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Systematic perturbations of SETD2, NSD1, NSD2, NSD3, and ASH1L reveal their distinct contributions to H3K36 methylation 对 SETD2、NSD1、NSD2、NSD3 和 ASH1L 的系统扰动揭示了它们对 H3K36 甲基化的不同贡献
IF 12.3 1区 生物学
Genome Biology Pub Date : 2024-10-10 DOI: 10.1186/s13059-024-03415-3
Gerry A. Shipman, Reinnier Padilla, Cynthia Horth, Bo Hu, Eric Bareke, Francisca N. Vitorino, Joanna M. Gongora, Benjamin A. Garcia, Chao Lu, Jacek Majewski
{"title":"Systematic perturbations of SETD2, NSD1, NSD2, NSD3, and ASH1L reveal their distinct contributions to H3K36 methylation","authors":"Gerry A. Shipman, Reinnier Padilla, Cynthia Horth, Bo Hu, Eric Bareke, Francisca N. Vitorino, Joanna M. Gongora, Benjamin A. Garcia, Chao Lu, Jacek Majewski","doi":"10.1186/s13059-024-03415-3","DOIUrl":"https://doi.org/10.1186/s13059-024-03415-3","url":null,"abstract":"Methylation of histone 3 lysine 36 (H3K36me) has emerged as an essential epigenetic component for the faithful regulation of gene expression. Despite its importance in development and disease, how the molecular agents collectively shape the H3K36me landscape is unclear. We use mouse mesenchymal stem cells to perturb the H3K36me methyltransferases (K36MTs) and infer the activities of the five most prominent enzymes: SETD2, NSD1, NSD2, NSD3, and ASH1L. We find that H3K36me2 is the most abundant of the three methylation states and is predominantly deposited at intergenic regions by NSD1, and partly by NSD2. In contrast, H3K36me1/3 are most abundant within exons and are positively correlated with gene expression. We demonstrate that while SETD2 deposits most H3K36me3, it may also deposit H3K36me2 within transcribed genes. Additionally, loss of SETD2 results in an increase of exonic H3K36me1, suggesting other (K36MTs) prime gene bodies with lower methylation states ahead of transcription. While NSD1/2 establish broad intergenic H3K36me2 domains, NSD3 deposits H3K36me2 peaks on active promoters and enhancers. Meanwhile, the activity of ASH1L is restricted to the regulatory elements of developmentally relevant genes, and our analyses implicate PBX2 as a potential recruitment factor. Within genes, SETD2 primarily deposits H3K36me3, while the other K36MTs deposit H3K36me1/2 independently of SETD2 activity. For the deposition of H3K36me1/2, we find a hierarchy of K36MT activities where NSD1 > NSD2 > NSD3 > ASH1L. While NSD1 and NSD2 are responsible for most genome-wide propagation of H3K36me2, the activities of NSD3 and ASH1L are confined to active regulatory elements.\u0000","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":null,"pages":null},"PeriodicalIF":12.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Visualizing scRNA-Seq data at population scale with GloScope 利用 GloScope 在种群规模上可视化 scRNA-Seq 数据
IF 12.3 1区 生物学
Genome Biology Pub Date : 2024-10-08 DOI: 10.1186/s13059-024-03398-1
Hao Wang, William Torous, Boying Gong, Elizabeth Purdom
{"title":"Visualizing scRNA-Seq data at population scale with GloScope","authors":"Hao Wang, William Torous, Boying Gong, Elizabeth Purdom","doi":"10.1186/s13059-024-03398-1","DOIUrl":"https://doi.org/10.1186/s13059-024-03398-1","url":null,"abstract":"Increasingly, scRNA-Seq studies explore cell populations across different samples and the effect of sample heterogeneity on organism’s phenotype. However, relatively few bioinformatic methods have been developed which adequately address the variation between samples for such population-level analyses. We propose a framework for representing the entire single-cell profile of a sample, which we call a GloScope representation. We implement GloScope on scRNA-Seq datasets from study designs ranging from 12 to over 300 samples and demonstrate how GloScope allows researchers to perform essential bioinformatic tasks at the sample-level, in particular visualization and quality control assessment.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":null,"pages":null},"PeriodicalIF":12.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
DEMINING: A deep learning model embedded framework to distinguish RNA editing from DNA mutations in RNA sequencing data DEMINING:嵌入深度学习模型的框架,用于区分 RNA 测序数据中的 RNA 编辑和 DNA 突变
IF 12.3 1区 生物学
Genome Biology Pub Date : 2024-10-08 DOI: 10.1186/s13059-024-03397-2
Zhi-Can Fu, Bao-Qing Gao, Fang Nan, Xu-Kai Ma, Li Yang
{"title":"DEMINING: A deep learning model embedded framework to distinguish RNA editing from DNA mutations in RNA sequencing data","authors":"Zhi-Can Fu, Bao-Qing Gao, Fang Nan, Xu-Kai Ma, Li Yang","doi":"10.1186/s13059-024-03397-2","DOIUrl":"https://doi.org/10.1186/s13059-024-03397-2","url":null,"abstract":"Precise calling of promiscuous adenosine-to-inosine RNA editing sites from transcriptomic datasets is hindered by DNA mutations and sequencing/mapping errors. Here, we present a stepwise computational framework, called DEMINING, to distinguish RNA editing and DNA mutations directly from RNA sequencing datasets, with an embedded deep learning model named DeepDDR. After transfer learning, DEMINING can also classify RNA editing sites and DNA mutations from non-primate sequencing samples. When applied in samples from acute myeloid leukemia patients, DEMINING uncovers previously underappreciated DNA mutation and RNA editing sites; some associated with the upregulated expression of host genes or the production of neoantigens.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":null,"pages":null},"PeriodicalIF":12.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Integrated large-scale metagenome assembly and multi-kingdom network analyses identify sex differences in the human nasal microbiome 综合大规模元基因组组装和多王国网络分析发现人类鼻腔微生物组的性别差异
IF 12.3 1区 生物学
Genome Biology Pub Date : 2024-10-08 DOI: 10.1186/s13059-024-03389-2
Yanmei Ju, Zhe Zhang, Mingliang Liu, Shutian Lin, Qiang Sun, Zewei Song, Weiting Liang, Xin Tong, Zhuye Jie, Haorong Lu, Kaiye Cai, Peishan Chen, Xin Jin, Wenwei Zhang, Xun Xu, Huanming Yang, Jian Wang, Yong Hou, Liang Xiao, Huijue Jia, Tao Zhang, Ruijin Guo
{"title":"Integrated large-scale metagenome assembly and multi-kingdom network analyses identify sex differences in the human nasal microbiome","authors":"Yanmei Ju, Zhe Zhang, Mingliang Liu, Shutian Lin, Qiang Sun, Zewei Song, Weiting Liang, Xin Tong, Zhuye Jie, Haorong Lu, Kaiye Cai, Peishan Chen, Xin Jin, Wenwei Zhang, Xun Xu, Huanming Yang, Jian Wang, Yong Hou, Liang Xiao, Huijue Jia, Tao Zhang, Ruijin Guo","doi":"10.1186/s13059-024-03389-2","DOIUrl":"https://doi.org/10.1186/s13059-024-03389-2","url":null,"abstract":"Respiratory diseases impose an immense health burden worldwide. Epidemiological studies have revealed extensive disparities in the incidence and severity of respiratory tract infections between men and women. It has been hypothesized that there might also be a nasal microbiome axis contributing to the observed sex disparities. Here, we study the nasal microbiome of healthy young adults in the largest cohort to date with 1593 individuals, using shotgun metagenomic sequencing. We compile the most comprehensive reference catalog for the nasal bacterial community containing 4197 metagenome-assembled genomes and integrate the mycobiome, to provide a valuable resource and a more holistic perspective for the understudied human nasal microbiome. We systematically evaluate sex differences and reveal extensive sex-specific features in both taxonomic and functional levels in the nasal microbiome. Through network analyses, we capture markedly higher ecological stability and antagonistic potentials in the female nasal microbiome compared to the male’s. The analysis of the keystone bacteria reveals that the sex-dependent evolutionary characteristics might have contributed to these differences. In summary, we construct the most comprehensive catalog of metagenome-assembled-genomes for the nasal bacterial community to provide a valuable resource for the understudied human nasal microbiome. On top of that, comparative analysis in relative abundance and microbial co-occurrence networks identify extensive sex differences in the respiratory tract community, which may help to further our understanding of the observed sex disparities in the respiratory diseases.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":null,"pages":null},"PeriodicalIF":12.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Optimizing and benchmarking polygenic risk scores with GWAS summary statistics 利用 GWAS 概要统计优化多基因风险评分并制定基准
IF 12.3 1区 生物学
Genome Biology Pub Date : 2024-10-08 DOI: 10.1186/s13059-024-03400-w
Zijie Zhao, Tim Gruenloh, Meiyi Yan, Yixuan Wu, Zhongxuan Sun, Jiacheng Miao, Yuchang Wu, Jie Song, Qiongshi Lu
{"title":"Optimizing and benchmarking polygenic risk scores with GWAS summary statistics","authors":"Zijie Zhao, Tim Gruenloh, Meiyi Yan, Yixuan Wu, Zhongxuan Sun, Jiacheng Miao, Yuchang Wu, Jie Song, Qiongshi Lu","doi":"10.1186/s13059-024-03400-w","DOIUrl":"https://doi.org/10.1186/s13059-024-03400-w","url":null,"abstract":"Polygenic risk score (PRS) is a major research topic in human genetics. However, a significant gap exists between PRS methodology and applications in practice due to often unavailable individual-level data for various PRS tasks including model fine-tuning, benchmarking, and ensemble learning. We introduce an innovative statistical framework to optimize and benchmark PRS models using summary statistics of genome-wide association studies. This framework builds upon our previous work and can fine-tune virtually all existing PRS models while accounting for linkage disequilibrium. In addition, we provide an ensemble learning strategy named PUMAS-ensemble to combine multiple PRS models into an ensemble score without requiring external data for model fitting. Through extensive simulations and analysis of many complex traits in the UK Biobank, we demonstrate that this approach closely approximates gold-standard analytical strategies based on external validation, and substantially outperforms state-of-the-art PRS methods. Our method is a powerful and general modeling technique that can continue to combine the best-performing PRS methods out there through ensemble learning and could become an integral component for all future PRS applications.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":null,"pages":null},"PeriodicalIF":12.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
APC mutations dysregulate alternative polyadenylation in cancer APC 突变会导致癌症中的替代多腺苷酸化失调
IF 12.3 1区 生物学
Genome Biology Pub Date : 2024-10-07 DOI: 10.1186/s13059-024-03406-4
Austin M. Gabel, Andrea E. Belleville, James D. Thomas, Jose Mario Bello Pineda, Robert K. Bradley
{"title":"APC mutations dysregulate alternative polyadenylation in cancer","authors":"Austin M. Gabel, Andrea E. Belleville, James D. Thomas, Jose Mario Bello Pineda, Robert K. Bradley","doi":"10.1186/s13059-024-03406-4","DOIUrl":"https://doi.org/10.1186/s13059-024-03406-4","url":null,"abstract":"Alternative polyadenylation (APA) affects most human genes and is recurrently dysregulated in all studied cancers. However, the mechanistic origins of this dysregulation are incompletely understood. We describe an unbiased analysis of molecular regulators of poly(A) site selection across The Cancer Genome Atlas and identify that colorectal adenocarcinoma is an outlier relative to all other cancer subtypes. This distinction arises from the frequent presence of loss-of-function APC mutations in colorectal adenocarcinoma, which are strongly associated with long 3′ UTR expression relative to tumors lacking APC mutations. APC knockout similarly dysregulates APA in human colon organoids. By mining previously published APC eCLIP data, we show that APC preferentially binds G- and C-rich motifs just upstream of proximal poly(A) sites. Lastly, we find that reduced APC expression is associated with APA dysregulation in tumor types lacking recurrent APC mutations. As APC has been previously identified as an RNA-binding protein that preferentially binds 3′ UTRs during mouse neurogenesis, our results suggest that APC promotes proximal poly(A) site use and that APC loss and altered expression contribute to pervasive APA dysregulation in cancers.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":null,"pages":null},"PeriodicalIF":12.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma 癌细胞和微环境细胞的体内扰动-序列分析剖析胶质母细胞瘤的肿瘤学驱动因素和放疗反应
IF 12.3 1区 生物学
Genome Biology Pub Date : 2024-10-07 DOI: 10.1186/s13059-024-03404-6
S. John Liu, Christopher Zou, Joanna Pak, Alexandra Morse, Dillon Pang, Timothy Casey-Clyde, Ashir A. Borah, David Wu, Kyounghee Seo, Thomas O’Loughlin, Daniel A. Lim, Tomoko Ozawa, Mitchel S. Berger, Roarke A. Kamber, William A. Weiss, David R. Raleigh, Luke A. Gilbert
{"title":"In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma","authors":"S. John Liu, Christopher Zou, Joanna Pak, Alexandra Morse, Dillon Pang, Timothy Casey-Clyde, Ashir A. Borah, David Wu, Kyounghee Seo, Thomas O’Loughlin, Daniel A. Lim, Tomoko Ozawa, Mitchel S. Berger, Roarke A. Kamber, William A. Weiss, David R. Raleigh, Luke A. Gilbert","doi":"10.1186/s13059-024-03404-6","DOIUrl":"https://doi.org/10.1186/s13059-024-03404-6","url":null,"abstract":"Genetic perturbation screens with single-cell readouts have enabled rich phenotyping of gene function and regulatory networks. These approaches have been challenging in vivo, especially in adult disease models such as cancer, which include mixtures of malignant and microenvironment cells. Glioblastoma (GBM) is a fatal cancer, and methods of systematically interrogating gene function and therapeutic targets in vivo, especially in combination with standard of care treatment such as radiotherapy, are lacking. Here, we iteratively develop a multiplex in vivo perturb-seq CRISPRi platform for single-cell genetic screens in cancer and tumor microenvironment cells that leverages intracranial convection enhanced delivery of sgRNA libraries into mouse models of GBM. Our platform enables potent silencing of drivers of in vivo growth and tumor maintenance as well as genes that sensitize GBM to radiotherapy. We find radiotherapy rewires transcriptional responses to genetic perturbations in an in vivo-dependent manner, revealing heterogenous patterns of treatment sensitization or resistance in GBM. Furthermore, we demonstrate targeting of genes that function in the tumor microenvironment, enabling alterations of ligand-receptor interactions between immune and stromal cells following in vivo CRISPRi perturbations that can affect tumor cell phagocytosis. In sum, we demonstrate the utility of multiplexed perturb-seq for in vivo single-cell dissection of adult cancer and normal tissue biology across multiple cell types in the context of therapeutic intervention, a platform with potential for broad application.\u0000","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":null,"pages":null},"PeriodicalIF":12.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Assessing and mitigating batch effects in large-scale omics studies 评估和减轻大规模组学研究中的批次效应
IF 12.3 1区 生物学
Genome Biology Pub Date : 2024-10-03 DOI: 10.1186/s13059-024-03401-9
Ying Yu, Yuanbang Mai, Yuanting Zheng, Leming Shi
{"title":"Assessing and mitigating batch effects in large-scale omics studies","authors":"Ying Yu, Yuanbang Mai, Yuanting Zheng, Leming Shi","doi":"10.1186/s13059-024-03401-9","DOIUrl":"https://doi.org/10.1186/s13059-024-03401-9","url":null,"abstract":"Batch effects in omics data are notoriously common technical variations unrelated to study objectives, and may result in misleading outcomes if uncorrected, or hinder biomedical discovery if over-corrected. Assessing and mitigating batch effects is crucial for ensuring the reliability and reproducibility of omics data and minimizing the impact of technical variations on biological interpretation. In this review, we highlight the profound negative impact of batch effects and the urgent need to address this challenging problem in large-scale omics studies. We summarize potential sources of batch effects, current progress in evaluating and correcting them, and consortium efforts aiming to tackle them.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":null,"pages":null},"PeriodicalIF":12.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Jointly benchmarking small and structural variant calls with vcfdist 利用 vcfdist 对小变异和结构变异调用进行联合基准测试
IF 12.3 1区 生物学
Genome Biology Pub Date : 2024-10-02 DOI: 10.1186/s13059-024-03394-5
Tim Dunn, Justin M. Zook, James M. Holt, Satish Narayanasamy
{"title":"Jointly benchmarking small and structural variant calls with vcfdist","authors":"Tim Dunn, Justin M. Zook, James M. Holt, Satish Narayanasamy","doi":"10.1186/s13059-024-03394-5","DOIUrl":"https://doi.org/10.1186/s13059-024-03394-5","url":null,"abstract":"In this work, we extend vcfdist to be the first variant call benchmarking tool to jointly evaluate phased single-nucleotide polymorphisms (SNPs), small insertions/deletions (INDELs), and structural variants (SVs) for the whole genome. First, we find that a joint evaluation of small and structural variants uniformly reduces measured errors for SNPs (− 28.9%), INDELs (− 19.3%), and SVs (− 52.4%) across three datasets. vcfdist also corrects a common flaw in phasing evaluations, reducing measured flip errors by over 50%. Lastly, we show that vcfdist is more accurate than previously published works and on par with the newest approaches while providing improved result interpretability.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":null,"pages":null},"PeriodicalIF":12.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 genome-wide association study reveals molecular mechanism underlying powdery mildew resistance in cucumber 全基因组关联研究揭示黄瓜抗白粉病的分子机制
IF 12.3 1区 生物学
Genome Biology Pub Date : 2024-10-02 DOI: 10.1186/s13059-024-03402-8
Xuewen Xu, Yujiao Du, Suhao Li, Ming Tan, Hamza Sohail, Xueli Liu, Xiaohua Qi, Xiaodong Yang, Xuehao Chen
{"title":"A genome-wide association study reveals molecular mechanism underlying powdery mildew resistance in cucumber","authors":"Xuewen Xu, Yujiao Du, Suhao Li, Ming Tan, Hamza Sohail, Xueli Liu, Xiaohua Qi, Xiaodong Yang, Xuehao Chen","doi":"10.1186/s13059-024-03402-8","DOIUrl":"https://doi.org/10.1186/s13059-024-03402-8","url":null,"abstract":"Powdery mildew is a disease with one of the most substantial impacts on cucumber production globally. The most efficient approach for controlling powdery mildew is the development of genetic resistance; however, few genes associated with inherent variations in cucumber powdery mildew resistance have been identified as of yet. In this study, we re-sequence 299 cucumber accessions, which are divided into four geographical groups. A genome-wide association study identifies 50 sites significantly associated with natural variations in powdery mildew resistance. Linkage disequilibrium analysis further divides these 50 sites into 32 linkage disequilibrium blocks containing 41 putative genes. Virus-induced gene silencing and gene expression analysis implicate CsGy5G015960, which encodes a phosphate transporter, as the candidate gene regulating powdery mildew resistance. On the basis of the resequencing data, we generate five CsGy5G015960 haplotypes, identifying Hap.1 as the haplotype most likely associated with powdery mildew resistance. In addition, we determine that a 29-bp InDel in the 3′ untranslated region of CsGy5G015960 is responsible for mRNA stability. Overexpression of CsGy5G015960Hap.1 in the susceptible line enhances powdery mildew resistance and phosphorus accumulation. Further comparative RNA-seq analysis demonstrates that CsGy5G015960Hap.1 may regulate cucumber powdery mildew resistance by maintaining a higher H2O2 level through the depletion of multiple class III peroxidases. Here we identify a candidate powdery mildew-resistant gene in cucumber using GWAS. The identified gene may be a promising target for molecular breeding and genetic engineering in cucumber to enhance powdery mildew resistance.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":null,"pages":null},"PeriodicalIF":12.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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