Mol. Genet. Genomics [JOURNAL]
Sun
200 papers
WGS-based in silico analysis of clinically-associated Klebsiella pneumoniae genomes: insights into antimicrobial resistance, virulence determinants, and plasmid dynamics.
Vijayakumar S, Ramaiah S
Mol Genet Genomics · 2026 Apr · PMID 41940992 · Publisher ↗
Klebsiella pneumoniae (K. pneumoniae) is a leading cause of nosocomial infections and is increasingly linked to multidrug resistance and hypervirulence. Comprehensive genomic characterization is essential for understandi...
Klebsiella pneumoniae (K. pneumoniae) is a leading cause of nosocomial infections and is increasingly linked to multidrug resistance and hypervirulence. Comprehensive genomic characterization is essential for understanding the emergence of multidrug resistant and hypervirulent K. pneumoniae strains. Therefore, this study comprehensively investigated the resistome, virulome, and plasmidome profile of 310 clinical K. pneumoniae genomes to elucidate genetic determinants of virulence and antimicrobial resistance (AMR). Multi-locus sequence typing identified 86 sequence types, with ST11 being the predominant lineage associated with KL64 and KL47 capsular types. Resistome analysis detected widespread β-lactam resistance genes, with most genomes carrying extended-spectrum β-lactamases (ESBLs). Carbapenemases namely KPC and NDM were detected in 31% and 15% of genomes respectively. The co-occurrence of multiple ESBLs (CTX-M, SHV, and TEM) within the same genome was observed in nearly half of the genomes (146/310), suggesting a strong genetic determinant of resistance to third-generation cephalosporins. ST23 genomes showed an increased abundance of siderophore-associated virulence genes, including aerobactin, yersiniabactin, and colibactin. Plasmidome profiling revealed that several resistance determinants were found on conjugative plasmids encoding β-lactamase and aminoglycoside resistance genes which underscores their potential for horizontal dissemination. The open pan-genome exhibited substantial diversity, with accessory genome enriched in mobilome-associated genes (14.6%) compared to core genome (0.1%). Overall, these results reveal the extensive genomic plasticity of K. pneumoniae and widespread distribution of resistance and virulence determinants, largely mediated by mobile genetic elements. These findings are pivotal for guiding future genomic surveillance and to support the development of targeted therapeutic approaches to combat AMR.
Exploratory identification of lycorine as a potential inhibitor of the ACP2/YME1L1 prognostic axis in esophageal squamous cell carcinoma: a multi-omics and computational hypothesis.
Chen F, Zhang J, Xu Y … +2 more , Wang Y, Cheng J
Mol Genet Genomics · 2026 Apr · PMID 41940976 · Publisher ↗
Esophageal squamous cell carcinoma (ESCC) continues to pose significant therapeutic challenges due to its aggressive behavior and suboptimal outcomes. The mitochondrial unfolded protein response (MUPR) pathway has emerge...
Esophageal squamous cell carcinoma (ESCC) continues to pose significant therapeutic challenges due to its aggressive behavior and suboptimal outcomes. The mitochondrial unfolded protein response (MUPR) pathway has emerged as a potential contributor to tumor progression, yet its role in ESCC prognosis and therapy remains insufficiently characterized. This study therefore seeks to systematically identify MUPR-associated prognostic genes in ESCC and to evaluate their potential as targets for therapeutic intervention. This study analyzed public databases to correlate MUPR pathway genes with ESCC prognosis, identifying YME1L1 and ACP2. These genes were used to construct a prognostic risk model, and single-cell RNA sequencing (scRNA-seq) was employed to determine their cellular expression patterns. Furthermore, the expression levels of the identified genes were experimentally validated in human ESCC cell lines using Reverse Transcription-quantitative PCR (RT-qPCR). Subsequently, the potential of these genes as drug targets was assessed. Following computational screening, lycorine emerged as a promising candidate. Rather than relying solely on molecular docking, this study performed molecular dynamics (MD) simulations to assess the stability of the binding interactions over time. The prognostic model was able to stratify patients into high- and low-risk groups that showed significantly different survival outcomes. At the cellular level, YME1L1 and ACP2 exhibited pronounced activity in B cells and neutrophils. RT-qPCR analysis demonstrated a significant downregulation of YME1L1 and ACP2 in ESCC cell lines compared to normal esophageal epithelial cells (P < 0.05), demonstrating high concordance between our bioinformatics predictions and experimental evidence. The drug screening identified lycorine as a promising candidate, with a predicted binding energy of − 9.0 kcal/mol to ACP2. MD simulations demonstrated the stability of these interactions: both the ACP2-lycorine and YME1L1-lycorine complexes remained stable throughout the simulation period, maintaining their structural integrity and key hydrogen bonds. This study identified ACP2 and YME1L1 as a novel prognostic signature in ESCC, supported by preliminary transcriptional validation, and proposed the natural compound lycorine as a computational candidate for inhibiting this axis. Our work established a conceptual link between prognostic biomarkers and a candidate therapeutic, providing a computationally derived rationale for future experimental and translational studies in ESCC. Further investigations are warranted to validate lycorine’s efficacy in vivo and to explore its potential synergy with existing therapies, with the ultimate goal of improving clinical outcomes.
Unraveling the molecular landscape: an overview on gene expression, epigenetic alterations, and therapeutic challenges in head and neck squamous cell carcinoma.
Natesan M, Mohan S, Gr B … +1 more , Nagarajan D
Mol Genet Genomics · 2026 Apr · PMID 41940897 · Publisher ↗
This review aimed to provide a comprehensive overview of the molecular landscape of HNSCC, focusing on key genetic alterations, epigenetic regulation, and therapeutic challenges associated with HNSCC. We highlighted the...
This review aimed to provide a comprehensive overview of the molecular landscape of HNSCC, focusing on key genetic alterations, epigenetic regulation, and therapeutic challenges associated with HNSCC. We highlighted the deregulations in key cellular signaling pathways, including PI3K/AKT/mTOR, Ras/Raf/MEK/ERK, Wnt/Beta-catenin, Notch, Hedgehog, Hippo-YAP/TAZ, and JAK/STAT, which contribute to tumor initiation, progression, and therapy resistance. In addition, we provided an overview of epigenetic mechanisms in HNSCC including DNA methylation changes, histone modifications, and non-coding RNA regulation. Emerging epigenetic therapeutic strategies under clinical investigation were also highlighted. Moreover, molecular and epigenetic signatures related to HPV-positive and HPV-negative HNSCC further emphasized the complexity and clinical heterogeneity of disease. Head and Neck Squamous Cell Carcinoma (HNSCC) represents a biologically complex malignancy characterized by molecular heterogeneity, high recurrence rate, and poor clinical outcome. A deeper understanding of the genetic and epigenetic mechanisms underlying HNSCC is essential for improving early diagnosis, and therapy response providing a better patient stratification. An extensive review of current literature was conducted using PubMed and Google Scholar which included 280 articles highlighting recent advancements in gene expression profiling in HNSCC. This review summarizes the complex molecular events in HNSCC emphasizing the key deregulations in cellular signaling pathways, differential gene expression regulated by epigenetic modifications. Understanding these molecular mechanisms may facilitate the identification of novel biomarkers and therapeutic targets, contributing to the development of more effective treatment for HNSCC.
Establishment of the chromid database and analysis of evolutionary research.
Liao Y, Wang B, Li Y … +3 more , Ni W, Li X, Hu S
Mol Genet Genomics · 2026 Apr · PMID 41940893 · Publisher ↗
In bacterial multireplicon genomes, in addition to the main chromosome, there is a widespread class of secondary replicons with a distinct evolutionary status known as chromids. These elements possess plasmid-like replic...
In bacterial multireplicon genomes, in addition to the main chromosome, there is a widespread class of secondary replicons with a distinct evolutionary status known as chromids. These elements possess plasmid-like replication and partitioning systems, while their nucleotide composition and gene functions are highly similar to those of the main chromosome. Therefore, chromids are considered to play important roles in the evolution of bacterial genome architecture and in environmental adaptation. With advances in long-read sequencing technologies and breakthroughs in bioinformatics methods, metagenomic data resources have been greatly expanded. Using our previously developed automated tool, "Chromid-Finder", we systematically identified and collected chromid sequences from large-scale metagenomic assemblies. These data were then uniformly curated, classified, and centrally managed to construct a public database platform dedicated to chromids-Chromid Database. On this basis, we conducted comprehensive analyses of the evolutionary and genetic characteristics of chromids. Phylogenetic analyses revealed the overall evolutionary landscape of chromids. Variation analyses showed that SNP distributions on chromids exhibit clear and well-organized patterns, depicting a dynamic population that is continuously adapting to the environment through fine-scale sequence tuning and non-coding regulatory mechanisms. Structural variation analyses further identified several hotspot regions significantly enriched in key genes related to metabolic functions, nutrient acquisition, and antibiotic resistance. The distribution patterns of recombination events suggest that their occurrence is likely driven primarily by non-phylogenetic factors such as environmental conditions and ecological niches. In addition, systematic quantification of heritable mobile genetic elements indicated that the number of integrative and conjugative elements (ICEs) largely determines the overall mobile element burden within chromids.
Multi-tope subunit vaccine for human anthrax through pan-genome-based reverse vaccinology approach.
Joseph R, Pandiarajan SK, Rajendhran J
Mol Genet Genomics · 2026 Apr · PMID 41917500 · Publisher ↗
Anthrax is a zoonotic disease caused by Bacillus anthracis and poses a serious threat to public health. Frequent anthrax outbreaks in wild animals and livestock in the tropical regions lead to mortality and substantial e...
Anthrax is a zoonotic disease caused by Bacillus anthracis and poses a serious threat to public health. Frequent anthrax outbreaks in wild animals and livestock in the tropical regions lead to mortality and substantial economic losses. Farm workers, veterinarians, and individuals in close contact with infected animals are at risk of contracting the infection. In this study, a multi-tope vaccine for humans was designed through a pan-genome-based reverse vaccinology approach. We predicted twelve proteins that can elicit both B-cell and T-cell-mediated immunity, from which we identified eighteen surface-exposed immunodominant epitopes. Among these, seven epitopes that showed epitope-HLA binding in 97.67% of the global population, with regional coverage of 99.23% in North America and 98.24% in Europe, were used to design a multi-tope subunit vaccine. The designed multi-tope vaccine exhibited strong interactions with MHC class I (-46.4 kcal/mol), MHC class II (-80.19 kcal/mol), TLR4 (-62.33 kcal/mol), and B-cell receptors (-40.62 kcal/mol). Normal mode analysis revealed structural stability of the vaccine-receptor complex with an eigenvalue of 5.734505 × 10⁻⁶. MD simulation showed stable RMSD with an average deviation of 1.39 nm, low RMSF, and consistent solvent exposure. The in silico immune simulation generated robust primary and secondary immune responses, characterized by elevated levels of IgG1 and IFN-γ. Recurring IL-2 surges indicated T-cell proliferation and memory formation. No long-lasting increase in pro-inflammatory cytokines was observed, indicating that the vaccine is safe, immunogenic, and less reactogenic. Collectively, the proposed multi-tope subunit vaccine can serve as a potential candidate for human anthrax.
An enhanced transformer model for detecting 1p36 deletion syndrome.
Mercy IA, Shanmugam R, Karunanidhi KM … +1 more , Chidambaram M
Mol Genet Genomics · 2026 Apr · PMID 41917487 · Publisher ↗
The most prevalent terminal chromosomal deletion disorder, chromosome 1p36 deletion syndrome, leads to developmental delays and intellectual disabilities and seizures and heart defects and distinct facial appearance. Tra...
The most prevalent terminal chromosomal deletion disorder, chromosome 1p36 deletion syndrome, leads to developmental delays and intellectual disabilities and seizures and heart defects and distinct facial appearance. Traditional cytogenetic methods, which include karyotyping, face difficulties in early detection of these abnormalities because it require extensive work and substantial time and it can only identify major genetic changes, which makes it unsuitable for detecting minor genomic alterations that occur during infancy. The field of Deep Learning (DL) has made progress toward improving genomic data analysis and disease-related gene identification since its introduction. Hence, the MultiSight Transformer functions as a proposed framework, which processes gene sequences through its multi-head self-attention mechanism to study 1p36 chromosome 1 deletion effects. The model used training and testing procedures on combined datasets which included genomic variations from chromosome 1 and 1p36 deletion regions that contained copy number variations linked to clinical symptoms of skeletal and gastrointestinal and cardiac and chronic kidney disease. The proposed method enables effective gene sequence classification and prediction of the contribution of 1p36 deletion syndrome to major clinical conditions. The experimental results show that the model reaches an accuracy of 0.97 and a precision of 0.90 and a recall of 0.9195 and an F1-score of 0.90 and an area under the curve (AUC) of 0.94 which demonstrates its strong predictive performance. The findings demonstrate that researchers can enhance the detection accuracy and efficiency of chromosome 1p36 deletion syndrome through the combination of transformer-based deep learning models with genomic data analysis. The findings 1p36 deletion detection research should support early diagnosis and clinical decision-making activities.
Comprehensive transcriptomic analysis highlights immune and cell-cycle dysregulation in Diamond-Blackfan Anaemia.
Goel I, Seethy A, Pethusamy K … +4 more , Kumar D, Dhar R, Seth T, Karmakar S
Mol Genet Genomics · 2026 Apr · PMID 41917474 · Publisher ↗
Diamond-Blackfan Anaemia (DBA) is a rare inherited bone marrow failure syndrome conventionally attributed to ribosomal protein gene haploinsufficiency, resulting in impaired ribosome assembly and compromised erythroid pr...
Diamond-Blackfan Anaemia (DBA) is a rare inherited bone marrow failure syndrome conventionally attributed to ribosomal protein gene haploinsufficiency, resulting in impaired ribosome assembly and compromised erythroid precursor viability. However, contemporary research reveals considerably more complex molecular mechanisms driving disease pathology. This study aimed to comprehensively characterise the transcriptional and post-transcriptional regulatory networks contributing to DBA pathogenesis using integrative mRNA–miRNA sequencing of patient-derived bone marrow specimens. Our analysis revealed extensive dysregulation across immune, proliferative, and erythroid differentiation pathways. A coordinated elevation of immune-associated genes, such as TNF, CXCL8, TLR2/4, and CD44, suggests the establishment of a hyperinflammatory bone marrow microenvironment. In contrast, significant downregulation of essential mitotic and epigenetic regulatory factors, particularly CDC25A/C, CDK1/2, and AURKA, reflects disrupted cell cycle dynamics and impaired hematopoietic proliferation. Integrative miRNA–mRNA analysis identified dysregulated miRNAs as critical mediators of these processes. Downregulation of anti-inflammatory miRNAs (e.g., miR-93-5p, miR-143-3p, miR-19a-3p) and upregulation of mitotic suppressor miRNAs (e.g., let-7a, miR-141, miR-31, miR-21) indicate post-transcriptional disruption of immune and cell-cycle balance. Together, these findings reveal a multifaceted regulatory framework in DBA where transcriptional and miRNA-mediated perturbations converge to drive immune activation and impaired erythropoiesis, challenging prevailing ribosomopathy-centric models and highlighting potential molecular targets for therapeutic intervention.
Breast cancer detection via targeted enzymatic methyl sequencing of plasma cell-free DNA.
Su H, Liu Y, Li Y … +7 more , Zheng H, Zhu X, He Z, Liao H, Lin Y, Yang Q, Chen H
Mol Genet Genomics · 2026 Apr · PMID 41917473 · Publisher ↗
Early detection of breast cancer (BC) is crucial for improving patient survival, yet current screening methods such as mammography exhibit limitations in sensitivity, especially in dense breasts. Circulating tumor DNA (c...
Early detection of breast cancer (BC) is crucial for improving patient survival, yet current screening methods such as mammography exhibit limitations in sensitivity, especially in dense breasts. Circulating tumor DNA (ctDNA) methylation has emerged as a promising noninvasive biomarker for cancer detection. This study aimed to identify BC-specific DNA methylation markers from plasma ctDNA and develop a machine learning model for the early and accurate detection of BC. We constructed a BC-specific methylation profile by analyzing differentially methylated positions (DMPs) between 75 paired BC and adjacent normal tissues from TCGA. A total of 396 plasma samples were prospectively collected and divided into training (94 BC, 144 controls), validation (31 BC, 48 controls), and test sets (31 BC, 48 controls). A machine learning model was built using BC-specific DMPs, and its performance was evaluated via ROC analysis. Correlation between methylation levels and conventional biomarkers (CEA, ER) was assessed using Pearson’s coefficient. We identified 107 DMPs from TCGA that exhibited high variance (> 0.001) in ctDNA. A model based on 21 DMPs achieved high accuracy in the training set (AUC = 0.972, sensitivity = 90.48%, specificity = 91.20%), with consistent performance in validation (AUC = 0.886) and test sets (AUC = 0.817). Methylation levels at four sites showed moderate to strong correlation with CEA and ER expression (all p < 0.05). This study demonstrates that a ctDNA methylation-based machine learning model can effectively distinguish BC from non-cancerous conditions with robust sensitivity and specificity, supporting its potential as a complementary tool for early BC detection. These findings underscore the clinical relevance of ctDNA methylation signatures and highlight the promise of integrating liquid biopsy with machine learning in future cancer screening strategies. This study provides a novel methylation-driven framework for BC screening that complements existing biomarkers. Future work should validate these markers in larger multi-center cohorts and explore their utility in monitoring treatment response and recurrence.
Hierarchical evolution of the proteobacterial essential chaperone SecB reveals non-neutral synonymous evolution under extreme purifying selection.
Pal A, Chaki MG
Mol Genet Genomics · 2026 Apr · PMID 41917298 · Publisher ↗
SecB is an essential cytosolic chaperone that mediates post-translational protein export through the bacterial Sec pathway. Although the secB gene evolves under strong purifying selection, its synonymous and higher-order...
SecB is an essential cytosolic chaperone that mediates post-translational protein export through the bacterial Sec pathway. Although the secB gene evolves under strong purifying selection, its synonymous and higher-order sequence evolution have not been examined in a lineage-resolved, integrative framework across the Proteobacteria phylum. A comprehensive comparative analysis of secB codon usage and selection patterns was conducted using broad proteobacterial sampling. Compositional metrics (GC1/GC2/GC3), neutrality plots, effective number of codons–GC3 relationships, relative synonymous codon usage, parity rule 2 bias, dinucleotide observed/expected ratios, codon-pair organization, codon adaptation index (CAI), and codon-based maximum-likelihood models were integrated within a unified analytical framework. Across all classes, ω values were uniformly < 1, confirming pervasive purifying selection at the protein level. Lineage-dependent modulation of selection intensity, with significant relaxation in Alphaproteobacteria and intensification in Gammaproteobacteria was also detected. GC3 exhibited substantial variability, whereas GC1 and GC2 remained tightly constrained, indicating buffering of amino-acid–encoding positions. CAI was significantly associated with the effective number of codons and GC3, supporting lineage-structured synonymous organization consistent with mutation–selection balance. Dinucleotide biases were conserved but varied in magnitude among the proteobacterial classes. These findings demonstrate that secB evolution is characterized by stable protein-level constraints combined with lineage-modulated synonymous and contextual organization. This integrative case analysis refines understanding of essential-gene evolution and generates experimentally testable predictions regarding translational robustness and synonymous constraint across proteobacterial lineages.
Investigating the shared genetic architecture between inflammatory bowel disease and pancreatitis: a genome-wide cross-trait analysis.
Qi HM, Liu TT, Chen JY … +9 more , Wang YH, Mao XT, Wang YC, Jin J, Lin X, Yang J, Zou WB, Kang L, Liao Z
Mol Genet Genomics · 2026 Apr · PMID 41917235 · Publisher ↗
Epidemiological studies suggested comorbidity between inflammatory bowel disease (IBD) and pancreatitis. However, little is known about their shared genetic architecture. Based on genome-wide association studies (GWAS),...
Epidemiological studies suggested comorbidity between inflammatory bowel disease (IBD) and pancreatitis. However, little is known about their shared genetic architecture. Based on genome-wide association studies (GWAS), we utilized Mendelian randomization (MR) method to investigate the causal relationships between IBD (including ulcerative colitis (UC) and Crohn's disease (CD)) and pancreatitis (including acute pancreatitis (AP) and chronic pancreatitis (CP)). Cross-trait meta-analysis was performed to detect pleiotropic loci between them. The heritability enrichment analysis was conducted to detect their shared disease-associated cell types. TWAS (transcriptome-wide association studies) was used to localize pancreatitis-associated genes in the intestine. MR suggested that UC has a positive causal effect on AP in European populations but CP in East Asian populations. Cross-trait meta-analysis identified 71 SNPs between IBD and pancreatitis. Among those, SNPs within the human Major Histocompatibility Complex (MHC) region are strongly enriched in dendritic cell differentiation pathway. Two SNPs outside of the MHC region were rs1260326 and rs117770045. The proxy SNP of rs117770045 was located on a pancreas exocrine-specific enhancer regulating TRPV6 and also associated with the T cell receptor beta genes. Colocalization analysis revealed that rs1265098 (MHC region) was colocalized among IBD, pancreatitis, and gut microbiota Ruminiclostridium 9. Heritability enrichment demonstrated that IBD and pancreatitis are both associated with dendritic cells. TWAS indicated that SPINK5 in the intestine was associated with pancreatitis. Our findings identify genetic risk-sharing loci and convergent immune pathways linking IBD and pancreatitis.
Genomic and functional landscape of antimicrobial peptides and lipopeptides from ginger honey-derived Bacillus subtilis.
Hafeez AB, Szweda P
Mol Genet Genomics · 2026 Apr · PMID 41917207 · Publisher ↗
Honey represents a unique ecological niche that harbors microorganisms with unexplored antimicrobial potential. This study aimed to isolate, characterize, and genomically evaluate Bacillus subtilis strains from multiflor...
Honey represents a unique ecological niche that harbors microorganisms with unexplored antimicrobial potential. This study aimed to isolate, characterize, and genomically evaluate Bacillus subtilis strains from multifloral ginger honey to assess their capacity for producing antimicrobial compounds and peptides. Two strains, Miodo8 and Miodo10, were characterized using phenotypic assays and whole-genome sequencing. Crude extracts obtained from optimized yeast peptone dextrose (YPD) fermentations demonstrated significant antimicrobial activity primarily against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and Listeria monocytogenes. Genome analysis revealed approximately 112 carbohydrate-active enzymes (CAZymes) and multiple biosynthetic gene clusters predicted to encode surfactin, fengycin, plipastatin, bacillibactin, bacillaene, subtilosin A, and pelgipeptin. The genomes also contained mobile genetic elements and prophages, indicating substantial genomic plasticity and potential horizontal gene exchange. Resistome analysis identified intrinsic and acquired determinants associated with resistance to bacitracin and selected aminoglycosides. Proteome-wide screening of antimicrobial peptides (AMPs) with PyAMPA predicted several high-confidence AMPs with canonical cationic and hydrophobic properties. Integrating phenotypic and genomic evidence demonstrates that honey-derived B. subtilis strains represent promising sources of antimicrobial metabolites and peptide candidates. Future studies require focusing on targeted metabolomic validation, structural characterization of predicted AMPs, and comprehensive safety assessment to enable biotechnological and therapeutic applications.
Mitogenomes of three Sinoxylon species and phylogenetic analysis of Bostrichoidea (Coleoptera).
Fan HM, Wang XY, Lin K … +4 more , Lu Q, Tao QH, Li J, Zheng XL
Mol Genet Genomics · 2026 Apr · PMID 41917170 · Publisher ↗
Species of the Bostrichidae family are well-known pests of agriculture, forest, and quarantine. In this study, we employed next-generation sequencing (NGS) to sequence the complete mitochondrial (mt) genomes of three Bos...
Species of the Bostrichidae family are well-known pests of agriculture, forest, and quarantine. In this study, we employed next-generation sequencing (NGS) to sequence the complete mitochondrial (mt) genomes of three Bostrichidae species, i.e., Sinoxylon japonicum, S. pygmaeum, and S. flabrarius. Comparative mitochondrial genome analysis revealed that the mitogenomes of these species ranged from 15,543 to 16,009 bp, containing 37 genes (13 protein-coding genes, 22 transfer RNAs, and two ribosomal RNAs) and a control region. The gene order and content are consistent with the conserved mitogenomic architecture of Coleoptera. Notably, distinct variations were identified in the start codons of two protein-coding genes (COX1 and ND6) and the stop codon of CYTB across the three species. Phylogenetic analyses based on maximum likelihood (ML) and Bayesian inference (BI) methods provide robust support for the monophyly of S. japonicum, S. pygmaeum, and S. flabrarius. Our findings elucidate the genomic characteristics of Bostrichidae and reconstruct the evolutionary relationships within this taxon, offering a foundational reference for future taxonomic and phylogenetic studies in the family.
The role of apoptotic genetic polymorphisms in prostate cancer susceptibility in a North West Spain population.
López-Trigo N, Caeiro B, Pérez-Pérez J … +4 more , Rodríguez-Alonso A, Aguín N, Rodríguez JA, Luis JR
Mol Genet Genomics · 2026 Mar · PMID 41915239 · Publisher ↗
Apoptosis and tumor suppression prevent cell proliferation in response to genomic damage. Polymorphisms in genes involved in these pathways can alter their function, facilitating the onset of cancer. Detecting these poly...
Apoptosis and tumor suppression prevent cell proliferation in response to genomic damage. Polymorphisms in genes involved in these pathways can alter their function, facilitating the onset of cancer. Detecting these polymorphisms would assess the individual risk of developing different types of cancer. Therefore, the main goal of this study is to analyze the association between a set of genetic polymorphisms involved in apoptosis and tumor suppression and the risk of developing prostate cancer (PCa) in a population from Galicia. Accordingly, we performed a case-control study with 291 patients diagnosed with PCa and 249 healthy controls. A total of 19 genetic polymorphisms located in loci BCL2, CASP9, CASP8, CASP7, FAS, FASLG, BIRC5, TP53, MDM2, and MDM4 were genotyped. Their association with PCa was approached from a global perspective and stratified by the body mass index (BMI). Globally, a statistically significant association with PCa was found for polymorphisms rs1052576 (CASP9) and rs990431 (BIRC5), with carriers of the G allele (OR = 2.14; p = 0.002) or the CC genotype (OR = 1.92; p = 0.037), respectively, manifesting greater susceptibility to the disease. The analyses stratified by BMI yielded statistically significant results for polymorphisms rs1052576 (CASP9), rs3740286 (FAS), rs9904341 (BIRC5), rs2279744 (MDM2), rs937283 (MDM2), and rs1380576 (MDM4), with odds ratios between 2.47 and 8.00 in overweight or obese participants. These results indicate the differential effect of allelic variants of six SNPs on prostate cancer risk in patients with overweight or obesity. Further studies in larger cohorts should be conducted to confirm these findings.
Complete mitochondrial genomes of five Geophagus species: insights into phylogenetic relationships and taxonomic paraphyly.
Chen XD, Sun CH, Hu W … +1 more , Lu CH
Mol Genet Genomics · 2026 Mar · PMID 41915218 · Publisher ↗
In the study of Neotropical cichlid diversity, the complex evolutionary history of the Amazon basin makes the species radiation of the genus Geophagus a subject of profound research value. However, traditional morphologi...
In the study of Neotropical cichlid diversity, the complex evolutionary history of the Amazon basin makes the species radiation of the genus Geophagus a subject of profound research value. However, traditional morphological classification remains controversial due to convergent evolution, requiring more robust genomic evidence to define clear taxonomic boundaries. This study conducted a comprehensive analysis of the mitochondrial genomes of five Geophagus species, focusing on gene arrangement characteristics, selective pressure distribution, and molecular phylogenetic relationships. The results demonstrate that the mitogenomes of this group exhibit highly conserved gene orders and are under strong purifying selection, maintaining the functional stability of the oxidative phosphorylation system; phylogenetic analysis confirms that all newly sequenced species belong to the Surinamensis complex and reaffirms the significant paraphyly within Geophagus. Specifically, the close relationship between Geophagus brasiliensis and Mikrogeophagus provides strong support for the taxonomic proposal to segregate the Brasiliensis complex from Geophagus sensu stricto, while also highlighting the taxonomic misplacement of groups such as Astronotus and Heros. This research not only enriches the genetic resource database for Neotropical cichlids but also provides critical genomic evidence for understanding the species radiation and biogeographic evolution of this group within the complex Amazonian river system.
A multistage cost-effective strategy for the molecular diagnosis of unexplained vision loss patients: practice in inherited ocular fundus disease.
Wang J, Li J, Dai L … +6 more , Zhu X, Long Y, Meng X, Li S, Huang X, Guo H
Mol Genet Genomics · 2026 Mar · PMID 41863617 · Publisher ↗
Inherited ocular fundus diseases are the most common causes of blindness with high heterogeneity. We established a tiered strategy for the molecular diagnosis of unexplained vision loss patients. Patients were screened w...
Inherited ocular fundus diseases are the most common causes of blindness with high heterogeneity. We established a tiered strategy for the molecular diagnosis of unexplained vision loss patients. Patients were screened with ophthalmological examinations followed by a tiered genetic diagnosis, including mitochondrial genome sequencing, multigene panel and whole exome sequencing. A total of 146 individuals with unexplained vision loss were enrolled, including 103 individuals with abnormal pattern visual evoked potential and 43 individuals with abnormal optic coherence tomography. Based on our tiered strategy for molecular diagnosis, 33 cases were diagnosed with Leber's hereditary optic neuropathy, with common or very rare mitochondrial variants. Moreover, 22 cases with monogenic disorders were diagnosed with 15 novel and 16 reported mutations. Our study reveals the genetic etiology of unexplained vision loss and expands the genetic variation spectrum. The tiered cost-effective strategy for molecular diagnosis improves genetic detection rates and is expected to be applied to future clinical practice.
Molecular characterization of H. pylori: genetic diversity and vacA s1m1/cagA+ prevalence in Western Algeria.
Ouali AB, Takwa S, Majda DS … +9 more , Amal E, Nabila BH, Bouchra B, Sarah CN, Meriem BB, Samira B, Joanna D, Yahia H, Nouria MD
Mol Genet Genomics · 2026 Mar · PMID 41862702 · Publisher ↗
Clinical outcomes of Helicobacter pylori infection range from chronic gastritis to peptic ulcer disease and gastric cancer. Yet data on strain diversity and clinical outcomes remain scarce in North Africa. This study aim...
Clinical outcomes of Helicobacter pylori infection range from chronic gastritis to peptic ulcer disease and gastric cancer. Yet data on strain diversity and clinical outcomes remain scarce in North Africa. This study aimed to characterise enzymatic and genetic variation among H. pylori isolates from symptomatic patients in western Algeria. From 428 patients, 72 H. pylori strains were isolated and purified; for genotypic analyses, 14 distinct strains were retained based on phenotypic diversity, clinical profiles, and DNA quality/quantity. Nitrate reductase activity, digestion of htrA and ureB, vacA (s1/m1) and cagA sequencing, and PCR-RFLP were performed. H. pylori was detected in 75% of chronic gastritis/gastric ulcer cases and 80% of duodenal ulcer cases. Nitrate reductase activity was high in duodenal-associated isolates (78.6% in bulbitis, 71.9% in bulbar ulcers), suggesting local adaptation. Seven distinct htrA/ureB profiles were identified. The vacA m1, vacA s1, and cagA genotypes were present in 80%, 10%, and 60% of isolates, respectively, with cagA restricted to m1-positive strains. Overall, these findings reveal a distinct enzymatic and genomic pattern of H. pylori in western Algeria, characterised by strain diversity, regional structural variants, and predominance of virulent genotypes. These results highlight the importance of local epidemiological and molecular surveillance and provide a basis for targeted management strategies. Further studies with larger cohorts and whole-genome sequencing are warranted to clarify the clinical impact of these regional H. pylori traits.
Whole-genome sequencing and analysis of Nocardia veterana isolates from keratitis patients.
Radhakrishnan V, Prajna L, Devarajan B … +1 more , Jeyakanthan J
Mol Genet Genomics · 2026 Mar · PMID 41843261 · Publisher ↗
In this study, we conducted whole-genome sequencing and comparative genomic analysis of two Nocardia veterana isolates (JJAEH1 and JJAEH2) from severe corneal ulcers to elucidate their pathogenic potential, antimicrobial...
In this study, we conducted whole-genome sequencing and comparative genomic analysis of two Nocardia veterana isolates (JJAEH1 and JJAEH2) from severe corneal ulcers to elucidate their pathogenic potential, antimicrobial resistance determinants, and genomic features associated with steroid–antibiotic interactions in keratitis. Genome assemblies, annotated with RAST and Prokka, ranged from 7.2 to 7.5 Mb with a GC content of ~ 68.2%. Pan-genome analysis (Panaroo) revealed conserved virulence determinants, including fbpA, fbpB, and fbpC (fibronectin-binding mycolyltransferases), stp (serine/threonine phosphatase), type VII secretion system genes (eccA3, eccB3, espG1), and siderophore-associated iron acquisition genes (mbtA, viuB), indicating roles in host adherence, invasion, and immune evasion. Both isolates also harbored steroid-responsive genes (choD, kstD, kshA/B, fadD, hsaA–D) and two-component systems (senX3–regX3, pdtaS, arlR), linking metabolic adaptation to antibiotic tolerance. JJAEH1 exhibited broad susceptibility, whereas JJAEH2 was multidrug-resistant, carrying multiple efflux pumps (mdtL, mdtH). Heavy metal resistance determinants for mercury (merR) and arsenic (arsA, arsB, arsC, acr3) were present in both isolates, suggesting enhanced survival environments and co-selection of resistance traits. Average nucleotide identity analysis confirmed > 99.99% similarity to N. veterana. In vitro assays demonstrated reduced amikacin susceptibility in the presence of prednisolone, suggesting potential corticosteroid-associated modulation. Overall, we provide genomic and phenotypic insights into virulence, antimicrobial resistance, and steroid responsiveness in ocular N. veterana and identify a modest decrease in amikacin inhibition in the presence of prednisolone in vitro, supporting further functional investigation of steroid–antibiotic interactions in nocardial keratitis.
Genotoxicity of Artificial Sweetener Combinations: An Integrated Drosophila melanogaster SMART Assay and Computational Modeling Approach.
Shankar N, Priyanka B, Janani DV … +6 more , Balaji P, Nivetha K, Vijayalakshmi J, Amshumala B, Selvan GT, Paul SFD
Mol Genet Genomics · 2026 Mar · PMID 41843242 · Publisher ↗
The increasing incorporation of multiple sweeteners into processed foods underscores the need to evaluate their combined genotoxicity. Epidemiological studies associate high intake of sweeteners with elevated risks of ca...
The increasing incorporation of multiple sweeteners into processed foods underscores the need to evaluate their combined genotoxicity. Epidemiological studies associate high intake of sweeteners with elevated risks of cardiovascular, cerebrovascular, and metabolic disorders, yet the genetic consequences of their combined consumption remain largely unexplored, highlighting the necessity of assessing their interactive genotoxic risks. This study therefore aimed to investigate the genotoxic and developmental toxicity of the widely used artificial sweeteners, acesulfame potassium (ACE K), aspartame (ASP), and stevia (S), individually and in relevant binary and ternary combinations (ACE K + ASP, ACE K + S, ASP + S, and ACE K + ASP + S) at 10, 30, and 50 mM. Genotoxicity was assessed using the Drosophila SMART assay, complemented by molecular docking and 100-ns dynamic simulations with the developmental regulators Engrailed (En) and Hedgehog (Hh), and toxicity prediction via ProTox-3.0. All sweeteners produced dose-dependent genotoxic effects, with ACE K–containing mixtures showing higher spot frequencies at 10 mM, while ASP + S exhibited stronger genotoxicity at 30 and 50 mM; the triple combination consistently mirrored the 10 mM trend. In silico analyses revealed higher binding affinities of ACE K toward En and Hh, aligning with in vivo observations. Collectively, these findings demonstrate concentration-dependent genotoxic risks associated with sweetener mixtures and indicate that formulations incorporating stevia may offer relatively safer alternatives for food applications.
Phosphorylation-dependent regulation of Eleven Lysine Rich Leukemia (ELL) uncovered by quantitative global phosphoproteomic analysis.
Kammarambath SR, Dcunha L, Fahma A … +5 more , Subair S, Gopalakrishnan AP, Shivamurthy PB, Madar IH, Raju R
Mol Genet Genomics · 2026 Mar · PMID 41843233 · Publisher ↗
Transcription elongation represents a key regulatory checkpoint that controls RNA polymerase II processivity and gene expression output. The human Eleven-nineteen lysine-rich leukemia (ELL) protein functions as a conserv...
Transcription elongation represents a key regulatory checkpoint that controls RNA polymerase II processivity and gene expression output. The human Eleven-nineteen lysine-rich leukemia (ELL) protein functions as a conserved RNA polymerase II elongation factor that enhances productive transcription by suppressing transient polymerase pausing and uniquely serves as the only Super Elongation Complex component capable of directly stimulating transcription elongation in vitro; however, the mechanisms governing its regulation through phosphorylation remain poorly defined. Here, we systematically curated and analysed the publicly available global phosphoproteomics datasets to characterise the phosphorylation landscape of ELL. Serine 309 (S309) emerged as the most frequently detected and consistently regulated phosphosite across multiple datasets. Phosphosite-specific co-regulation analysis identified coordinated phosphorylation patterns across ELL (S309) and proteins involved in transcriptional regulation and DDR, including PBRM1 (S648), where phosphorylation at S648 is associated with Double Strand Break induced transcriptional silencing. Additionally, ATM (S1885) and TP53 (S392), the core proteins associated with DNA damage response and previously identified binary interactors of ELL, show consistent co-regulation with (S309), along with several phosphosites reported in cancer-related datasets. Together, our findings explore the phosphorylation landscape of ELL by identifying S309 as its predominant phosphosite and establish a framework for future studies to define how the ELL phosphorylation contributes to transcriptional regulation, DNA damage response pathways and tumor-associated processes.
Discovery of novel circular RNAs of the apoptosis-related BAX gene in breast cancer, by combining nanopore and next-generation sequencing.
Katsaraki K, Vatsellas G, Kontos CK
Mol Genet Genomics · 2026 Mar · PMID 41843205 · Full text
Circular RNAs (circRNAs) have emerged as significant regulators of cancer biology. However, the characterization and the regulatory potential of circRNAs deriving from key apoptotic genes remain poorly understood in brea...
Circular RNAs (circRNAs) have emerged as significant regulators of cancer biology. However, the characterization and the regulatory potential of circRNAs deriving from key apoptotic genes remain poorly understood in breast cancer. We aimed to comprehensively characterize circRNAs originating from the pro-apoptotic BAX gene and predict their regulatory potential in BC signaling. Targeted amplification of circular BAX transcripts was conducted in eleven cancerous and one non-cancerous breast cell lines, followed by third-generation (nanopore) and next-generation sequencing. Finally, extensive bioinformatic analysis was conducted. Therefore, we identified 106 circRNAs, 82 of which were novel. These circRNAs exhibited diverse biogenesis features, including exon skipping, intron retention, and rare inclusion of exon 5. Expression profiling revealed subtype-specific patterns, with several circRNAs being detected only in triple-negative or luminal BC subtypes, while circ-BAX-55b was detected exclusively in the non-cancerous cell line. Many circRNAs were predicted to sponge miRNAs such as miR-152-5p, miR-4802-5p, and miR-3619-5p, potentially modulating signaling pathways including MAPK, PI3K/AKT, and NFκB. Extensive sponging of miR-152-5p, which targets BAX mRNA, suggests a feedback mechanism modulating apoptosis. Several circRNAs also contain binding sites for RNA-binding proteins (RBPs) such as RBM6 and HNRNPF, possibly dictating RNA fate. Overlapping miRNA and RBP-binding sites imply complex competitive or cooperative interactions. Additionally, multiple circRNAs, such as circ-BAX-6c, displayed translation-related features. In conclusion, these findings reveal a novel repertoire of BAX circRNAs with putative roles in BC signaling and apoptosis regulation. Moreover, they constitute a valuable resource for functional studies as well as potential biomarkers or therapeutic targets in breastcancer.
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