Functional & Integrative Genomics最新文献

{"title":"Genome-wide meta-analysis dissects the genetic basis and health implications of circulating taurine","authors":"Siquan Zhou,&nbsp;Jiani Tan,&nbsp;Xinlong Li,&nbsp;Zhichang Ran,&nbsp;Jiayuan He,&nbsp;Yanliu Li,&nbsp;Xin Yuan,&nbsp;Yuanqi Hu,&nbsp;Menglei Chen,&nbsp;Yihe Dai,&nbsp;Xiaoyu Wang,&nbsp;Xueting Liu,&nbsp;Ruirui Li,&nbsp;Yujie Xu,&nbsp;Guo Cheng,&nbsp;Jingyuan Xiong","doi":"10.1007/s10142-026-02067-9","DOIUrl":"10.1007/s10142-026-02067-9","url":null,"abstract":"<div><p>Taurine is a semiessential micronutrient critical to many biological processes. However, the genetic variation and the relationships between circulating taurine and human health are unclear. Here, we conducted the largest genome-wide meta-analysis to date, integrating summary statistics from five publicly available independent genome-wide association studies (GWAS) on circulating taurine levels in 36,490 European individuals. We employed LiftOver to harmonize genomic coordinates across the summary statistics derived from five large European cohorts with plasma taurine measurements, followed by a comprehensive genome-wide meta-analysis of both common and rare genetic variants. We utilized functional mapping and annotation and functional annotation of variants to identify genomic loci and variants and estimated global and local single-nucleotide polymorphism heritability using linkage disequilibrium score regression. In our study, we identified six common and two rare variant loci associated with circulating taurine and prioritized novel taurine-associated genes outside of the taurine transporter (<i>SLC6A13</i>) related to glutathione metabolism and neurotransmitter transport using an integrative pipeline. We used genetic proxies of circulating taurine to assess genetically supported putative causal associations on more than 17,000 clinical phenotypes via a phenome-wide Mendelian randomization analysis and demonstrated that genetically predicted circulating taurine shows evidence consistent with potential causal impacts on cancers, hypertension, neurodevelopment, abundance of <i>Bifidobacterium</i>, and brain phenotypes, among several others. We also identified genetic evidence consistent with modifiable relationships between circulating taurine and exposures, including bone mineral density, serum lactate, glycoproteins and creatinine. Collectively, this study systematically dissects the genetic basis of circulating taurine and highlights high-priority disease phenotypes requiring subsequent experimental validation for taurine-targeted nutritional and pharmacological strategies.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Senescence-independent SASP drives tumor-macrophage inflammatory cascade and therapeutic resistance in HNSCC","authors":"Zhaodi Nan,&nbsp;Yikun Mei,&nbsp;Qinran Zhang,&nbsp;Xun Qu,&nbsp;Lian Liu,&nbsp;Dong Zhang","doi":"10.1007/s10142-026-02048-y","DOIUrl":"10.1007/s10142-026-02048-y","url":null,"abstract":"<div><p>Head and neck squamous cell carcinoma (HNSCC) exhibits profound resistance to chemoradiotherapy and immune checkpoint inhibition, which is closely associated with therapy-induced cellular senescence. However, the regulatory mechanism of the senescence-independent senescence-associated secretory phenotype (SASP) driven by double-stranded RNA (dsRNA)-mediated innate immune activation after chemoradiotherapy remains largely unknown. The dsRNA mimic polyinosinic-polycytidylic acid [poly(I:C)] was used to stimulate CAL27 cells, with chloroquine (CQ) intervention to inhibit autophagy. Integrated transcriptomic analysis, in vitro functional assays and clinical specimen validation were performed to explore the regulation, transcellular cascade and prognostic value of senescence-independent SASP. dsRNA-mediated innate immune stimulation triggered NF-κB-dependent senescence-independent SASP in an autophagy-dependent manner without inducing proliferative arrest or classic senescence marker expression. CXCL1 was identified as a candidate key mediator of this SASP subtype. Furthermore, senescence-independent SASP initiates an IL-6-mediated transcellular inflammatory cascade to activate SASP in tumor-associated macrophages, remodeling the immunosuppressive tumor microenvironment. Autophagy inhibition effectively suppressed this SASP, reduced IL-6 secretion and disrupted the tumor-macrophage inflammatory loop. Clinically, the TLR3-autophagy-NF-κB-IL-6 signature was validated as a reliable prognostic biomarker for oral squamous cell carcinoma (HNSCC). This study reveals a novel autophagy-NF-κB-IL-6 axis governing senescence-independent SASP and the downstream inflammatory cascade in HNSCC, representing a promising therapeutic strategy to improve chemoradiotherapy plus immunotherapy efficacy.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-phenotype and cross-species integrative genomic prioritization of FOXF2 and FOXC1 at a cerebral small vessel disease locus","authors":"Yannan Liu,&nbsp;Shuai Tong,&nbsp;Yongjun Peng","doi":"10.1007/s10142-026-02070-0","DOIUrl":"10.1007/s10142-026-02070-0","url":null,"abstract":"<div><p>Cerebral small vessel disease (CSVD) is genetically heterogeneous, and translating regional association signals into biologically plausible effector-gene hypotheses remains challenging. We performed a cross-phenotype and cross-species integrative genomic analysis of the <i>FOXF2</i>-centered proximal chromosome 6 region using publicly available genome-wide association study summary statistics for lacunar stroke, small-vessel disease ischemic stroke subtype and white matter hyperintensity volume. The chr6:0–2.5 Mb interval was treated as the primary regional analysis, whereas <i>FOXF2</i> ± 1 Mb and <i>FOXF2</i> ± 500 kb were examined as nested sensitivity windows. Linkage disequilibrium, regional gene annotation, quantitative trait locus evidence, colocalization, fine-mapping, GWAS Catalog records and human and mouse brain vascular transcriptomic data were integrated within a predefined candidate-prioritization framework. Lacunar stroke showed the strongest regional evidence, with rs7766042 meeting the predefined broad-window local correction threshold, although no signal reached conventional genome-wide significance. The SVD ischemic stroke subtype and WMH signals did not meet their corresponding local correction thresholds. Phenotype-specific lead variants showed low pairwise linkage disequilibrium, a pattern consistent with regional signal heterogeneity but not sufficient to establish distinct causal signals. <i>FOXF2</i> and <i>FOXC1</i> were prioritized as leading neurovascular candidates, whereas <i>EXOC2</i> and <i>GMDS</i> were retained as secondary positional candidates. Several regional variants overlapped <i>FOXF2</i> eQTL annotations; however, formal colocalization showed little evidence for a shared causal variant (PP.H4 = 0.0604), and fine-mapping did not resolve a single causal variant. Human and mouse brain vascular transcriptomic analyses provided cross-species expression-based cellular context for <i>FOXF2</i> and <i>FOXC1</i>. These findings support regional candidate-gene prioritization at the proximal chromosome 6 locus while emphasizing that the available evidence does not establish a definitive multi-signal or multi-gene causal architecture.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-resolved testing of network-pharmacology candidates in dilated cardiomyopathy: PI3K–AKT-associated transcriptional differences are distributed across cardiac lineages and are not enriched above a genome-wide background","authors":"Yingying Qian,&nbsp;Haitao Tian,&nbsp;Shuaihong Zhao,&nbsp;Yanjiao Bian,&nbsp;Hongyang Yu,&nbsp;Ang Di,&nbsp;Yingshuang Jia,&nbsp;Shaodan Li,&nbsp;Runquan Sun","doi":"10.1007/s10142-026-02059-9","DOIUrl":"10.1007/s10142-026-02059-9","url":null,"abstract":"<div><p>Network pharmacology nominates targets but cannot show that they are altered in the relevant cell, distinguishable from a hypothesis-free analysis of the same data, or linked to disease. Taking the candidates nominated for Yangxin Decoction in dilated cardiomyopathy (DCM) and viral myocarditis, we asked how many survive independent functional-genomic testing. Few did. A direct-evidence intersection returned 61 genes, but across four bulk cardiac datasets the set was differentially expressed no more often than the transcriptome-wide background in any human cohort, and <i>AKT1</i> was significant in none. Donor-pseudobulk single-nucleus RNA sequencing of 52 DCM and 18 control donors showed higher <i>AKT1</i> (log2 fold change 0.351, adjusted <i>P</i> = 3.32 × 10^− 4), <i>PIK3CA</i> and <i>GSK3B</i> and lower <i>STAT3</i> in cardiomyocytes; no fold-change threshold was applied, and the <i>AKT1</i> difference is small. These differences were robust to nucleus depth, sex, age, ventricle and DCM genotype; in an independent single-nucleus DCM cohort <i>AKT1</i> (0.530) and <i>STAT3</i> (− 0.771) replicated at FDR &lt; 0.05, <i>PIK3CA</i> was directionally consistent, and <i>GSK3B</i> did not replicate. Three further tests constrain the interpretation. A disease × cell-type interaction model showed that <i>PIK3CA</i> is altered in most cardiac lineages and significantly more in fibroblasts than in cardiomyocytes, endothelial or immune populations, whereas the <i>AKT1</i> difference, although significant only in cardiomyocytes, could not be shown to differ from that in most other lineages, so it reflects detection rather than demonstrated restriction. A whole-heart pseudobulk of the same donors still detected <i>AKT1</i> (adjusted <i>P</i> = 6.8 × 10^− 3), so cellular dilution does not explain the negative bulk-microarray result. Benchmarked against an unbiased genome-wide analysis of the same cardiomyocyte comparison, the nominated 61-gene set was not enriched (46.7% versus a 41.3% background, <i>P</i> = 0.281) and <i>AKT1</i> ranked 2,182 of 14,586. A prespecified screen found no cis-eQTL instrument for <i>AKT1</i>; a single whole-blood <i>MTOR</i> Wald ratio was not supported by colocalization. These are cell-type-resolved transcriptional differences in dilated cardiomyopathy, not evidence that Yangxin Decoction engages PI3K–AKT signalling and not a validated therapeutic mechanism.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL14-mediated m6A modification of CXCL9 mRNA regulates macrophage CS polarization to suppress OSCC growth and stemness","authors":"Bo Yang,&nbsp;Feng Liu,&nbsp;Yanfang Qiu,&nbsp;Wenqiong Wu,&nbsp;Hailin Zhang,&nbsp;Haolei Tan,&nbsp;Cuihong Jiang","doi":"10.1007/s10142-026-02053-1","DOIUrl":"10.1007/s10142-026-02053-1","url":null,"abstract":"<div><p>Oral squamous cell carcinoma (OSCC), the most prevalent histological subtype of oral cancer, is characterized by an immunosuppressive tumor microenvironment (TME) predominantly modulated by tumor-associated macrophages (TAMs). The CXCL9/SPP1 ratio (CS ratio) has been validated as a more reliable prognostic biomarker than the conventional M1/M2 classification. Although methyltransferase-like 14 (METTL14) participates in TAM polarization, its specific role in regulating the CS balance in OSCC remains elusive. This investigation elucidates the mechanism by which METTL14 modulates TAM CS polarization and affects OSCC growth and stemness. We utilized single-cell RNA sequencing (scRNA-seq) data for OSCC and normal samples from Gene Expression Omnibus (GEO) to characterize TAM CS polarization and screen critical regulatory molecules. To independently validate the expression of key candidate genes, we additionally analyzed three independent bulk transcriptomics cohorts from GEO, comprising 330 patient tissue samples. A METTL14-overexpressing TAM model was constructed to explore the effects of METTL14 on CS polarization and OSCC growth and stemness. The target gene of METTL14-mediated m6A modification was identified using the RM2Target database and validated by cellular experiments. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an m6A reader protein, mediates the downstream biological effects of this epigenetic modification. Finally, the impact of METTL14-driven TAM CS polarization on OSCC tumor growth and stemness was verified in vitro and in vivo in a macrophage-specific Mettl14 knockout mouse model. scRNA-seq re-analysis uncovered mutually exclusive CXCL9⁺ and SPP1⁺ TAM populations in OSCC. METTL14 was markedly enriched and co-expressed in CXCL9⁺ TAMs, where it showed a negative correlation with cancer stemness pathways. Independent validation in three bulk transcriptomics cohorts (n = 330) confirmed significant differential expression of CXCL9 and METTL14 between OSCC tumor and normal tissues. In vitro, METTL14 overexpression in TAMs promoted CXCL9⁺ TAM generation and suppressed OSCC cell growth and stemness, an effect attributed to METTL14-mediated m6A modification of CXCL9 mRNA, which was recognized and stabilized by the m6A reader protein IGF2BP3. Consistently, in vivo assays using macrophage-specific METTL14-knockout mice revealed that METTL14 knockdown reduced m6A modification levels of CXCL9 mRNA, promoted the polarization of TAMs toward the SPP1⁺ phenotype, and ultimately accelerated OSCC tumor growth and enhanced cancer stemness. Collectively, this study identifies a novel mechanism wherein METTL14 regulates TAM CS polarization by promoting m6A modification of CXCL9 mRNA, thereby driving TAMs towards a CXCL9⁺ phenotype and suppressing OSCC growth and stemness.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into gallic acid–induced autophagy in triple negative breast cancer through network pharmacology, molecular docking, and in vitro validation","authors":"Essha Chatterjee,&nbsp;Biswajit Dey,&nbsp;Ankush Bansode,&nbsp;Santanu Basak,&nbsp;Anamika Sharma,&nbsp;Santosh Kumar Guru","doi":"10.1007/s10142-026-02058-w","DOIUrl":"10.1007/s10142-026-02058-w","url":null,"abstract":"<div><p>Gallic acid (GA), a natural polyphenol, has been enormously recognized for its anticancer properties across multiple cancer types, including triple-negative breast cancer (TNBC), yet its precise molecular mechanisms underlying its effects on TNBC, particularly those related to autophagy, remain unclear. This investigation sought to elucidate the autophagy-related targets and pathways modulated by GA in TNBC by integrating network pharmacology, bioinformatics, molecular docking, and in vitro validation. Network pharmacology identified 23 overlapping targets between GA, TNBC, and autophagy-related gene sets, including key genes such as CASP3, TP53, AKT1, PIK3CA, and HIF-1 A. Protein-Protein Interaction network analysis revealed ten hub genes as central nodes in GA’s action mechanism. Gene Ontology enrichment highlighted biological processes such as DNA damage response, protein phosphorylation, and regulation of apoptosis and autophagy. KEGG pathway analysis further indicated enrichment in pathways related to EGFR inhibitor resistance, insulin signaling, autophagy, and apoptosis, among others. Molecular docking demonstrated strong binding affinities between GA and the identified autophagy modulatory genes. In vitro experiments showed that GA inhibited the proliferation and migration of BT-549 and HCC1395 TNBC cells while inducing autophagy. Induction of autophagy by GA in the BT-549 and HCC1395 cell lines was proved by acridine orange, MAP1LC3B fluorescence, and western blotting of key autophagy regulators. Taken together, this integrated approach, combining network pharmacology and experimental validation, identified key targets and signaling pathways through which GA regulates autophagy in TNBC. These findings enhance our understanding of GA’s anticancer mechanisms and support its plausible development as a therapeutic entity for TNBC.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacology, single-cell transcriptomics, machine learning and experimental validation identifying CHEK2 and HPGD as key therapeutic targets of berberine in diabetic nephropathy","authors":"Youmin Pu,&nbsp;Huan Chang,&nbsp;Wei Chen,&nbsp;Huhai Zhang,&nbsp;Wenjie Chen,&nbsp;Hongwen Zhao,&nbsp;Daodong Sun","doi":"10.1007/s10142-026-02052-2","DOIUrl":"10.1007/s10142-026-02052-2","url":null,"abstract":"<div><p>Diabetic nephropathy (DN) is a severe microvascular complication of diabetes with limited therapeutic options. Berberine exhibits renoprotective potential, yet its precise molecular targets and mechanisms of action in DN remain unclear. Berberine targets were retrieved from TCMSP, SEA, and SwissTargetPrediction databases. Bulk transcriptomic microarray datasets (GSE96804, GSE30122) and single-cell RNA sequencing (scRNA-seq) dataset (GSE131882) were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were applied to GSE96804, followed by single-cell analysis and high-dimensional WGCNA (hdWGCNA) on podocytes. Key targets were refined via protein-protein interaction (PPI) network topology, random forest, and SHAP analysis. Molecular docking, 100 ns molecular dynamics (MD) simulations, and MM/PBSA calculations were performed to elucidate binding mechanisms. In vitro validation used human podocytes exposed to high glucose (30 mM, 48 h) ± berberine, with knockdown and overexpression plasmids transfected for rescue experiments. Single-cell analysis identified a total of 11 renal cell types; in DN, the number of podocytes was significantly reduced, and their intercellular communication was the most intense. CHEK2 and HPGD were identified as key targets—CHEK2 expression is upregulated in DN, whilst HPGD expression is downregulated—and both targets demonstrated robust diagnostic performance using nomogram, receiver operating characteristic curves, and decision curve analysis. Molecular docking revealed high binding affinities (CHEK2: -8.8 kcal/mol; HPGD: -9.9 kcal/mol), supported by stable molecular dynamics trajectories and favourable MM/PBSA binding free energies. In vitro, berberine normalised CHEK2 and HPGD expression, improved cell viability, reduced apoptosis, and restored structural markers of podocytes (Nephrin, Podocin, WT1), inhibited fibrotic proteins (Collagen I, fibronectin, α-SMA), and alleviated oxidative stress (decreased ROS, decreased MDA, increased SOD, increased GSH-Px). Importantly, rescue experiments demonstrated that the renoprotective effects of berberine were functionally dependent on CHEK2 and HPGD modulation in this in vitro model: CHEK2 gene silencing or HPGD overexpression further enhanced berberine’s protective effects, whereas CHEK2 overexpression or HPGD gene silencing abolished this protection and restored the cellular phenotype to that observed under hyperglycaemic conditions. This comprehensive multi-omics study, incorporating rescue experiments, identified CHEK2 and HPGD as functionally important candidate mediators of berberine’s renoprotective effects in DN, providing preliminary mechanistic insights to inform precision diagnosis and targeted therapeutic strategies.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-region transcriptomic framework reveals global and region-specific ubiquitin-proteasome system biomarkers in Alzheimer's disease","authors":"Apurva Lakra,&nbsp;Pravir Kumar","doi":"10.1007/s10142-026-02061-1","DOIUrl":"10.1007/s10142-026-02061-1","url":null,"abstract":"<div><p>The involvement of ubiquitin-proteasome system (UPS) impairment in Alzheimer’s disease (AD) is increasing gradually yet the molecular organization of the system throughout the AD brain is poorly understood, as is the distribution of molecular markers. To systemically identify UPS-associated molecular signatures, we carried out a multi-region transcriptomic analysis of six different brain regions in AD patients and age-matched controls. The molecular perturbation of regions recapitulated the known regional vulnerability hierarchy with significant changes observed in the entorhinal cortex and hippocampus as well as middle temporal gyrus and posterior cingulate. A synchronized downregulation of UPS components was observed in the vulnerable regions indicating towards the extensive dysfunction of ubiquitin-mediated protein surveillance and proteasomal degradation. The consistent features associated with UPS disruption were linked with synaptic dysfunction, mitochondrial impairment and loss of proteostatic homeostasis as revealed by the functional analyses. We formulated a framework based on composite prioritization which combined several aspects like differential expression, network topology, regional consistency and diagnostic performance for the purpose of identifying strong biomarker candidates. The analysis revealed the most eminent global biomarkers of AD associated with UPS, namely, PSMB4, SNCA, PSMB7, PSMD1, and UBE3A. UBE2R1 (CDC34) was used to define region-specific biomarker signatures in the entorhinal cortex, UBC in the hippocampus, PSMA3 in middle temporal gyrus, PSMD4 in posterior cingulate cortex and UBE2V2 in superior frontal gyrus. These exploratory results provide the first systems-level biomarker atlas of UPS dysfunction in distinct AD brain regions and suggest that there are potential global and region-specific UPS signatures that could be used in diagnostics and drug development.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative genomic and phenotypic analyses reveal broad-spectrum antifungal activity and biocontrol potential in Bacillus ayatagriensis","authors":"Vinícius de Souza,&nbsp;Raissa Vitória Viana de Carvalho,&nbsp;Edilania Pereira da Silva,&nbsp;Isaac Farias Cansanção,&nbsp;Edineia Bonin,&nbsp;Leandro Teodoski Spolaor,&nbsp;Adriane Freire Araújo Feitoza,&nbsp;Adailson Feitoza de Jesus Santos","doi":"10.1007/s10142-026-02063-z","DOIUrl":"10.1007/s10142-026-02063-z","url":null,"abstract":"<div><p>The Caatinga biome represents an important reservoir of microbial biodiversity that remains largely unexplored for the development of agricultural bioinputs. In this study, genomic analyses and phenotypic assays were integrated to investigate the biocontrol potential of two <i>Bacillus</i> strains isolated from this environment. Phylogenomic analyses identified the isolates as <i>Bacillus subtilis</i> BSS.245 and <i>Bacillus ayatagriensis</i> BSS.246. The genomes comprised 4.10 and 4.01 Mb, with GC contents of 43.67% and 46.58%, encoding 4,077 and 3,852 genes, respectively. Genome mining revealed biosynthesis-related gene clusters associated with the production of antimicrobial metabolites, including bacilysin, bacillibactin, fengycin, and surfactin. <i>B. ayatagriensis</i> BSS.246 exclusively harbored clusters for macrolactin H and difficidin biosynthesis, compounds widely recognized for their antimicrobial activity. Genes potentially involved in plant growth promotion, stress adaptation, and plant–microbe interactions were also identified. Phenotypic assays demonstrated tolerance to reduced water availability, salinity, and elevated temperature in both strains, as well as exopolysaccharide production. Both strains exhibited broad-spectrum antifungal activity against <i>Alternaria</i>, <i>Colletotrichum</i>, <i>Corynespora</i>, <i>Fusarium</i>, <i>Lasiodiplodia</i>, <i>Macrophomina</i>, <i>Rhizoctonia</i>, and <i>Sclerotinia</i> species, with mycelial growth inhibition ranging from 58.04% to 100.00%. To our knowledge, this study provides the first experimental evidence of the antifungal potential of <i>B. ayatagriensis</i>, expanding the current knowledge of this recently described species. These findings identify both strains as promising agricultural microbial resources and provide a basis for further evaluation of their potential for phytopathogen management and plant-associated applications.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing next-generation molecular technologies for precision control of Tuta absoluta and Helicoverpa armigera in tomato","authors":"Amina Amin Ch.,&nbsp;Noman Nazik,&nbsp;Muniba Shahid,&nbsp;Misbah Saleem,&nbsp;Areesha Nadeem,&nbsp;Faisal Saeed,&nbsp;Abdul Qayyum Rao,&nbsp;Iqbal Rashid,&nbsp;Allah Bakhsh","doi":"10.1007/s10142-026-02064-y","DOIUrl":"10.1007/s10142-026-02064-y","url":null,"abstract":"<div><p>Tomato (<i>Solanum lycopersicum</i>) is one of the most significant vegetable crops cultivated around the world. Among biotic stresses, production of tomato is severely affected by insect pests mainly by tomato fruit borer (<i>Helicoverpa armigera</i>) and tomato leaf miner (<i>Tuta absoluta</i>). Traditionally to manage the destruction caused by insect pests, farmers mostly used chemical insecticides and by different cultural practices. Use of chemical pesticides is of great concern as it is harmful for the environment and other living beings and with the passage of time, insects develop resistance against pesticides. Latest progress in molecular biology enables scientists to develop next generation pest management approaches that are more precise, environment friendly and sustainable. This review describes nascent molecular approaches to manage tomato pests, like transgenic expression of insecticidal proteins such as of <i>Bacillus thuringiensis</i> (Bt) toxins, RNAi (RNA interference) strategies including HIGS and SIGS, genome editing by CRISPR-Cas, protease inhibitors and male sterility. These strategies not only enhance resistance of crop against pests but also are safe for environment and other organisms. This review also addresses the combination of different molecular approaches and pyramiding of genes involve in delaying resistance. Overall, these advanced molecular approaches providing sustainable resistance against insect pests have been discussed.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}