Front Genet [JOURNAL]
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200 papers
Comparative genomics across illuminates the evolutionary basis of flax domestication, genome diversification, and seed oil biosynthesis.
Yi L, Sa R, Mu Y … +5 more , Zhang J, He R, Song Y, Zhou Y, Chen Y
Front Genet · 2026 · PMID 42376280 · Full text
Flax ( L.) is a globally significant dual-purpose crop cultivated for both bast fiber and seed oil, yet the genomic basis of its diversification and domestication from wild relatives remains incompletely understood. In t...
Flax ( L.) is a globally significant dual-purpose crop cultivated for both bast fiber and seed oil, yet the genomic basis of its diversification and domestication from wild relatives remains incompletely understood. In this study, we performed a comprehensive comparative genomic analysis of 11 accessions-including five cultivated flax accessions and their wild progenitor -alongside two outgroups ( and ). To reduce annotation heterogeneity, we uniformly re-annotated all genomes using the deep-learning-based ANNEVO pipeline, which reduced apparent gene fragmentation and maintained broadly comparable annotation completeness under a unified framework. Phylogenomic analysis resolved a pre-domestication macro-evolutionary gene family expansion in the - lineage, providing standing genetic variation that subsequently diverged into pathways enriched for cell wall biogenesis in fiber flax and lipid/photosynthetic metabolism in oil flax. Genome-wide NLR analysis revealed a globally contracted immune receptor repertoire in and quantitative stability between cultivated flax and , while chromosomal distribution and synteny analyses indicated that a major NLR-rich region differs in chromosome assignment between and cultivated flax rather than providing definitive evidence for cluster gain or complete cluster loss. Furthermore, genome size variation across was predominantly driven by transposable elements, with remarkably recent bursts of long terminal repeat (LTR) retrotransposons (<0.5 Mya) shared by cultivated flax and L. bienne but clearly predating human domestication, indicating an inherited repeat landscape rather than a domestication-associated event. Finally, analysis of fatty acid desaturases revealed striking evolutionary asymmetry: the FAD3 family remained highly conserved, whereas FAD2 exhibited exceptional plasticity, characterized by lineage-specific tandem expansions and a putative large structural absence associated with the contracted FAD2 repertoire in the oil flax accession T397. Together, these findings provide a standardized genomic framework for and illuminate the structural variations, repeat dynamics, and pre-adaptive gene duplications that may have contributed to flax domestication and agronomic specialization.
scCCVGBen for benchmarking of single-cell representation learning anchored on a centroid-coupled variational graph attention autoencoder across scRNA-seq and scATAC-seq.
Fu Z, Fu J, Chen C … +4 more , Zhang K, Wang J, Ran T, Wang S
Front Genet · 2026 · PMID 42376279 · Full text
Single-cell omics routinely profile millions of cells across the transcriptome and the epigenome. However, embeddings used for clustering, trajectory inference, and visualization remain unstable: stochastic variational a...
Single-cell omics routinely profile millions of cells across the transcriptome and the epigenome. However, embeddings used for clustering, trajectory inference, and visualization remain unstable: stochastic variational autoencoders inject sampling noise at inference, and methods reported on idiosyncratic cohorts defeat head-to-head comparison. We introduce scCCVGBen, a benchmark of single-cell representation-learning methods. Its reference configuration is a centroid-coupled variational graph autoencoder built from three design choices: the centroid (deterministic posterior mean) used as the inference embedding, a coupling-regularized dual-reconstruction bottleneck, and a graph attention encoder over a -nearest-neighbor cell-cell graph. We assess this configuration within a decoupled benchmark that varies the algorithmic core, encoder backbone, graph construction, dataset cohort, and evaluation suite as independent axes. The cohort, drawn from the Gene Expression Omnibus (GEO) and the European Nucleotide Archive (ENA), balances scRNA-seq and scATAC-seq equally and spans hematopoiesis, neuronal differentiation, immune populations, organ atlases, tumor microenvironments, and developmental time courses. Across the cohort, scCCVGBen improves average silhouette width by and intrinsic-overall geometry by over a stochastic variational encoder (VAE) on paired scRNA-seq; gains over scVI reach and , and on scATAC-seq, the gain over PeakVI on intrinsic geometry reaches . Robustness analyses across 14 graph encoders and 5 graph-construction strategies show where alternative architectures remain competitive. Three paired hematopoietic case studies: sleep-disrupted bone marrow alongside a gastric tumor atlas, cord blood megakaryopoiesis alongside aged hematopoietic stem cells, and radiation-injury hematopoiesis alongside the COVID-19 bronchoalveolar landscape, recover coherent latent-gene programs spanning hematopoietic, epithelial-stromal, megakaryocytic, and antiviral-macrophage axes. The benchmark cohort, per-method scores, and per-dataset metadata are released through three companion sites: a Hugo atlas, a Next.js interactive cohort browser, and a cross-tool discovery surface, so the cohort can be inspected without cloning the source repository. The result is a stable, interpretable embedding that carries cleanly from benchmarking to biological discovery.
Codon usage bias and molecular evolution of across avian lineages.
Zhou Z, Yang J, Dissanayake DSB … +3 more , Schwanz L, Georges A, Xiong L
Front Genet · 2026 · PMID 42376278 · Full text
BACKGROUND: Dnajc15, encoding the methylation-controlled J-protein (MCJ) of the HSP40 family, is an endogenous repressor of the mitochondrial respiratory chain and a key regulator of mitochondrial metabolism. The codon u...
BACKGROUND: Dnajc15, encoding the methylation-controlled J-protein (MCJ) of the HSP40 family, is an endogenous repressor of the mitochondrial respiratory chain and a key regulator of mitochondrial metabolism. The codon usage patterns and molecular evolution of Dnajc15 in birds remain largely uncharacterized. METHODS: We present the first systematic characterization of Dnajc15 codon usage patterns and adaptive evolution across 27 bird species representative of 11 avian orders, using codon usage bias analysis, PAML-based selection pressure analysis, and gene family analysis. RESULTS: Codon usage bias analysis revealed a preference for A/U-ending codons and weak overall codon bias (effective codon number: 51.72-61.00). Selection analyses indicated predominant purifying selection (ω = 0.33). The M7 vs. M8 site model identified four candidate positively selected sites (positions 8, 17, 19, and 57), located in the N-terminal region and J-domain of the MCJ protein, though this signal was not corroborated by the M1a vs. M2a comparison, suggesting at most limited or episodic positive selection. Dnajc15 was retained across all examined vertebrate lineages despite widespread contraction of other Dnajc family members. CONCLUSION: Dnajc15 is a highly conserved component of the avian mitochondrial regulatory system, with limited evidence for adaptive variation at a small number of candidate sites, consistent with strong long-term functional constraint.
CircRNAs in hepatic lipid metabolism: regulatory mechanisms and clinical implications.
Zeng Y, Gao M
Front Genet · 2026 · PMID 42376277 · Full text
Hepatic lipid metabolism homeostasis is crucial for maintaining metabolic health, and its disruption is a central factor in the development of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and meta...
Hepatic lipid metabolism homeostasis is crucial for maintaining metabolic health, and its disruption is a central factor in the development of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD). Circular RNAs (circRNAs),a novel class of non-coding RNAs characterized by their covalently closed loop structures and remarkable stability, have emerged as key regulators of gene expression. Recent studies have revealed that circRNAs play significant roles in modulating critical hepatic lipid metabolism signaling pathways, including AMPK, mTOR, PPAR, and SREBP. This review systematically summarizes the latest advances in understanding how circRNAs influence these pathways through mechanisms such as acting as molecular sponges for microRNAs, interacting with proteins, and potentially encoding functional peptides. We critically evaluate the experimental models used in key studies, distinguishing between , , and clinical evidence, and discuss the context-dependent nature of circRNA function. Furthermore, the potential of circRNAs as diagnostic biomarkers and therapeutic targets for NAFLD and MASLD is discussed, highlighting their clinical relevance alongside a balanced assessment of the challenges facing clinical translation. By integrating current research findings, this review aims to provide a comprehensive theoretical foundation for elucidating the regulatory networks governing hepatic lipid metabolism and for developing innovative intervention strategies against metabolic liver diseases.
Development and validation of diagnostic KASP markers for MYMIV resistance in urdbean.
Sen Gupta D, Kumar S, Kumar J … +7 more , Das SP, Kumar S, Parihar AK, Banik S, Souframanien J, Katiyar PK, Dixit GP
Front Genet · 2026 · PMID 42371416 · Full text
Mungbean Yellow Mosaic India Virus (MYMIV) is a major constraint to productivity in urdbean, necessitating the development of reliable molecular markers for resistance breeding. The present study reports the development...
Mungbean Yellow Mosaic India Virus (MYMIV) is a major constraint to productivity in urdbean, necessitating the development of reliable molecular markers for resistance breeding. The present study reports the development of two Kompetitive Allele Specific PCR (KASP) markers for the Tobacco Mosaic Virus () resistance gene and the resistance gene. These markers enable reliable discrimination between resistant and susceptible genotypes in urdbean. The highly MYMIV-resistant genotypes identified in this study possessed resistance alleles for both genes, whereas other resistant genotypes carried the resistance allele for either one of the two genes. This finding broadens the scope of marker-assisted pyramiding of these resistance alleles to enhance the genetic resistance of susceptible or moderately resistant genotypes. Among the urdbean genotypes, most resistant genotypes harboured the resistance allele (GG) for the gene. However, only two highly resistant genotypes (IPU11-02 and PU-31) possessed resistance allele for both the (GG) and (TT) genes. In mungbean, the susceptible allele (AA) of the F-box/LRR gene was observed in 12 genotypes, while the remaining 12 genotypes exhibited a null allele, indicating the absence of amplification. This allelic distribution, along with the gene status, largely explains the comparatively lower degree of genetic resistance to MYMIV in mungbean relative to urdbean. The developed KASP markers were further validated across six additional species. Most genotypes from these species carried the susceptible allele for the gene, except PRR 2007-2 of , which exhibited a high level of resistance to MYMIV under field conditions. For the gene, no alleleic amplification was observed in most genotypes from six species, suggesting the presence of divergent or novel alleles; however, PRR 2007-2 showed amplification with the susceptible allele (AA). In conclusion, the KASP markers developed for the and genes provide an efficient and robust tool for marker-assisted introgression of MYMIV resistance alleles. Notably, these markers are effective and applicable in urdbean. These markers can be readily used in breeding programs, including inter-specific crosses involving diverse species, to accelerate the development of MYMIV-resistant cultivars/germplasm.
Detection and evaluation of copy number variation using both linked-read and short-read sequencing in New Zealand dairy cattle.
Wang Y, Nugroho T, Johnson TJJ … +2 more , Couldrey C, Harris BL
Front Genet · 2026 · PMID 42369227 · Full text
In recent years, genetic studies have made significant progress in identifying single-nucleotide polymorphisms (SNPs) associated with cattle health and production traits. However, it is still challenging to identify and...
In recent years, genetic studies have made significant progress in identifying single-nucleotide polymorphisms (SNPs) associated with cattle health and production traits. However, it is still challenging to identify and validate more complicated forms of variation, such as copy number variation (CNV) and other types of structural variation (SV). In this study, SV regions were identified using 37 New Zealand dairy cattle with linked-read sequence data. A transmission-based framework was used to validate these variants at the population scale. 62,438 putative autosomal SV regions were identified with the LongRanger pipeline following the 10x Genomics recommendations. Copy number states for these regions were subsequently estimated via a read-depth based genotyping method using CNVpytor in a population-representative cohort of 2306 animals using Illumina short-read sequencing technology. Mendelian inheritance of copy number states was assessed using linear mixed models incorporating pedigree information, and transmission levels were used to quantify the biological validity of each CNV region. Transmission levels ranged widely, with a mean of 0.5162 across all regions, where higher transmission levels were proportionally enriched for larger SVs. A total of 7218 CNV regions exhibited high transmission levels (>0.9), indicating strong evidence of inheritance. Among these, 7136 overlapped CNV regions reported in one or more public datasets, while 82 high-confidence regions represent previously unreported variants. High-transmission CNV regions tended to show clear, discrete inheritance patterns in trio families, providing the biological evidence that these CNVs are inherited within the population. Together, these results demonstrate that integrating linked-read sequencing with population-scale transmission-based validation provides a robust framework for identifying high-confidence CNV regions. This catalogue of validated CNV regions represents an important resource for downstream functional analyses and the incorporation of structural variation into genomic selection and breeding programs.
Clock-related neuropeptides in .
Colizzi FS, Liessem S, Morales-Poole JR … +2 more , Martínez-Torres D, Helfrich-Förster C
Front Genet · 2026 · PMID 42369226 · Full text
INTRODUCTION: The pea aphid () is a strongly photoperiodic insect. Although the involvement of the circadian clock in insect photoperiodism is well established, the neuronal and molecular mechanisms by which clock neuron...
INTRODUCTION: The pea aphid () is a strongly photoperiodic insect. Although the involvement of the circadian clock in insect photoperiodism is well established, the neuronal and molecular mechanisms by which clock neurons convey photoperiodic information remain largely unknown. Neuropeptides commonly act as neuromessengers in circadian clock neurons, yet little is known about the neuropeptidergic organization of the circadian clock in the pea aphid. METHODS: Here, we characterized the complete set of neuropeptides in the aphid brain and, using a combination of transcriptomic and peptidomic approaches, and investigated the neuropeptides expressed in the circadian clock neurons using immunohistochemistry. RESULTS: We confirmed a large number of peptides, including several peptides described for the first time in this species. Furthermore, we found that circadian clock neurons express a variety of these neuropeptides, some of which overlapped within the same clock neuron type. In the lateral clock neurons, we found Pigment-Dispersing Factor, FMRFamide, Orcokinin a and Allatotropin, a neuropeptide profile that closely resembles that of cockroach clock neurons but differs markedly from that of the fruit fly, with the exception of Pigment-Dispersing Factor. In dorsal clock neurons, which are homologous to those that are presynaptic to insulin-producing cells in , we detected Allatostatin A, Diuretic Hormone 31, FMRFamide, and Myoinhibitory peptide. DISCUSSION: Together, our findings provide the first comprehensive map of neuropeptides associated with the pea aphid circadian clock, offering new insights into how clock neurons may regulate seasonal responses and establishing a foundation for future functional studies of neuropeptide-mediated photoperiodism.
Correction: Clinical variant interpretation comparing two saturation genome editing-based functional studies for .
Shin JH, Park KS, Kim YG … +3 more , Jang MA, Jang JH, Kim JW
Front Genet · 2026 · PMID 42369225 · Full text
[This corrects the article DOI: 10.3389/fgene.2026.1803717.].
[This corrects the article DOI: 10.3389/fgene.2026.1803717.].
Japanese attitudes toward human brain organoid research: broad support amid ethical concerns.
Sawai T, Koike M, Kataoka M
Front Genet · 2026 · PMID 42358433 · Full text
INTRODUCTION: Human brain organoids are three-dimensional neural structures derived from human pluripotent and tissue stem cells. As the ethical implications of this research have sparked significant debate, it is essent...
INTRODUCTION: Human brain organoids are three-dimensional neural structures derived from human pluripotent and tissue stem cells. As the ethical implications of this research have sparked significant debate, it is essential to gauge public opinion to ensure that the research aligns with societal values and ethical standards. METHODS: To understand public perceptions of human brain organoid research, we conducted an online survey targeting Japanese individuals. The survey explored expectations, concerns, and agreements regarding this type of research. RESULTS: The results from 326 participants revealed high expectations especially for applied and clinical research but significant ethical concerns, particularly regarding unanticipated risks and commercialization. Moreover, comprehension test scores showed a weak positive correlation with support for various research objectives, indicating that informed individuals may view this type of research favorably. DISCUSSION: Japanese citizens are generally supportive of human brain organoid research, yet various ethical concerns are identified as well. Our findings indicate that to foster responsible innovation in this field, public engagement and informed discussions are essential, which will dispel citizens' misconceptions and ensure that their views are meaningfully incorporated into research practices and future regulations.
A heterozygous variant associated with PAPA syndrome: a Chinese case report and literature review.
Wang M, Zhang P, Shen M
Front Genet · 2026 · PMID 42358432 · Full text
Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant hereditary autoinflammatory disease caused by gene variants and belongs to the -associated inflammatory diseases (PAIDs). I...
Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant hereditary autoinflammatory disease caused by gene variants and belongs to the -associated inflammatory diseases (PAIDs). Its core clinical manifestations include recurrent pyogenic arthritis, pyoderma gangrenosum, and severe acne with onset in childhood or adolescence. Some patients may also present with multisystem involvement, such as inflammatory bowel disease and scleritis. Inflammation markers, such as CRP and ESR, are often significantly elevated. Treatment mainly involves targeted inhibition of inflammatory pathways, such as IL-1 inhibitors and TNF-α inhibitors. In this article, we report a Chinese patient with PAPA syndrome with disease onset at 13 years of age, whose main manifestations were pyoderma gangrenosum and acne. Genetic testing revealed a gene variant (c.748G>A, p.Glu250Lys). We also reviewed recent literature on PAPA syndrome, summarizing its clinical manifestations, diagnosis, and treatment to enhance physicians' understanding of the condition.
Case Report: clinical manifestations and imaging features associated with PANK2 c.940C>T variant in PKAN with symmetric basal ganglia calcification.
Liang F, Ban R, Li J … +8 more , Li J, Li S, Chen J, Wang D, Liu Y, Luo Z, Li J, Wang L
Front Genet · 2026 · PMID 42344522 · Full text
BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is the most common subtype of neurodegeneration with brain iron accumulation and is classically associated with pallidal iron deposition and the "eye-of...
BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is the most common subtype of neurodegeneration with brain iron accumulation and is classically associated with pallidal iron deposition and the "eye-of-the-tiger" sign on MRI. However, atypical clinicoradiological presentations may complicate recognition. CASE PRESENTATION: We report a 35-year-old woman with adolescent-onset, slowly progressive dystonia characterized by involuntary mouth opening, tongue protrusion, abnormal limb posturing, gait impairment, and cognitive decline. Neuroimaging showed pallidal signal abnormalities compatible with an eye-of-the-tiger-like pattern together with symmetric basal ganglia calcification. Genetic testing identified a homozygous PANK2 variant, NM_001386393.1:c.940C>T [p.(Leu314Phe)], with family segregation consistent with autosomal recessive inheritance. According to the clinical laboratory report, the variant was classified as likely pathogenic under the ACMG/AMP framework (PM2_supporting, PM3_strong, and PP3_moderate). Conservation assessment, computational prediction, and structural modeling supported a deleterious effect, although direct functional validation was not available. Additional findings included acanthocytosis, mild hyperhomocysteinemia, and electrophysiological evidence of peripheral nerve involvement. CONCLUSION: This case highlights an atypical but clinically informative PKAN presentation in which pallidal iron deposition coexisted with symmetric basal ganglia calcification. PKAN should remain in the differential diagnosis of slowly progressive dystonia even when neuroimaging is not fully classic. The possible links among CoA dysregulation, iron deposition, calcification, and associated peripheral findings should be regarded as hypothesis-generating.
Fetal Y chromosome abnormalities cause false-low fetal fraction in NIPT: a retrospective analysis of 24,101 pregnant women.
Hu S, Zhou L, Xu Y … +8 more , Wu W, Jiang N, Hao Y, Zhang H, Liu Y, Wu W, Wu B, Liu W
Front Genet · 2026 · PMID 42344521 · Full text
BACKGROUND: Low fetal fraction is a common cause of NIPT no-call results, leading to repeat sampling and delayed clinical decisions. In cases of fetal sex chromosome abnormalities (SCAs), the standard Y chromosome-based...
BACKGROUND: Low fetal fraction is a common cause of NIPT no-call results, leading to repeat sampling and delayed clinical decisions. In cases of fetal sex chromosome abnormalities (SCAs), the standard Y chromosome-based method for estimating fetal fraction (FF) may be unreliable, potentially leading to misinterpretation of low-FF results. METHODS: We retrospectively analyzed 24,101 pregnant women who underwent NIPT between January 2023 and January 2025. FF was estimated using the Y chromosome-based method for male fetuses and FF-QuantSC for female fetuses. Confirmatory invasive testing was performed for high-risk or failed cases. RESULTS: The SCA prevalence was significantly higher in the low-FF group (FF<3.5%, n = 70) than in the adequate-FF group (FF ≥ 3.5%, n = 24,020), representing a ∼78-fold increased risk (11.43% versus 0.21%; OR = 78.227, < 0.001). All eight SCAs in the low-FF group involved Y-chromosome abnormalities. Re-estimation using FF-QuantSC corrected the FF to a reportable level in all eight cases, confirming "false-low" FF, estimation using the Y chromosome-based method. Subsequent NIPT analysis, enabled by the qualified FF, successfully reported high-risk results for SCAs (45,X or Y deletions). Moreover, analysis of Y-chromosome read distribution profiles in these eight low-FF cases provided visual clues suggestive of these Y-chromosome abnormalities. CONCLUSION: Low FF in NIPT is strongly associated with fetal Y-chromosome abnormalities, suggesting that Y chromosome-based FF estimation may produce a "false-low" FF in some cases with fetal Y-chromosome abnormalities. We suggest that re-estimating FF using FF-QuantSC combined with Y-chromosome read distribution analysis may be considered before reporting test failure.
The relationship between DNA damage and repair and the occurrence and development of disease.
Sun C, Li H, Xia F … +2 more , Zhang X, Han X
Front Genet · 2026 · PMID 42344520 · Full text
DNA damage can lead to the development of diseases such as tumors. To counteract this, organisms have evolved various repair mechanisms targeting different types of damage. In eukaryotes, there are four main types of DNA...
DNA damage can lead to the development of diseases such as tumors. To counteract this, organisms have evolved various repair mechanisms targeting different types of damage. In eukaryotes, there are four main types of DNA repair: nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), and double-strand break repair (DSB repair). NER can remove large fragments of DNA damage, BER can repair damage to individual bases, MMR is used to repair base mismatch, while DSB repair includes two mechanisms: non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ directly connects the broken ends without a template, while HR uses intact sister chromatids as repair templates. Studying DNA damage and repair mechanisms can pave the way for developing new clinical drugs.
LPIN3 emerges as a diagnostic biomarker in Moyamoya disease revealing immune-lipid metabolic crosstalk.
Lu Z, Qiu X, Zhou L … +13 more , Li X, Lu H, Wang S, Chen J, Bian L, Lin J, Zhao W, Zhao W, Gao X, Zhang J, Chen S, Li Z, Wang Z
Front Genet · 2026 · PMID 42338983 · Full text
BACKGROUND: Moyamoya disease (MMD) is a progressive cerebrovascular disorder characterized by stenosis or occlusion of the terminal portions of the internal carotid arteries and their proximal branches, accompanied by th...
BACKGROUND: Moyamoya disease (MMD) is a progressive cerebrovascular disorder characterized by stenosis or occlusion of the terminal portions of the internal carotid arteries and their proximal branches, accompanied by the formation of abnormal collateral vessel networks. It represents a leading cause of ischemic and hemorrhagic stroke in both pediatric and adult populations. However, a comprehensive understanding of the molecular drivers underlying the hallmark vascular pathology of MMD remains elusive. Emerging evidence indicates that dysregulated lipid metabolism significantly contributes to MMD susceptibility and disease severity; nevertheless, its precise mechanistic roles in MMD pathogenesis have not been thoroughly investigated. METHODS: We integrated three publicly available gene expression datasets comprising MMD patients and non-MMD controls (GSE189993, GSE157628, and GSE141024). Following rigorous batch-effect correction, differential expression analysis was performed to identify differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and machine learning approaches were then integrated to prioritize hub genes. Immune cell infiltration analysis was conducted for the identified hub genes. Subsequently, functional enrichment analysis, immune infiltration profiling, and protein-protein interaction (PPI) network construction were further performed. Validation was carried out using an independent external dataset (GSE249254) as well as experiments-including hypoxia-treated human endothelial cells and patient-derived tissue samples-to assess mRNA and protein expression levels. Finally, a Transcription Factor (TF)-miRNA-mRNA regulatory network was constructed, and potential therapeutic compounds targeting MMD were predicted via computational screening. RESULTS: A total of 2,288 DEGs were identified. GSEA revealed significant enrichment of pathways related to lipid metabolism and immune responses. WGCNA identified MMD-associated co-expression modules, and integrative machine learning prioritized four hub genes: LPIN3, PPT2, ACSS1, and INPPL1. A diagnostic nomogram built upon these four genes demonstrated robust predictive performance, with an area under the curve (AUC) of 0.91. Immune infiltration analysis revealed that the abundance of B cells in the MMD patient group was significantly lower than that in the control group, with statistical significance. Notably, LPIN3 expression was significantly upregulated in MMD. It was the only hub gene whose upregulation at the mRNA level was consistently validated in both the external validation set (GSE249254) and models. Subsequent immunohistochemical (IHC) experiments further corroborated this finding at the protein level, highlighting its potential as an independent biomarker. Furthermore, leveraging the hub gene network, seven candidate compounds with potential therapeutic relevance to MMD were predicted. CONCLUSION: This study delineates the immune-lipid metabolic transcriptomic characteristics of MMD, identifies novel molecular determinants of disease pathogenesis, and validates LPIN3 as a promising diagnostic biomarker. Collectively, these findings provide critical mechanistic insights into MMD etiology and offer a foundation for developing improved diagnostic strategies and targeted therapeutic interventions.
Editorial: Advancements in head and neck tumor treatment strategy driven by the perspective of precision oncology.
Liao L, Feng Q, Xie S
Front Genet · 2026 · PMID 42338982 · Full text
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Mapping metabolic reprogramming dynamics across pancreatic neuroendocrine tumor cell differentiation at single-cell transcriptomic resolution.
Yu P, Xiao J
Front Genet · 2026 · PMID 42338981 · Full text
BACKGROUND: The metabolic switch between oxidative phosphorylation (OXPHOS) and aerobic glycolysis is a fundamental feature of tumor biology. Its dynamic regulation during pancreatic neuroendocrine tumor (pNET) cell diff...
BACKGROUND: The metabolic switch between oxidative phosphorylation (OXPHOS) and aerobic glycolysis is a fundamental feature of tumor biology. Its dynamic regulation during pancreatic neuroendocrine tumor (pNET) cell differentiation remains poorly characterized, especially at single-cell resolution. METHODS: We analyzed publicly available single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus database to profile pNET cells at single-cell resolution. Sequencing data were processed through a standard analytical workflow including pseudotime ordering, low-dimensional visualization, co-expression network construction, and metabolic state estimation. To validate key transcriptional patterns, we measured the mRNA and protein levels of selected genes in BON-1 and QGP-1 cells using quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Through single-cell analysis, we resolved the cell population into ten transcriptionally distinct clusters, annotated into major cell types including PT-like tumor cells, TAL-like cells, DCT-like cells, CNT/CD-like cells, endothelial cells, fibroblasts, immune cells, and podocyte-like cells, with PT-like tumor cells constituting the dominant fraction (67%). Canonical marker genes SLC34A1, SLC5A2, LRP2, CUBN, ALDOB, and GATM confirmed the identity of the PT-like tumor cell population on UMAP embedding. Metabolic state annotation identified three states-OXPHOS-high, Mixed, and Glycolysis-high-distributed differentially across PT sub-clusters. Differential expression analysis between glycolysis-high and OXPHOS-high states identified 247 significant genes: OXPHOS genes including ATP5F1B, ATP5F1A, COX4I1, NDUFA1, and NDUFS1 were strongly upregulated in OXPHOS-high cells, while glycolytic enzymes including HK1, HK2, ENO1, PKM, and ALDOA were enriched in glycolysis-high cells. A gradient boosting classifier distinguished metabolic states with ROC AUC = 0.673 and PR AUC = 0.689, with MALAT1 emerging as the most discriminative and conserved feature. Intercellular communication analysis identified prominent TGFB1→TGFBR1, SPP1→CD44, VEGFA→KDR, CXCL12→CXCR4, EGF→EGFR, and FGF2→FGFR1 signaling axes. qRT-PCR confirmed coordinated metabolic gene changes in BON-1 and QGP-1 cells (r = 0.91, P < 0.01). ELISA confirmed corresponding protein-level alterations. CONCLUSION: The metabolic program of pNET cells shifts from OXPHOS-dominant to glycolysis-dominant states along the differentiation trajectory. MALAT1, ATP5F1B, PKM, and NDUFS1 are positioned as key regulatory nodes. These findings refine current understanding of metabolic reprogramming during pNET differentiation and suggest targeting the OXPHOS-to-glycolysis transition as a potential therapeutic strategy in pancreatic neuroendocrine tumors.
Case Report: Deciphering a complex chromosomal rearrangement causing premature ovarian insufficiency, short stature, and mild intellectual disability using long-read sequencing.
Cheng Q, Peng Q, Lv F … +4 more , Zeng X, Chen X, Li S, Lu X
Front Genet · 2026 · PMID 42338980 · Full text
OBJECTIVE: Premature ovarian insufficiency (POI) with short stature and mild intellectual disability can have diverse genetic etiologies. We aimed to decipher the genetic basis of this complex phenotype in a 26-year-old...
OBJECTIVE: Premature ovarian insufficiency (POI) with short stature and mild intellectual disability can have diverse genetic etiologies. We aimed to decipher the genetic basis of this complex phenotype in a 26-year-old female with a karyotype lacking aneuploidy. DESIGN AND METHODS: This is a case study integrated with comprehensive genetic analyses. After standard techniques (karyotyping, CNV-seq, WES) failed to yield a diagnosis, Oxford Nanopore long-read sequencing was employed to map chromosomal breakpoints at single-base resolution. X-inactivation (XCI) analysis was also performed. RESULTS: Long-read sequencing refined the karyotype to 46,X,t(X; 3;8) (q25; q21p21; p21),t(17; 22)(q21.2; q13) and identified direct disruptions of TAFA5, LARS2, and MYLK. XCI analysis demonstrated highly skewed XCI (5.35%), indicating preferential inactivation of the structurally normal X chromosome. CONCLUSION: We propose that highly skewed XCI is the primary driver of the patient's POI and short stature, while the three disrupted genes may serve as modifying factors. This study underscores the value of long-read sequencing in resolving CCRs and the importance of XCI analysis in female patients with X-chromosome rearrangements.
BUB1 in cancer genetics and oncogenomics: from chromosomal instability to therapeutic vulnerabilities.
Wang S, Liu S, Zhou Y … +2 more , Wang H, Chen J
Front Genet · 2026 · PMID 42338979 · Full text
BUB1 is a serine/threonine kinase and a core component of the spindle assembly checkpoint that safeguards faithful chromosome segregation during mitosis. Accumulating studies have shown that BUB1 is aberrantly expressed...
BUB1 is a serine/threonine kinase and a core component of the spindle assembly checkpoint that safeguards faithful chromosome segregation during mitosis. Accumulating studies have shown that BUB1 is aberrantly expressed across multiple malignancies and contributes to tumor progression through both canonical mitotic functions and noncanonical extramitotic activities. In this review, we summarize the genetic and functional roles of BUB1 in cancer, with a focus on its involvement in chromosomal instability, aneuploidy, therapeutic resistance, and immune evasion. We discuss how BUB1 dysregulation is associated with adverse clinicopathological features and poor prognosis in several tumor types, while also highlighting context-dependent heterogeneity across cancers. Mechanistically, BUB1 contributes to malignant phenotypes by modulating mitotic checkpoint signaling, DNA damage responses, epithelial-mesenchymal transition, ferroptosis sensitivity, cancer stemness, and innate immune signaling. We further review current preclinical evidence supporting BUB1 as a therapeutic target, including the antitumor activity of small-molecule inhibitors and their synergistic potential in combination with radiotherapy, platinum agents, taxanes, and PARP inhibitors. Finally, we outline key unresolved questions, including the critical and still unresolved distinction between kinase-dependent and scaffold-dependent functions-which directly impacts inhibitor design and druggability-toxicity concerns in normal proliferating tissues, and the need for biomarker-guided patient stratification. Collectively, BUB1 represents a preclinically supported but still incompletely validated target in cancer genetics and oncogenomics.
Knowledge mapping of alström syndrome research: a bibliometric and visualization analysis based on WoS data from 2000 to 2025.
Zhang H, Fu H, Sui X … +8 more , Si S, Zhang Y, Li K, Wang M, Song Z, Yang Y, Liu Z, Zhang G
Front Genet · 2026 · PMID 42338978 · Full text
Alström syndrome (ALMS) is an ultra-rare autosomal recessive disorder caused by mutations in the gene, leading to a complex spectrum of multi-organ failure, including early-onset sensory loss, obesity, and cardiomyopath...
Alström syndrome (ALMS) is an ultra-rare autosomal recessive disorder caused by mutations in the gene, leading to a complex spectrum of multi-organ failure, including early-onset sensory loss, obesity, and cardiomyopathy. Despite its clinical significance, a systematic overview of the global research landscape and the intellectual evolution of this field over the past 2 decades remains absent. This study was undertaken to conduct a comprehensive bibliometric and visualization analysis of ALMS research from 2000 to 2025, aiming to identify foundational contributions, evaluate international collaboration patterns, and pinpoint emerging research frontiers. Utilizing data from the Web of Science Core Collection, 345 relevant English-language articles and reviews were analyzed using VOSviewer, CiteSpace, and the R-bibliometrix package. Our findings revealed an exponential growth phase in publications post-2020, with developed nations dominating the research output and Jackson Laboratory serving as a critical international hub. Prolific contributors such as Jan D. Marshall and Pietro Maffei have established dense collaboration networks that facilitate the transition of ALMS research from early genetic characterization to contemporary precision medicine. Keyword and co-citation analysis further highlight a thematic shift toward "ciliopathy" contexts, with recent hotspots focusing on "whole exome sequencing" and the management of "cardiomyopathy". These results imply that while our understanding of ALMS pathogenesis is maturing, significant challenges in phenotypic heterogeneity and the lack of targeted therapies persist. Future research should prioritize interdisciplinary resource integration and the application of advanced genomics to optimize clinical management and patient outcomes in this complex rare disease.
Editorial: Refining precision medicine through AI and multi-omics integration.
Serio VB, Du PF, Frullanti E … +1 more , Palmieri M
Front Genet · 2026 · PMID 42338977 · Full text
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