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PubMed2026

Research on identification of key genes and immune-metabolic mechanisms in atrial fibrillation through integrated multi-cohort transcriptomic analysis and machine learning.

This study aimed to integrate multiple datasets for the identification of atrial fibrillation (AF)-related differentially expressed genes (DEGs), analyze their underlying mechanisms through functional enrichment and machine learning, construct diagnostic models, and explore immune-metabolic interactions to provide novel biomarkers and theoretical foundations. Gene expression datasets were integrated and normalized, with batch effects removed using principal component analysis. Differential expression analysis, functional enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways), and machine learning-based feature gene selection and model construction were performed. Shapley additive explanations analysis was utilized to interpret the constructed models, while gene set enrichment analysis, gene set variation analysis, and immune cell infiltration analysis were conducted to investigate the associations between feature genes and immune infiltration. After integrating and normalizing gene expression data and eliminating batch effects via principal component analysis, 6 DEGs were identified, including 4 upregulated and 2 down-regulated ones. Functional enrichment analysis showed these DEGs were significantly enriched in neuro-related biological processes and pathways, indicating their key roles in AF pathogenesis. Five key feature genes were selected using LASSO, random forest, and support vector machine-recursive feature elimination algorithms. They had significant expression differences between the AF and control groups (P < .001) and were located on distinct chromosomes. The constructed random forest and support vector machine models performed excellently (area under the curve ≥ 0.85). Shapley additive explanations analysis revealed TNNI1 contributed most to model prediction, with its expression significantly positively correlated with immune cell infiltration. Gene set enrichment analysis and gene set variation analysis analyses further showed feature genes participated in AF pathogenesis by regulating immune modulation, metabolic pathways, and autophagy. Immune cell infiltration analysis found altered proportions of T-cell subsets and M0 macrophages in the AF group, along with complex links between feature gene expression and immune cell function. This study systematically elucidated the unique gene expression patterns and key regulatory pathways associated with AF, clarifying the crucial roles of feature genes in immune regulation, metabolic imbalance, and cellular dysfunction. These findings provide a theoretical basis and potential therapeutic targets for understanding AF pathogenesis and developing targeted treatment strategies.

Atrial Fibrillation↗

PubMed1993

Olive: a key gene required for chlorophyll biosynthesis in Antirrhinum majus.

Olive (oli) is a recessive nuclear mutation of Antirrhinum majus which reduces the level of chlorophyll pigmentation and affects the ultrastructure of chloroplasts. The oli-605 allele carries a Tam3 transposon insertion which has allowed the locus to be isolated. The oli gene encodes a large putative protein of 153 kDa which shows homology to the products of two bacterial genes necessary for tetrapyrrole-metal chelation during the synthesis of bacteriochlorophyll or cobyrinic acid. We therefore propose that the product of the oli gene is necessary for a key step of chlorophyll synthesis: the chelation of magnesium by protoporphyrin IX. Somatic reversion of the oli-605 allele produces chimeric plants which indicate that the oli gene functions cell-autonomously. Expression of oli is restricted to photosynthetic cells and repressed by light, suggesting that it may be involved in regulating the rate of chlorophyll synthesis in green tissues.

Amino Acid Sequence↗

PubMed2004

AtGA3ox2, a key gene responsible for bioactive gibberellin biosynthesis, is regulated during embryogenesis by LEAFY COTYLEDON2 and FUSCA3 in Arabidopsis.

Embryonic regulators LEC2 (LEAFY COTYLEDON2) and FUS3 (FUSCA3) are involved in multiple aspects of Arabidopsis (Arabidopsis thaliana) seed development, including repression of leaf traits and premature germination and activation of seed storage protein genes. In this study, we show that gibberellin (GA) hormone biosynthesis is regulated by LEC2 and FUS3 pathways. The level of bioactive GAs is increased in immature seeds of lec2 and fus3 mutants relative to wild-type level. In addition, we show that the formation of ectopic trichome cells on lec2 and fus3 embryos is a GA-dependent process as in true leaves, suggesting that the GA pathway is misactivated in embryonic mutants. We next demonstrate that the GA-biosynthesis gene AtGA3ox2, which encodes the key enzyme AtGA3ox2 that catalyzes the conversion of inactive to bioactive GAs, is ectopically activated in embryos of the two mutants. Interestingly, both beta-glucuronidase reporter gene expression and in situ hybridization indicate that FUS3 represses AtGA3ox2 expression mainly in epidermal cells of embryo axis, which is distinct from AtGA3ox2 pattern at germination. Finally, we show that the FUS3 protein physically interacts with two RY elements (CATGCATG) present in the AtGA3ox2 promoter. This work suggests that GA biosynthesis is directly controlled by embryonic regulators during Arabidopsis embryonic development.

Arabidopsis↗

PubMed2006

Plant cell wall biosynthesis: genetic, biochemical and functional genomics approaches to the identification of key genes.

Cell walls are dynamic structures that represent key determinants of overall plant form, plant growth and development, and the responses of plants to environmental and pathogen-induced stresses. Walls play centrally important roles in the quality and processing of plant-based foods for both human and animal consumption, and in the production of fibres during pulp and paper manufacture. In the future, wall material that constitutes the major proportion of cereal straws and other crop residues will find increasing application as a source of renewable fuel and composite manufacture. Although the chemical structures of most wall constituents have been defined in detail, the enzymes involved in their synthesis and remodelling remain largely undefined, particularly those involved in polysaccharide biosynthesis. There have been real recent advances in our understanding of cellulose biosynthesis in plants, but, with few exceptions, the identities and modes of action of polysaccharide synthases and other glycosyltransferases that mediate the biosynthesis of the major non-cellulosic wall polysaccharides are not known. Nevertheless, emerging functional genomics and molecular genetics technologies are now allowing us to re-examine the central questions related to wall biosynthesis. The availability of the rice, Populus trichocarpa and Arabidopsis genome sequences, a variety of mutant populations, high-density genetic maps for cereals and other industrially important plants, high-throughput genome and transcript analysis systems, extensive publicly available genomics resources and an increasing armoury of analysis systems for the definition of candidate gene function will together allow us to take a systems approach to the description of wall biosynthesis in plants.

Biotechnology↗

PubMed2005

Community-level analysis: key genes of CO2-reductive acetogenesis.

CO2-reductive acetogenic bacteria are ubiquitous in anaerobic habitats and are physiologically and phylogenetically diverse. The latter characteristics have rendered their diversity in natural environments, their distributions, and their ecological function(s) difficult to assess. Recently introduced polymerase chain reaction (PCR) primers for specific amplification of the structural gene encoding formyltetrahydrofolate synthetase (FTHFS, EC 6.3.4.3), a key enzyme in the acetyl-CoA pathway of acetogenesis, have facilitated studies of acetogen diversity and ecology. These primers amplify an approximately 1100-bp segment of the FTHFS gene. FTHFS sequences have been recovered from authentic acetogens, from sulfate reducing bacteria, and from a variety of other nonacetogenic bacteria. Phylogenetic analyses segregated these sequences into distinct clusters, only one of which contained sequences from known acetogens. This chapter describes the PCR primers, defines conditions for successful amplification of FTHFS sequences, and details the phylogenetic analysis of the FTHFS sequences. Information on the types of sequences that have been recovered from natural acetogen habitats and how they have been interpreted is also included.

Acetic Acid↗

PubMed2001

SPT genes: key players in the regulation of transcription, chromatin structure and other cellular processes.

Suppressor of Ty (SPT) genes were originally identified through a genetic screen for mutations in the yeast Saccharomyces cerevisiae that restore gene expression disrupted by the insertion of the transposon Ty. Classic members of the SPT gene family, SPT11, SPT12, and SPT15, encode for the histones H2A and H2B, and for TATA-binding protein (TBP), respectively. Over the past few years, molecular complexes and cellular functions in which other SPT gene products involve have been discovered through genetic and biochemical studies in yeast and several other organisms: Key regulators of transcription and chromatin structure, such as DSIF, SAGA, and FACT, all contain SPT gene products as essential subunits. In addition, accumulating evidence suggests that SPT gene products play more diverse roles, including roles in DNA replication, DNA recombination and developmental regulation. Here we review the current understanding of the functions and roles of the SPT genes, with special emphasis on the role of SPT5 in transcript elongation and in neuronal development in vertebrates.

Animals↗

PubMed1997

Identification of key gene products required for acquisition of plasmin-like enzymatic activity by group A streptococci.

Group A streptococci incubated in human plasma can acquire a plasmin-like enzymatic activity. This process involves at least two bacterial proteins and two human protein cofactors. In this study, the key bacterial proteins were identified by using a series of isogenic mutants of group A isolate, CS101. These studies confirm a key role for the secreted plasminogen activator, streptokinase, and identify the major surface fibrinogen-binding protein as the product of the mrp gene. The requirement for human fibrinogen and plasminogen as key cofactors was also confirmed.

Bacterial Proteins↗

PubMed2003

Inactivation of mshB, a key gene in the mycothiol biosynthesis pathway in Mycobacterium smegmatis.

The mshB gene encoding N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase (MshB) is a key enzyme in mycothiol biosynthesis. Disruption of mshB in Mycobacterium smegmatis resulted in decreased production of mycothiol (5-10 % of the parent strain mc(2)155) but did not abolish mycothiol synthesis completely. Complementation of the MshB(-) mutants with the mshB gene resulted in increased mycothiol production towards the exponential and stationary phases of the bacterial growth cycle. These results suggest that another enzyme is capable of mycothiol biosynthesis by providing N-acetylglucosaminylinositol deacetylation activity in the absence of MshB. One of the candidate enzymes capable of carrying out such reactions is the MshB orthologue mycothiol amide hydrolase, MCA. However, epichromosomal expression of mca in the MshB(-) mutants did not restore mycothiol levels to the level of the parent strain. Unlike other mutants, which have little or no detectable levels of mycothiol, the MshB(-) mutant did not exhibit increased resistance to isoniazid. However, the MshB(-) mutant was resistant to ethionamide. Phenotypic analysis of other mutants lacking mycothiol revealed that MshA(-) mutants also exhibit ethionamide resistance but that a MshC(-)mutant was sensitive to ethionamide, suggesting that mycothiol or its early intermediates influence ethionamide activation.

Amidohydrolases↗

PubMed2005

Estrogen-repressed genes -- key mediators of estrogen action?

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Animals↗

PubMed2026

Functional identification of the key gene Eh-fadB in nicosulfuron degradation by Enterobacter hormaechei ES1 based on multi-omics and enzymatic characterization.

Nicosulfuron is a sulfonylurea herbicide with residues that pose ecological risks in agricultural soils. Here we elucidated the degradation mechanism of Enterobacter hormaechei ES1 through whole-genome sequencing, transcriptomics, metabolomics, gene knockout, heterologous expression, and soil bioremediation assays. Under nicosulfuron stress, ES1 upregulated antioxidant enzymes including SOD, POD, and CAT, along with glutathione synthesis, to scavenge excess reactive oxygen species. HPLC-TOF-MS identified degradation intermediates such as ADMP and ASDM, indicating initial cleavage of the sulfonylurea bridge. Integrated multi-omics prioritized Eh-fadB, encoding a fatty acid β-oxidation multifunctional enzyme, as a novel degradative gene. Targeted knockout of Eh-fadB reduced nicosulfuron degradation from 87.6% to 37.04%, while genetic complementation restored nearly full activity. Purified Eh-FadB directly converted nicosulfuron, with optimal performance at 30 °C and pH 5-6; its activity was enhanced by Na+ and Pb2+ but inhibited by Fe3+. Molecular docking and dynamics identified His-450 and Asn-427 as key residues for substrate binding. In contaminated soil, inoculation with ES1 reduced nicosulfuron content within 21 days and promoted recovery of dehydrogenase and urease activities. This study provides the first genetic and biochemical evidence that a FadB-type enzyme participates in nicosulfuron catabolism, supporting sulfonylurea bridge cleavage and its potential for soil bioremediation.

Eh-fadB↗

PubMed2005

Long-term hypoxia represses the expression of key genes regulating cortisol biosynthesis in the near-term ovine fetus.

Basal plasma ACTH(1-39) concentrations are elevated in long-term hypoxic (LTH) fetal sheep. This study was designed to determine whether the expression of genes regulating cortisol biosynthesis was altered after LTH. Pregnant ewes were maintained at high altitude (3,820 m) from day 30 of gestation to near term, when the animals were transported to the laboratory. Reduced PO2 was maintained by nitrogen infusion through a maternal tracheal catheter. On days 137-141, fetal adrenal glands were collected from LTH and normoxic control fetuses. Real-time PCR was used to quantify mRNA for steroidogenic acute regulatory protein, 17alpha-hydroxylase (CYP17), 21-hydroxylase (CYP21), cholesterol side-chain cleavage (CYP11A1), 3beta-hydroxysteroid dehydrogenase type II (HSD3B2), and the ACTH receptor. We analyzed mRNA by slot-blot hybridization and also quantified mRNA for transcription factors necessary for adrenocortical development by quantitative real-time PCR: steroidogenic factor 1 and dosage-sensitive sex reversal, adrenal hypoplasia congenital, critical region on the X chromosome (DAX-1). Protein was quantified by Western blot analysis. Adrenal mRNAs for CYP17, CYP11A1, and the ACTH receptor were significantly reduced in LTH fetal sheep compared with levels shown in controls. Similarly, CYP11A1 protein and CYP17 protein were reduced in the LTH group. CYP21, steroidogenic acute regulatory protein, HSD3B2, steroidogenic factor 1, and DAX-1 expressions were not altered in response to LTH. We conclude that expression of two key steroidogenic enzymes (CYP17, CYP11A1) regulating cortisol biosynthesis and the ACTH receptor is lower in response to LTH. This likely represents an adaptive response to LTH, to prevent excessive cortisol production that would restrict fetal growth and potentially induce preterm delivery.

Adrenal Glands↗

PubMed1998

HIV-1 regulatory/accessory genes: keys to unraveling viral and host cell biology.

Human immunodeficiency virus type-1 (HIV-1) manipulates fundamental host cell processes in sophisticated ways to achieve optimum replicative efficiency. Recent studies have provided new details on the molecular interactions of HIV-1 with its host cell. For example, HIV-1 encodes a protein that regulates transcriptional elongation by interacting with a cellular cyclin-dependent kinase, another that activates the specific nuclear export of viral RNA, and several others that affect the intracellular trafficking of viral and host cell proteins. Detailed analysis of the interplay between these viral proteins and normal cellular activities has provided new insights into central questions of virology and host cell biology.

Animals↗

PubMed2026

Bioinformatics Analysis and Experimental Validation of Key Genes Associated With Hypoxia and Ischemia in Myocardial Infarction.

BACKGROUND: This study aimed to screen and identify core hypoxia-ischemia-related genes associated with myocardial infarction (MI). METHOD: Two transcriptomic datasets, GSE97320 and GSE48060, were retrieved from the Gene Expression Omnibus (GEO) database. After data integration and batch effect elimination, differential expression analysis was performed to screen differentially expressed genes (DEGs), and the corresponding visualization analysis was conducted. Hypoxia-ischemia-related genes were acquired from the GeneCards database; hypoxia-ischemia related genes (HIRGs) were subsequently identified by intersecting the retrieved genes with screened DEGs. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were implemented to explore the biological functions and underlying signaling pathways of HIRGs. A combination of protein-protein interaction (PPI) network analysis and random forest (RF) algorithm was applied to screen hub genes from HIRGs. The external GEO dataset GSE66360 was utilized to validate the expression patterns of candidate hub genes. Furthermore, an acute myocardial infarction (AMI) mouse model was established, and quantitative real-time polymerase chain reaction (qPCR) was performed to detect the mRNA expression levels of hub genes in myocardial tissues for in vivo validation. RESULTS: A total of 633 DEGs and 308 hypoxia-ischemia-related genes were screened in the present study, among which 21 overlapping HIRGs were obtained. PLAUR and IL1B were finally identified as two hub genes from HIRGs based on PPI network and random forest algorithm. The qPCR results revealed that the expression levels of PLAUR and IL1B were significantly upregulated in the AMI group compared with the sham operation group (p < 0.05). CONCLUSION: The present findings demonstrated that PLAUR and IL1B serve as pivotal genes involved in the pathological hypoxia-ischemia process of AMI. These two genes may act as novel biomarkers and promising therapeutic targets for the recognition and clinical intervention of hypoxia-ischemia injury following AMI.

Myocardial Infarction↗

PubMed2004

Expression of key genes of fatty acid oxidation, including adiponectin receptors, in skeletal muscle of Type 2 diabetic patients.

AIMS/HYPOTHESIS: Defective oxidation of long-chain fatty acids is a feature of insulin resistance and Type 2 diabetes. Our aim was to compare the expression levels of the genes encoding the major proteins and enzymes of this pathway in skeletal muscle of healthy subjects and Type 2 diabetic patients. METHODS: The basal and insulin-regulated mRNA concentration of 16 genes was quantified using real-time PCR in skeletal muscle biopsies taken before and at the end of a 3-hour hyperinsulinaemic-euglycaemic clamp in healthy lean subjects and in insulin-resistant obese patients with manifest Type 2 diabetes. RESULTS: Acetyl CoA carboxylase-2 mRNA expression was increased 2.5-fold in the muscle of the diabetic patients. The expression of carnitine palmitoyl transferase-1, of the two adiponectin receptors and of genes involved in fatty acid transport and activation was not altered in diabetic patients. Hyperinsulinaemia for 3 hours increased the expression of several genes of fatty acid oxidation, including adiponectin receptor-1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha. It also reduced pyruvate dehydrogenase 4 mRNA levels. The effects of insulin on gene expression were markedly altered in the muscle of Type 2 diabetic patients except for adiponectin receptor-1 and pyruvate dehydrogenase 4 mRNAs. CONCLUSIONS/INTERPRETATION: The expression of adiponectin receptors was not altered in the muscle of Type 2 diabetic patients. The observed overexpression of acetyl CoA carboxylase-2 is consistent with the hypothesis that increased skeletal muscle malonyl CoA concentrations in Type 2 diabetes may contribute to the inhibition of long-chain fatty acid oxidation.

Blood Glucose↗

PubMed2026

Proteomics combined with single-cell sequencing reveals key genes and computational lead compound related to ligamentum flavum hypertrophy, lactate metabolism and lactate modification.

Ligamentum flavum hypertrophy (LFH) is a hallmark pathological feature of lumbar spinal stenosis; however, its underlying molecular mechanisms remain incompletely understood. Lactate metabolism and related lactylation modifications have emerged as critical links between cellular metabolism and epigenetic regulation, with established roles in various fibrotic and inflammatory diseases. Nevertheless, the specific contribution of lactylation to LFH pathogenesis remains unexplored. In this study, we integrated proteomic profiling of ligamentum flavum tissues with single-cell transcriptomic data to identify differentially expressed proteins associated with LFH. Cross-referencing these genes with genes involved in lactate metabolism and lactylation yielded 16 candidate genes. Through functional enrichment analysis, protein-protein interaction network construction, and GraphBAN model prediction, we identified five hub genes (NDUFS2, HMOX1, SPR, FABP5, and PFKP) and two potential lead compounds (ZINC000014879975 and ZINC000242437513). Molecular docking analysis confirmed favorable binding affinities between these compounds, suggesting that they may serve as potential lead compounds worthy of further experimental investigation. Single-cell analysis further revealed that macrophages occupy a central position in the LFH microenvironment, resulting in pronounced metabolic reprogramming and remodeling of intercellular communication networks, particularly via the MIF-CD74/CD44 axis, under pathological conditions.

Proteomics↗

PubMed2004

PfMyb1, a Plasmodium falciparum transcription factor, is required for intra-erythrocytic growth and controls key genes for cell cycle regulation.

During the complex life cycle of Plasmodium falciparum, divided between mosquito and human hosts, the regulation of morphologic changes implies a fine control of transcriptional regulation. Transcriptional control, however, and in particular its molecular actors, transcription factors and regulatory motifs, are as yet poorly described in Plasmodium. In order to decipher the molecular mechanisms implicated in transcriptional regulation, a transcription factor belonging to the tryptophan cluster family was studied. In a previous work, the PfMyb1 protein, contained in nuclear extracts, was shown to have DNA binding activity and to interact specifically with myb regulatory elements. We used long pfmyb1 double-stranded RNA (dsRNA) to interfere with the cognate messenger expression. Parasite cultures treated with pfmyb1 dsRNA exhibited a 40% growth inhibition when compared with either untreated cultures or cultures treated with unrelated dsRNA, and parasite mortality occurred during trophozoite to schizont transition. In addition, the pfmyb1 transcript and protein decreased by as much as 80% in treated trophozoite cultures at the time of their maximum expression. The global effect of this partial loss of transcript and protein was investigated using a thematic DNA microarray encompassing genes involved in signal transduction, cell cycle and transcriptional regulation. SAM software enabled us to identify several genes that were differentially expressed and probably directly or indirectly under the control of PfMyb1. Using chromatin immuno-precipitation, we demonstrated that PfMyb1 binds, within the parasite nuclei, to several promoters and therefore participates directly in the transcriptional regulation of the corresponding genes. This study provides the first evidence of a regulation network involving a Plasmodium transcription factor.

Animals↗

PubMed2026

A novel reusable transcriptome-wide association study workflow used to map key genes linked to important cattle traits.

Transcriptome-wide association studies (TWAS) are a powerful approach for studying the genes underlying complex traits by directly integrating GWAS and gene expression datasets. In cattle, they have been previously applied to identify genes driving fertility, milk production, and health. However, these studies have also highlighted several challenges, from difficulties in reproducing these complex analyses to limitations from poor genotype calls, especially when called directly from RNA sequencing data. To address these and other challenges, for the H2020 BovReg Project, we have developed a streamlined, species-agnostic, and reusable Nextflow TWAS workflow to integrate transcriptomic and GWAS summary statistic datasets. Our workflow first generates accurate genotype calls and gene expression prediction models from transcriptomic datasets and then applies these tools to impute gene expression levels into GWAS cohorts, enabling the association of genes with traits of interest. We explore optimal strategies for calling genetic variants directly from transcriptomic data and illustrate that using imputation approaches specifically designed for low-pass sequencing data can improve variant calling over previously adopted methods. We demonstrate the utility of our TWAS workflow by applying it to both novel and publicly available GWAS cohorts for cattle, detecting novel gene-trait associations for complex traits. Using a new transcriptome annotation of the cattle genome generated for the BovReg project we also illustrate how previously un-assayable associations can be detected. The results and the workflow we present, provide a new resource for the community and contribute to a better understanding of the molecular drivers of complex traits in cattle with the goal of eventually leveraging this information in future breeding decisions.

Animals↗

PubMed2005

Community-level analysis: key genes of aerobic methane oxidation.

Aerobic methane-oxidizing bacteria (methanotrophs) are a diverse group of bacteria that are currently represented by 13 recognized genera. They play a major role in the global methane cycle and are widespread in nature with representatives found in soils, freshwater, seawater, freshwater and marine sediments, peat bogs and at extremes of temperature, salinity, and pH. There has been an interest in methanotrophs for their potential in bioremediation processes. Methanotroph diversity and ecology are often studied using the "functional" genes pmoA, mmoX, and mxaF, encoding subunits of the particulate methane monooxygenase, soluble methane monooxygenase, and the methanol dehydrogenase, respectively. This chapter describes methods used to detect and analyze these functional genes.

Alcohol Oxidoreductases↗