Co-expression Network Construction Research Articles

Integrated analyses reveal the diagnostic and predictive values of COL5A2 and association with immune environment in Crohn's disease.

The pathogenesis of Crohn's disease (CD) involves abnormal immune cell infiltration and dysregulated immune response. Therefore, thorough research on immune cell abnormalities in CD is crucial for improved treatment of this disease. Single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data of CD were obtained from the Gene Expression Omnibus (GEO) database. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) networks evaluated the proportion of immune infiltrating cells, constructed co-expression network and identified key genes, respectively. Based on the dataset (GSE134809), 15 cell clusters were defined and labeled as different cell types. Among the 11 modules, the yellow module had the closest relationship with plasma cells (cluster 5). Confirmed using RNA sequencing and IHC assay, the expression of COL5A2 in CD samples was higher than that in control samples. Furthermore, the COL5A2 protein expression remarkably decreased in the group of patients who responded to anti-tumor necrosis factor (TNF) treatments, compared to the non-response group. The comprehensive analyses described here provided novel insight into the landscape of CD-associated immune environment. In addition, COL5A2 were identified as potential diagnostic indicators for CD, as well as promising predictive markers for CD patients.

Conserved regulatory switches for the transition from natal down to juvenile feather in birds

The transition from natal downs for heat conservation to juvenile feathers for simple flight is a remarkable environmental adaptation process in avian evolution. However, the underlying epigenetic mechanism for this primary feather transition is mostly unknown. Here we conducted time-ordered gene co-expression network construction, epigenetic analysis, and functional perturbations in developing feather follicles to elucidate four downy-juvenile feather transition events. We report that extracellular matrix reorganization leads to peripheral pulp formation, which mediates epithelial-mesenchymal interactions for branching morphogenesis. α-SMA (ACTA2) compartmentalizes dermal papilla stem cells for feather renewal cycling. LEF1 works as a key hub of Wnt signaling to build rachis and converts radial downy to bilateral symmetry. Novel usage of scale keratins strengthens feather sheath with SOX14 as the epigenetic regulator. We show that this primary feather transition is largely conserved in chicken (precocial) and zebra finch (altricial) and discuss the possibility that this evolutionary adaptation process started in feathered dinosaurs.

MRNA and miRNA expression profiles reveal the potential roles of RLRs signaling pathway and mitophagy in duck hepatitis A virus type 1 infection

Duck hepatitis A virus 1 (DHAV-1) is the primary cause of duck viral hepatitis, leading to sudden mortality in ducklings and significant economic losses in the duck industry. However, little is known about how DHAV-1 affects duckling liver at the molecular level. We conducted an analysis comparing the expression patterns of mRNAs and miRNAs in DHAV-1-infected duckling livers to understand the underlying mechanisms and dynamic changes. We identified 6,818 differentially expressed mRNAs (DEGs) and 144 differentially expressed microRNAs (DEMs) during DHAV-1 infection. Functional enrichment analysis of DEGs and miRNA target genes using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed their potential involvement in innate antiviral immunity, mitophagy, and pyroptosis. We constructed coexpression networks of mRNA-miRNA interactions and confirmed key DEMs (novel-mir333, novel-mir288, novel-mir197, and novel-mir71) using RT-qPCR. Further investigation demonstrated that DHAV-1 activates the RLRs signaling pathway, disrupts mitophagy, and induces pyroptosis. In conclusion, DHAV-1-induced antiviral immunity is closely linked to mitophagy, suggesting it could be a promising therapeutic target.

Role of CENPF and NDC80 in the rehabilitation nursing of hepatocellular carcinoma and cirrhosis: An observational study.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors globally and often develops on the foundation of chronic liver disease or cirrhosis. Cirrhosis is a clinically prevalent chronic progressive liver disease characterized by diffuse liver damage resulting from long-term or repeated actions of 1 or more etiological factors. However, the impact of CENPF and nuclear division cycle 80 (NDC80) genes on rehabilitation nursing of HCC and cirrhosis remains unclear. HCC and cirrhosis datasets GSE63898 and GSE89377 profile files were downloaded from the gene expression omnibus database generated on platforms GPL13667 and GPL6947, respectively. Differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis (WGCNA), construction and analysis of protein-protein interaction (PPI) networks, functional enrichment analysis, gene set enrichment analysis (GSEA), survival analysis, immune infiltration analysis, and comparative toxicogenomics database (CTD) analysis were conducted. Gene expression heatmaps were plotted. miRNAs regulating central DEGs were selected through TargetScan. A total of 626 DEGs were identified. According to gene ontology (GO) analysis, they were primarily enriched in small molecule metabolic processes, drug metabolic processes, binding of identical proteins, and lipid metabolic processes. Kyoto Encyclopedia of Gene and Genome (KEGG) analysis results indicated that the target genes were mainly enriched in metabolic pathways, phagosomes, glycine, serine, and threonine metabolism. The construction and analysis of the PPI network revealed 3 core genes (NDC80, CENPF, RRM2). Gene expression heatmaps showed that core genes (CENPF, NDC80) were highly expressed in HCC and cirrhosis samples. CTD analysis found that 2 genes (CENPF and NDC80) were associated with liver, jaundice, ascites, fever, dyspepsia, and hepatic encephalopathy. CENPF and NDC80 are highly expressed in HCC and cirrhosis, and CENPF and NDC80 might be the biomarkers of rehabilitation nursing of HCC and cirrhosis.

Comprehensive analysis of macrophage-related genes in prostate cancer by integrated analysis of single-cell and bulk RNA sequencing.

Macrophages, as essential components of the tumor immune microenvironment (TIME), could promote growth and invasion in many cancers. However, the role of macrophages in tumor microenvironment (TME) and immunotherapy in PCa is largely unexplored at present. Here, we investigated the roles of macrophage-related genes in molecular stratification, prognosis, TME, and immunotherapeutic response in PCa. Public databases provided single-cell RNA sequencing (scRNA-seq) and bulk RNAseq data. Using the Seurat R package, scRNA-seq data was processed and macrophage clusters were identified automatically and manually. Using the CellChat R package, intercellular communication analysis revealed that tumor-associated macrophages (TAMs) interact with other cells in the PCa TME primarily through MIF - (CD74+CXCR4) and MIF - (CD74+CD44) ligand-receptor pairs. We constructed coexpression networks of macrophages using the WGCNA to identify macrophage-related genes. Using the R package ConsensusClusterPlus, unsupervised hierarchical clustering analysis identified two distinct macrophage-associated subtypes, which have significantly different pathway activation status, TIME, and immunotherapeutic efficacy. Next, an 8-gene macrophage-related risk signature (MRS) was established through the LASSO Cox regression analysis with 10-fold cross-validation, and the performance of the MRS was validated in eight external PCa cohorts. The high-risk group had more active immune-related functions, more infiltrating immune cells, higher HLA and immune checkpoint gene expression, higher immune scores, and lower TIDE scores. Finally, the NCF4 gene has been identified as the hub gene in MRS using the "mgeneSim" function.

Transgressive and subgenome expression level dominance and co-expression network analyses at the early fiber development in allopolyploid Gossypium

Polyploidization can lead to the emergence of new species. Allotetraploid cotton arose through hybridization and whole genome duplication of its diploid A and D genome progenitors. As a prominent global fiber crop, cotton serves as an excellent model organism for exploring plant evolutionary biology and fiber development, particularly in polyploidization. This study utilized transcriptomics to analyze expression difference between diploid and allotetraploid cotton, aiming to further the understanding of transcriptomic dynamics associated at different fiber developmental stages during polyploidization process. In this study, we identified additive and non-additive genes and clarified the contributions of non-additive genes during the tetraploid formation process. Furthermore, we constructed a gene co-expression network, providing new insights into the transcriptional regulation of polyploid cotton fiber development. Among non-additive genes, more A genome-biased expression level dominance (ELD-A) than D genome (ELD-D) occurred in the tetraploids. In Gossypium hirsutum, ELD-A genes played major roles during initial elongation, exerting greater dominance in fiber development. Transgressive genes impacted early fiber development in Gossypium barbadense. While the At subgenome profoundly influences tetraploid fiber development, Dt sub-genome activation, inheritance and sub/neo-functionalization promote superior high-yield traits. By constructing co-expression networks, we identified key fiber developmental candidate genes, providing valuable resources for functional research and breeding perspectives to develop superior cotton varieties.

ICARUS v3, a massively scalable web server for single-cell RNA-seq analysis of millions of cells.

In recent years, improvements in throughput of single-cell RNA-seq have resulted in a significant increase in the number of cells profiled. The generation of single-cell RNA-seq datasets comprising >1 million cells is becoming increasingly common, giving rise to demands for more efficient computational workflows. We present an update to our single-cell RNA-seq analysis web server application, ICARUS (available at https://launch.icarus-scrnaseq.cloud.edu.au) that allows effective analysis of large-scale single-cell RNA-seq datasets. ICARUS v3 utilizes the geometric cell sketching method to subsample cells from the overall dataset for dimensionality reduction and clustering that can be then projected to the large dataset. We then extend this functionality to select a representative subset of cells for downstream data analysis applications including differential expression analysis, gene co-expression network construction, gene regulatory network construction, trajectory analysis, cell-cell communication inference, and cell cluster associations to GWAS traits. We demonstrate analysis of single-cell RNA-seq datasets using ICARUS v3 of 1.3 million cells completed within the hour. ICARUS is available at https://launch.icarus-scrnaseq.cloud.edu.au.

Breaking down barriers: comprehensive functional analysis of the Aspergillus niger chitin synthase repertoire

BackgroundMembers of the fungal kingdom are heterotrophic eukaryotes encased in a chitin containing cell wall. This polymer is vital for cell wall stiffness and, ultimately, cell shape. Most fungal genomes contain numerous putative chitin synthase encoding genes. However, systematic functional analysis of the full chitin synthase catalogue in a given species is rare. This greatly limits fundamental understanding and potential applications of manipulating chitin synthesis across the fungal kingdom.ResultsIn this study, we conducted in silico profiling and subsequently deleted all predicted chitin synthase encoding genes in the multipurpose cell factory Aspergillus niger. Phylogenetic analysis suggested nine chitin synthases evolved as three distinct groups. Transcript profiling and co-expression network construction revealed remarkably independent expression, strongly supporting specific role(s) for the respective chitin synthases. Deletion mutants confirmed all genes were dispensable for germination, yet impacted colony spore titres, chitin content at hyphal septa, and internal architecture of submerged fungal pellets. We were also able to assign specific roles to individual chitin synthases, including those impacting colony radial growth rates (ChsE, ChsF), lateral cell wall chitin content (CsmA), chemical genetic interactions with a secreted antifungal protein (CsmA, CsmB, ChsE, ChsF), resistance to therapeutics (ChsE), and those that modulated pellet diameter in liquid culture (ChsA, ChsB). From an applied perspective, we show chsF deletion increases total protein in culture supernatant over threefold compared to the control strain, indicating engineering filamentous fungal chitin content is a high priority yet underexplored strategy for strain optimization.ConclusionThis study has conducted extensive analysis for the full chitin synthase encoding gene repertoire of A. niger. For the first time we reveal both redundant and non-redundant functional roles of chitin synthases in this fungus. Our data shed light on the complex, multifaceted, and dynamic role of chitin in fungal growth, morphology, survival, and secretion, thus improving fundamental understanding and opening new avenues for biotechnological applications in fungi.

Prodromal Parkinson disease signs are predicted by a whole-blood inflammatory transcriptional signature in young Pink1−/− rats

BackgroundParkinson disease (PD) is the fastest growing neurodegenerative disease. The molecular pathology of PD in the prodromal phase is poorly understood; as such, there are no specific prognostic or diagnostic tests. A validated Pink1 genetic knockout rat was used to model early-onset and progressive PD. Male Pink1−/− rats exhibit progressive declines in ultrasonic vocalizations as well as hindlimb and forelimb motor deficits by mid-to-late adulthood. Previous RNA-sequencing work identified upregulation of genes involved in disease pathways and inflammation within the brainstem and vocal fold muscle. The purpose of this study was to identify gene pathways within the whole blood of young Pink1−/− rats (3 months of age) and to link gene expression to early acoustical changes. To accomplish this, limb motor testing (open field and cylinder tests) and ultrasonic vocalization data were collected, immediately followed by the collection of whole blood and RNA extraction. Illumina® Total RNA-Seq TruSeq platform was used to profile differential expression of genes. Statistically significant genes were identified and Weighted Gene Co-expression Network Analysis was used to construct co-expression networks and modules from the whole blood gene expression dataset as well as the open field, cylinder, and USV acoustical dataset. ENRICHR was used to identify the top up-regulated biological pathways.ResultsThe data suggest that inflammation and interferon signaling upregulation in the whole blood is present during early PD. We also identified genes involved in the dysregulation of ribosomal protein and RNA processing gene expression as well as prion protein gene expression.ConclusionsThese data identified several potential blood biomarkers and pathways that may be linked to anxiety and vocalization acoustic parameters and are key candidates for future drug-repurposing work and comparison to human datasets.

Profiling and functional analysis of circular RNAs in yaks intramuscular fat.

Circular RNAs (circRNAs) are a new class of endogenous RNA regulating gene expression. However, the regulatory mechanisms of lipid metabolism in yaks involved in circRNAs remain poorly understood. The IMF plays a crucial role in the quality of yak meat, to greatly improve the meat quality. In this study, the fatty acid profiles of yak IMF were determined and circRNAs were sequenced. The results showed that the total of polyunsaturated fatty acid (PUFA) content of adult yak muscle was significantly higher than that in yak calves (p < 0.05). A total of 29,021 circRNAs were identified in IMF tissue, notably, 99 differentially expressed (DE) circRNAs were identified, to be associated with fat deposition, the most significant of which were circ_12686, circ_6918, circ_3582, ci_106and ci_123 (A circRNA composed of exons is labelled 'circRNA'and a circRNA composed of introns is labelled 'ciRNA'). KEGG pathway enrichment analysis showed that the differential circRNAs were enriched in four pathways associated with fat deposition (e.g., the peroxisome proliferator-activated receptor signalling, fatty acid degradation, sphingolipid metabolismand sphingolipid signalling pathways). We also constructed co-expression networks of DE circRNA-miRNA using high-throughput sequencing in IMF deposition, from which revealed that ci_106 target binding of bta-miR-130b, bta-miR-148a, bta-miR-15a, bta-miR-34a, bta-miR-130a, bta-miR-17-5pand ci_123 target binding of bta-miR-150 were involved in adipogenesis. The study revealed the role of the circRNAs in the IMF deposition in yak and its influence on meat quality the findings demonstrated the circRNA differences in the development of IMF with the increase of age, thus providing a theoretical basis for further research on the molecular mechanism of IMF deposition in yaks.

Genome-wide identification of dysregulated alternative splicing and RNA-binding proteins involved in atopic dermatitis.

Objectives: We explored the role and molecular mechanisms of RNA-binding proteins (RBPs) and their regulated alternative splicing events (RASEs) in the pathogenesis of atopic dermatitis (AD). Methods: We downloaded RNA-seq data (GSE121212) from 10 healthy control skin samples (healthy, Ctrl), 10 non-lesional skin samples with AD damage (non-lesional, NL), and 10 lesional skin samples with AD damage (lesional, LS). We performed the analysis of differentially expressed genes (DEGs), differentially expressed RBPs (DE-RBPs), alternative splicing (AS), functional enrichment, the co-expression of RBPs and RASEs, and quantitative polymerase chain reaction (qPCR). Results: We identified 60 DE-RBP genes by intersecting 2141 RBP genes from existing reports with overall 2697 DEGs. Most of the DE-RBP genes were found to be upregulated in the AD LS group and related to immune and apoptosis pathways. We observed different ASEs and RASEs among the healthy, AD NL, and AD LS groups. In particular, alt3p and alt5p were the main ASEs and RASEs in AD NL and AD LS groups, compared to the healthy group. Furthermore, we constructed co-expression networks of DE-RBPs and RAS, with particular enrichment in biological pathways including cytoskeleton organization, inflammation, and immunity. Subsequently, we selected seven genes that are commonly present in these three pathways to assess their expression levels in the peripheral blood mononuclear cells (PBMCs) from both healthy individuals and AD patients. The results demonstrated the upregulation of four genes (IFI16, S100A9, PKM, and ENO1) in the PBMCs of AD patients, which is highly consistent with DE-RBP genes analysis. Finally, we selected four RAS genes regulated by RBPs that were related to immune pathways and examined their RASEs in PBMCs from both AD patients and healthy controls. The results revealed an increased percentage of RASEs in the DDX60 gene in AD, which is highly consistent with AS analysis. Conclusion: Dysregulated RBPs and their associated RASEs may have a significant regulatory role in the development of AD and could be potential therapeutic targets in the future.

Transcriptomic effects of paternal cocaine-seeking on the reward circuitry of male offspring

It has been previously established that paternal development of a strong incentive motivation for cocaine can predispose offspring to develop high cocaine-seeking behavior, as opposed to sole exposure to the drug that results in drug resistance in offspring. However, the adaptive changes of the reward circuitry have not been fully elucidated. To infer the key nuclei and possible hub genes that determine susceptibility to addiction in offspring, rats were randomly assigned to three groups, cocaine self-administration (CSA), yoked administration (Yoke), and saline self-administration (SSA), and used to generate F1. We conducted a comprehensive transcriptomic analysis of the male F1 offspring across seven relevant brain regions, both under drug-naïve conditions and after cocaine self-administration. Pairwise differentially expressed gene analysis revealed that the orbitofrontal cortex (OFC) exhibited more pronounced transcriptomic changes in response to cocaine exposure, while the dorsal hippocampus (dHip), dorsal striatum (dStr), and ventral tegmental area (VTA) exhibited changes that were more closely associated with the paternal voluntary cocaine-seeking behavior. Consistently, these nuclei showed decreased dopamine levels, elevated neuronal activation, and elevated between-nuclei correlations, indicating dopamine-centered rewiring of the midbrain circuit in the CSA offspring. To determine if possible regulatory cascades exist that drive the expression changes, we constructed co-expression networks induced by paternal drug addiction and identified three key clusters, primarily driven by transcriptional factors such as MYT1L, POU3F4, and NEUROD6, leading to changes of genes regulating axonogenesis, synapse organization, and membrane potential, respectively. Collectively, our data highlight vulnerable neurocircuitry and novel regulatory candidates with therapeutic potential for disrupting the transgenerational inheritance of vulnerability to cocaine addiction.

Hub Genes and Pathways Related to Lemon (Citrus limon) Leaf Response to Plenodomus tracheiphilus Infection and Influenced by Pseudomonas mediterranea Biocontrol Activity.

The lemon industry in the Mediterranean basin is strongly threatened by "mal secco" disease (MSD) caused by the fungus Plenodomus tracheiphlilus. Leaf pretreatments with Pseudomonas mediterranea 3C have been proposed as innovative tools for eco-sustainable interventions aimed at controlling the disease. In this study, by exploiting the results of previously performed RNAseq analysis, WCGNA was conducted among gene expression patterns in both inoculated (Pt) and pretreated and fungus-inoculated lemon plants (Citrus limon L.) (3CPt), and two indicators of fungal infection, i.e., the amount of fungus DNA measured in planta and the disease index (DI). The aims of this work were (a) to identify gene modules significantly associated with those traits, (b) to construct co-expression networks related to mal secco disease; (c) to define the effect and action mechanisms of P. mediterranea by comparing the networks. The results led to the identification of nine hub genes in the networks, with three of them belonging to receptor-like kinases (RLK), such as HERK1, CLAVATA1 and LRR, which play crucial roles in plant-pathogen interaction. Moreover, the comparison between networks indicated that the expression of those receptors is not induced in the presence of P. mediterranea, suggesting how powerful WCGNA is in discovering crucial genes that must undergo further investigation and be eventually knocked out.

Comparative analysis of the nucleus accumbens transcriptional features in multiple depressive animal models

Chronic stress is deemed a significant clinical contributor to depression. The use of animal models of chronic stress can fully reveal the complex pathological mechanisms and their changing trends in the pathogenesis of depression, which is crucial for both disease prevention and therapy. It is also unknown how various forms of stress differ in their impact on animal physiology and behavior. The nucleus accumbens (NAc), an essential brain area for the pathophysiology of depression, and its underlying neural mechanisms remain unclear. Here, we systematically compared transcriptional signatures in the NAc of four chronic stress models in rats: chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS), learned helplessness (LH), chronic restraint stress (CRS). The majority of differentially expressed genes (DEGs) were unique to a single depression model, while the rank-rank hypergeometric overlap analysis showed that the CSDS and CRS models had the greatest overlap, and the CRS and CUMS models had the least. Then, we performed pathway analysis of the differential genes and found that the neuroactive ligand-receptor interaction pathway was significantly enriched not only in the LH, CRS and CSDS stress models, but also significantly enriched in stress genes that were also altered in at least two stress models. Finally, we found three hub genes (Dcx, Tnc and Wdfy4) by constructing co-expression networks for stress genes.In summary, our research has the potential to offer fresh insights into the molecular mechanisms underlying depression induced by different types of stress, highlighting both their similarities and differences. It may provide valuable clues for understanding the pathogenesis of depression.

In-depth analysis of immune cell landscapes reveals differences between lung adenocarcinoma and lung squamous cell carcinoma

BackgroundLung cancer is the leading cause of cancer deaths globally, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being major subtypes. Immunotherapy has emerged as a promising approach for the treatment of lung cancer, but understanding the underlying mechanisms of immune dysregulation is crucial for the development of effective therapies. This study aimed to investigate the distinctive cellular features of LUAD and LUSC and identify potential biomarkers associated with the pathogenesis and clinical outcomes of each subtype.MethodsWe used digital cytometry techniques to analyze the RNA-Seq data of 1128 lung cancer patients from The Cancer Genome Atlas (TCGA) database. The abundance of cell subtypes and ecotypes in LUAD and LUSC patients was quantified. Univariate survival analysis was used to investigate their associations with patient overall survival (OS). Differential gene expression analysis and gene co-expression network construction were carried out to explore the gene expression patterns of LUSC patients with distinct survival outcomes. Scratch wound-healing assay, colony formation assay, and transwell assay were used to validate the candidate drugs for LUSC treatment.ResultsWe found differential expression of cell subtypes between LUAD and LUSC, with certain cell subtypes being prognostic for survival in both subtypes. We also identified differential gene expression and gene co-expression modules associated with macrophages.3/PCs.2 ratio in LUSC patients with distinct survival outcomes. Furthermore, ecotype ratios were found to be prognostic in both subtypes and machine learning models showed that certain cell subtypes, such as epithelial.cells.1, epithelial.cells.5, and endothelial.cells.2 are important for predicting LUSC. Ginkgolide B and triamterene can inhibit the proliferation, invasion, and migration of LUSC cell lines.ConclusionWe provide insight into the distinctive cellular features of LUAD and LUSC, and identify potential biomarkers associated with the pathogenesis and clinical outcomes of each subtype. Ginkgolide B and triamterene could be promising drugs for LUSC treatment.

A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma

The HAND2-AS1 (HAND2 Antisense RNA 1) Long noncoding RNA (lncRNA) has emerged as a participant in the initiation of various cancer types, underscoring its pivotal involvement in both oncological processes and immune responses. To gain deeper insights into the functional nuances of HAND2-AS1 and identify novel avenues for cancer immunotherapy, a comprehensive evaluation of this gene was undertaken. Here, based on the co-expression network analysis and construction of interacting lncRNA–mRNA genes, we introduce the HAND2-AS1 lncRNA, emphasizing its key roles in tumorigenesis and immune regulation. Our study spans across 33 distinct cancer types, revealing the HAND2-AS1’s aberrant expression patterns, methylation variations, mutational signatures, and immune engagement. Across a majority of tumors, HAND2-AS1 exhibited a propensity for down-regulation, remarkably an association with poor survival outcomes. The outcomes of functional enrichment analyses strongly suggest HAND2-AS1’s engagement in tumor progression and its association with various immune pathways across diverse tumor classifications. Additionally, a positive correlation emerged between HAND2-AS1 expression and the infiltration levels of key immune cells, encompassing not only immunosuppressive entities such as tumor-associated macrophages, cancer-associated fibroblasts, and Tregs, but also immune effector cells like NK cells and CD8+ T cells, spanning a pan-cancer context. Furthermore, the differential expression of HAND2-AS1 appears to have downstream consequences on various pathways, thus implicating it as a potential regulator in diverse cancer types. Finally, we have employed CRC tumor and normal samples to carry out clinical validation of HAND2-AS1. Our study unveils HAND2-AS1’s potential as a pan-cancer tumor suppressor, and its essential role in the tumorigenesis and immune surveillance. The increased HAND2-AS1 expression emerges as a promising candidate for prognostic evaluation, therapeutic strategy, and a focal point for immunotherapeutic interventions.

Differential co-expression network analysis elucidated genes associated with sensitivity to farnesyltransferase inhibitor and prognosis of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease and the most common form of acute leukemia with a poor prognosis. Due to its complexity, the disease requires the identification of biomarkers for reliable prognosis. To identify potential disease genes that regulate patient prognosis, we used differential co-expression network analysis and transcriptomics data from relapsed, refractory, and previously untreated AML patients based on their response to treatment in the present study. In addition, we combined functional genomics and transcriptomics data to identify novel and therapeutically potential systems biomarkers for patients who do or do not respond to treatment. As a result, we constructed co-expression networks for response and non-response cases and identified a highly interconnected group of genes consisting of SECISBP2L, MAN1A2, PRPF31, VASP, and SNAPC1 in the response network and a group consisting of PHTF2, SLC11A2, PDLIM5, OTUB1, and KLRD1 in the non-response network, both of which showed high prognostic performance with hazard ratios of 4.12 and 3.66, respectively. Remarkably, ETS1, GATA2, AR, YBX1, and FOXP3 were found to be important transcription factors in both networks. The prognostic indicators reported here could be considered as a resource for identifying tumorigenesis and chemoresistance to farnesyltransferase inhibitor. They could help identify important research directions for the development of new prognostic and therapeutic techniques for AML.

Construction of Cotton Verticillium wilt Resistance Co-expression Network and Identification of Hub Genes

Construction of Cotton Verticillium wilt Resistance Co-expression Network and Identification of Hub Genes

Integrated metabolome and transcriptome reveals the mechanism of the flower coloration in cashew Anacardium occidentale

Cashew is a widely attractive food in the world with high nutritional value for human health. Flower color is an important trait that plays a key role in reproductive ecology and species evolution in cashew plants. In this study, we chose two cashew cultivars for research objects characterized as different flower coloration. B2_5 exhibited steady white color during flowering, while B7 exhibited a color transition from white to red in its blooming period. However, the molecular mechanisms underlying flower coloration in both cashew cultivars remains unclear. By comparative metabolome analysis, we identified 8 flavonoid compounds were markedly accumulated in B7 during flowering, especially delphinidin-3-O-glucoside and peonidin-3-glucoside. These hub metabolites explained the variety difference in flower coloration between B7 and B2_5 cashew cultivars. Further transcriptome analysis identified 9 key structural genes in flavonoid biosynthesis that were significantly up-regulated, especially CHI, FLS and LAR, which explained the variety difference in flower coloration between both cashew cultivars. The construction of co-expression network showed RAP2-2, NAC22, MYB78, MYB62 and MYB1 probably modulated the expression of three candidate structural genes. This study sheds light on the molecular mechanism of flower coloration in B7 cultivar and reveals the variety difference in flower coloration between two cultivars, these results expect to provide a worthy guidance for flower coloration in cashew.

Transcriptome and coexpression network analysis reveals properties and candidate genes associated with grape (Vitis vinifera L.) heat tolerance.

Temperature is one of the most important environmental factors affecting grape season growth and geographical distribution. With global warming and the increasing occurrence of extreme high-temperature weather, the impact of high temperatures on grape production has intensified. Therefore, identifying the molecular regulatory networks and key genes involved in grape heat tolerance is crucial for improving the resistance of grapes and promoting sustainable development in grape production. In this study, we observed the phenotypes and cellular structures of four grape varieties, namely, Thompson Seedless (TS), Brilliant Seedless (BS), Jumeigui (JMG), and Shine Muscat (SM), in the naturally high-temperature environment of Turpan. Heat tolerance evaluations were conducted. RNA-seq was performed on 36 samples of the four varieties under three temperature conditions (28°C, 35°C, and 42°C). Through differential expression analysis revealed the fewest differentially expressed genes (DEGs) between the heat-tolerant materials BS and JMG, and the DEGs common to 1890 were identified among the four varieties. The number of differentially expressed genes within the materials was similar, with a total of 3767 common DEGs identified among the four varieties. KEGG enrichment analysis revealed that fatty acid metabolism, starch and sucrose metabolism, plant hormone signal transduction, the MAPK signaling pathway, and plant-pathogen interactions were enriched in both between different temperatures of the same material, and between different materials of the same temperature. We also conducted statistical and expression pattern analyses of differentially expressed transcription factors. Based on Weighted correlation network analysis (WGCNA), four specific modules highly correlated with grape heat tolerance were identified by constructing coexpression networks. By calculating the connectivity of genes within the modules and expression analysis, six candidate genes (VIT_04s0044g01430, VIT_17s0000g09190, VIT_01s0011g01350, VIT_01s0011g03330, VIT_04s0008g05610, and VIT_16s0022g00540) related to heat tolerance were discovered. These findings provide a theoretical foundation for further understanding the molecular mechanisms of grape heat tolerance and offer new gene resources for studying heat tolerance in grapes.