Functional & Integrative Genomics最新文献

{"title":"Genetically informed prioritization of immune checkpoint–associated genes in head and neck cancer highlights HGF and AKT1","authors":"Mengjie Zheng,&nbsp;Hao Zhu,&nbsp;Jun Kong,&nbsp;Li Zhang","doi":"10.1007/s10142-026-02049-x","DOIUrl":"10.1007/s10142-026-02049-x","url":null,"abstract":"<div><p>Immune checkpoint inhibitors are used to treat head and neck cancer (HNC), but clinical responses vary, and systematic genetic evaluation is needed to prioritize candidate susceptibility genes. We applied summary-data-based Mendelian randomization (SMR) and HEIDI testing to screen 624 immune checkpoint–related genes, integrating GWAS data from the Million Veteran Program with blood-derived multi-omics QTLs, and explored replication in FinnGen. Two-sample MR sensitivity analyses (MR-Egger, weighted median, MR-PRESSO) assessed pleiotropy for prioritized candidates, which were further contextualized using tumor expression and survival outcomes (overall survival [OS], progression-free interval [PFI]) in The Cancer Genome Atlas (TCGA-HNSC) cohort. Several SMR-prioritized genes showed directional concordance between genetically predicted effects and tumor expression, including the protective candidate <i>HGF</i> (OR_SMR = 0.37, <i>P</i> = 0.010) and the risk-associated <i>AKT1</i> (OR_SMR = 1.19, <i>P</i> = 0.024). Both were further supported by two-sample MR sensitivity analyses (<i>HGF</i>: OR_IVW = 0.72, <i>P</i> = 0.007; <i>AKT1</i>: OR_IVW = 1.17, <i>P</i> = 0.009), with no evidence of horizontal pleiotropy (Egger intercept <i>P</i> &gt; 0.05). Higher tumor <i>HGF</i> expression correlated with better OS (HR_Cox = 0.70, <i>P</i> = 0.008) and PFI (HR_Cox = 0.72, <i>P</i> = 0.020), whereas higher <i>AKT1</i> expression correlated with poorer OS (HR_Cox = 1.42, <i>P</i> = 0.010). None of the eQTL or pQTL associations replicated in FinnGen. By integrating genetic signals with tumor transcriptomic and clinical data, this study prioritized immune checkpoint–related genes potentially involved in HNC susceptibility. <i>HGF</i> and <i>AKT1</i> emerged as the most consistently supported candidates, showing convergent tumor transcriptomic and survival support despite lacking genetic replication in FinnGen, providing a foundation for further biological investigation.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-026-02049-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023592","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":"Single-cell and spatial transcriptomics inform mechanistic physiology in non-model animals","authors":"Adnan Amin,&nbsp;Wajid Zaman","doi":"10.1007/s10142-026-02054-0","DOIUrl":"10.1007/s10142-026-02054-0","url":null,"abstract":"<div><p>Comparative physiology increasingly requires cellular resolution at the level of cell types, tissue microenvironments, and regulatory programs that associate genotype with function under environmental variation. Bulk transcriptomics and tissue-level assays have revealed pathways associated with stress responses, metabolic shifts, and developmental transitions; however, they average signals across heterogeneous cell populations and frequently obscure which cells contribute to physiological phenotypes. Single-cell RNA sequencing (scRNA-seq), single-nucleus RNA sequencing (snRNA-seq), and spatial transcriptomics (ST) address complementary aspects of this limitation by resolving transcriptional heterogeneity and, for spatial approaches, preserving tissue context. These technologies are extending beyond classical biomedical models to non-model animals, enabling discovery of cell states, comparison of cell-type evolution, and spatially informed hypotheses concerning ionoregulation, respiration, immune defense, endocrine signaling, regeneration, and symbiosis. This review provides a physiology-centered blueprint for applying these approaches to non-model species and critically evaluates dissociation and preservation bias, genome annotation, seasonal and ecological variation, biological replication, pseudoreplication, cross-species integration, and spatial resolution. We distinguish descriptive mapping, replicate-aware association, mechanistic hypothesis generation, and causal validation because expression patterns, colocalization, trajectories, and ligand–receptor predictions do not by themselves demonstrate mechanism. Practical reporting and validation standards are proposed to improve reproducibility and connect cellular maps with independent physiological measurements and perturbation experiments.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023402","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":"Comprehensive genome-based characterization and pan-genome analysis of Bacillus paranthracis SM02 isolated from a fermented food ecosystem","authors":"Jaganathan Gowri Shankar,&nbsp;Rajkumar Sudharsan,&nbsp;Mebanjop Lyngdoh,&nbsp;Denyoung Umbon,&nbsp;Thokchom Thajamanbi Chanu,&nbsp;Nachimuthu Senthil Kumar,&nbsp;Pulapet Sowmya,&nbsp;Kesavan Markkandan,&nbsp;S. Thangminlal Vaiphei","doi":"10.1007/s10142-026-02060-2","DOIUrl":"10.1007/s10142-026-02060-2","url":null,"abstract":"<div><p>Fermented foods represent complex microbial ecosystems in which spore-forming <i>Bacillus</i> species persist due to their stress tolerance and metabolic versatility. In the present study, whole-genome sequencing was applied to characterize <i>Bacillus paranthracis</i> SM02, a strain isolated from a traditional fermented sword bean food, with the aim of resolving its taxonomic position and genomic features related to adaptation and biosafety. Whole genome sequencing generated a 5.50 Mb draft genome assembled into 65 contigs with an N50 of 257,567 bp and a GC content of 35.13%, comprising 5,567 predicted protein-coding genes. Average nucleotide identity values exceeding 95% with reference genomes and phylogenomic analysis based on conserved orthologs confirmed the placement of SM02 within the <i>B. paranthracis</i> lineage. Genome annotation identified 35 AMR genes, including putative resistance determinants such as <i>fosB</i> and <i>bcrA–C</i>, along with conserved antibiotic target-associated genes such as <i>gyrA</i>, <i>gyrB</i>, <i>rpoB</i>, and <i>mprF</i>. These findings represent genomic predictions and do not by themselves establish phenotypic antimicrobial resistance. Virulence-associated genes such as <i>nhe</i>A, <i>nhe</i>B, <i>nhe</i>C, <i>alo</i>, <i>inh</i>A, <i>cod</i>Y, and <i>sig</i>B, along with oxidative stress response genes (<i>sod</i>A, sodC), were detected. Genes linked to biofilm-associated lifestyles, including <i>lux</i>S, <i>lsr</i>R, <i>rpo</i>N, <i>hfq</i>, and polysaccharide metabolism genes (<i>glg</i>A, <i>glg</i>C), were also present. Pan-genome analysis of sixteen <i>B. paranthracis</i> genomes revealed an open pan-genome comprising approximately 7,500–8,000 gene families with a conserved core of nearly 3,900 gene families, while SM02 contained 1,086 accessory and 133 strain-specific genes. Overall, the results revealed a conserved genomic backbone coupled with a flexible accessory genome, suggesting genomic features that may contribute to adaptation within the fermented food environment.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029429","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":"Mutations in untranslated non-coding regions of EGFR, AKT1 & HRAS modulate their expression regulatory networks to facilitate progression of colorectal cancer","authors":"Iqra Abdullah,&nbsp;Samina Ejaz","doi":"10.1007/s10142-026-02050-4","DOIUrl":"10.1007/s10142-026-02050-4","url":null,"abstract":"<div><p>Mutations in the untranslated region (UTR) of a gene dysregulate its expression by disrupting the regulatory elements. Defective EGFR, AKT1, and HRAS are known to promote colorectal cancer (CRC) by activating oncogenic signaling pathways. The current study aimed to screen the Pakistani CRC patients for UTR mutations of EGFR, AKT1, and HRAS genes and investigate the functional impact of detected mutations on regulatory elements. The genomes of CRC patients were analyzed by whole-exome sequencing. All the identified UTR mutations were subjected to extensive in silico analysis to study the functional consequences on pathogenicity, oncogenicity, regulatory elements, mRNA structure, transcription factor binding sites, and miRNA binding sites. Moreover, miRNA expression, pathway, protein-protein interaction and gene enrichment analysis were also performed. The present study identified UTR mutations of EGFR (<i>n</i> = 5), AKT1 (<i>n</i> = 6), and HRAS (<i>n</i> = 3) in Pakistani CRC patients. Among 5ʹ UTR mutations of EGFR, c.-216G &gt; T causes loss of TF and motif sequences, c.-191 A &gt; C increases strength of the motif sequences, AKT1: c.-463dupG, c.-47 C &gt; T, and c.-478G &gt; C, and HRAS: c.-101 C &gt; T mutations stabilize the mRNA structure and alter the motif sequence and transcription factor binding sites. Whereas 3ʹ UTR mutations of EGFR c.*281dupA and c.*774T &gt; C and AKT1 c.*301C &gt; T cause loss of oncomiR sites. PPI and pathway enrichment analysis show that EGFR, AKT1, and HRAS interact with other oncogenes. This study reported the presence of damaging mutations in the regulatory region, which may alter the expression of EGFR, AKT1, and HRAS. The information thus generated could facilitate designing personalized therapy.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023663","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":"Genome of the tardigrade Cucumibius annulatus: functional annotation and specific proteins","authors":"Daria Makarova,&nbsp;Denis Tumanov,&nbsp;Elena Nassonova,&nbsp;Mikhail Rayko","doi":"10.1007/s10142-026-02055-z","DOIUrl":"10.1007/s10142-026-02055-z","url":null,"abstract":"<div><p>Tardigrades are microscopic invertebrates renowned for their capacity to survive extreme environmental conditions, yet stress tolerance strategies vary substantially across the phylum. Here we present the first genome assembly and annotation for the superfamily Isohypsibioidea — the most basal group within the order Parachela — represented by freshwater species <i>Cucumibius annulatus</i>. The draft genome (73 Mb, N50 = 96.4 kb, BUSCO 87.1%) was assembled from short-read data. Orthogroup-based comparison against three reference tardigrades and two ecdysozoan outgroups (<i>Caenorhabditis elegans</i>, <i>Drosophila melanogaster</i>) identified a set of orthogroups unique to <i>C. annulatus</i>. Canonical tardigrade heat-soluble protein families (CAHS, SAHS, MAHS) are present but at lower copy numbers than in other sequenced Parachela, and trehalose biosynthesis enzymes are absent, consistent with the non-anhydrobiotic lifestyle of the species. This study provides a genomic resource for a newly established genus and a comparative framework for interpreting ancestral genomic features of Parachela.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011836","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":"Identification and expression validation of key genes of Xiaozhengtongluo formula in the treatment of diabetic nephropathy by Mendelian randomization","authors":"Zhao Liu,&nbsp;Moxixuan Liu,&nbsp;Haina Wu,&nbsp;Ying Zhang,&nbsp;Zhiqiang Chen,&nbsp;Xiaona Wei,&nbsp;Yun Ma,&nbsp;Xinai Wang,&nbsp;Hui Gao,&nbsp;Jinmei Zheng,&nbsp;Jing Liang","doi":"10.1007/s10142-026-02045-1","DOIUrl":"10.1007/s10142-026-02045-1","url":null,"abstract":"<div><p>Xiaozhengtongluo formula (XZTL) has a positive effect on the treatment of diabetic nephropathy (DN), but its mechanism is not fully understood. Therefore, it is important to explore the key genes of XZTL in the treatment of DN. Differentially expressed genes (DEGs) between DN and control obtained from GSE96804, drug target genes of XZTL, and disease target genes of DN obtained from public databases were intersected. Genes of intersection were defined as candidate genes. Next, Mendelian randomization (MR) analysis was used to ascertain the causal associations between candidate genes and DN. Afterwards, key genes were confirmed through receiver operating characteristic (ROC) curve analysis and expression validation. Subsequently, enrichment analysis, molecular regulatory network analysis, and molecular docking were conducted. Finally, experimental verification of the expression levels of key genes was performed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Altogether, 29 candidate genes were screened via MR analysis, identifying APOD, IGFBP3, and LPL as significantly associated with DN. IGFBP3 and APOD were risk factors, whereas LPL was protective. Consistent expression trends across training and validation datasets defined them as key genes. All three were co-enriched in 26 pathways, including oxidative phosphorylation. Regulatory networks showed MIR497HG/hsa-miR-19a-3p regulated IGFBP3, and NEAT1/hsa-miR-29a-3p regulated LPL; IGFBP3 and LPL were co-targeted by SP3 and SP1. Molecular docking revealed APOD-baicalein, LPL-oleic acid, and IGFBP3-quercetin binding, suggesting therapeutic potential. RT-qPCR confirmed aberrant expression of these genes in DN, which was normalized by XZTL intervention. In this study, three key genes (APOD, IGFBP3, and LPL) of XZTL in the treatment of DN were finally obtained, providing mechanistic clues for understanding XZTL’s multi-target mechanism and providing experimentally tractable candidate targets for DN molecular subtyping, targeted therapeutic development, and precision medicine approaches in TCM.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-026-02045-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986786","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":"An lncRNA-aware single-cell framework with donor-level validation identifies reproducible MEG3 enrichment in human liver sinusoidal endothelial cells","authors":"Hidenori Tani","doi":"10.1007/s10142-026-02051-3","DOIUrl":"10.1007/s10142-026-02051-3","url":null,"abstract":"<div><p>Long non-coding RNAs (lncRNAs) associated with metabolic liver disease are usually identified from bulk tissue, which cannot resolve the hepatic cell types that express them, and default single-cell pipelines discard most lncRNAs at feature selection. We present an lncRNA-aware single-cell analysis framework — retaining all detectable GENCODE v45 lncRNAs during highly variable gene selection — combined with donor-level validation that guards against pseudoreplication. The framework applies to already published data and needs no lncRNA-specific protocol. Applying it to the human Liver Cell Atlas (Gene Expression Omnibus accession GSE192742; 152,559 annotated cells, 16 donors), and using the source publication’s own cell-type annotation, we found <i>MEG3</i> enriched in liver sinusoidal endothelial cells (LSECs) in abundance as well as in detection frequency: donor-level pseudobulk expression was 6.27 counts per 10,000 versus 1.05 in the next-ranked cell type, and the LSEC pseudobulk value exceeded the pooled non-LSEC value in all nine informative donors (paired Wilcoxon signed-rank: two-sided <i>P</i> = 0.0039, one-sided <i>P</i> = 0.0020). The LSEC-enriched detection pattern reproduced in an independent five-donor atlas (all five donors concordant). <i>KCNQ1OT1</i> was not LSEC-specific. Benchmarking our clustering against the published annotation showed that two marker-scored lineages contained none of their nominal cell type; separately, the candidates returned by a within-lineage pseudotime screen were driven entirely by non-endothelial cells contaminating the LSEC lineage: correlations of |ρ| &gt; 0.31 fell below 0.10 within correctly annotated endothelial cells and reversed sign in one quarter of alternative roots. We therefore report the pseudotime screen as a negative result, and provide the framework, the annotation audit and the two-cohort analysis as a reproducible resource.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986785","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 transcriptomic, spatial and functional-genomic analysis identifies a UFMylation-related vascular-stromal program and prioritizes WWTR1 in glioblastoma","authors":"Junqing Yan,&nbsp;Jingliang Ye,&nbsp;Wenbo Qian,&nbsp;Junle Zhu,&nbsp;Zhiping Wan,&nbsp;Haoheng Wang,&nbsp;Xiangtian Meng,&nbsp;Jinmao Gu,&nbsp;Feng Chen,&nbsp;Chun Luo","doi":"10.1007/s10142-026-02046-0","DOIUrl":"10.1007/s10142-026-02046-0","url":null,"abstract":"<div><p>Glioblastoma (GBM) contains spatially organized stress-adaptive and vascular niches. Because transcript abundance does not measure UFM1 conjugation, we asked whether a UFMylation-related transcriptional axis identifies a reproducible tissue program and alters candidate prioritization. In 518 unique primary TCGA-GBM tumors profiled on the Affymetrix HT Human Genome U133A array, weighted gene co-expression network analysis of 8,000 variable genes yielded 12 modules. The 278-gene green module ranked first across nine prespecified traits (mean |r|=0.637). Direct overlap comprised 1/3 measurable UFMylation-core, 5/19 ER-stress/UPR, and 2/15 proteostasis genes; after excluding overlapping genes, correlations with the green eigengene remained significant (<i>r</i> = 0.373, 0.831, 0.639, and 0.699 for UFMylation-core, ER-stress/UPR, proteostasis, and composite scores, respectively). The green score was associated with overall survival per standard-deviation increase (HR 1.17, 95% CI 1.07–1.28), although clinical adjustment attenuated the estimate. In a 10-sample single-cell dataset, sample-level scores were higher in pericytes and endothelial cells than in malignant cells. Donor-aware IvyGAP analysis supported regional organization, whereas one Visium section showed stronger concordance with ER-stress/UPR and mesenchymal scores than with the UFMylation-core score. CellChat indicated pathway-selective rather than global remodeling of inferred vascular communication. Layer ablation moved WWTR1 from rank 48 using WGCNA alone to rank 4 overall and rank 1 among non-common-essential genes after cross-platform integration. These findings define an ER-stress/mesenchymal-weighted, UFMylation-related vascular-stromal transcriptional association and nominate WWTR1 for experimental testing.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981779","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":"A comprehensive map of the bovine mobilome and their epigenetic regulation of mastitis","authors":"Naisu Yang \u0000 (,&nbsp;),&nbsp;Mengqi Wang \u0000 (,&nbsp;),&nbsp;Sarah E. Abanda Mbili,&nbsp;Antony T. Vincent,&nbsp;Chengyi Song \u0000 (,&nbsp;),&nbsp;Eveline M. Ibeagha-Awemu","doi":"10.1007/s10142-026-01970-5","DOIUrl":"10.1007/s10142-026-01970-5","url":null,"abstract":"<div><p>Retrotransposons are major components of mammalian genomes, yet their genome-wide annotation and epigenetic regulation in cattle remain incompletely characterized. Here, we present a comprehensive annotation and integrative epigenomic analysis of major retrotransposon classes in the bovine genome, with emphasis on DNA methylation patterns and their potential roles in subclinical mastitis. Using a multi-step <i>de novo</i> pipeline, we identified and classified long interspersed nuclear elements (LINEs), short interspersed nuclear elements (SINEs), and endogenous retroviruses (ERVs) in the bovine reference genome, including three LINE families, seven SINE families, and 20 ERV families. Retrotransposons accounted for ~ 40% of the genome, with LINEs representing the largest fraction. Evolutionary analysis suggested that BosL1A1, BosSINEL, BosERV1, and BosERV16 are the most recently active families. DNA methylation profiles in milk somatic cells showed consistently high levels across retrotransposons, with widespread hypermethylation in cows with <i>Staphylococcus aureus</i>–induced subclinical mastitis. We identified 20,839 differentially methylated retrotransposons, 3,306 of which overlapped differentially expressed genes. Promoter- and exon-overlapping elements showed inverse correlations between methylation and gene expression, and enriched genes are involved in immune and transport pathways. These results provide a comprehensive bovine mobilome resource and indicate that retrotransposon methylation is associated with gene regulation and host responses to mastitis.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-026-01970-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981809","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":"Integrative analysis and experiment validation of SLC12A8 as a biomarker for the malignant transition from endometriosis to endometriosis associated ovarian cancer","authors":"Yingyu Dou,&nbsp;Bairong Xia","doi":"10.1007/s10142-026-02047-z","DOIUrl":"10.1007/s10142-026-02047-z","url":null,"abstract":"<div><p>Endometriosis (EM) is a chronic inflammatory, estrogen‑dependent benign gynecological disorder. A subset of patients with EM may subsequently develop endometriosis‑associated ovarian cancer (EAOC), implying a biological continuum between these two conditions. Nevertheless, the molecular events underlying the progression from benign endometriotic lesions toward EAOC remain incompletely characterized. In this study, transcriptomic datasets retrieved from the GEO database were interrogated through differentially expressed gene screening, functional enrichment analysis, and weighted gene co‑expression network analysis (WGCNA) to identify key genes and pathways relevant to EM and EAOC. Candidate genes were further prioritized by integrating survival analysis via the Kaplan‑Meier Plotter, LASSO regression, random‑forest modeling, and CIBERSORT immune‑infiltration profiling. Loss and gain‑of‑function cellular models were established using siRNA and overexpression plasmids, and in‑vitro functional assays were performed to characterize the phenotypic effects of target genes.We identified several candidate genes associated with EM and EAOC and evaluated their discriminatory performance. Among them, SLC12A8 elevated expression across EM and EAOC tissues and exhibited moderate diagnostic capacity. Higher SLC12A8 expression was also associated with poorer prognosis in EAOC patients. In‑vitro experiments further demonstrated that SLC12A8 modulates proliferation, invasion, and migration in both EM and EAOC cell lines. Collectively, our exploratory research findings support SLC12A8 as a candidate functional mediator and potential biomarker linked to EM‑EAOC pathological progression, thereby extending the mechanistic understanding of these disorders.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975351","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}