Genes最新文献

{"title":"Genome-Wide Identification and Characterization of the <i>MAG2</i> Gene Family in <i>Medicago sativa</i>.","authors":"Caiqin Xu, Tao Zhou, Ying Huang, Yihan Yang, Jing Liu, Lu Yang, Qian Li, Xiqiang Liu, Bo Zhang","doi":"10.3390/genes17091111","DOIUrl":"10.3390/genes17091111","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Vesicular trafficking mediates the transport of proteins and other cellular components between intracellular organelles. The MAG2 complex serves as a key tethering factor mediating ER-Golgi retrograde vesicle transport, and has been implicated in plant growth, development, and stress responses. <b>Methods:</b> In this study, seven <i>MAG2</i> family genes were identified in <i>Medicago sativa</i> from the Zhongmu No. 4 reference genome using hidden Markov model searches (HMM) and BLASTP analysis. <b>Results:</b> Phylogenetic analysis assigned four genes to the MAG2 subfamily and three genes to the MAG2L subfamily. Chromosomal distribution and collinearity analyses indicated that segmental duplication potentially contributed to the expansion of the MAG2 family in alfalfa. Gene structure and conserved motif analyses revealed a high degree of conservation among the identified members, with Motif 10 occurring specifically in the MAG2 subfamily. Subcellular localization prediction analysis predicted that four MsMAG2 proteins were localized in chloroplasts, two in the nucleus, and one in the peroxisome. Analysis of promoter sequences identified numerous cis-regulatory elements associated with responses to hormones, light, and environmental stress, suggesting that <i>MsMAG2</i> genes may participate in plant development and environmental adaptation. Furthermore, genome-wide association analysis identified <i>MsMAG2L2</i> that can be associated with tillering. <b>Conclusions:</b> These results provide a comprehensive genome-wide characterization of the <i>MAG2</i> gene family in alfalfa and establish a basis for further investigating the functional associations of MsMAG2L2 in branch development.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Clock</i>-Related Genes Mark a Developmental Cortical Maturation Program Associated with Stage-Resolved Responses to Prenatal Immune Activation.","authors":"Yilin Wang, Shanshan Li, Xin Jin","doi":"10.3390/genes17091107","DOIUrl":"10.3390/genes17091107","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives:&lt;/b&gt; Sleep and circadian disturbances are common in neurodevelopmental conditions, yet the developmental cortical programs linking clock-related transcriptional regulators to disease vulnerability remain unclear. &lt;b&gt;Methods:&lt;/b&gt; Here, we integrated human developmental brain transcriptomes, weighted gene co-expression network analysis (WGCNA), human and mouse cortical single-cell atlases, prenatal immune activation transcriptomes, and ASD postmortem brain datasets to characterize the developmental architecture of BrainSpan-derived cortical programs and examine their behavior in perturbational and disease contexts. &lt;b&gt;Results:&lt;/b&gt; In the BrainSpan frontal cortex, canonical clock-related genes followed structured but heterogeneous developmental trajectories rather than behaving as a coordinated oscillator-like unit. WGCNA identified a postnatal-rising BrainSpan-derived primary developmental module that was strongly associated with developmental age and enriched for synaptic signaling, neurotransmitter transport, ion transport, membrane excitability, cellular respiration, metabolic regulation, and proteostatic processes. Network analysis placed multiple canonical clock-related and clock-regulatory genes, including NPAS2, BHLHE40, BHLHE41, PER family members, RORA, NR1D1/2, and CLOCK, within a broader neuronal and homeostatic co-expression architecture, although their module-membership strengths varied substantially. Projection onto a human cortical developmental single-cell atlas revealed a non-uniform distribution of the corrected BrainSpan-derived developmental signature, with relatively higher scores in excitatory and inhibitory neuronal populations and lower scores in neuroblast and radial glial populations. A mouse cortical developmental single-cell atlas provided a comparative view of the stage- and cell-type-dependent expression of clock-related genes and the transferred developmental signature during corticogenesis. In a Poly(I:C)-based maternal immune activation dataset, litter-aware reanalysis identified stage-resolved genome-wide transcriptional responses following E12.5 exposure. However, neither the aggregate core clock-gene expression score nor the independently transferred BrainSpan-derived developmental signature showed a significant overall treatment effect or collection-stage-by-treatment interaction, indicating that this bulk dataset provides a perturbational context rather than evidence for selective disruption of the developmental program. An exploratory region-stratified analysis of GSE28521 yielded near-null effects for the BrainSpan-derived developmental signature, with confidence intervals crossing zero across all examined regions. These ASD postmortem findings were therefore treated as a boundary assessment rather than evidence of ASD-specific convergence. &lt;b&gt;Conclusions:&lt;/b&gt; Collectively, these findings position clock-related genes as components of a developmentally regulated cortical maturati","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statistical Visibility of Curated TF-Target Regulatory Relationships and Reverse Consistency of Top-Ranked TF-Gene Pairs in Single-Cell Expression Data.","authors":"Wenqing Feng, Zejun Zhang, Zheng Wu, Chengyu Yuan, Jinlei Sun, Guoqiang Wang, Yunqing Liu","doi":"10.3390/genes17091110","DOIUrl":"10.3390/genes17091110","url":null,"abstract":"<p><strong>Background/objectives: </strong>Large language models and automated analytical tools show potential for biomedical text understanding, knowledge integration, and single-cell data interpretation, but interpretations of specific gene regulatory relationships still require empirical grounding. For TF-target relationships, one relevant constraint is whether curated regulatory edges show detectable expression-level statistical evidence in the single-cell data being interpreted, because such evidence may vary across cellular states, conditions, and regulatory mechanisms. We therefore evaluated the statistical visibility of known transcription factor (TF)-target relationships in single-cell expression space to aid the interpretation of regulatory inference and automated-tool outputs.</p><p><strong>Methods: </strong>We performed two complementary analyses: first, testing whether curated TF-target edges showed stronger pair-level associations than matched background gene pairs; and second, assessing whether high-scoring TF-gene pairs corresponded to existing regulatory knowledge and whether their target genes showed pathway coherence.</p><p><strong>Results: </strong>Across four peripheral blood mononuclear cell (PBMC) datasets, four adult tissues, and seven adult cell types, curated TF-target relationships showed weak but reproducible statistical visibility rather than strong separation. For all five association metrics, the mean area under the precision-recall curve (AUPRC) was only slightly above the random-ranking baseline of 0.5. High-scoring pairs were more often supported by curated resources, and their target genes showed context-specific Hallmark pathway coherence.</p><p><strong>Conclusions: </strong>Single-cell expression associations can provide useful but limited statistical clues for TF-target regulation and should be interpreted as complementary rather than definitive regulatory evidence.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling Disulfidptosis and Cuproptosis Vulnerabilities in Pterygium: A Transcriptomic Analysis and In-Silico Drug Repurposing Strategy.","authors":"İdris Sarıkaya, Recep Kılıç","doi":"10.3390/genes17091105","DOIUrl":"10.3390/genes17091105","url":null,"abstract":"<p><strong>Objectives: </strong>Pterygium is an invasive, hyperproliferative fibrovascular disorder of the ocular surface characterized by frequent postoperative recurrence and resistance to apoptosis. This study investigated transcriptional alterations in genes related to the regulated cell death pathways disulfidptosis and cuproptosis in pterygium and explored potential pharmacological candidates through in-silico drug repurposing.</p><p><strong>Methods: </strong>High-throughput RNA-sequencing data (GEO accession GSE155776) from primary pterygium tissues (<i>n</i> = 8) and healthy conjunctival controls (<i>n</i> = 8) were analyzed. The expression profiles of 15 disulfidptosis-related and 13 cuproptosis-related genes were evaluated. Differential expression signatures were subsequently analyzed using the L1000CDS2 platform in reverse mode to identify perturbagens with transcriptional effects opposing the pterygium-associated signature.</p><p><strong>Results: </strong>Transcriptomic analysis demonstrated marked alterations in actin-cytoskeletal genes, with profound downregulation of <i>ACTB</i> and <i>WASF2</i> and upregulation of <i>DSTN</i> and <i>CAPZA1</i>, suggesting a potential vulnerability to disulfide stress. Cuproptosis-related analysis showed increased expression of mitochondrial metabolic genes, including <i>PDHB</i> and <i>DLD</i>, together with significant overexpression of the copper transporter <i>SLC31A1</i>, consistent with transcriptional remodeling of mitochondrial metabolic and copper-handling programs. In-silico drug repurposing identified several FDA-approved drugs with anti-correlative perturbational profiles, including Auranofin, Ouabain, Digitoxin, and Neratinib.</p><p><strong>Conclusions: </strong>Pterygium is associated with coordinated transcriptional alterations involving disulfidptosis- and cuproptosis-related gene networks, suggesting potential structural and metabolic vulnerabilities. In-silico drug repurposing identified several pharmacological candidates whose transcriptional effects oppose the observed disease-associated signature. These findings provide a rationale for further experimental investigation of these pathways and candidate compounds in pterygium.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanopore Ultra-Long Sequencing for FSHD: From Molecular Diagnosis to Preimplantation Genetic Testing.","authors":"Jingjing Li, Yongjie Cheng, Lin Su, Chengyuan Yan, Zhenhua Cao","doi":"10.3390/genes17091104","DOIUrl":"10.3390/genes17091104","url":null,"abstract":"<p><p>Facioscapulohumeral muscular dystrophy (FSHD) is a genetically and epigenetically complex autosomal dominant myopathy that presents formidable challenges to molecular diagnosis and reproductive intervention. The disease is caused by aberrant derepression of the <i>DUX4</i> retrogene within the D4Z4 macrosatellite repeat array at chromosome 4q35, triggered either by pathological contraction of the array on a permissive 4qA haplotype (FSHD1, ~95% of cases) or by mutations in epigenetic modifier genes <i>SMCHD1</i>, <i>DNMT3B</i>, and <i>LRIF1</i> that lead to global D4Z4 hypomethylation (FSHD2, ~5% of cases). Traditional approaches (Southern blotting, optical genome mapping, bisulfite sequencing) are discontinuous and labor-intensive. Nanopore ultra-long read sequencing spans the entire D4Z4 array in single reads, simultaneously resolving repeat number, haplotype, and allele-specific CpG methylation without bisulfite conversion. With the telomere-to-telomere (T2T-CHM13) reference genome, long-range haplotype phasing enables preimplantation genetic testing for monogenic conditions (PGT-M) for families with de novo pathogenic variants and somatic mosaicism, groups previously excluded from reproductive genetic intervention. This review systematically examines FSHD molecular mechanisms, the Nanopore diagnostic workflow integrated with T2T-CHM13, Nanopore-based PGT-M clinical data, and future perspectives including R11 pore chemistry, AI-driven bioinformatics, CRISPR-targeted enrichment, and multi-omics integration.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The <i>Cucurbita ficifolia</i> Mitochondrial Genome: Repeat-Rich Architecture, Plastid Homology, and Synteny Turnover Across Cucurbitaceae.","authors":"Jun Yang, Xinhui Li, Huilin Cheng, Yingfeng Luo, Weifan Wu, Xin Lu, Chengcheng Ling","doi":"10.3390/genes17091103","DOIUrl":"10.3390/genes17091103","url":null,"abstract":"<p><p><b>Background:</b><i>Cucurbita ficifolia</i> (figleaf gourd) is an agriculturally useful cucurbit germplasm and rootstock, but its mitochondrial genome has not been examined in a comparative family-level framework. We aimed to characterize its mitochondrial reference sequence and evaluate coding composition, repetitive DNA, plastid homology, bioinformatic RNA-editing predictions, phylogenetic placement, and genome-scale synteny. <b>Methods:</b> PacBio Revio sequencing generated 933,158 high-fidelity (HiFi) reads totaling 14.294 Gb, with a read N50 of 15.6 kb. The 784,544-bp mitochondrial reference (GenBank accession PZ823090) was assembled with Oatk and evaluated using graph topology, competitive read-back, and junction-spanning alignments. Codon usage, repeats, mitochondrial-plastid homologous regions, bioinformatic C-to-U RNA-editing predictions, conserved-gene phylogeny, and whole-mitogenome synteny were analyzed. <b>Results:</b> The reference had 43.09% GC content and contained 38 distinct protein-coding genes represented by 42 loci, 26 tRNA types represented by 37 loci, and three rRNAs. Competitive read-back retained 40,971 primary mitochondrial alignments (MAPQ ≥ 20), yielding a mean depth of 547.26× and 100% breadth at ≥100×. The terminal-to-start adjacency was supported by 366 HiFi reads with ≥2-kb anchors on each side. We identified 322 simple-sequence repeats, 115 tandem repeats, and 2374 dispersed repeat pairs. For the largest 392-bp direct repeat, the two native junctions were supported by 268 and 308 reads, whereas the two reciprocal junctions were supported by one and zero reads. Ninety-one significant plastid matches collapsed to 73 mitochondrial loci and covered 74,784 unique mitochondrial bases (9.53%). Deepred-Mt generated 494 bioinformatic C-to-U RNA-editing predictions in 37 genes, and phylogenomics placed <i>C. ficifolia</i> as sister to the <i>C. pepo</i>-<i>C. maxima</i> pair with maximal support despite extensive synteny turnover. <b>Conclusions:</b> The <i>C. ficifolia</i> mitogenome combines a conserved coding repertoire with abundant short repeats, appreciable plastid homology, and extensive rearrangement. Read evidence supports the submitted terminal-to-start adjacency but does not establish a unique or predominant circular molecule in vivo; likewise, the largest repeat showed no robust reciprocal-junction signal. All RNA-editing sites reported here are bioinformatic predictions rather than transcript-validated events.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Identification and Characterization of the Annexin (ANN) Gene Family in Potato (<i>Solanum tuberosum</i> L.) and Its Role in Salt Stress Response Revealed by Integrated Transcriptome and WGCNA Analysis.","authors":"Qingsheng Zhou, Jingchong Li","doi":"10.3390/genes17091094","DOIUrl":"10.3390/genes17091094","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Soil salinization threatens global potato production, yet the molecular mechanisms underlying salt tolerance remain poorly understood. This study aimed to elucidate dynamic transcriptomic responses to salt stress, identify key regulatory genes, and characterize the corresponding gene family and its stress-responsive roles. <b>Methods:</b> Potato cv. Atlantic plantlets were subjected to 150 mM NaCl stress, with samples collected at 0, 3, 12, 24, and 48 h. Physiological and transcriptomic analyses were performed. WGCNA was employed to identify salt-responsive modules. Genome-wide identification, phylogenetic analysis, gene structure characterization, conserved motif analysis, and promoter cis-element prediction of the annexin gene family were conducted. <b>Results:</b> Transcriptome sequencing identified 1394 differentially expressed genes (DEGs) that were consistently responsive to salt stress, with functional enrichment highlighting stress signaling, hormone transduction, and phenylpropanoid biosynthesis pathways. Weighted gene co-expression network analysis (WGCNA) revealed the MEblack module as the key salt-responsive regulatory module, in which annexin genes exhibited high intramodular connectivity. Genome-wide identification uncovered nine annexin genes (<i>StANN1</i>-<i>StANN9</i>), characterized by uneven chromosomal distribution, conserved exon-intron structures and annexin repeat domains, and expansion through tandem, proximal and segmental duplication under purifying selection. Promoter analysis revealed abundant stress-responsive cis-elements, including ABRE and DRE/CRT motifs, in salt-inducible annexins. Expression profiling demonstrated that <i>StANN5</i> and <i>StANN6</i> were continuously upregulated under prolonged salt stress, whereas <i>StANN2</i> and <i>StANN3</i> showed transient early induction. <b>Conclusions:</b> These findings establish the central role of annexins in calcium signaling, redox homeostasis, and hormone-mediated stress adaptation, providing candidate targets for molecular breeding of salt-tolerant potato varieties.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Utility of Germline Whole-Exome Sequencing Beyond Multigene Panels in Hereditary Cancer.","authors":"Anastasia Dell'Elice, Lucia Lombardi, Federico Anaclerio, Claudia Palmarini, Nicole Canale, Lorenzo Secondi, Gregorio Stratta, Marco Vitali, Maria Saveria Tavoletta, Simona Grossi, Alessandra Babore, Cristina Milillo, Melania Dovizio, Patrizia Ballerini, Valentina Gatta, Liborio Stuppia, Ivana Antonucci","doi":"10.3390/genes17091102","DOIUrl":"10.3390/genes17091102","url":null,"abstract":"<p><p>Germline Whole-Exome Sequencing (WES) has emerged as a powerful genomic approach for investigating Hereditary Cancer predisposition through the comprehensive analysis of coding regions across the genome. Although multigene panels currently represent the standard diagnostic approach for Hereditary Cancer assessment, a substantial proportion of high-risk individuals and families remain molecularly unexplained. In this setting, germline WES may serve as a valuable second-tier strategy by identifying pathogenic variants in genes not routinely included in conventional testing panels and by addressing part of the unresolved \"missing heritability\" observed across Hereditary Cancer syndromes. Increasing evidence supports its application in hereditary breast and ovarian cancer, Lynch-like syndrome, colorectal polyposis, hereditary diffuse gastric cancer, and ovarian cancer predisposition, where WES has contributed to the identification of additional susceptibility genes and improved molecular characterization. Beyond Hereditary Cancer diagnostics, exome-based approaches have also been explored for tumour profiling, homologous recombination deficiency (HRD) assessment, biomarker discovery, and therapeutic stratification. However, despite its significant potential, the clinical implementation of WES remains challenging because of the high burden of variants of uncertain significance (VUS), difficulties in variant interpretation, incidental findings, and the need for robust functional validation of candidate genes. This review critically examines the current evidence supporting the clinical utility of germline WES in Hereditary Cancer syndromes, focusing on the clinical scenarios in which WES may provide meaningful additional information beyond multigene panels, its diagnostic yield, limitations, and future perspectives in precision oncology.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Omics Mendelian Randomization Maps Lipid-Related Brain Cell-Type Associations with Kidney Disease.","authors":"Jiani Deng, Boning Cao, Fengjie Zheng, Sinan Ai, Yaoxian Wang, Xu Wang","doi":"10.3390/genes17091097","DOIUrl":"10.3390/genes17091097","url":null,"abstract":"<p><p><b>Background:</b> Cellular heterogeneity limits causal inference in complex diseases. We applied an established cell-type-stratified Mendelian randomization (csMR) framework, originally developed by Hao et al. (2024), to investigate whether lipid phenotypes affect kidney disease through distinct brain cell populations, extended by a proteome-wide mediation component. <b>Methods:</b> Using Bayesian colocalization (posterior probability of hypothesis 4 [PPH4], ≥0.8) and multidimensional instrumental variable selection, we evaluated cell-type-stratified MR-supported associations of five lipid traits across ten brain cell or tissue strata with kidney disease risk. Instrumental variables were derived from published genome-wide association studies and human brain single-cell expression quantitative trait locus (eQTL) maps. An exploratory proteomic mediation analysis using the Difference Method was performed with UKB-PPP as the discovery resource and deCODE as the external validation resource, with mediation signals interpreted as hypothesis-generating. For the primary csMR analysis, multiple testing was corrected separately within each lipid trait using a Bonferroni threshold of 3.33 × 10^-4, corresponding to 150 cell/tissue-by-outcome tests per lipid trait. <b>Results:</b> In csMR analyses, cholesterol-related lipids showed cell-type-stratified associations with kidney disease, most prominently in oligodendrocyte-related analyses (max β on the log-odds scale = 1.025). LDL-related associations with broad chronic glomerular disease were most evident in excitatory neuron-related analyses. Dual-cohort proteomic analysis prioritized plasma proteins, including SNAP29 and ICAM4, as candidate protein-associated signals for exploratory mediation analysis. These findings represent genetic colocalization and Mendelian randomization-supported associations, not experimentally established mechanisms, and should be interpreted as hypothesis-generating. <b>Conclusions:</b> This study provides a cell-type-resolved genetic and proteomic association map linking lipid traits, brain cell strata, and kidney disease outcomes, offering hypotheses for future experimental validation.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Codon Usage Bias Analysis of Chloroplast Genomes in Six Cucurbitaceae Species.","authors":"Yongjie Xia, Zhuoran Huang","doi":"10.3390/genes17091095","DOIUrl":"10.3390/genes17091095","url":null,"abstract":"<p><p><b>Background and Objectives</b>: Codon usage bias (CUB), the non-uniform usage of synonymous codons, is prevalent in plant chloroplast genomes and plays important roles in gene expression and genome evolution. However, systematic comparisons of CUB patterns across genera in the Cucurbitaceae family remain limited. This study aimed to characterize CUB patterns and identify their driving forces in the chloroplast genomes of six Cucurbitaceae species. <b>Methods</b>: We analyzed the complete chloroplast genomes of six Cucurbitaceae species, watermelon (<i>Citrullus lanatus</i>), melon (<i>Cucumis melo</i>), cucumber (<i>Cucumis sativus</i>), pumpkin (<i>Cucurbita moschata</i>), wax gourd (<i>Benincasa hispida</i>), and bitter gourd (<i>Momordica charantia</i>). CUB patterns were assessed using ENC-plot, neutrality plot, and PR2-plot analyses, all implemented through a custom, reproducible Python-based workflow. <b>Results</b>: The overall codon usage bias was weak across all six species, with a clear preference for A/U-ending codons. Candidate preferred codons (hereafter referred to as optimal codons for brevity) identified independently within each species were largely shared across the six species, although species-specific codons were also detected. Combined ENC-plot, neutrality plot, and PR2-plot analyses suggest that natural selection, rather than mutation pressure, is the dominant force shaping CUB in these genomes, although these approaches provide indirect evidence. <b>Conclusions</b>: These findings provide a reference for codon optimization of exogenous genes in chloroplast genetic engineering of Cucurbitaceae crops. The Python-based workflow developed in this study also offers a transparent, reproducible alternative to conventional CUB analysis approaches.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}