BMC Medical Genomics[JOURNAL]
Sun
200 papers
Elucidating the mechanisms of bisphenols-induced male spermatogenesis disorder via network toxicology, molecular docking and bioinformatics.
Tian M, Wu Y, Tian M … +2 more , Zhu L, Li G
BMC Med Genomics · 2026 Jan · PMID 41593631 · Full text
Bisphenols (BPs), are extensively utilized in various manufacturing industries, leading to increased human exposure and detection in diverse environments, posing potential risks to reproductive health. This study endeavo...
Bisphenols (BPs), are extensively utilized in various manufacturing industries, leading to increased human exposure and detection in diverse environments, posing potential risks to reproductive health. This study endeavors to investigate whether seven BP compounds result in male spermatogenesis disorder (SD) and explore the underlying molecular mechanisms involved. Network toxicology was integrated with molecular docking technology and bioinformatics data to systematically elucidate the roles, underlying targets and pathological mechanisms of each BP compound in the SD process. Network toxicology analysis revealed that all seven BPs induced SD through similar mechanisms. The protein-protein interaction (PPI) network identified key targets implicated in SD induced by each BP, while enrichment analysis highlighted that BPs primarily affected SD through hormone-dependent pathways, cell proliferation, apoptosis, and prostate cancer pathways. Molecular docking further confirmed the pivotal role of these targets in BPs-induced SD. Additionally, analysis of Gene Expression Omnibus (GEO) data demonstrated significant differential expression of these genes in the SD patients compared to normal controls. These results underscored the crucial effects of genes such as BCL2, PARP1, AKT1, EGFR, ESR1, ESR2, HIF1A, HSP90AA1 and GSK3B in the development of SD. Collectively, these findings indicated that BPs exposure could contribute to the onset of SD as an environmental trigger, while offering theoretical insights into the molecular mechanisms associated with BPs-elicited SD.
Discovery of new MicroRNAs and their mRNA targets in patients with acute ischemic stroke.
Eyileten C, Wicik Z, Gasecka A … +8 more , Ahmadova S, Di Martino MT, Mucha J, Mirowska-Guzel D, De Rosa S, Kurkowska-Jastrzebska I, Czlonkowska A, Postula M
BMC Med Genomics · 2026 Jan · PMID 41580787 · Full text
BACKGROUND: In this study, we applied microarray, bioinformatics, and qRT-PCR techniques to identify miRNAs and their target genes in plasma obtained from acute ischemic stroke patients and matching controls. METHODS: Mi...
BACKGROUND: In this study, we applied microarray, bioinformatics, and qRT-PCR techniques to identify miRNAs and their target genes in plasma obtained from acute ischemic stroke patients and matching controls. METHODS: Microarray analyses were performed with 24-h acute ischemic stroke vs. healthy individuals and CV-risk factors matched control group plasma samples. Statistical analysis of gene expression was performed using TAC and R, with a focus on robust methods suitable for the small sample size, and miRNA target prediction was conducted using a previously established in-house wizbionet R package. Top non-coding regulators of ischemia (miR-18a-5p, miR-4467, miR-199a-5p and miR-3135b) and their predicted target genes (ANKRD12, HIF1A, GNAI2, GRIN1) were detected via qRT-PCR. RESULTS: 146 upregulated and 258 downregulated differentially expressed RNAs were detected by microarray analysis. Using the multiMiR R package for target prediction, 67 upregulated and 125 downregulated mRNAs were mapped. Functional enrichment analysis revealed that upregulated miRNAs were associated with pathways like BDNF and IL-2 signaling, while downregulated miRNAs were linked to neurodevelopmental and NGF pathways. MiR-18a-5p and miR-199a-5p were significantly elevated in stroke patients at both day 1 and day 7 compared to healthy individuals and CV-matched controls (p < 0.05 for all). miR-4467 was lower at day 1 versus both controls (p < 0.05) but markedly increased by day 7 (p < 0.001), remaining higher than in controls (p < 0.05). miR-3135b showed persistent downregulation at both time points (p < 0.05). ROC analysis confirmed diagnostic value for all miRNAs, with the highest AUC for miR-199a-5p (0.89, 95% CI: 0.81–0.97, p < 0.001), followed by miR-3135b (0.88), miR-4467 (0.80), and miR-18a-5p (0.73; p = 0.002). For potential role in dynamic post-stroke molecular responses perspective, utility, miR-4467 increased significantly during hospitalization (p < 0.001). GNAI2 mRNA was significantly elevated at day 1 versus controls (p < 0.05). ANKRD12 was consistently lower at both day 1 and day 7 compared to controls (p < 0.05). GRIN1 was reduced at admission (p = 0.006) but normalized by day 7 (p > 0.05). ROC analysis showed diagnostic significance for ANKRD12, GNAI2, and GRIN1 (AUC = 0.683, 0.698, 0.693). CONCLUSION: Our integrated miRNA/mRNA analysis identified distinct molecular signatures in acute ischemic stroke, with 146 upregulated and 258 downregulated RNAs, implicating key neuroinflammatory and neuroprotective pathways, including BDNF, IL-2, and NGF signaling. Among the validated candidates, miR-199a-5p, miR-3135b, miR-4467, and miR-18a-5p demonstrated diagnostic potential, while miR-4467, together with GNAI2 and HIF1A, showed post-stroke dynamic relevance, reflecting early transcriptomic adaptations following ischemic injury.
Analysis of LRP1 gene mutation in developmental dysplasia of the hip: a case series.
Cheng T, Zhang W, Cheng H
BMC Med Genomics · 2026 Jan · PMID 41580695 · Full text
Developmental dysplasia of the hip (DDH) is a multifactorial disorder that affects 0.56-3.8% of newborns worldwide. Recent research has identified several candidate genes potentially involved in DDH pathogenesis, with LR...
Developmental dysplasia of the hip (DDH) is a multifactorial disorder that affects 0.56-3.8% of newborns worldwide. Recent research has identified several candidate genes potentially involved in DDH pathogenesis, with LRP1 investigated as a candidate gene due to its regulatory role in cartilage development. This study presents a genetic analysis of two female DDH patients (17 and 26 years old) diagnosed through radiographic examination. Genomic DNA was extracted from peripheral blood samples of the two female patients with DDH. We performed targeted genetic analysis of LRP1 exons 6, 32, 40, and 74, which have been previously implicated in DDH pathogenesis. DNA was extracted from peripheral blood samples, amplified via polymerase chain reaction (PCR), and analyzed using Sanger sequencing. Despite clear clinical DDH diagnoses, neither patient carried mutations in the examined LRP1 exons and displayed only wild-type sequences. These findings indicate that no pathogenic LRP1 variants were detected in these two DDH patients. This case report provides preliminary descriptive data on LRP1 exonic regions in DDH. The absence of detected variants in these specific loci suggests that future investigations should utilize high-throughput sequencing strategies in larger cohorts to more comprehensively explore the genetic basis of the disorder.
The heterozygous c.2241G>C variation in FGFR2 may cause autosomal dominant Kirner's deformity in a Chinese Han pedigree.
Ma M, Li H, Wu X … +3 more , Guo K, Chen S, Zhao S
BMC Med Genomics · 2026 Jan · PMID 41572294 · Full text
OBJECTIVE: Kirner’s deformity is a progressive deformity of the distal phalange of the little finger in a volar and radial direction. The FGFR2 gene plays a critical role in skeletal development and growth, with abnormal...
OBJECTIVE: Kirner’s deformity is a progressive deformity of the distal phalange of the little finger in a volar and radial direction. The FGFR2 gene plays a critical role in skeletal development and growth, with abnormal expression and activation of FGFR2 being associated with skeletal abnormalities. This study presents a family with Kirner’s deformity involving multiple patients. METHODS: Whole-exome sequencing was performed. SIFT, MutationTaster and Gerp+, while Clustal Omega was used for conservative analysis. In addition, I-TASSER was used to predict the 3D protein model. PyMOL was used for comparative analysis between abnormal and normal proteins. RESULTS: Sequencing data revealed that the proband, affected father, and son all carried a heterozygous missense variation c.2241G>C (p. Q747H) in FGFR2. Bioinformatic analysis suggested the potential pathogenicity of this variation. While the spatial structure of the protein variant was not significantly altered, the FGFR2 variation (p.Q747H) disrupted a hydrogen bond between Gln 747 and Ser 746, leading to significant changes in ligand and enzyme binding active sites. This structural alteration is predicted to impair binding to the Mg2+ ligand, thereby potentially disrupting downstream signaling pathways. This proposed mechanism provides a plausible explanation for the observed abnormal expression of bone development genes. CONCLUSION: These findings are consistent with a model in which the novel FGFR2 variant could impair protein function, a hypothesis that warrants further investigation. Our study identifies a new variant in the variational spectrum of Kirner’s deformity and expands the variational spectrum of the FGFR2 gene.
Clinical significance and impact on the cell behaviors of miR-758-5p/MMP-2 axis in ovarian cancer cells.
Gao Q, Li Y
BMC Med Genomics · 2026 Jan · PMID 41555418 · Full text
BACKGROUND: Ovarian cancer (OC) is one of the most lethal gynecological malignant tumors globally. OBJECTIVES: The objective of this research was to investigate the clinical significance and biological roles of the micro...
BACKGROUND: Ovarian cancer (OC) is one of the most lethal gynecological malignant tumors globally. OBJECTIVES: The objective of this research was to investigate the clinical significance and biological roles of the microRNA (miR)-758-5p/MMP-2 axis in OC. MATERIALS AND METHODS: This study recruited 150 epithelial ovarian cancer (EOC) patients. The Kaplan-Meier survival analysis examined the association between miR-758-5p levels and patient survival outcomes. Cox regression analysis identified critical factors influencing patient mortality risk. RT-qPCR quantified the expression of miR-758-5p and matrix metalloproteinase-2 (MMP-2). Cell proliferation was assessed by the CCK-8 assay, while cell migration and invasion were evaluated by the Transwell assay. Flow cytometry was utilized to measure the cell’s apoptosis rate. The dual-luciferase reporter assay confirmed the targeted regulatory relationship. RESULTS: MiR-758-5p was reduced in EOC patients (P < 0.0001). The expression of miR-758-5p (HR = 0.272, 95%CI = 0.131–0.561, P < 0.001), lymph node metastasis (HR = 1.951, 95%CI = 1.085–3.506, P = 0.026), and tumor stage (HR = 2.125, 95%CI = 1.108–4.078, P = 0.023) were critical factors influencing patient mortality risk. Specifically, high expression of miR-758-5p was significantly correlated with improved patient survival outcomes. Moreover, elevated levels of miR-758-5p effectively suppress the proliferation, migration, and invasion of OC cells while promoting apoptosis (P < 0.0001). The study further revealed that miR-758-5p directly negatively regulated MMP-2 expression. Overexpression of MMP-2 partially counteracted the effects of the miR-758-5p mimic on cell behavior (P < 0.0001). CONCLUSION: The miR-758-5p/MMP-2 axis may play a critical role in the OC progression.
TMEM201 regulates tumor malignancy and immune microenvironment in lower-grade glioma.
Shen F, Guo S
BMC Med Genomics · 2026 Jan · PMID 41555358 · Full text
BACKGROUND: TMEM201, a nuclear membrane protein, is thought to play an important role in tumor progression, but its involvement in lower-grade glioma (LGG) remains unclear. This study aims to investigate the impact of TM...
BACKGROUND: TMEM201, a nuclear membrane protein, is thought to play an important role in tumor progression, but its involvement in lower-grade glioma (LGG) remains unclear. This study aims to investigate the impact of TMEM201 expression on the prognosis, clinical characteristics, and biological behaviors of LGG. METHODS: RNA expression data from the TCGA, CGGA, and GEO databases were analyzed to explore the correlation between TMEM201 expression and clinical features of LGG. In vitro and in vivo experiments were conducted to assess the effects of TMEM201 knockdown on cell proliferation, migration, and tumorigenic potential. DNA methylation sites associated with TMEM201 were analyzed, and KEGG pathway enrichment was performed to identify the molecular mechanisms underlying TMEM201’s role in LGG. RESULTS: The analysis showed that high TMEM201 expression was associated with poor prognosis, higher WHO grade, and tumor recurrence in LGG patients. Survival analysis confirmed that elevated TMEM201 levels correlated with shorter survival. Knockdown of TMEM201 in SHG44 cells led to significant inhibition of cell proliferation, migration, and tumor formation in vivo. DNA methylation analysis identified key sites regulating TMEM201 expression, and KEGG analysis revealed pathways such as HIF-1, VEGF, and Notch that contribute to tumor progression. CONCLUSION: TMEM201 acts as a potential oncogene in LGG by influencing key cellular signaling pathways and tumor behaviors. It is an independent risk factor for poor prognosis and may serve as a promising biomarker for diagnosis and personalized treatment. This study provides valuable insights into the molecular mechanisms of LGG progression and highlights TMEM201 as a therapeutic target.
First published report of the FLCN c.1222 C > T (p.Gln408Ter) variant in a Chinese family with Birt-Hogg-Dubé syndrome and literature review.
Huang S, Chen Z, Zhang L … +2 more , Ding X, Miu K
BMC Med Genomics · 2026 Jan · PMID 41549261 · Full text
BACKGROUND: Birt–Hogg–Dubé syndrome (BHDS) is a rare inherited disorder defined by skin lesions, pulmonary cysts, spontaneous pneumothorax, and renal neoplasia. Mutations in the FLCN gene are known causes, and identifyin...
BACKGROUND: Birt–Hogg–Dubé syndrome (BHDS) is a rare inherited disorder defined by skin lesions, pulmonary cysts, spontaneous pneumothorax, and renal neoplasia. Mutations in the FLCN gene are known causes, and identifying specific variants in different populations is essential for elucidating genotype-phenotype correlations. METHODS: We investigated a Chinese family with suspected BHDS. The proband was admitted to the Affiliated Cangnan Hospital of Wenzhou Medical University in October 2023. Comprehensive clinical evaluations and imaging studies were performed. Peripheral blood samples were collected from the proband and available family members after obtaining informed consent. Whole-exome sequencing (WES) was conducted to identify potential variants in the FLCN gene. Candidate variants were subsequently validated by Sanger sequencing and analyzed for co-segregation within the family. Pathogenicity was assessed in accordance with the American College of Medical Genetics and Genomics (ACMG) guidelines. To illustrate the structural impact of the variant, a three-dimensional model of the folliculin protein was generated using SWISS-MODEL and visualized with PyMOL. RESULTS: The proband exhibited bilateral pulmonary cysts, a small left-sided pneumothorax, a left renal mass, and possible cutaneous manifestations. Family evaluation identified pulmonary cysts in multiple children, with pneumothorax in some and a history of lobectomy in two. Genetic testing revealed a heterozygous FLCN nonsense variant, NM_144997.7:c.1222 C > T (p.Gln408Ter), in the proband and one son, while her husband and asymptomatic daughter were noncarriers. This variant meets ACMG criteria for pathogenicity. Structural modeling demonstrated that the premature stop codon truncates folliculin at residue 408, eliminating most of the C-terminal domain and severely compromising protein integrity. Although this variant is listed in ClinVar (RCV001953597) as pathogenic, detailed phenotypic documentation has been limited, and it has not been previously described in Chinese BHDS patients. CONCLUSIONS: We describe, to our knowledge, the first report of the FLCN NM_144997.7:c.1222 C > T (p.Gln408Ter) variant in a Chinese BHDS family and characterize its associated clinical phenotype. These findings extend the known FLCN variant spectrum, enhance population-specific genotype–phenotype understanding, and offer meaningful evidence for clinical diagnosis and genetic counseling.
Decoding the diabetes-pancreatic adenocarcinoma connection: the critical role of PILRA in intermediate monocyte activity.
Lv C, Liu Z, Zhang S … +3 more , Yang S, Wang G, Xiao J
BMC Med Genomics · 2026 Jan · PMID 41546015 · Full text
Diabetes is a well-known risk factor for pancreatic adenocarcinoma (PAAD), yet the underlying molecular mechanisms remain unclear. This study employs single-cell sequencing to analyze gene expression patterns and uses Me...
Diabetes is a well-known risk factor for pancreatic adenocarcinoma (PAAD), yet the underlying molecular mechanisms remain unclear. This study employs single-cell sequencing to analyze gene expression patterns and uses Mendelian randomization to assess the association between genetic variations in specific genes and the risk of PAAD. Our findings reveal a significant reduction in the proportion of monocytes in patients with both diabetes and PAAD. Monocytes play a crucial role in the progression of both diseases. Notably, we identified an increase in intermediate monocytes (CD14 + + CD16+) in both conditions. These cells exhibit significant activation of the LGALS9-CD45 receptor, increased metabolic activity, and enhanced involvement in disease pathways. We demonstrate that intermediate monocytes are key cellular players in the link between diabetes and PAAD. Using dual-sample Mendelian randomization, we identified genetic variations in PILRA, a highly variable gene in intermediate monocytes, as a risk factor for PAAD. PILRA + intermediate monocytes show higher metabolic activity and stronger immune cell communication compared to PILRA- cells, suggesting an important role in tumor microenvironment regulation and immune cell activation inhibition. This biological function is associated with cytokine-mediated signaling, focal adhesion, and NOD-like receptor signaling pathways. RT-qPCR validation of PBMC samples indicates a statistically significant, progressive increase in PILRA expression in patients with PAAD, diabetes, and those with both conditions. In summary, this study uncovers the critical role of intermediate monocytes in diabetes-induced PAAD and proposes PILRA as a potential therapeutic target.
Benchmarking Illumina and Oxford Nanopore Technologies (ONT) sequencing platforms for whole genome sequencing of bacterial genomes and use in clinical microbiology.
Purushothaman S, Roloff T, Egli A … +1 more , Seth-Smith HM
BMC Med Genomics · 2026 Jan · PMID 41540427 · Full text
BACKGROUND: In microbial diagnostics, whole-genome sequencing (WGS) is used to address key questions such as species identification, presence of antimicrobial resistance genes (ARGs), virulence genes, and outbreak detect...
BACKGROUND: In microbial diagnostics, whole-genome sequencing (WGS) is used to address key questions such as species identification, presence of antimicrobial resistance genes (ARGs), virulence genes, and outbreak detection. The choice of sequencing technology is crucial to ensure high-quality data, cost-effectiveness, and efficient reporting times. We aimed to compare Illumina (short-read) and ONT (long-read) sequencing methods for WGS on different bacterial species for base accuracy and reliable taxonomic and ARG identification. MATERIALS AND METHODS: We used clinical isolates of ESKAPE pathogens (n = 12) and ATCC strains (n = 8) of varying %G + C. Illumina sequencing was performed on MiSeq (PE150) and ONT sequencing using GridION with R9.4.1 and R10.4.1 flowcells. Base-calling was performed using Guppy, Dorado, and Rerio software. We performed de novo assembly with Unicycler for Illumina and Flye for ONT, and two types of hybrid assemblies, Unicycler and Polypolish. We annotated genomes with Bakta and assessed the quality (QUAST, GTDB-Tk). We identified ARGs (AMRFinderPlus) and plasmids (MOB-suite). We mapped reads and called SNPs using Minimap2, Pilon, vcftools, and Snippy (Illumina). Core genome MLST analysis was conducted with Ridom Seqsphere+. RESULTS: We observed that Illumina sequencing provided consistently high-quality reads (median Q-score 35), whereas for ONT R10.4.1, SUP model showed higher median quality (median Q-score 15.3) compared to R9.4.1 (median Q-score 13.9, SUP model). We observed that Illumina-based assemblies generated fewer genes annotated as disrupted; for ONT assemblies, the base-caller affects assembly annotation accuracy, with High accuracy (HAC) and Super accuracy (SUP) base-calling models perform better than FAST model. ONT assemblies resolved rRNA operons better than Illumina assemblies. Sequencing errors were determined by SNP calling, and varied widely by species, with ONT often generating more sequencing errors compared to Illumina. Hybrid assemblies combine accuracy and completeness effectively. Taxonomic identification and ARG detection were reliable across all methods. CONCLUSION: Combining Illumina and ONT technologies yielded optimal bacterial genome sequencing results, leveraging the high accuracy of short reads and improved contiguity of ONT long reads. The HAC and SUP ONT models with Dorado notably enhance genome assembly annotation and resolution of complex regions, although species-specific issues, likely due to repeat regions and base modifications, remain challenging even in SUP model with Dorado. Hybrid approaches currently offer the most comprehensive and accurate genome assemblies for clinical microbiology. For reliable cgMLST even using the most recent ONT methods, resolution must be assessed on a species-by-species basis.
North Carolina primary care provider perspectives on expanded genomic screening in children.
Branch EK, Roberts MC, Waltz M … +8 more , deJong NA, Milko LV, Foreman AK, Foss K, Giric S, Boynton MH, Berg JS, Schilling S
BMC Med Genomics · 2026 Jan · PMID 41540409 · Full text
BACKGROUND: Expanding pediatric genomic screening beyond current newborn screening presents both opportunities and challenges to primary care providers. We are developing a novel paradigm called Age-Based Genomic Screeni...
BACKGROUND: Expanding pediatric genomic screening beyond current newborn screening presents both opportunities and challenges to primary care providers. We are developing a novel paradigm called Age-Based Genomic Screening (ABGS), which will incorporate targeted genomic sequencing for select, highly actionable genetic conditions into routine care at relevant time-points throughout childhood. METHODS: We disseminated an electronic survey to family medicine and pediatric primary care clinicians in North Carolina to identify potential ABGS implementation determinants and strategies to address them. Survey items were modeled on constructs previously identified as important to genomic medicine and assessed perceived utility, benefits, barriers, and facilitators of implementing targeted genomic screening in pediatric primary care. Data were analyzed using descriptive statistics and content analysis, as appropriate. RESULTS: A total of 93 individuals completed the survey. Over 85% of respondents agreed that genomic screening was important and impactful in their patient care but about 30% lacked confidence in their ability to implement it in their practice. The most cited benefits of the ABGS program were related to readiness for implementation and the evidence, strength, and quality of the intervention. The most concerning barriers included cost for patients and available resources, with 87% and 75% of respondents having extreme or moderate concern for these barriers, respectively. CONCLUSIONS: Our findings have implications both for the design of the ABGS pilot program and directions for future research in genomic implementation. In particular, the blueprint for the pilot program must include specific plans for ensuring primary care providers have the time and resources available for shared decision making with their patients about engaging in genomic screening. CLINICAL TRIAL REGISTRY: Clinical trial number: not applicable
Single-cell sequencing-based analysis of CD4 + T-cell and B-cell heterogeneity in patients with lupus nephritis.
Cheng LL, Tang ZF, Li M … +3 more , Chen JJ, Shang SS, Huang CB
BMC Med Genomics · 2026 Jan · PMID 41540405 · Full text
OBJECTIVE: Systemic lupus erythematosus (SLE) is a prevalent chronic autoimmune disorder that can affect various organs and tissues throughout the body, with the kidneys being the most commonly involved, often leading to...
OBJECTIVE: Systemic lupus erythematosus (SLE) is a prevalent chronic autoimmune disorder that can affect various organs and tissues throughout the body, with the kidneys being the most commonly involved, often leading to lupus nephritis (LN). Immune cells, notably CD4 + T cells and B cells, are crucial in the development of SLE. Investigating the heterogeneity of CD4 + T cells and B cells in patients with LN using single-cell technology is of significant importance. METHODS: With informed consent, this study explored the profiles of LN CD4 + T and B cells through single-cell transcriptome sequencing of peripheral blood mononuclear cell (PBMC) samples from three LN patients and three Normal Control(NC). Initially, the cells were segregated into immune cell clusters using cellular lineage-based clustering. Subsequently, CD4 + T and B cells were further categorized, and marker genes influencing LN CD4 + T and B cells were identified using differential analysis and publicly available data. The differentially expressed genes in LN patients were then functionally analyzed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) enrichment analyses. Additionally, cell communication analysis was conducted to examine the primary secretory pathways of immune cells, along with the profiles of numerous specific cell subtypes and ligand-receptor pairs. RESULTS: In this study, we successfully mapped PBMC cells through single-cell sequencing of LN, and 69,069 single cells were clustered into 8 immune cell subpopulations using dimensionality reduction. These subpopulations included Neutrophils, NK cells, CD4 + T cells, CD8 + T cells, B cells, Macrophages, and Dendritic cells. Further subdivision of CD4 + T cells and B cells into subpopulations revealed that CD4 + T cells were divided into seven subpopulations, namely Tn, Th2, Th1, Tem, Treg, Tm, and Th17 subpopulations. The marker genes of each subpopulation mainly included CCR7, SELL, LEF1, TCF7, MALAT1, GZMA, IL7R, TGFB1, CCL5, KLRB1, CD4, and STAT3, among others. B cells were further divided into six subpopulations, namely Fo-B, AIM2 + Bcell, TCF4 + Bcell, Unknown (to be defined), B1-ATMBCs, and Trans-Bcell, with marker genes including TCL1A, IGHD, FCER2, AIM2, IGHA1, and JCHAIN.The GO enrichment analysis of each cell subpopulation focused on the regulation of lymphocyte activation, cellular response to type I interferon, and other processes. The KEGG analysis concentrated on the chemokine signaling pathway and cytokine-cytokine receptor interactions. Cell communication analysis revealed that the ligand-receptor pairs of the eight immune cell subpopulations were distributed across 11 signaling pathways, including ANNEXIN, BAFF, BAG, CCL, CXCL, FLT3, GALECTIN, GRN, IL16, MIF, and RESISTIN pathways. Three of these important ligand-receptor pairs were CD74 + CXCR4, CD74 + CD44, and IL16-CD4.Communication analysis of T and B cells revealed two-by-two interactions between CD4 + T, CD8 + T, and B cells, with the strongest interaction strengths observed between CD4 + T and CD8 + T, and between CD8 + T and B cells. CellChat identified 22 ligand-receptor pairs in 3 cell subsets, distributed across 12 signaling pathways, including ADGRE5, CD22, CD45, CD99, CLEC, ICAM, ITGB2, LCK, MHC-I, MIF, SELPG, and SEMA4 pathways. The most prominent signaling pathways were MHC-I, MIF, and CLEC, with major ligand-receptor pairs being HLA-B - CD8B, MIF - (CD74 + CXCR4), and CLEC2C - KLRB1. CONCLUSION: In summary, we clarified the immune cell profile of PBMCs from LN patients, with a focus on characterizing the heterogeneity of CD4 + T cells and B cells. We identified several specific cellular subtypes and ligand-receptor pairs, which suggest potential therapeutic targets for lupus erythematosus.
Cytogenetics in the genomics era: why karyotyping still matters.
Chebly A
BMC Med Genomics · 2026 Jan · PMID 41535841 · Full text
Despite advances in next-generation sequencing and optical genome mapping, conventional cytogenetics, particularly karyotyping, remain indispensable in modern medical genomics. It continues to provide critical diagnostic...
Despite advances in next-generation sequencing and optical genome mapping, conventional cytogenetics, particularly karyotyping, remain indispensable in modern medical genomics. It continues to provide critical diagnostic value in constitutional and hematological disorders, offering cost-effective detection of chromosomal abnormalities and complementing molecular tools, especially in complex cases and resource-limited settings.
Seminal long non-coding RNAs as prognostic non-invasive biomarkers in non-obstructive azoospermia.
Abdallah HY, Hosny N, Ahmed N … +1 more , Ismail EA
BMC Med Genomics · 2026 Jan · PMID 41530831 · Full text
BACKGROUND: Non-obstructive azoospermia (NOA) is a multifactorial disease with high genetic and phenotypic heterogeneity. The main NOA pathogenesis is still unknown, which makes it challenging to find precise biomarkers...
BACKGROUND: Non-obstructive azoospermia (NOA) is a multifactorial disease with high genetic and phenotypic heterogeneity. The main NOA pathogenesis is still unknown, which makes it challenging to find precise biomarkers for this condition. Long non-coding RNAs (lncRNAs) have been linked to many processes related to male reproductive health, such as spermatogenesis and sperm maturation. So, this study investigated a panel of seven lncRNAs from the seminal plasma of patients with NOA, which has the potential to be used as noninvasive prognostic biomarkers in NOA. METHODS: The differential gene expression for seven seminal lncRNAs was assessed for 106 male subjects—53 patients with NOA and 53 normal male volunteers using qRT-PCR —followed by correlational and bioinformatics analysis for the study results. RESULTS: Six lncRNAs - CDKN2B-AS1, H19, Linc-ROR, MALAT1, MIAT, and TUG1 - showed significant differential expression between NOA and normal males. Regarding the potency of this panel as NOA diagnostic biomarkers, TUG1 (0.94), CDKN2B-AS1 (0.90), H19 (0.90), Linc-ROR (0.87), and MALAT1 (0.80) showed to be excellent biomarkers. On the other side, the potency of this panel as prognostic biomarkers for TESE outcome prediction showed that Linc-ROR, TUG1, CDKN2B-AS1, and H19 were very good biomarkers. CONCLUSION: LncRNAs hold the potential to improve the current knowledge about male infertility pathogenesis by highlighting their role in the pathophysiology of NOA and their potential clinical utility in its diagnosis and prognosis.
CDK9 Inhibition with enitociclib reveals influence on HERV and LINE RNA abundances in whole blood, T-, and B-Cell lines.
Dopkins N, Michael S, Liotta N … +2 more , Roldan FS, Nixon DF
BMC Med Genomics · 2026 Jan · PMID 41530765 · Full text
Endogenous retroelements (EREs) comprise a significant portion of the human genome and there is a growing appreciation for their roles in eukaryotic physiology. In lymphomas, EREs may contribute to proto-oncogene express...
Endogenous retroelements (EREs) comprise a significant portion of the human genome and there is a growing appreciation for their roles in eukaryotic physiology. In lymphomas, EREs may contribute to proto-oncogene expression and their RNA expression can be useful to better define lymphoma sub-classifications. Several emerging cancer therapies suggest that targeting ERE expression may even be beneficial to patient outcome. In this study, we investigated how enitociclib, a CDK9 inhibitor, impacted ERE expression over time. Using in vitro models of T and B lymphocytes, we found that CDK9 inhibition upregulates transcriptional abundances of ERE RNAs in a cell type- and temporal- specific manner. Leveraging this data with data collected from a retrospective cohort of patients with lymphomas receiving enitociclib, we found that ERE activity was initially downregulated, followed by a substantial upregulation in expression before a return to baseline expression levels within forty-eight hours. These results showed that ERE activity is differentially sensitive to CDK9 inhibition and highlights the complexity of interactions between the P-TEFb complex and nascent ERE RNAs.
Identification and validation of PANoptosis-related genes in ankylosing spondylitis.
Shan Z, Li J, Mu X … +2 more , Zhang J, Ren S
BMC Med Genomics · 2026 Jan · PMID 41526902 · Full text
Ankylosing spondylitis (AS) is a common immune inflammatory disease. PANoptosis, as a novel programmed cell death pathway, its mechanism of action in ankylosing spondylitis remains unclear. Therefore, this study aims to...
Ankylosing spondylitis (AS) is a common immune inflammatory disease. PANoptosis, as a novel programmed cell death pathway, its mechanism of action in ankylosing spondylitis remains unclear. Therefore, this study aims to clarify the role of a novel programmed cell death pattern - PANoptosis - in the pathogenesis of ankylosing spondylitis (AS), and to screen and verify key genes (APRGS), providing new ideas for the diagnosis and treatment of AS. Based on multiple gene expression datasets (GSE25101, GSE73754, GSE11886, GSE134290) of AS patients and known gene libraries related to panoptosis, by integrating differential expression genes analysis (DEGs), weighted gene co-expression network analysis (WGCNA), protein-protein interaction network (PPI), and three machine learning algorithms (RF, LASSO-logistic regression, SVM), six core APRGs were identified: AIM2, TNF, IFNG, CASP8, ADAR, ALKBH5. These genes are significantly enriched in signaling pathways such as NOD-like receptors, TNF and p53, and exhibit excellent diagnostic efficacy for as (ROC analysis). Immune infiltration analysis revealed that as patients had characteristics such as an increase in activated NK cells and CD4+ t cells. In vivo validation was carried out by establishing a rat model of as induced by complete freesier adjuvant (CFA). HE staining showed that obvious inflammatory infiltration and abnormal ossification occurred in the sacroiliac joint of the model rats, and the levels of serum pro-inflammatory factors (TNF-α, IL-6) increased, and anti-inflammatory factors (IL-10, IL-4) significantly decreased. Molecular testing confirmed that the expression of RIPK1 protein was upregulated. The mRNA and protein expressions of AIM2, TNF, IFNG, CASP8 and ALKBH5 in core APRGs were significantly increased, while the expression of ADAR was decreased. Our research has clarified that PANoptosis drives chronic inflammation and bone destruction in as through the synergistic action of six key genes: AIM2, TNF, IFNG, CASP8, ADAR, and ALKBH5, involving NOD-like receptors, TNF, and p53 pathways. These genes are potential diagnostic markers and therapeutic targets for as, providing an important basis for the development of targeted intervention strategies.
Identification of differentially expressed genes associated with tracheal injury recovery in a rabbit model of septic shock.
Zhang P, Lu H, Li X … +6 more , Tian Y, Tian W, Ma S, Liu C, Liu X, Huang L
BMC Med Genomics · 2026 Jan · PMID 41495808 · Full text
BACKGROUND: Sepsis is a syndrome caused by the host's inflammatory response to an infection with an unknown mechanism. This study aimed to identify differentially expressed genes (DEGs) potentially involved in the develo...
BACKGROUND: Sepsis is a syndrome caused by the host's inflammatory response to an infection with an unknown mechanism. This study aimed to identify differentially expressed genes (DEGs) potentially involved in the development and recovery of tracheal injury from septic shock. METHODS: Nine New Zealand white rabbits were randomized to control (CON), septic shock model (SS), and septic shock norepinephrine treatment (SSNE) groups (each group n = 3). The SS and SSNE groups were injected with lipopolysaccharide to induce septic shock. The SSNE group was administered Ringer lactate with norepinephrine to maintain normal blood pressure. All animals underwent cuffed endotracheal intubation for 2 h. The injured tracheal segment was harvested. RNA sequencing was performed to identify the DEGs, followed by bioinformatics analysis, and pathological staining (both HE and Masson) was performed for pathological evaluation. Bioinformatics analysis included principal component analysis (PCA), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) network construction. Key findings were validated by qRT-PCR and immunohistochemistry. RESULTS: We obtained 124 upregulated and 28 downregulated DEGs in SS vs. CON groups, along with 60 upregulated and 178 downregulated DEGs in SSNE vs. SS groups. The pathological score showed that trachea tissue in the SS group had the highest score. The protein-protein interaction (PPI) prediction identified APOB and CD36 as the hub genes. The molecular experiments further confirmed that at mRNA and protein levels, APOB was significantly upregulated, while CD36 was significantly downregulated. Subsequent qRT-PCR and immunohistochemical analyses confirmed that APOB expression was significantly upregulated while CD36 was downregulated in the septic shock group, a trend partially reversed by norepinephrine treatment. CONCLUSIONS: Our study results suggest that APOB and CD36 may be involved in the pathogenesis of tracheal injury recovery in septic shock patients treated with NE. CLINICAL TRIAL NUMBER: Not applicable.
Defining an approach to empower clinical geneticists to do genomic reanalysis.
Segal MM, McEntagart M, Deng AT … +10 more , Haworth A, King B, Rogers A, Filby J, Short J, Hash MG, Rives LC, Ezell KM, Undiagnosed Diseases Network, Phillips JA
BMC Med Genomics · 2026 Jan · PMID 41491999 · Full text
BACKGROUND: Sequencing reanalysis can benefit from the inclusion of new information about the patient and from the literature. We studied approaches needed to make reanalysis part of routine follow-up by clinical genetic...
BACKGROUND: Sequencing reanalysis can benefit from the inclusion of new information about the patient and from the literature. We studied approaches needed to make reanalysis part of routine follow-up by clinical geneticists. METHODS: Reanalysis used the SimulConsult diagnostic decision support software, which generates a pertinence metric for gene zygosities determined from the variant table and the patient's findings. Twenty patients had routine exome sequencing at St. George's Hospital (London, UK). Twenty were admitted to the Undiagnosed Diseases Network at Vanderbilt University Medical Center (VUMC) and had all remained undiagnosed despite previous evaluations and sequencing. RESULTS: For St. George's cases, reanalysis picked 7 of the 7 initial diagnoses plus 2 diagnoses found later, and suggested another diagnosis with a gene absent from the variant table. For VUMC, reanalysis picked 5 of 8 diagnoses that were in the variant tables, and suggested a non-coding variant absent from the variant table. CONCLUSION: Rapid reanalysis by clinicians could increase the yield of genetic diagnosis with minimal effort and no new lab expenses. For the routine cases at St. George's, diagnostic yield increased from 7 to 10 (43%). Capabilities that could further increase yield include joint variant calling, robust phenotyping, clinical correlation after sequencing, and adding CNV data to variant tables.
Association between PNPLA3 rs738409 and susceptibility to etiology-specific liver cirrhosis: a systematic review and meta-analysis.
Yang S, Cheng A
BMC Med Genomics · 2026 Jan · PMID 41491174 · Full text
BACKGROUND AND AIM: PNPLA3 rs738409 reduces the triglyceride hydrolase activity. This systematic review and meta-analysis aimed to assess the association between PNPLA3 rs738409 polymorphism and the risk of liver cirrhos...
BACKGROUND AND AIM: PNPLA3 rs738409 reduces the triglyceride hydrolase activity. This systematic review and meta-analysis aimed to assess the association between PNPLA3 rs738409 polymorphism and the risk of liver cirrhosis across various etiologies. METHODS: Potential articles were selected from PubMed, Embase, Cochrane Library, and Web of Science databases, guided by well-defined inclusion and exclusion criteria. The quality of each article was rigorously evaluated using the Newcastle-Ottawa Scale (NOS). Association between PNPLA3 rs738409 and liver cirrhosis was expressed in terms of odds ratios (ORs) accompanied by 95% confidence intervals (CIs). RESULTS: This meta-analysis encompassed 21 studies (22 tests, comprising 79102 controls and 4006 cases). The aggregate findings revealed a notable positive correlation between the rs738409 and the risk of liver cirrhosis across all genetic models: G vs. C (OR = 1.75, 95% CI = 1.64-1.86), GC vs. CC (OR = 1.77, 95% CI = 1.61-1.94), GG vs. CC (OR = 2.69, 95% CI = 2.34-3.08), GG vs. CG + CC (OR = 2.02, 95% CI = 1.79-2.28), and GG + CG vs. CC (OR = 1.99, 95% CI = 1.82-2.17). There was a pronounced heterogeneity observed across all genetic models, and might be induced by race and control groups. Subgroup analyses showed significant association respectively in Caucasian and Asian, as well as healthy controls, ALD and other liver diseases control types. CONCLUSION: PNPLA3 rs738409 polymorphism has been robustly linked to an increased risk of etiology-specific liver cirrhosis.
Overexpression of cancer testis antigens in gastric cancer and their correlations with the patients' clinicopathological characteristics.
Alimardani M, Rahimi H, Ghasemi A … +3 more , Moghbeli M, Gholamin M, Abbaszadegan MR
BMC Med Genomics · 2025 Dec · PMID 41469662 · Full text
BACKGROUND: Cancer-testis antigens are typically expressed in malignant cells, germ-line cells, and the placenta. Given their potential as targets for cancer immunotherapy, it is essential to profile their expression. Th...
BACKGROUND: Cancer-testis antigens are typically expressed in malignant cells, germ-line cells, and the placenta. Given their potential as targets for cancer immunotherapy, it is essential to profile their expression. This study examines the clinical significance of MAGE-A4, LAGE-1, and NY-ESO expression levels in gastric cancer compared to normal tissues. METHODS: RNA was isolated from fresh gastric specimens of 76 patients diagnosed with GC before any therapeutic intervention. The Real-Time PCR evaluated the MAGE-A4, LAGE-1, and NY-ESO relative mRNA levels. Gene expression was normalized to GAPDH using the ΔΔCt method. Fold changes > 2 with p < 0.05 were considered statistically significant. RESULTS: The results indicated that the elevated mRNA expression levels of MAGE-A4, LAGE-1, and NY-ESO were observed in 21.05%, 22.38%, and 26.32% of the cases, respectively. Furthermore, a substantial upregulation of NY-ESO was noted in non-cardia tumors with T1/2 depth of invasion (p = 0.021). This marked increase in NY-ESO expression was also observed in primary-stage tumors situated in non-cardia regions (p = 0.026). MAGE-A4 expression tended to be higher in lymph node–negative tumors, while NY-ESO expression was associated with overall survival, and LAGE-1 showed variable expression. CONCLUSION: Our research demonstrates that MAGE-A4, LAGE-1, and NY-ESO expression are often upregulated in patients with GC. This overexpression in GC tumors is significantly associated with poor prognosis. Therefore, these may serve as a significant prognostic indicator for gastric cancer, and the cancer-testis antigens could represent a potential therapeutic target for a gastric cancer vaccine.
Exploring the genetic landscape of COVID-19 susceptibility and severity among patients in Türkiye.
Er AG, Çakır Y, Er B … +7 more , Burduroğlu HC, Çakmak M, Özışık L, Tanrıöver MD, Topeli A, Son YA, Ünal S
BMC Med Genomics · 2025 Dec · PMID 41466405 · Full text
BACKGROUND: One of the most challenging factors for clinicians in managing COVID-19 has been differences in the clinical course. To investigate the parameters associated with severe disease in detail, along with examinin...
BACKGROUND: One of the most challenging factors for clinicians in managing COVID-19 has been differences in the clinical course. To investigate the parameters associated with severe disease in detail, along with examining known risk factors such as advanced age and comorbidities, understanding personal genetic factors is necessary, as the clinical course may change due to differences in the host genome. METHODS: Human genetic variants reported to be associated with severe disease were genotyped in 68 patients in COVID-19 medical wards and 52 in COVID-19 intensive care units at Hacettepe University Adult Hospital. RESULTS: The rs17860115 variant was significantly more prevalent in our cohort than in the European (non-Finish) population, whereas the rs2298659, rs2298661, rs4290734, and rs9271609 variants were significantly less common, which may reflect genetic differentiation, selective pressures, or protective factors within this population. While no significant association was found between variants and disease severity, notably, the ACE2 rs1548474 allele frequency was 38.0% in the ICU group and 22.9% in the non-ICU group (OR = 2.06; 95% CI 1.10–3.90; p = 0.02). CONCLUSION: These findings emphasize the importance of examining genetic differences both within and across populations when developing new strategies for disease control and public health policies, particularly for infectious diseases such as COVID-19. They also point to the necessity for further research involving larger and more varied populations to validate these associations and to investigate the genetic factors that may drive them.
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