. Exercise reversed the injury of neuronal synaptic plasticity and the downregulation of astrocytic NDRG2 in diabetic mice, which succeeded in attenuating DACD. The deficiency of NDRG2 aggravated the activation of complement C3 by accelerating the phosphorylation of NF-κB, ultimately leading to synaptic injury and cognitive dysfunction. Conversely, the overexpression of NDRG2 promoted astrocytic remodeling by inhibiting complement C3, thus attenuating synaptic injury and cognitive dysfunction. Meanwhile, C3aR blockade rescued dendritic spines loss and cognitive deficits in diabetic mice. Moreover, the average DSST score of diabetic patients was significantly lower than that of non-diabetic peers. Levels of complement C3 in human serum were elevated in diabetic patients compared to those in non-diabetic patients. Our findings illustrate the effectiveness and integrative mechanism of NDRG2-induced improvement of cognition from a multi-omics perspective. Additionally, they confirm that the expression of NDRG2 is closely related to cognitive function in diabetic mice and the activation of complement cascades accelerated impairment of neuronal synaptic plasticity. NDRG2 acts as a regulator of astrocytic-neuronal interaction via NF-κB/C3/C3aR signaling to restore synaptic function in diabetic mice. This study was supported by the National Natural Science Foundation of China (No. 81974540, 81801899, 81971290), the Key Research and Development Program of Shaanxi (Program No. 2022ZDLSF02-09) and Fundamental Research Funds for the Central Universities (Grant No. xzy022019020).

Identification of molecular subgroups in osteomyelitis induced by staphylococcus aureus infection through gene expression profiles

BackgroundStaphylococcus aureus (S. aureus) infection-induced osteomyelitis (OM) is an inflammatory bone disease accompanied by persistent bone destruction, and the treatment is challenging because of its tendency to recur. Present study was aimed to explore the molecular subgroups of S. aureus infection-induced OM and to deepen the mechanistic understanding for molecularly targeted treatment of OM.MethodsIntegration of 164 OM samples and 60 healthy samples from three datasets of the Gene Expression Omnibus (GEO) database. OM patients were classified into different molecular subgroups based on unsupervised algorithms and correlations of clinical characteristics between subgroups were analyzed. Next, The CIBERSORT algorithm was used to evaluate the proportion of immune cell infiltration in different OM subgroups. Weighted gene co-expression analysis (WGCNA) was used to identify different gene modules and explore the relationship with clinical characteristics, and further annotated OM subgroups and gene modules by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.ResultsTwo subgroups with excellent consistency were identified in this study, subgroup and hospital length of stay were independent predictors of OM. Compared with subgroup I, OM patients in subgroup II had longer hospital length of stay and more severe disease. Meanwhile, the infiltration proportions of monocytes and macrophages M0 were higher in patients of OM subgroup II. Finally, combined with the characteristics of the KEGG enrichment modules, the expression of osteoclast differentiation-related genes such as CTSK was upregulated in OM subgroup II, which may be closely associated with more severe OM patients.ConclusionThe current study showed that OM subgroup II had longer hospital length of stay and more severe disease, the osteoclast differentiation pathway and the main target CTSK contribute to our deeper understanding for the molecular mechanisms associated with S. aureus infection-induced OM, and the construction of molecular subgroups suggested the necessity for different subgroups of patients to receive individualized treatment.

Identification of the Key Transcription Factors Regulating the Expression of the Genes Associated with Barley Malt Quality during Malting

Barley malt is produced through a malting process; it begins with steeping followed by germination and kilning, in which dramatic changes happen for a large number of physiological and biochemical traits in barley seeds. The objectives of this study were to comprehensively investigate the phenotypic changes during malting, and identify the key regulators that modulate the expression of genes associated with malt quality traits. The results showed that there was a significant positive correlation between gibberellic acid (GA) content and the activities of some hydrolytic enzymes, including α-amylases, β-amylases, and limit dextrinase (LD), and a significant negative correlation between GA and β-glucan content. Starch content had little change, but starch granules were pitted severely during malting. Weighted gene coexpression analysis (WGCNA) identified the genes associated with the greatest changes of the examined malt traits during malting. The correlation analysis and protein-protein interaction (PPI) analysis detected several key transcriptional factor (TF) regulating genes associated with malt quality. These genes and TFs regulating malting traits are potentially useful in barley breeding for malt quality improvement.

Identification of immune-related genes in acute myocardial infarction based on integrated bioinformatical methods and experimental verification.

Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. The etiology of AMI is complex and has not been fully defined. In recent years, the role of immune response in the development, progression and prognosis of AMI has received increasing attention. The aim of this study was to identify key genes associated with the immune response in AMI and to analyze their immune infiltration. The study included a total of two GEO databases, containing 83 patients with AMI and 54 healthy individuals. We used the linear model of microarray data (limma) package to find the differentially expressed genes associated with AMI, performing weighted gene co-expression analysis (WGCNA) to further identify the genes associated with inflammatory response to AMI. We found the final hub genes through the protein-protein interaction (PPI) network and least absolute shrinkage and selection operator (LASSO) regression model. To verify the above conclusions, we constructed mice AMI model, extracting myocardial tissue to perform qRT-PCR. Furthermore, the CIBERSORT tool for immune cells infiltration analysis was also carried out. A total of 5,425 significant up-regulated and 2,126 down-regulated genes were found in GSE66360 and GSE24519. A total of 116 immune-related genes in close association with AMI were screened by WGCNA analysis. These genes were mostly clustered in the immune response on the basis of GO and KEGG enrichment. With construction of PPI network and LASSO regression analysis, this research found three hub genes (SOCS2, FFAR2, MYO10) among these differentially expressed genes. The immune cell infiltration results revealed that significant differences could be found on T cells CD4 memory activated, Tregs (regulatory T cells), macrophages M2, neutrophils, T cells CD8, T cells CD4 naive, eosinophils between controls and AMI patients.

LncRNA analysis of mAb producing CHO clones reveals marker and engineering potential

Long non-coding RNAs (lncRNAs) are a potential new cell line engineering tool for improvement of yield and stability of CHO cells. In this study, we performed RNA sequencing of mAb producer CHO clones to study the lncRNA and protein coding transcriptome in relation to productivity. First, a robust linear model was used to identify genes correlating to productivity. To unravel specific patterns in expression of these genes, we employed weighted gene coexpression analysis (WGCNA) to find coexpressed modules, looking both for lncRNAs and coding genes. There was little overlap in the genes associated with productivity between the two products studied, possibly due to the difference in absolute range of productivity between the two mAbs. Therefore, we focused on the product with higher productivity and stronger candidate lncRNAs. To evaluate their potential as engineering targets, these candidate lncRNAs were transiently overexpressed or deleted by stable CRISPR Cas9 knock out both in a high and a low productivity subclone. We found that the thus achieved expression level of the identified lncRNAs, as confirmed by qPCR, does correlate well to productivity, so that they represent good markers that may be used for early clone selection. Additionally, we found that the deletion of one tested lncRNA region decreased viable cell density (VCD), prolonged culture time and increased cell size, final titer and specific productivity per cell. These results demonstrate the feasibility and usefulness of engineering lncRNA expression in production cell lines.

Priming grapevine with lipopolysaccharide confers systemic resistance to Pierce's disease and identifies a peroxidase linked to defense priming.

Priming is an adaptive mechanism that fortifies plant defense by enhancing activation of induced defense responses following pathogen challenge. Microorganisms have signature microbe-associated molecular patterns (MAMPs) that induce the primed state. The lipopolysaccharide (LPS) MAMP isolated from the xylem-limited pathogenic bacterium, Xylella fastidiosa, acts as a priming stimulus in Vitis vinifera grapevines. Grapevines primed with LPS developed significantly less internal tyloses and external disease symptoms than naive vines. Differential gene expression analysis indicated major transcriptomic reprogramming during the priming and postpathogen challenge phases. Furthermore, the number of differentially expressed genes increased temporally and spatially in primed vines, but not in naive vines during the postpathogen challenge phase. Using a weighted gene co-expression analysis, we determined that primed vines have more genes that are co-expressed in both local and systemic petioles than naive vines indicating an inherent synchronicity that underlies the systemic response to this vascular pathogen specific to primed plants. We identified a cationic peroxidase, VviCP1, that was upregulated during the priming and postpathogen challenge phases in an LPS-dependent manner. Transgenic expression of VviCP1 conferred significant disease resistance, thus, demonstrating that grapevine is a robust model for mining and expressing genes linked to defense priming and disease resistance.

WGCNA based identification of hub genes associated with cold response and development in Apis mellifera metamorphic pupae.

Honeybee is a crucial pollinator in nature, and plays an indispensable role in both agricultural production and scientific research. In recent decades, honeybee was challenged with health problems by biotic and abiotic stresses. As a key ecological factor, temperature has been proved to have an impact on the survival and production efficiency of honeybees. Previous studies have demonstrated that low temperature stress can affect honeybee pupation and shorten adult longevity. However, the molecular mechanism underlying the effects of low temperatures on honeybee growth and development during their developmental period remain poorly understood. In this paper, the weighted gene co-expression analysis (WGCNA) was employed to explore the molecular mechanisms underpinnings of honeybees' respond to low temperatures (20°C) during four distinct developmental stages: large-larvae, prepupae, early-pupae and mid-pupae. Through an extensive transcriptome analysis, thirteen gene co-expression modules were identified and analyzed in relation to honeybee development and stress responses. The darkorange module was found to be associated with low temperature stress, with its genes primarily involved in autophagy-animal, endocytosis and MAPK signaling pathways. Four hub genes were identified within this module, namely, loc726497, loc409791, loc410923, and loc550857, which may contribute to honeybee resistance to low temperature and provide insight into the underlying mechanism. The gene expression patterns of grey60 and black modules were found to correspond to the developmental stages of prepupae and early-pupae, respectively, with the hub genes loc409494, loc725756, loc552457, loc726158, Ip3k and Lcch3 in grey60 module likely involved in brain development, and the hub genes loc410555 in black module potentially related to exoskeleton development. The brown module genes exhibited a distinct pattern of overexpression in mid-pupae specimens, with genes primarily enriched in oxidative phosphorylation, citrate cycle and other pathways, which may be related to the formation of bee flying muscle. No related gene expression module was found for mature larvae stage. These findings provide valuable insights into the developmental process of honeybees at molecular level during the capped brood stage.

Integrative analysis of metabolite and transcriptome reveals biosynthetic pathway and candidate genes for eupatilin and jaceosidin biosynthesis in Artemisia argyi.

Artemisia argyi (A. argyi) is a medicinal plant belonging to the Asteraceae family and Artemisia genus. Flavonoids abundant in A. argyi are associated with anti-inflammatory, anticancer, and antioxidative effects. Eupatilin and jaceosidin are representative polymethoxy flavonoids with medicinal properties significant enough to warrant the development of drugs using their components. However, the biosynthetic pathways and related genes of these compounds have not been fully explored in A. argyi. This study comprehensively analyzed the transcriptome data and flavonoids contents from four different tissues of A. argyi (young leaves, old leaves, trichomes collected from stems, and stems without trichomes) for the first time. We obtained 41,398 unigenes through the de-novo assembly of transcriptome data and mined promising candidate genes involved in the biosynthesis of eupatilin and jaceosidin using differentially expressed genes, hierarchical clustering, phylogenetic tree, and weighted gene co-expression analysis. Our analysis led to the identification of a total of 7,265 DEGs, among which 153 genes were annotated as flavonoid-related genes. In particular, we were able to identify eight putative flavone-6-hydroxylase (F6H) genes, which were responsible for providing a methyl group acceptor into flavone basic skeleton. Furthermore, five O-methyltransferases (OMTs) gene were identified, which were required for the site-specific O-methylation during the biosynthesis of eupatilin and jaceosidin. Although further validation would be necessary, our findings pave the way for the modification and mass-production of pharmacologically important polymethoxy flavonoids through genetic engineering and synthetic biological approaches.

Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans.

Sarcopenia, characterized by age-related loss of muscle mass, strength, and decreased physical performance, is a growing public health challenge amid the rapidly ageing population. As there are no approved drugs that target sarcopenia, it has become increasingly urgent to identify promising pharmacological interventions. In this study, we conducted an integrative drug repurposing analysis utilizing three distinct approaches. Firstly, we analyzed skeletal muscle transcriptomic sequencing data in humans and mice using gene differential expression analysis, weighted gene co-expression analysis, and gene set enrichment analysis. Subsequently, we employed gene expression profile similarity assessment, hub gene expression reversal, and disease-related pathway enrichment to identify and repurpose candidate drugs, followed by the integration of findings with rank aggregation algorithms. Vorinostat, the top-ranking drug, was also validated in an in vitro study, which demonstrated its efficacy in promoting muscle fiber formation. Although still requiring further validation in animal models and human clinical trials, these results suggest a promising drug repurposing prospect in the treatment and prevention of sarcopenia.

Blood Proteomics Analysis Reveals Potential Biomarkers and Convergent Dysregulated Pathways in Autism Spectrum Disorder: A Pilot Study.

Autism spectrum disorder (ASD) is an umbrella term that encompasses several disabling neurodevelopmental conditions. These conditions are characterized by impaired manifestation in social and communication skills with repetitive and restrictive behaviors or interests. Thus far, there are no approved biomarkers for ASD screening and diagnosis; also, the current diagnosis depends heavily on a physician's assessment and family's awareness of ASD symptoms. Identifying blood proteomic biomarkers and performing deep blood proteome profiling could highlight common underlying dysfunctions between cases of ASD, given its heterogeneous nature, thus laying the foundation for large-scale blood-based biomarker discovery studies. This study measured the expression of 1196 serum proteins using proximity extension assay (PEA) technology. The screened serum samples included ASD cases (n = 91) and healthy controls (n = 30) between 6 and 15 years of age. Our findings revealed 251 differentially expressed proteins between ASD and healthy controls, of which 237 proteins were significantly upregulated and 14 proteins were significantly downregulated. Machine learning analysis identified 15 proteins that could be biomarkers for ASD with an area under the curve (AUC) = 0.876 using support vector machine (SVM). Gene Ontology (GO) analysis of the top differentially expressed proteins (TopDE) and weighted gene co-expression analysis (WGCNA) revealed dysregulation of SNARE vesicular transport and ErbB pathways in ASD cases. Furthermore, correlation analysis showed that proteins from those pathways correlate with ASD severity. Further validation and verification of the identified biomarkers and pathways are warranted.

Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models.

Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a substantial public health crisis that exacts tremendous personal and financial costs on patients and society. Sharp increases in cocaine use drive the urgent need for better mechanistic insight into this chronic relapsing brain disorder that currently lacks effective treatment options. To investigate the transcriptomic changes involved, we conducted RNA sequencing on two striatal brain regions that are heavily implicated in CUD, the nucleus accumbens and caudate nucleus, from men suffering from CUD and matched controls. Weighted gene coexpression analyses identified CUD-specific gene networks enriched in ionotropic receptors and linked to lowered neuroinflammation, contrasting the proinflammatory responses found in opioid use disorder. Integration of comprehensive transcriptomic datasets from mouse cocaine self-administration models revealed evolutionarily conserved gene networks in CUD that implicate especially D1 medium spiny neurons as drivers of cocaine-induced plasticity.

Structure of co-expression networks of Bifidobacterium species in response to human milk oligosaccharides.

Biological systems respond to environmental perturbations and a large diversity of compounds through gene interactions, and these genetic factors comprise complex networks. Experimental information from transcriptomic studies has allowed the identification of gene networks that contribute to our understanding of microbial adaptations. In this study, we analyzed the gene co-expression networks of three Bifidobacterium species in response to different types of human milk oligosaccharides (HMO) using weighted gene co-expression analysis (WGCNA). RNA-seq data obtained from Geo Datasets were obtained for Bifidobacterium longum subsp. Infantis, Bifidobacterium bifidum and Bifidobacterium longum subsp. Longum. Between 10 and 20 co-expressing modules were obtained for each dataset. HMO-associated genes appeared in the modules with more genes for B. infantis and B. bifidum, in contrast with B. longum. Hub genes were identified in each module, and in general they participated in conserved essential processes. Certain modules were differentially enriched with LacI-like transcription factors, and others with certain metabolic pathways such as the biosynthesis of secondary metabolites. The three Bifidobacterium transcriptomes showed distinct regulation patterns for HMO utilization. HMO-associated genes in B. infantis co-expressed in two modules according to their participation in galactose or N-Acetylglucosamine utilization. Instead, B. bifidum showed a less structured co-expression of genes participating in HMO utilization. Finally, this category of genes in B. longum clustered in a small module, indicating a lack of co-expression with main cell processes and suggesting a recent acquisition. This study highlights distinct co-expression architectures in these bifidobacterial genomes during HMO consumption, and contributes to understanding gene regulation and co-expression in these species of the gut microbiome.

Identifying the key genes of Epstein-Barr virus-regulated tumour immune microenvironment of gastric carcinomas.

The Epstein-Barr virus (EBV) is involved in the carcinogenesis of gastric cancer (GC) upon infection of normal cell and induces a highly variable composition of the tumour microenvironment (TME). However, systematic bioinformatics analysis of key genes associated with EBV regulation of immune infiltration is still lacking. In the present study, the TCGA and GEO databases were recruited to analyse the association between EBV infection and the profile of immune infiltration in GC. The weighted gene co-expression analysis (WGCNA) was applied to shed light on the key gene modules associated with EBV-associated immune infiltration in GC. 204 GC tissues were used to analysed the expression of key hub genes by using the immunohistochemical method. Real-time PCR was used to evaluate the association between the expression of EBV latent/lytic genes and key immune infiltration genes. Our results suggested that EBV infection changed the TME of GC mainly regulates the TIICs. The top three hub genes of blue (GBP1, IRF1, and LAP3) and brown (BIN2, ITGAL, and LILRB1) modules as representative genes were associated with EBV infection and GC immune infiltration. Furthermore, EBV-encoded LMP1 expression is account for the overexpression of GBP1 and IRF1. EBV infection significantly changes the TME of GC, and the activation of key immune genes was more dependent on the invasiveness of the whole EBV virion instead of single EBV latent/lytic gene expression.

MiR-196a-5p Correlates with Chronic Atrophic Gastritis Progression to Gastric Cancer and Induces Malignant Biological Behaviors of Gastric Cancer Cells by Targeting ACER2.

As the prognosis of early gastric cancer (EGC) is significantly better than that of advanced gastric cancer (AGC), the development of biomarkers to monitor the progression of chronic atrophic gastritis (CAG) to gastric cancer (GC) is essential. Stomach tissue miRNA and mRNA sequences from patients with chronic non-atrophic gastritis (CNAG), CAG, precancerous lesions of gastric cancer (PLGC), and GC were analyzed. A publicly available GC-related miRNA microarray dataset was obtained from the Gene Expression Omnibus database. Spearman's correlation and differential gene analyses, and clinical validation were used to identify novel miRNAs correlating with CAG progression to GC. miRNA targets were predicted using weighted gene co-expression analysis and databases. A dual-luciferase reporter assay was performed to check for direct interaction between miR-196a-5p and ACER2. The CCK-8 and wound healing assays, and flow cytometry were performed to evaluate cell proliferation, migration, and apoptosis. miR-196a-5p was correlated with CAG progression to GC. Overexpression of miR-196a-5p promoted GC cell proliferation and migration and inhibited apoptosis, whereas suppression of miR-196a-5p exerted the opposite effect. Based on the prediction and luciferase assays, ACER2 was identified as the target of miR-196a-5p. ACER2 was downregulated in GC cell lines. Knockdown of ACER2 increased GC cell proliferation rates and migration ability and inhibited apoptosis, while ACER2 overexpression led to the opposite effect. miR-196a-5p correlated with CAG progression to GC and induced malignant biological behaviors of GC cells by targeting ACER2, providing a novel monitoring biomarker and target for GC prevention.

Metal mixtures modeling identifies birth weight-associated gene networks in the placentas of children born extremely preterm

Prenatal exposure to toxic metals is linked to numerous adverse birth and later-in-life outcomes. These outcomes are tied to disrupted biological processes in fetal-derived tissues including the placenta and umbilical cord yet the precise pathways are understudied in these target tissues. We set out to examine the relationship between metal concentrations in umbilical cord and altered gene expression networks in placental tissue. These novel relationships were investigated in a subset of the Extremely Low Gestational Age Newborn (ELGAN) cohort (n = 226). Prenatal exposure to 11 metals/metalloids was measured using inductively coupled plasma tandem-mass spectrometry (ICP-MS/MS) in cord tissue, ensuring passage through the placental barrier. RNA-sequencing was used to quantify >37,000 mRNA transcripts. Differentially expressed genes (DEGs) were identified with respect to each metal. Weighted gene co-expression analysis identified gene networks modulated by metals. Two innovative mixtures modeling techniques, namely principal components analysis and quantile-based g-computation, were employed to identify genes/gene networks associated with multi-metal exposure. Individually, lead was associated with the strongest genomic response of 191 DEGs. Joint lead and cadmium exposure was related to 657 DEGs, including DNA Methyl Transferase 1 (DNMT1). These genes were enriched for the Eukaryotic Initiation Factor 2 (EIF2) pathway. Four gene networks, each containing genes within a Nuclear Factor kappa-light-chain-enhancer of Activated B Cells (NF-kB)-mediated network, were significantly increased in average expression level in relation to increases in all metal concentrations. All four of these metal mixture-associated gene networks were negatively correlated with important predictors of neonatal health including birth weight, placenta weight, and fetal growth. Bringing together novel methodologies from epidemiological mixtures analyses and toxicogenomics, applied to a unique cohort of extremely preterm children, the present study highlighted critical genes and pathways in the placenta dysregulated by prenatal metal mixtures. These represent potential mechanisms underlying the developmental origins of metal-induced disease.

Transcriptomic and weighted gene co-expression network analysis of tropic and temperate maize inbred lines recovering from heat stress

Heat stress (HS) causes imbalance of cellular homeostasis, growth impairment and extensively yield loss in crop production. In the present study, the tropic maize inbred CIMBL55 showed more thermotolerance than the maize temperate inbred B73, with less leaf damage rate and ROS accumulation. Transcriptome profiling of CIMBL55 and B73 upon (exposing at 45 ℃ for 0, 1, and 6 h) and post (recovering at 28 ℃ for 1 and 6 h) HS were further assessed and a total of 20204 DEGs were identified. Functional annotation revealed that HS activated unfolded protein response in endoplasmic reticulum in both two inbreds. Moreover, in CIMBL55, far more primary and secondary metabolism pathways were transcriptional altered. Afterwards, weighted gene co-expression analysis grouped all expressed genes into eighteen co-expressed modules. Four HS responsive and four CIMBL55 recovery-related modules were subsequently identified. Highly connected genes (hub genes) in these modules were characterized as transcription factors, heat shock proteins, Ca2+ signaling related genes and various enzymes. Moreover, one hub gene, ZmHsftf13 was verified to positively regulate thermotolerance by heterologous expressing in Arabidopsis and its Mu insertion mutant. The present research provides promising genes related to HS response in maize and is of great significance for breeding.

Comparative transcriptomics reveals unique pine wood decay strategies in the Sparassis latifolia

Sparassis latifolia is a valuable edible mushroom, growing on fresh pine wood sawdust substrate. However, the mechanistic bases are poorly understood. The gene expression profiles of S. latifolia were analyzed from submerged cultures with fresh pine wood sawdust substrate for different time (0 h, 1 h, 6 h, 1 day, 5 days, and 10 days, respectively). The total number of differentially expressed genes (DEGs) identified under pine sawdust inducing was 2,659 compared to 0 h (CK). And 1,073, 520, 385, 424, and 257 DEGs were identified at the five time points, respectively. There were 34 genes in common at all inoculated time points, including FAD/NAD(P)-binding domain-containing protein, glucose methanol choline (GMC) oxidoreductase, flavin-containing monooxygenase, and taurine catabolism dioxygenase. Weighted gene co-expression analysis (WGCNA) was then used to compare the molecular characteristics among the groups and identified that the blue module had the highest correlation with the time induced by pine wood sawdust. There were 102 DEGs out of 125 genes in the blue model, which were most enriched in nitronate monooxygenase activity, dioxygenase activity, and oxidation–reduction process GO terms (p < 0.05), and peroxisome in KEGG pathway. This may provide clues into mechanisms that S. latifolia can grow on fresh pine wood sawdust substrate.