Genes最新文献

{"title":"Effect of Storage Time on DNA Obtained from Umbilical Cord Used in Forensic Identification.","authors":"Marta Ortega-Martínez, Devani Moreno-Sánchez, Jenifer Hernández-Martínez, María-de-Lourdes Chávez-Briones, Yareth Gopar-Cuevas, Jaime García-Juárez, Gilberto Jaramillo-Rangel","doi":"10.3390/genes17091066","DOIUrl":"10.3390/genes17091066","url":null,"abstract":"<p><strong>Background/objectives: </strong>In the identification of human remains, their genetic profile can be compared with that obtained from biological samples of the person from whom they are suspected to have come. Our aim was to evaluate the effect of storage time on DNA obtained from umbilical cord that could be used as a reference in forensic identification.</p><p><strong>Methods: </strong>Fifteen umbilical cords stored by the donors in their homes for a period of between 0.5 and 47 years were collected. Saliva samples were obtained for use as a reference. DNA extraction was performed using the PrepFiler Express BTA™ Forensic DNA Extraction Kit and quantified using the Quantifiler™ HP DNA quantification kit. STR profiling was performed using the GlobalFiler™ PCR Amplification Kit. Alleles were detected using an ABI PRISM^® 3500 genetic analyzer.</p><p><strong>Results: </strong>In samples from 0.5 to 21 years of age, DNA concentration and degradation index (DI) did not follow a linear pattern over time; the genetic profiles obtained matched that of the corresponding saliva sample. Older samples showed lower DNA concentration values and higher DIs. The percentage of alleles recovered decreased to 31% in the oldest umbilical cord analyzed. However, from a sample stored for 31 years, a DNA concentration and DI similar to the younger samples were obtained, along with a complete STR profile.</p><p><strong>Conclusions: </strong>It is possible to obtain STR profiles useful for forensic identification from umbilical cords even after decades of storage; however, success is highly variable and cannot be predicted from storage time alone.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060239","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":"Integrating RNA-Seq, Transcription Factor Annotation, and WGCNA Identifies Key Candidate Genes in Upland Cotton Seedlings Under Short-Term Drought Stress.","authors":"Gang Wang, Wanli Han, Zhibin Zhang, Xiaomei Ma, Hai Zhao, Yandi Yao, Fuxiang Zhao, Jinxin Qiao, Xiang Zhang, Yu Yu, Hongguang Liu","doi":"10.3390/genes17091068","DOIUrl":"10.3390/genes17091068","url":null,"abstract":"<p><p><b>Background:</b> Drought is one of the major abiotic stresses that affect and limit cotton growth and production. However, transcriptome differences between drought-tolerant and drought-susceptible cotton lines remain largely unknown. <b>Methods and Results:</b> In this study, two upland cotton cultivars, the drought-tolerant XLZ80 and drought-sensitive XLZ61, were subjected to comparative phenotypic and transcriptomic analyses under drought stress. Phenotypic evaluation showed that XLZ80 exhibited only mild leaf wilting, whereas XLZ61 displayed severe wilting symptoms after drought stress. RNA-seq analysis revealed that differentially expressed genes in XLZ80 were specifically enriched in pathways related to phosphatidylinositol signaling, phenylalanine metabolism, MAPK signaling, and betaine biosynthesis, while DEGs in XLZ61 were primarily involved in basal metabolic processes. A total of 9302 core DEGs were identified across and between the cultivars and were grouped into eight dynamic expression clusters containing 841 transcription factors. Weighted gene co-expression network analysis further identified three key modules associated with drought tolerance. Twelve hub genes, including <i>GH_D02G2153</i> (MADS-box) and <i>GH_A05G1087</i> (bZIP), were identified as central regulators. qRT-PCR validation confirmed that these genes exhibited faster and stronger induction in the tolerant cultivar. In summary, this study deepens the transcriptional-level understanding of drought stress responses in cotton and provides valuable gene resources for breeding drought-resistant cultivars.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060269","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":"Integrative Identification of Candidate Protein Targets and Compounds for Dystonia Using Mendelian Randomization, Single-Cell RNA Sequencing, and Network Pharmacology.","authors":"Lin Chen, Ming-Juan Fang, Nan Cheng, Yin Xu","doi":"10.3390/genes17091067","DOIUrl":"10.3390/genes17091067","url":null,"abstract":"<p><strong>Background: </strong>Dystonia is a severe neurological disorder with enigmatic pathogenesis. Current treatment options are limited in preventing the disease progression, underscoring the urgent need for new targeted therapeutic agents to develop more effective therapies.</p><p><strong>Methods: </strong>We performed a proteome-wide Mendelian randomization (MR) study and sensitivity analyses to evaluate the causal relationships between dystonia and proteins. GO and KEGG enrichment analysis of dystonia-associated proteins was conducted. Then, we built PPI network and identified the expression of hub-genes in specific brain neurons in single-cell sequencing data. Additionally, we performed drug enrichment analysis of hub-genes, and employed network pharmacology and molecular docking methods to identify potential drugs for dystonia.</p><p><strong>Results: </strong>Our study identified genetically predicted associations consistent with a potential causal effect between 51 proteins and risk of dystonia. GO and KEGG enrichment analyses revealed that these proteins are involved cellular response to transforming growth factor-β stimulation and cytokine-cytokine receptor interaction. Notably, the PPI network exhibited 21 community relationships within the regulatory network among the 51 dystonia-associated proteins identified. The single-cell RNA annotations for brain cluster specificity revealed Tumor necrosis factor (TNF) was highly expressed in microglia cells. Drug enrichment analysis identified five traditional Chinese medicine monomers (paeoniflorin, artesunate, ginsenoside Rh1, psoralen, and quercetin dihydrate) as candidates for molecular docking analysis. Among these, paeoniflorin-TNF, quercetin dihydrate-TNF, and artesunate-TNF exhibited the highest binding energy (-9.1 kcal/mol).</p><p><strong>Conclusions: </strong>Our molecular-docking analysis suggested that traditional Chinese medicine monomers including paeoniflorin, quercetin dihydrate, and artesunate may serve as promising candidates for future drug development.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060293","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":"Selective Whole-Blood Expression of Interferon-Stimulated Genes and TLR3/TLR7 in Type 1 Diabetes with Minimal Enterovirus-Targeted Amplification in Whole Blood.","authors":"Ilaria Galliano, Francesca Nardo, Davide Tinti, Cecilia Nobili, Paola Montanari, Cristina Calvi, Michela Trada, Luisa De Sanctis, Massimiliano Bergallo","doi":"10.3390/genes17091065","DOIUrl":"10.3390/genes17091065","url":null,"abstract":"<p><strong>Background: </strong>Enteroviruses (EVs) have been proposed as environmental triggers in type 1 diabetes (T1D), potentially through activation of innate immune pathways and type I interferon (IFN) responses. However, the relationship between detectable viral infection and IFN-related transcriptional responses remains unclear.</p><p><strong>Methods: </strong>In this cross-sectional, exploratory study, peripheral blood samples from individuals with new-onset T1D, established T1D, and healthy controls were analyzed by an enterovirus <i>5'NCR</i>-targeted RT-PCR assay and for the expression of innate immune receptors (<i>TLR3</i>, <i>TLR7</i>, <i>TLR8</i>), interferon-stimulated genes (<i>IFI27</i>, <i>IFIT1</i>, <i>ISG15</i>, <i>IFI44L</i>, <i>RSAD2</i>, <i>SIGLEC1</i>), and <i>FOXP3</i>, assessed as an exploratory marker related to regulatory T-cell biology potentially influenced by type I interferon signaling. Gene expression was assessed by quantitative RT-PCR, and comparisons were performed between groups.</p><p><strong>Results: </strong>Enterovirus-targeted amplification was observed in only one T1D sample under the applied assay conditions. In the setting of limited enterovirus-targeted amplification under the applied assay conditions, <i>TLR3</i> was significantly increased in established T1D, while <i>TLR7</i> was increased in both new-onset and established T1D, with the highest levels in established disease; these differences remained significant after correction for multiple comparisons across the full gene panel. <i>TLR8</i> was unchanged. Several of the selected interferon-stimulated genes showed group-specific expression patterns: <i>IFI27</i> and <i>RSAD2</i> were significantly increased in new-onset T1D, whereas <i>IFIT1</i> and <i>ISG15</i> were more evident in established T1D. <i>SIGLEC1</i> and <i>IFI44L</i> showed no significant differences. <i>FOXP3</i> transcript abundance was also increased in both diabetic groups, a finding that correlated with lymphocyte proportion and is interpreted with caution.</p><p><strong>Conclusions: </strong>These findings indicate group-specific differences in whole-blood transcript expression of selected RNA-sensing and IFN-related genes in T1D under conditions in which enterovirus-targeted amplification was observed in only one sample. Given the cross-sectional whole-blood design and the analytical limitations of the EV assay, these results are hypothesis-generating and do not establish the presence or absence of systemic enterovirus infection or functional pathway activation.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060382","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":"Genetic Basis of Tobacco Use Disorder.","authors":"Guillermo Gervasini","doi":"10.3390/genes17091064","DOIUrl":"10.3390/genes17091064","url":null,"abstract":"<p><p>Tobacco use disorder (TUD) is a complex multifactorial condition resulting from the interplay between nicotine-induced neurobiological adaptations, behavioral and learning processes, environmental influences, and individual genetic susceptibility. Genetic research has progressively evolved from twin and family studies through candidate-gene approaches to large-scale genome-wide association studies (GWAS), substantially improving our understanding of the genetic architecture of tobacco use and nicotine dependence. This review summarizes the current evidence on the genetic basis of TUD, with particular emphasis on major biological pathways. We also discuss the limitations of early candidate-gene studies and the paradigm shift introduced by large GWAS and meta-analyses, and polygenic risk scores, which indicate that tobacco use and nicotine dependence have a highly polygenic and pleiotropic architecture. Finally, we review the potential clinical applications of genetic information in smoking-cessation treatment, while highlighting current limitations in clinical translation. In the future, it is clear that a multidisciplinary approach-combining genetics, clinical practice, and social sciences-will be necessary to transform tobacco use management into a precision-based model and reduce its impact on public health.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060312","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":"Cross-Model Uncertainty-Aware Minimal Editing of Cis-Regulatory Elements for Cell-Type-Selective Design.","authors":"Angran Xia, Changwei Wang, Yemao Xia","doi":"10.3390/genes17091062","DOIUrl":"10.3390/genes17091062","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Cis-regulatory elements (CREs) help mediate cell-type-selective gene expression, yet sequence-to-activity models are rarely converted into compact, experimentally tractable variant panels that retain natural regulatory scaffolds. We developed SafeEdit-CRE to select minimal edits that preserve cross-model specificity while reducing predictive uncertainty, yielding an auditable CRE variant library for reporter-screening prioritization. <b>Methods:</b> SafeEdit-CRE combines the published Malinois sequence-activity predictor with an architecture-distinct reviewer ensemble, validation-calibrated uncertainty, sequence-domain controls, and constrained beam search. Natural 200 nt CREs were edited under fixed substitution budgets of 1, 5, 10, or 20 nucleotides and evaluated by a separately trained multi-kernel ensemble kept entirely separate from candidate generation. <b>Results:</b> Across 600 held-out CRE parents in K562, HepG2, and SK-N-SH cells, SafeEdit-CRE achieved a mean cross-model specificity-margin gain of 0.877 versus 0.822 for greedy editing (paired difference 0.055; 95% CI 0.040-0.071). Relative to a compute-matched primary-model beam, SafeEdit-CRE yielded a similar cross-model specificity-margin gain (difference -0.004; 95% CI -0.011-0.004) with lower ensemble uncertainty (0.314 vs. 0.335). In a locked 90-parent benchmark, 60.6% of designs passed all nine prespecified sequence and model-agreement checks, compared with 38.8% for greedy and 13.1% for random substitution (paired difference 21.8 percentage points; 95% CI 18.3-25.3). <b>Conclusions:</b> SafeEdit-CRE reduced 3240 designs to 74 Tier A computational candidates prioritized for reporter screening across three cell types and four edit budgets. By separating search from cross-model audit and enforcing explicit edit budgets and sequence-domain safeguards, the framework provides a reproducible and auditable approach to computational CRE prioritization, regulatory-grammar studies, and synthetic regulatory-element design.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059760","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":"GWAS-by-Subtraction Resolves Coronary Artery Disease-Related and Model-Defined Residual Genetic Components of Ischaemic Stroke.","authors":"Binyang Wang, Yuxue Wang, Yong Yin","doi":"10.3390/genes17091061","DOIUrl":"10.3390/genes17091061","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Genetic overlap between any ischaemic stroke (AIS) and coronary artery disease (CAD) can obscure associations less closely tied to coronary risk. We aimed to separate coronary-shared from residual AIS genetic effects. <b>Methods:</b> We applied GWAS-by-subtraction to GIGASTROKE AIS and UK Biobank/CARDIoGRAMplusC4D CAD summary statistics. A Cholesky model separated a CAD-related shared component (F1) from a model-defined residual AIS component (F2). We tested model order, factor covariance, population prevalence, CAD input, LD reference and sample-size parameter then characterised loci using FUMA, SuSiE-RSS, genetic correlation, MAGMA, SMR/HEIDI and targeted colocalisation. <b>Results:</b> AIS and CAD had a genetic correlation of 0.490. F1 and F2 had SNP heritabilities of 0.0251 and 0.00414, and F2 contained 14 FUMA loci. F2 Z scores remained correlated across covariance (minimum r = 0.994), prevalence (minimum r = 0.998) and alternative-CAD analyses (r = 0.984). Reverse ordering produced reallocation of source-trait signal. At rs974819, the T allele was associated positively with CAD and negatively with marginal AIS, producing a model-derived CAD-AIS-discordant F2 association. Source-trait colocalisation showed that NBEAL1, PHACTR1 and PDGFD signals were present in one or both input-trait analyses, whereas the F11 protein signal aligned with AIS and F2. In a potentially overlapping FinnGen cross-implementation analysis, all 13 F2 lead variants showed concordant directions. Within overlapping stroke-subtype analyses, F2 showed stronger alignment with cardioembolic stroke. <b>Conclusions:</b> GWAS-by-subtraction resolved a model-defined residual AIS component that was stable across covariance, prevalence and CAD-input specifications, supporting a component-based view of AIS genetic effects after modelling shared coronary architecture.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060232","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 of the <i>APRR2</i> Gene Family and Rind Color Trait Analysis in Zucchini (<i>Cucurbita pepo</i>).","authors":"Tongsheng Liu, Shuo Li, Ke Wu, Xinbin Wang, Xiaoyang Sun, Wenqi Ding","doi":"10.3390/genes17091063","DOIUrl":"10.3390/genes17091063","url":null,"abstract":"<p><p>Rind color is an important quality trait in zucchini (<i>Cucurbita pepo</i>). As a core transcription factor in plant pigment biosynthesis, <i>APRR2</i> plays a conserved yet mechanistically diverse regulatory role in the formation of rind color in various vegetables. However, the APRR2 transcription factor regulates rind color but has not been systematically identified in <i>C</i>. <i>pepo</i>. In this study, 50 <i>APRR2</i> genes were defined by the presence of the conserved REC domain verified. These genes were identified and found to be unevenly distributed across the 20 chromosomes, primarily expanded through tandem duplication events. Phylogenetic and structural analysis classified these genes into three distinct subgroups, all featuring the conserved REC domain essential for pigment regulation but exhibiting variations in motifs and intron-exon structures. Promoter analysis revealed abundant light-responsive, hormone-responsive and stress-responsive elements that may contribute to environmental adaptation and photomorphogenesis. Crucially, transcriptome analysis during rind development (0 and 10 days after pollination) in green (GR) and white (WR) rind lines demonstrated profound functional divergence. Expression clusters indicated temporal shifts in metabolism and enriched \"circadian rhythm-plant\" and \"photosynthesis\" pathways in WR at 0 DAP. Specific <i>APRR2</i> genes were tightly correlated with rind color. qPCR validation of the 24 selected <i>APRR2</i> genes classified them into four trend groups based on the direction of expression change at 10 DAP. In total, 14 genes were upregulated in both GR and WR, 6 were downregulated in both lines, 1 was upregulated in GR but downregulated in WR, and 3 were downregulated in GR but upregulated in WR. Furthermore, protein-protein interaction prediction and yeast two-hybrid (Y2H) assays detected a physical interaction in yeast between a core APRR2 protein and a bHLH62 transcription factor, suggesting a potential interaction that may be involved in rind color regulation, pending in planta validation. The study first identified the members of the <i>APRR2</i> gene family in <i>C</i>. <i>pepo</i> and conducted a bioinformatics analysis on them. The study establishes the molecular basis of APRR2 function and offers valuable resources for breeding improved <i>C</i>. <i>pepo</i> varieties.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060090","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 of the <i>PsatGST</i> Gene Family and Expression Analysis Under Freezing Stress in Peas (<i>Pisum sativum</i> L.).","authors":"Zaoxia Niu, Lijuan Zhang, Bolin Sun, Gengmei Min, Zongwen Chai, Yang Shao","doi":"10.3390/genes17091052","DOIUrl":"10.3390/genes17091052","url":null,"abstract":"<p><strong>Background: </strong>Glutathione S-transferases (GSTs) play pivotal roles in plant growth, abiotic stress responses, detoxification of xenobiotics, and maintenance of redox homeostasis.</p><p><strong>Methods: </strong>In this study, transcriptomic analysis was employed to identify differentially expressed genes (DEGs) in the pea cultivar DX27 under freezing stress (-4 °C) at 3, 6, and 12 h.</p><p><strong>Results: </strong>GO and KEGG enrichment analyses of global transcriptomic data further reveal that DEGs are significantly enriched in the following functional categories: oxidation-reduction processes, stress responses, glutathione metabolism, and secondary metabolite biosynthesis. A total of 52 <i>PsatGST</i> genes were identified and classified into nine subfamilies based on phylogenetic relationships. Chromosomal localization revealed a non-random distribution across seven chromosomes. Promoter cis-element analysis indicated that <i>PsatGST</i> genes harbor diverse regulatory elements associated with light responsiveness, hormone signaling (auxin, abscisic acid, gibberellin, salicylic acid, and MeJA), and abiotic/biotic stress responses. <i>PsatGSTF2</i> expression analysis showed pronounced up-regulation under freezing stress (-4 °C) at 3, 6, and 12 h.</p><p><strong>Conclusions: </strong>These findings provide a foundational framework for understanding the evolutionary history and functional diversification of the <i>PsatGST</i> gene family and offer valuable candidate genes for the breeding of stress-tolerant pea varieties.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060162","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":"Gut Microbiota and Metabolic Pathway Signatures for Inflammatory Bowel Disease Identified via Subject-Stratified Random Forest Based on the Longitudinal HMP2 Cohort.","authors":"Qiupeng Du, Lu Xing, Chenchen Zhu, Ping Li","doi":"10.3390/genes17091053","DOIUrl":"10.3390/genes17091053","url":null,"abstract":"<p><p><b>Background:</b> Inflammatory bowel disease (IBD) is characterised by severe intestinal microbial dysbiosis. Most machine learning diagnostic models built on the longitudinal HMP2 cohort suffer serious data leakage from random sample-level cross-validation splitting, which leads to artificially inflated AUC values. Additionally, incomplete reporting of microbial preprocessing, random forest hyperparameters and multi-dimensional evaluation metrics reduces the reproducibility of existing research. <b>Methods:</b> We re-analysed the public HMP2 (IBDMDB) longitudinal metagenomic dataset containing 130 unique subjects (103 IBD/27 healthy controls) and 1627 longitudinal faecal samples. Raw 585 species were filtered by a minimum relative abundance of 1 × 10^-5 and sample prevalence ≥20%, retaining 89 taxa; all 1135 metabolic pathways were retained. CLR transformation was applied to compositional abundance data. We performed Wilcoxon differential testing with Benjamini-Hochberg FDR correction, alpha/beta diversity analysis, and three random forest models (filtered species, all FDR-significant pathways, strictly filtered pathways). Critical improvements included subject-ID-stratified 5-fold cross-validation repeated 5 times, within-fold training-set-only feature importance calculation, and class weighting to balance unbalanced IBD/control samples. PERMANOVA with subject stratification and PERMDISP dispersion test were implemented with 999 fixed-seed permutations. <b>Results:</b> All four alpha diversity indices were significantly lower in IBD patients (all <i>p</i> < 0.0001). Subject-stratified PERMANOVA showed disease status only explained 1.18% of total Bray-Curtis community variance (R² = 0.0118, <i>p</i> = 1); PERMDISP detected significant group dispersion heterogeneity (<i>p</i> = 0.027). We identified 63 differentially abundant species and 695 perturbed pathways at FDR < 0.05. Canonical butyrate producers <i>Faecalibacterium prausnitzii</i> and <i>Roseburia hominis</i> showed no significant inter-group differences. Bootstrap 1000-resampling AUC 95% CIs indicated moderate classification performance: species model (0.626-0.705, mean AUC = 0.665), all-significant-pathway model (0.645-0.712, mean AUC = 0.679), strict-pathway model (0.620-0.685, mean AUC = 0.654). <i>Alistipes putredinis</i> and peptidoglycan biosynthesis I were the top taxonomic and pathway biomarkers, respectively. <b>Conclusions:</b> This study established a leakage-free machine learning pipeline for longitudinal microbiome cohorts via subject-level cross-validation splitting. The moderate AUC values eliminate false high performance caused by sample leakage, and we provide reliable candidate microbial and metabolic biomarkers for IBD. Restricted by single-cohort internal validation and unadjusted medication confounders, these markers still require independent multi-centre external verification before clinical translation.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060185","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}