Frontiers in Genetics

Multi-omics analysis to identify the dynamic changes of immune cells and marker genes in renal fibrosis

2026-04-02

Wen Yi, Mingrong Cao, Xiaojun Tan, Guocheng Du, Jingdong Li

IntroductionRenal fibrosis is a common pathological feature of chronic kidney disease and a major driver of progression to end-stage renal disease, but its molecular mechanisms remain incompletely understood.MethodsWe integrated multi-omics datasets from GEO and published studies, including mRNA, protein, miRNA, and circRNA data from unilateral ureteral obstruction (UUO) models, TGF-β-induced in vitro fibrosis models, and human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Exo). Differential expression analysis, functional enrichment, immune infiltration analysis, fuzzy c-means clustering, weighted gene co-expression network analysis, and ceRNA network construction were performed, with selected findings further validated experimentally.ResultsWe identified stable fibrosis-associated genes and proteins, with metabolic dysregulation emerging as a prominent feature of renal fibrosis. Time-series analysis revealed dynamic transcriptional changes during UUO progression. Comparative analysis showed that in vitro fibrosis models reproduced only part of the in vivo molecular landscape. Immune analyses consistently highlighted macrophages, especially M2-like macrophages, and also suggested a potential role for B cells. In addition, we identified immune-related hub genes and constructed fibrosis-associated ceRNA networks linked to macrophage regulation. Several miRNAs enriched in HucMSC-Exo, particularly miR-30a-5p, were predicted to counteract fibrosis, and exosome treatment alleviated renal injury, macrophage infiltration, and fibrotic marker expression.ConclusionThese findings provide a comprehensive view of the molecular and immune landscape of renal fibrosis, clarify key differences between in vivo and in vitro fibrosis models, and suggest potential therapeutic targets for antifibrotic intervention.

Federated, governed, and interoperable? The emerging architecture of public human genomic data infrastructures: a European perspective

2026-04-01

Marco Antonio Tangaro, Matteo Chiara, Graziano Pesole, Federico Zambelli

Public infrastructures for human genomic data are increasingly incorporating federated approaches alongside centralized and cloud-native models, yet operational federation remains constrained by unsolved challenges at the legal, semantic, and technical layers. We describe the current landscape along three analytical axes, taking a primarily European perspective while drawing on global examples to highlight broader trends. First, we compare architectural models, centralized archives such as the European Genome-phenome Archive (EGA) and the database of Genotypes and Phenotypes (dbGaP), cloud-native platforms for data analysis, and federated networks exemplified by the European Genomic Data Infrastructure (GDI), highlighting their specific trade-offs on scalability, sovereignty, and analytical flexibility. Second, we examine the governance layer, from the tension between the GDPR’s consent requirements and large-scale secondary use, through the European Health Data Space (EHDS) and Health Data Access Bodies, to machine-readable authorization via GA4GH Passports and the Data Use Ontology. Third, we assess interoperability and semantic alignment, including the role of GA4GH technical standards, FAIR metadata principles, and emerging schema harmonization efforts such as the German Human Genome-Phenome Archive (GHGA). We argue that the central challenge is no longer building individual platforms, but aligning heterogeneous regulatory interpretations, metadata models, and trust frameworks across jurisdictions. Addressing this alignment gap will determine whether federated genomics delivers on its promise of large-scale, privacy-preserving data reuse.

Serum tumor markers combined with HRCT for malignancy risk assessment of solitary pulmonary nodules: a retrospective study

2026-04-01

Yong Zhou, Shuitang Wang, Yongqiu Zhang

IntroductionThis study aims to investigate the correlation between serum tumor markers (CEA, NSE, CA-125, and CYFRA 21-1) and imaging findings in patients with solitary pulmonary nodules, and to assess their value in predicting the risk of malignancy.MethodsA retrospective analysis was conducted on 110 patients with solitary pulmonary nodules, of whom 45 were benign and 65 were malignant. The clinical data, serum tumor marker levels, CT imaging findings, and diagnostic efficacy of single and combined tests were compared between the two groups.ResultsSerum levels of CEA, CA-125, CYFRA 21-1, and NSE in the malignant nodule group were significantly higher than those in the benign nodule group (P < 0.001). CT imaging revealed that patients with malignant nodules typically exhibited characteristics such as deep lobulation, pleural indentation, short fine spiculation, and multiple cystic lucencies, whereas the benign nodule group more commonly displayed pleural thickening and satellite lesions. The diagnostic efficacy of combined CT and tumor marker testing was significantly superior to that of single tests, with a sensitivity of 96.9% and an accuracy of 87.3%. The area under the curve (AUC) of the combined detection was significantly higher than that of any single indicator (P < 0.05).DiscussionThe combined detection of serum tumor markers and high-resolution CT imaging findings has high clinical value in the diagnosis of benign and malignant solitary pulmonary nodules, offering a more precise basis for cancer risk assessment.

Renpenning syndrome caused by the c.459_462delAGAG mutation in PQBP1: a case report and literature review

2026-03-30

Mengting Zhang, Mengli Liu, Rongrong Wang, Fuxiang Ma, Guoshun Mao

BackgroundRenpenning syndrome (OMIM: 309500) is a rare X-linked intellectual disability caused by variations in the polyglutamine-binding protein 1 (PQBP1) gene, characterized by moderate to severe intellectual disability, microcephaly, short stature, lean body, small testes, and abnormal facial features.MethodsComprehensive clinical evaluation and whole exome sequencing were performed to identify the genetic basis of the clinical presentation in a 4-year-7-month-old male proband from a Chinese family. Detected variants underwent validation and familial segregation analysis by Sanger sequencing. Additionally, a literature review was conducted to analyze PQBP1-related genotype-phenotype correlations.ResultsThe proband exhibited typical manifestations of Renpenning syndrome, including severe global developmental delay, microcephaly, short stature, and characteristic facial features. Additionally, he presented with rare anal atresia and co-occurring autism spectrum disorder (ASD). Whole exome sequencing identified a hemizygous PQBP1 frameshift variant, NM_001032382.2:c.459_462delAGAG (p.Arg153fs) (VCV000010980.79), in the proband. Sanger sequencing confirmed this variant was maternally inherited.ConclusionThis report describes the first Chinese case of Renpenning syndrome caused by the PQBP1 c.459_462delAGAG variant, presenting with the core phenotype plus anal atresia and ASD. This case expands recognition of the clinical spectrum associated with PQBP1 variants.

Case Report: Prenatal genetic analysis of a rare fetus with 45, X/46, X, dic r (Y; Y)/46, X, r(Y) karyotype

2026-03-30

Guosheng Deng, Xiafei Liang, Yuqing Lai, Jujie Song, Jinjie Pan, Yinghong Lu, Lili Li, Yunning Liang

ObjectiveTo perform a genetic analysis of a rare complex chimeric fetus with a 45,X/46,X,dic r(Y; Y)/46,X,r(Y) karyotype, indicated by NIPT as having sex chromosome abnormalities but with normal ultrasound findings. This study underscores the critical role of integrating multiple molecular cytogenetic techniques in deciphering such complex cases, which is essential for accurate prognosis and personalized genetic counseling. The findings aim to deepen the understanding of genotype-phenotype correlations in rare chromosomal mosaicism and to guide clinical management.MethodAmniotic fluid was collected from a pregnant woman with an abnormal sex chromosome indicated by NIPT. Combined detection using G-banding karyotype analysis, fluorescence in situ hybridization (FISH), and low-depth whole-genome copy number variation sequencing (CNV-seq) techniques was performed. Simultaneously collect peripheral blood samples from the fetus’s parents for CNV-seq detection and paternal chromosomal karyotype analysis. The infant underwent comprehensive postnatal follow-up, including physical examination, growth assessment, developmental screening, sex hormone profiling, Y chromosome microdeletion testing, and scrotal ultrasound at 19 months of age.ResultThe male fetus was confirmed to have a complex karyotype through combined analysis of chromosomal G-band technology, FISH, and CNV-seq. The findings included a dicentric ring Y chromosome with mosaicism for Yp and Yq deletions, as well as a 1.40 Mb duplication in the 7q11.23 region, resulting in the karyotype: 45,X[82]/46,X,dic r(Y; Y)(p11.31q11.23; p11.31q11.23)[13]/46,X,r(Y)(p11.31q11.23) [5]dn. The father’s karyotype was normal, suggesting a de novo mutation. Maternal CNV-seq was normal, while paternal CNV-seq identified the same 1.40 Mb 7q11.23 duplication, indicating paternal inheritance of this pathogenic variant. After genetic counseling, the parents proceeded with the pregnancy. On 27 June 2024, at 35+5 weeks of gestation, they gave birth to a live male infant naturally, with a length of 48 cm and a weight of 2800 g. No obvious abnormalities were observed in the appearance.ConclusionThe integration of G-banding, FISH, and CNV-seq enables accurate diagnosis of complex ring Y chromosome mosaicism, providing crucial information for genetic counseling and clinical management. The clinical phenotype depends on the ring chromosome’s structure, breakpoints, and the degree of mosaicism.

Editorial: Advances in molecular genetics of Marfan syndrome and related disorders

2026-03-30

Georgia Damoraki

Advances in algorithms for normalizer gene selection in qRT-PCR: implications for cancer biology and precision medicine

2026-03-27

Abhay Kumar Pathak, Sukhad Kural, Lalit Kumar, Sumit Saini, Manjari Gupta

Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) plays a significant role in gene expression analysis in cancer research and precision medicine. It allows precise quantification of gene expression variation which is necessary for understanding tumor biology, identifying predictive biomarkers and developing therapeutics interventions. However the accuracy and stability of qRT-PCR data heavily rely on finding stable reference genes. The gene stability refers to minimal variation in expression levels of a candidate reference gene across different biological conditions, sample groups and technical replicates. Traditionally, housekeeping genes such as β-actin, GAPDH and 18S rRNA have been used for normalization but consistency and variation can vary under different experimental settings. Over time, mathematical and statistical tools such as geNorm, NormFinder, BestKeeper and gQuant have been developed to find most stable reference genes. These algorithms have become essential in ensuring accurate and reproducible data in cancer research, where gene expression profiles can vary significantly across different tumor types, stages and individual patients. This review focuses on the progression and advancements of traditional and advanced reference gene selection methods, applications in cancer research and their significant role in precision medicine. It presents an overview of the commonly employed normalizers, outlining their respective advantages and limitations, and includes a concise discussion on the assessment of gene stability across diverse experimental contexts. Additionally, it emphasizes their use in cancer research and their importance in enhancing the accuracy and consistency of gene expression normalization, particularly within precision medicine.