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Identification of cross-talk pathways and PANoptosis-related genes in periodontitis and atherosclerosis by bioinformatics analysis and machine learning 通过生物信息学分析和机器学习鉴定牙周炎和动脉粥样硬化的串音通路和panoptosis相关基因
IF 3 2区 生物学
Genomics Pub Date : 2025-09-10 DOI: 10.1016/j.ygeno.2025.111106
Nan Yang , Shiqun Sun , Xiantao Chen , Tongtong Yan , Nan Gu , Zhihui Liu
{"title":"Identification of cross-talk pathways and PANoptosis-related genes in periodontitis and atherosclerosis by bioinformatics analysis and machine learning","authors":"Nan Yang ,&nbsp;Shiqun Sun ,&nbsp;Xiantao Chen ,&nbsp;Tongtong Yan ,&nbsp;Nan Gu ,&nbsp;Zhihui Liu","doi":"10.1016/j.ygeno.2025.111106","DOIUrl":"10.1016/j.ygeno.2025.111106","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Periodontitis(PD) is a chronic inflammatory disease that poses a serious threat to oral health and is one of the risk factors for atherosclerosis(AS). A growing body of evidence suggests that the two diseases are closely related. However, current studies have yet to fully understand the common genes and common mechanisms between PD and AS. This study aimed to screen the tandem genes of PD and AS and the potential relationship between the tandem genes and pan-apoptosis-related genes. By analyzing the relationship between the core genes and immune cells, it will provide new targets for clinical treatment.</div></div><div><h3>Materials and methods</h3><div>The PD and AS datasets were downloaded from the GEO database and differential expression analysis was performed to obtain DEGs. AS-related genes were downloaded from the GeneCards database, and PANoptosis-related genes were obtained through literature review. AS-related genes were merged into AS DEGs, and overlapping DEGs were cross-talk genes for PD and AS. Protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software. Pearson coefficients were used to calculate the correlation between cross-talk genes and PANoptosis-related genes in the PD and AS datasets. The intersection of cross-talk genes and PANoptosis-related genes was defined as cross-talk-PANoptosis genes. Core genes were screened using ROC analysis and XGBoost. PPI sub-network, gene-biological processes and gene-pathway networks were constructed based on the core genes. In addition, immune infiltration on the PD and AS datasets was analyzed using the CIBERSORT algorithm.</div></div><div><h3>Results</h3><div>285 cross-talk genes overlapped between PD DEGs and AS DEGs. The intersection of cross-talk genes with 109 PANoptosis-related genes was defined as cross-talk-PAoptosis genes. ROC and XGBoost showed that MLKL, ZBP1, CD14, and IL6 were more accurate than the other cross-talk-PAoptosis genes in predicting the diseases, and were better in terms of the overall characteristics. GO and KEGG analyses showed that these four core genes were involved in the immune and inflammatory response of the organism. The results of immune infiltration showed that Monocytes and Mast cells resting were altered to a greater extent in PD and AS patients. Finally, 24 drugs related to the core genes were retrieved from the DGIDB database.</div></div><div><h3>Conclusions</h3><div>This study reveals the joint mechanism between PD and AS associated with PANoptosis. Analyzing the four core genes and immune cells may provide new therapeutic directions for the pathogenesis of PD combined with AS.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111106"},"PeriodicalIF":3.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A modular pipeline for evidence-integrated genome annotation across species: A case study on Schmidtea mediterranea 跨物种证据整合基因组注释的模块化管道:以地中海Schmidtea mediterranea为例
IF 3 2区 生物学
Genomics Pub Date : 2025-09-08 DOI: 10.1016/j.ygeno.2025.111104
Anastasiia Zaremba, Małgorzata Marszałek-Zeńczak, Annasha Dutta, Anna Samelak-Czajka, Paulina Jackowiak
{"title":"A modular pipeline for evidence-integrated genome annotation across species: A case study on Schmidtea mediterranea","authors":"Anastasiia Zaremba,&nbsp;Małgorzata Marszałek-Zeńczak,&nbsp;Annasha Dutta,&nbsp;Anna Samelak-Czajka,&nbsp;Paulina Jackowiak","doi":"10.1016/j.ygeno.2025.111104","DOIUrl":"10.1016/j.ygeno.2025.111104","url":null,"abstract":"<div><div>Despite advancements in genome annotation tools, challenges persist for non-classical model organisms with limited genomic resources, such as <em>Schmidtea mediterranea</em>. To address these challenges, we developed a flexible and scalable genome annotation pipeline that integrates short-read (Illumina) and long-read (PacBio) sequencing technologies. The pipeline combines reference-based and <em>de novo</em> assembly methods, effectively handling genomic variability and alternative splicing events. To improve splice site detection accuracy, DeepSplice deep learning predictions are used. Functional annotation is conducted to filter out low-confidence transcripts and ensure biological relevance. Applying this pipeline to the asexual strain of <em>S. mediterranea</em> revealed thousands of previously undescribed putative genes and transcripts, and improved the existing gene models, highlighting its utility in annotating complex, underexplored genomes. The modularity and comprehensiveness of our pipeline ensure its adaptability for genome annotation across diverse species, making it a valuable tool for annotating genomes of non-model organisms and supporting broader genomic research. The source code and implementation details are available at <span><span>https://github.com/Norreanea/SmedAnno</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 6","pages":"Article 111104"},"PeriodicalIF":3.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Decoding oxygen preference: Machine learning discovers functional genes in Bacteria. 解码氧偏好:机器学习发现细菌的功能基因。
IF 3 2区 生物学
Genomics Pub Date : 2025-09-01 Epub Date: 2025-08-06 DOI: 10.1016/j.ygeno.2025.111095
Siqi Wan, Haida Liu, Geyi Zhu, Yuanming Geng, Wenhao Li, Lijuan Chen, Yunhua Zhang, Guomin Han
{"title":"Decoding oxygen preference: Machine learning discovers functional genes in Bacteria.","authors":"Siqi Wan, Haida Liu, Geyi Zhu, Yuanming Geng, Wenhao Li, Lijuan Chen, Yunhua Zhang, Guomin Han","doi":"10.1016/j.ygeno.2025.111095","DOIUrl":"10.1016/j.ygeno.2025.111095","url":null,"abstract":"<p><p>Predicting bacterial oxygen preference and identifying associated genes is critical in microbiology. This study developed a machine learning model using genomic features to predict bacterial oxygen preference and discover potential functional genes. Trained on a dataset of 1813 bacterial genomes, a Random Forest model achieved 90.62 % accuracy in predicting oxygen preference, outperforming prior methods. Feature analysis pinpointed key protein domains and candidate genes. Experimental overexpression of model-identified genes (encoding SOD, SAM radical enzyme, GCV-T, FDH domains) in Escherichia coli enhanced growth under aerobic conditions, validating their role in oxygen adaptation. Applying the model to rumen metagenomes revealed a predominantly anaerobic community. This work establishes machine learning as an effective strategy for bacterial oxygen preference prediction and functional gene identification, offering a novel strategy and tool for in-depth understanding of bacterial oxygen adaptation mechanisms, discovering key functional genes, and efficient exploration of uncultured microbial resources.</p>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":" ","pages":"111095"},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Response of primary mammary epithelial cells to pathogen challenge in dairy cows with divergent genomic breeding values for udder health 奶牛原代乳腺上皮细胞对病原菌攻击的响应
IF 3 2区 生物学
Genomics Pub Date : 2025-08-26 DOI: 10.1016/j.ygeno.2025.111102
Terhi Iso-Touru , Daniel Fischer , Frank Panitz , Suvi Taponen , Zexi Cai , Goutam Sahana , Ilma Tapio , Johanna Vilkki
{"title":"Response of primary mammary epithelial cells to pathogen challenge in dairy cows with divergent genomic breeding values for udder health","authors":"Terhi Iso-Touru ,&nbsp;Daniel Fischer ,&nbsp;Frank Panitz ,&nbsp;Suvi Taponen ,&nbsp;Zexi Cai ,&nbsp;Goutam Sahana ,&nbsp;Ilma Tapio ,&nbsp;Johanna Vilkki","doi":"10.1016/j.ygeno.2025.111102","DOIUrl":"10.1016/j.ygeno.2025.111102","url":null,"abstract":"<div><div>This study focuses on the initial cellular response to a causal pathogen in the mammary gland of dairy cows aiming to uncover genomic features associated with mastitis resistance. We analyzed transcriptomes from <em>Escherichia coli</em> -challenged primary bovine mammary epithelial cells derived from milk of cows with high or low genomic index value for udder health. The most striking difference was the markedly higher number of differentially expressed genes post-challenge in the low mastitis resistance group. Gene enrichment analysis indicates a slightly delayed adaptive immune response and early modification of primary metabolic processes in the low mastitis resistance group. Notably, there was no overlap between the DEGs or their potential cis-eQTL with the location of candidate SNPs from association studies of the same cow population. This implies that the genes and pathways involved in the early immune response in the mammary epithelium may not be central for phenotypic mastitis resistance.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111102"},"PeriodicalIF":3.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative transcriptomic analysis reveals bioluminescence-related genes in firely Pyrocoelia pectoralis 比较转录组学分析揭示了胸火绒的生物发光相关基因
IF 3 2区 生物学
Genomics Pub Date : 2025-08-24 DOI: 10.1016/j.ygeno.2025.111101
Guobao Wang , Lei Nie , Huanxin Li
{"title":"Comparative transcriptomic analysis reveals bioluminescence-related genes in firely Pyrocoelia pectoralis","authors":"Guobao Wang ,&nbsp;Lei Nie ,&nbsp;Huanxin Li","doi":"10.1016/j.ygeno.2025.111101","DOIUrl":"10.1016/j.ygeno.2025.111101","url":null,"abstract":"<div><div>Bioluminescence in fireflies is dependent on luciferin metabolism in luminous organs. Our study applied RNA-seq to compare the transcriptome profiles between the luminous and non-luminous tissues from the larvae of the firely <em>Pyrocoelia pectoralis</em>. Genes that were differentially expressed between the two tissue samples were screened to identify candidate genes involved in luciferin metabolism. Among which, cystathionine gamma-lyase, 4-hydroxyphenylpyruvate dioxygenase, and β-glucosidase 2 were upregulated, whereas cysteine dioxygenase type 1 was downregulated in the luminous group compared to that in the non-luminous group, suggesting that these genes may participate in the synthesis of luciferin precursors including L-cysteine and 1, 4-benzoquinone. Several genes encoding 4-coumarate: CoA ligases were upregulated in the luminous organs compared to that in the non-luminous organs, indicating that they may be involved in the formation of 2-<em>S</em>-cysteinylhydroquinone, an intermediate in the luciferin biosynthesis pathway. A sterol carrier protein 2 (<em>Scp2</em>) gene (58 kDa) was speculated to play a role similar to that of ScpXs, which are involved in β-oxidation in peroxisomes of <em>P. pectoralis</em>. Moreover, the expression levels of genes encoding acyl-CoA thioesterases, alpha-methylacyl-CoA racemase, bifunctional 3′-phosphoadenosine 5′-phosphosulfate synthase 1, and luciferin sulfotransferase were higher in the luminous tissues than those in the non-luminous tissues, suggesting their possible roles in the biosynthesis and storage of D-luciferin. Overall, the results of this study may serve as a theoretical basis for further elucidation of the bioluminescence-related mechanisms in <em>P. pectoralis</em>.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111101"},"PeriodicalIF":3.0,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deciphering the complete mitochondrial genome of Halogeton glomeratus structural features and RNA editing events 解读肾小球盐藻线粒体全基因组结构特征和RNA编辑事件
IF 3 2区 生物学
Genomics Pub Date : 2025-08-19 DOI: 10.1016/j.ygeno.2025.111099
Juncheng Wang , Huanqiang Guo , Lirong Yao , Erjing Si , Baochun Li , Yaxiong Meng , Xiaole Ma , Ke Yang , Hong Zhang , Xunwu Shang , Huajun Wang
{"title":"Deciphering the complete mitochondrial genome of Halogeton glomeratus structural features and RNA editing events","authors":"Juncheng Wang ,&nbsp;Huanqiang Guo ,&nbsp;Lirong Yao ,&nbsp;Erjing Si ,&nbsp;Baochun Li ,&nbsp;Yaxiong Meng ,&nbsp;Xiaole Ma ,&nbsp;Ke Yang ,&nbsp;Hong Zhang ,&nbsp;Xunwu Shang ,&nbsp;Huajun Wang","doi":"10.1016/j.ygeno.2025.111099","DOIUrl":"10.1016/j.ygeno.2025.111099","url":null,"abstract":"<div><div><em>Halogeton glomeratus</em>, a halophytic species in the Amaranthaceae family, is well adapted to extreme saline-alkaline environments. To better understand its adaptive mechanisms at the genomic level, we assembled and analyzed the complete mitochondrial genome (mitogenome) of <em>H. glomeratus</em>. The genomic DNA was extracted and libraries were constructed for Illumina short-read and Oxford Nanopore long-read sequencing. The mitogenome was assembled using a hybrid strategy combining GetOrganelle, PMAT, and Unicycler, with gene annotation performed via CPGAVAS2, CPGView, and the PMGA web server. The final assembly revealed a multipartite mitogenome comprising three chromosomes: two circular chromosomes (168,414 bp and 144,793 bp) and one additional chromosome (19,991 bp) treated as linear in this analysis, although alternative configurations may exist. Twelve mitochondrial plastid DNA (MTPT) sequences were identified, accounting for 0.75 % of the mitogenome, with considerable variation in sequence length and composition compared to related species. Phylogenetic analysis based on 35 mitogenomes confirmed the evolutionary position of <em>H. glomeratus</em> within Amaranthaceae. Furthermore, 354 RNA editing sites were identified in 28 protein-coding genes (PCGs), and 136 editing sites were detected in 35 distinct open reading frames (ORFs), including events that generated novel start and stop codons. The <em>H. glomeratus</em> mitogenome exhibits complex structural organization and inter-organellar sequence migration. These findings offer valuable insights into mitochondrial genome evolution and may contribute to understanding the molecular mechanisms underlying halophyte adaptation.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111099"},"PeriodicalIF":3.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From sequences to prebreeding: Chromosome-level genome assemblies, comparative annotation, and a public database for Minghui 86 and Minhui 3301 从序列到预育种:明慧86和明慧3301染色体水平基因组组装、比较注释和公共数据库
IF 3 2区 生物学
Genomics Pub Date : 2025-08-19 DOI: 10.1016/j.ygeno.2025.111100
Yue Wang , Guangwei Chen , Min Lin, Leibo Pan, Feng Wang, Shaohua Yang, Zaijie Chen
{"title":"From sequences to prebreeding: Chromosome-level genome assemblies, comparative annotation, and a public database for Minghui 86 and Minhui 3301","authors":"Yue Wang ,&nbsp;Guangwei Chen ,&nbsp;Min Lin,&nbsp;Leibo Pan,&nbsp;Feng Wang,&nbsp;Shaohua Yang,&nbsp;Zaijie Chen","doi":"10.1016/j.ygeno.2025.111100","DOIUrl":"10.1016/j.ygeno.2025.111100","url":null,"abstract":"<div><div>Innovative breeding technologies routinely require genome-wide information for selecting individuals to enhance the genetic gain for multiple traits. Minghui 86 (MH86) and Minhui 3301 (MH3301) are two widely utilized hybrid rice restorer lines serving as significant core parents in rice breeding programs. Decoding their genomic information will provide substantial convenience for subsequent breeding applications. This study successfully assembled the genomes of MH86 and MH3301 at the chromosomal level and annotated their genes. This work elucidated the genetic information underlying their germplasm characteristics and establishing a foundation for future breeding efforts. To facilitate the utilization of the genomic sequences and annotation data from MH86 and MH3301, a genomic database (<span><span>http://cropdesign.cn/</span><svg><path></path></svg></span>) was developed. This database integrates results from targeted resequencing analyses conducted on 1256 rice germplasm samples, facilitating genotype retrieval for molecular design breeding initiatives. Furthermore, it offers various functionalities including search capabilities, sequence alignment tools, and more.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111100"},"PeriodicalIF":3.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multi-omics dissection of super-enhancer heterogeneity reveals subtype-specific transcriptional drivers in triple-negative breast cancer 超增强子异质性的多组学解剖揭示了三阴性乳腺癌中亚型特异性转录驱动因素。
IF 3 2区 生物学
Genomics Pub Date : 2025-08-13 DOI: 10.1016/j.ygeno.2025.111097
Zhilin Lu , Zhenchang Wang , Wenyong Zhu, Shuyang Cai, Xiao Sun, Hao Huang
{"title":"Multi-omics dissection of super-enhancer heterogeneity reveals subtype-specific transcriptional drivers in triple-negative breast cancer","authors":"Zhilin Lu ,&nbsp;Zhenchang Wang ,&nbsp;Wenyong Zhu,&nbsp;Shuyang Cai,&nbsp;Xiao Sun,&nbsp;Hao Huang","doi":"10.1016/j.ygeno.2025.111097","DOIUrl":"10.1016/j.ygeno.2025.111097","url":null,"abstract":"<div><div>As a clinically heterogeneous breast cancer subtype, triple-negative breast cancer (TNBC) currently lacks effective targeted therapies. The subtype-specific heterogeneity of tumor phenotypes and gene expression programs poses challenges for the treatment of TNBC. However, while progress has been made in understanding the epigenetic and molecular mechanisms of TNBC, studies on the role of super-enhancers (SEs) in TNBC remain limited, particularly in the exploration of preclinical models at the subtype level. This study constructed a transcriptome-driven subtype classifier for cell lines, characterized epigenetic heterogeneity in the Fudan University Shanghai Cancer Center (FUSCC) TNBC subtypes, and mapped subtype-specific super-enhancers landscape. We revealed SE-mediated regulatory mechanisms underlying subtype divergence and proposed epigenetically informed therapeutic targets. We identified ZNF703 as a regulator in the LAR subtype and NesBCL11A in the BLIS subtype, both with clinical implications. This research offers new insights into TNBC's molecular mechanisms and potential targets for subtype-specific therapies.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111097"},"PeriodicalIF":3.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of APOBEC mutagenesis in the progression and therapeutic guidance of pancreatic cancer APOBEC突变在胰腺癌进展中的作用及治疗指导。
IF 3 2区 生物学
Genomics Pub Date : 2025-08-12 DOI: 10.1016/j.ygeno.2025.111098
Xiaozhou Yu , Guangcong Shen , Ziyun Liu , Parhat Kaysar , Xiaobin Shang , Bo Ni , Weihao Zhang , Yaoyao Zhou , Yongjie Xie , Weishuai Liu
{"title":"The role of APOBEC mutagenesis in the progression and therapeutic guidance of pancreatic cancer","authors":"Xiaozhou Yu ,&nbsp;Guangcong Shen ,&nbsp;Ziyun Liu ,&nbsp;Parhat Kaysar ,&nbsp;Xiaobin Shang ,&nbsp;Bo Ni ,&nbsp;Weihao Zhang ,&nbsp;Yaoyao Zhou ,&nbsp;Yongjie Xie ,&nbsp;Weishuai Liu","doi":"10.1016/j.ygeno.2025.111098","DOIUrl":"10.1016/j.ygeno.2025.111098","url":null,"abstract":"<div><h3>Background</h3><div>APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) family-mediated mutagenesis is widespread in human cancers. However, we still have a limited understanding of the biological features and clinical relevance of APOBEC mutagenesis in cancer, particularly in pancreatic cancer.</div></div><div><h3>Methods</h3><div>In this study, we conducted a comprehensive analysis of various data, including whole-exome sequencing (WES), targeted next-generation sequencing (NGS), transcriptome analysis (both bulk RNA-seq and single-cell RNA-seq), immune profiling, immune checkpoint blockade (ICB) response, patient survival, and drug sensitivity. We used various bioinformatics and statistical methods to uncover the distributional features, microenvironmental changes, and clinical significance of APOBEC mutagenesis in pancreatic adenocarcinoma (PAAD).</div></div><div><h3>Results</h3><div>APOBEC mutagenesis significantly influenced mutation patterns in PAAD. Higher enrichment scores of APOBEC mutagenesis signature (APMs) were associated with survival prognosis, immune remodeling, and potential responses to immune checkpoint blockade (ICB) in PAAD patients. In pancreatic cancer, APOBEC3A and APOBEC1 played important roles in malignant progression and cell differentiation in the tumor microenvironment and mediated enhanced CAF-tumor cell communication in the microenvironment, while APMs were also involved in the formation of an immunosuppressive microenvironment in pancreatic cancer through multiple pathways. Additionally, we developed and validated a machine learning model related to APOBEC mutagenesis across various cohorts of PAAD to predict poor survival prognosis. We also conducted drug sensitivity analyses to identify irinotecan as the drug with the highest inhibitory effect on APMs. Subsequently, in vitro experiments verified that irinotecan significantly inhibited pancreatic tumor cell proliferation. Our findings showed that irinotecan significantly reduced the proliferation, metastasis, and glycolysis of pancreatic tumor cells. It also decreased the expression levels of activation markers in cancer-associated fibroblasts (CAFs), including CD73, ACTA2, and COL1A1. In vivo experiments demonstrated that irinotecan could remodel the immune microenvironment by inhibiting Tregs, and combined with Treg inhibitors, it could effectively reduce the tumor burden of PAAD.</div></div><div><h3>Conclusion</h3><div>Our study illustrated the characterization of APOBEC mutagenesis in multiple cancer types and highlighted its potential value as a prognostic and immunotherapeutic biomarker for PAAD, and finally demonstrated the effectiveness of irinotecan, an inhibitor of APMs, in vivo and in vitro experiments.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111098"},"PeriodicalIF":3.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic dissection of two elite japonica varieties reveals founder transmission and selection in breeding 两个粳稻优良品种的遗传剖析揭示了育种中的奠基遗传和选择。
IF 3 2区 生物学
Genomics Pub Date : 2025-08-08 DOI: 10.1016/j.ygeno.2025.111096
Junhua Ye , Ying Yan , Lixia Zhang , Kai Wang , Hang Yang , Zhenying Shi , Zejun Hu , Liming Cao , Shujun Wu
{"title":"Genetic dissection of two elite japonica varieties reveals founder transmission and selection in breeding","authors":"Junhua Ye ,&nbsp;Ying Yan ,&nbsp;Lixia Zhang ,&nbsp;Kai Wang ,&nbsp;Hang Yang ,&nbsp;Zhenying Shi ,&nbsp;Zejun Hu ,&nbsp;Liming Cao ,&nbsp;Shujun Wu","doi":"10.1016/j.ygeno.2025.111096","DOIUrl":"10.1016/j.ygeno.2025.111096","url":null,"abstract":"<div><div>Understanding the genetic basis of elite rice varieties is conducive to the strategic utilization of genetic resources in modern breeding programs. To elucidate the genetic component and transmission across pedigrees, we investigated two elite inbred <em>japonica</em> varieties, Huruan1212 (HR1212) and Hugeng137 (HG137), through whole-genome sequencing with an average depth of 38.2× and pedigree analysis. We identified specific SNPs and enriched pathways underlying HR1212's excellent eating and cooking quality and HG137's stress resistance. Genomic scans traced the contributions of founder parents Xiushui04 and Wuyugeng3, revealing transmission patterns of favorable alleles across generations. Notably, the shared identity-by-descent (sIBD) segments of the two pedigrees overlapped by 74 Mb, total formed 118.42 Mb of conserved genetic segments, with validation in other founder-derived lines. This research provides valuable insights for utilizing founder parents and elite varieties and highlights the critical need to implement genome-informed breeding strategies in future breeding practice.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 5","pages":"Article 111096"},"PeriodicalIF":3.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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