Nature geneticsPub Date : 2025-04-21DOI: 10.1038/s41588-025-02161-x
Siqi Chen, Ruiyang Liu, Chia-Kuei Mo, Michael C. Wendl, Andrew Houston, Preet Lal, Yanyan Zhao, Wagma Caravan, Andrew T. Shinkle, Atieh Abedin-Do, Nataly Naser Al Deen, Kazuhito Sato, Xiang Li, André Luiz N. Targino da Costa, Yize Li, Alla Karpova, John M. Herndon, Maxim N. Artyomov, Joshua B. Rubin, Sanjay Jain, Xue Li, Sheila A. Stewart, Li Ding, Feng Chen
{"title":"Multi-omic and spatial analysis of mouse kidneys highlights sex-specific differences in gene regulation across the lifespan","authors":"Siqi Chen, Ruiyang Liu, Chia-Kuei Mo, Michael C. Wendl, Andrew Houston, Preet Lal, Yanyan Zhao, Wagma Caravan, Andrew T. Shinkle, Atieh Abedin-Do, Nataly Naser Al Deen, Kazuhito Sato, Xiang Li, André Luiz N. Targino da Costa, Yize Li, Alla Karpova, John M. Herndon, Maxim N. Artyomov, Joshua B. Rubin, Sanjay Jain, Xue Li, Sheila A. Stewart, Li Ding, Feng Chen","doi":"10.1038/s41588-025-02161-x","DOIUrl":"10.1038/s41588-025-02161-x","url":null,"abstract":"There is a sex bias in the incidence and progression of many kidney diseases. To better understand such sexual dimorphism, we integrated data from six platforms, characterizing 76 kidney samples from 68 mice at six developmental and adult time points, creating a molecular atlas of the mouse kidney across the lifespan for both sexes. We show that proximal tubules have the most sex-biased differentially expressed genes emerging after 3 weeks of age and are associated with hormonal regulations. We reveal potential mechanisms involving both direct and indirect regulation by androgens and estrogens. Spatial profiling identifies distinct sex-biased spatial patterns in the cortex and outer stripe of the outer medulla. Additionally, older mice exhibit more aging-related gene alterations in loops of Henle, proximal tubules and collecting ducts in a sex-dependent manner. Our results enhance the understanding of spatially resolved gene expression and hormone regulation underlying kidney sexual dimorphism across the lifespan. Multi-omic analysis of the developing mouse kidney shows strong sex-dependent differences in gene expression during development and aging. These differences are likely mediated by sex hormones.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 5","pages":"1213-1227"},"PeriodicalIF":31.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-025-02161-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature geneticsPub Date : 2025-04-21DOI: 10.1038/s41588-025-02169-3
Ajay Nadig, Joseph M. Replogle, Angela N. Pogson, Mukundh Murthy, Steven A. McCarroll, Jonathan S. Weissman, Elise B. Robinson, Luke J. O’Connor
{"title":"Transcriptome-wide analysis of differential expression in perturbation atlases","authors":"Ajay Nadig, Joseph M. Replogle, Angela N. Pogson, Mukundh Murthy, Steven A. McCarroll, Jonathan S. Weissman, Elise B. Robinson, Luke J. O’Connor","doi":"10.1038/s41588-025-02169-3","DOIUrl":"10.1038/s41588-025-02169-3","url":null,"abstract":"Single-cell CRISPR screens such as Perturb-seq enable transcriptomic profiling of genetic perturbations at scale. However, the data produced by these screens are noisy, and many effects may go undetected. Here we introduce transcriptome-wide analysis of differential expression (TRADE)—a statistical model for the distribution of true differential expression effects that accounts for estimation error appropriately. TRADE estimates the ‘transcriptome-wide impact’, which quantifies the total effect of a perturbation across the transcriptome. Analyzing several large Perturb-seq datasets, we show that many transcriptional effects remain undetected in standard analyses but emerge in aggregate using TRADE. A typical gene perturbation affects an estimated 45 genes, whereas a typical essential gene affects over 500. We find moderate consistency of perturbation effects across cell types, identify perturbations where transcriptional responses vary qualitatively across dosage levels and clarify the relationship between genetic and transcriptomic correlations across neuropsychiatric disorders. Transcriptome-wide analysis of differential expression (TRADE) is a broadly applicable tool for characterizing patterns of differential expression across the genome.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 5","pages":"1228-1237"},"PeriodicalIF":31.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853197","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}
Nature geneticsPub Date : 2025-04-17DOI: 10.1038/s41588-025-02157-7
Jinyang Zhang, Fangqing Zhao
{"title":"Circular RNA discovery with emerging sequencing and deep learning technologies","authors":"Jinyang Zhang, Fangqing Zhao","doi":"10.1038/s41588-025-02157-7","DOIUrl":"10.1038/s41588-025-02157-7","url":null,"abstract":"Circular RNA (circRNA) represents a type of RNA molecule characterized by a closed-loop structure that is distinct from linear RNA counterparts. Recent studies have revealed the emerging role of these circular transcripts in gene regulation and disease pathogenesis. However, their low expression levels and high sequence similarity to linear RNAs present substantial challenges for circRNA detection and characterization. Recent advances in long-read and single-cell RNA sequencing technologies, coupled with sophisticated deep learning-based algorithms, have revolutionized the investigation of circRNAs at unprecedented resolution and scale. This Review summarizes recent breakthroughs in circRNA discovery, characterization and functional analysis algorithms. We also discuss the challenges associated with integrating large-scale circRNA sequencing data and explore the potential future development of artificial intelligence (AI)-driven algorithms to unlock the full potential of circRNA research in biomedical applications. This Review discusses recent advances in circular RNA discovery afforded by breakthroughs in sequencing technologies and deep learning-based algorithms and highlights outstanding challenges in integrating large-scale circular RNA datasets.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 5","pages":"1089-1102"},"PeriodicalIF":31.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841742","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}
Nature geneticsPub Date : 2025-04-16DOI: 10.1038/s41588-025-02163-9
Maayan Baron, Mohita Tagore, Patrick Wall, Fan Zheng, Dalia Barkley, Itai Yanai, Jing Yang, Maija Kiuru, Richard M. White, Trey Ideker
{"title":"Desmosome mutations impact the tumor microenvironment to promote melanoma proliferation","authors":"Maayan Baron, Mohita Tagore, Patrick Wall, Fan Zheng, Dalia Barkley, Itai Yanai, Jing Yang, Maija Kiuru, Richard M. White, Trey Ideker","doi":"10.1038/s41588-025-02163-9","DOIUrl":"10.1038/s41588-025-02163-9","url":null,"abstract":"Desmosomes are transmembrane protein complexes that contribute to cell–cell adhesion in epithelia and other tissues. Here, we report the discovery of frequent genetic alterations in the desmosome in human cancers, with the strongest signal seen in cutaneous melanoma, where desmosomes are mutated in more than 70% of cases. In primary but not metastatic melanoma biopsies, the burden of coding mutations in desmosome genes is associated with a strong reduction in desmosome gene expression. Analysis by spatial transcriptomics and protein immunofluorescence suggests that these decreases in expression occur in keratinocytes in the microenvironment rather than in primary melanoma cells. In further support of a microenvironmental origin, we find that desmosome gene knockdown in keratinocytes yields markedly increased proliferation of adjacent melanoma cells in keratinocyte and melanoma cocultures. Similar increases in melanoma proliferation are observed in media preconditioned with desmosome-deficient keratinocytes. Thus, gradual accumulation of desmosome mutations in neighboring cells may prime melanoma cells for neoplastic transformation. In cutaneous melanoma, desmosome genes are frequently affected by coding mutations that decrease their expression. This decrease in expression occurs predominantly in keratinocytes in the tumor microenvironment and can induce hyperproliferation of adjacent melanoma cells in coculture.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 5","pages":"1179-1188"},"PeriodicalIF":31.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837082","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}
Nature geneticsPub Date : 2025-04-16DOI: 10.1038/s41588-025-02166-6
Wei Li, Chong Chu, Taikui Zhang, Haochen Sun, Shiyao Wang, Zeyuan Liu, Zijun Wang, Hui Li, Yuqi Li, Xingtan Zhang, Zhiqiang Geng, Youqing Wang, Yi Li, Hengtao Zhang, Weishu Fan, Yi Wang, Xuefeng Xu, Lailiang Cheng, Dehui Zhang, Yao Xiong, Huixia Li, Bowen Zhou, Qingmei Guan, Cecilia H. Deng, Yongming Han, Hong Ma, Zhenhai Han
{"title":"Pan-genome analysis reveals the evolution and diversity of Malus","authors":"Wei Li, Chong Chu, Taikui Zhang, Haochen Sun, Shiyao Wang, Zeyuan Liu, Zijun Wang, Hui Li, Yuqi Li, Xingtan Zhang, Zhiqiang Geng, Youqing Wang, Yi Li, Hengtao Zhang, Weishu Fan, Yi Wang, Xuefeng Xu, Lailiang Cheng, Dehui Zhang, Yao Xiong, Huixia Li, Bowen Zhou, Qingmei Guan, Cecilia H. Deng, Yongming Han, Hong Ma, Zhenhai Han","doi":"10.1038/s41588-025-02166-6","DOIUrl":"10.1038/s41588-025-02166-6","url":null,"abstract":"Malus Mill., a genus of temperate perennial trees with great agricultural and ecological value, has diversified through hybridization, polyploidy and environmental adaptation. Limited genomic resources for wild Malus species have hindered the understanding of their evolutionary history and genetic diversity. We sequenced and assembled 30 high-quality Malus genomes, representing 20 diploids and 10 polyploids across major evolutionary lineages and geographical regions. Phylogenomic analyses revealed ancient gene duplications and conversions, while six newly defined genome types, including an ancestral type shared by polyploid species, facilitated the detection of strong signals for extensive introgressions. The graph-based pan-genome captured shared and species-specific structural variations, facilitating the development of a molecular marker for apple scab resistance. Our pipeline for analyzing selective sweep identified a mutation in MdMYB5 having reduced cold and disease resistance during domestication. This study advances Malus genomics, uncovering genetic diversity and evolutionary insights while enhancing breeding for desirable traits. A graph-based pan-genome constructed from 30 genome assemblies covering Malus domestica ‘Golden Delicious’ and 29 wild diploid or polyploid Malus species highlights structural variation and genome evolution in the Malus genus.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 5","pages":"1274-1286"},"PeriodicalIF":31.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-025-02166-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature geneticsPub Date : 2025-04-16DOI: 10.1038/s41588-025-02133-1
Patricia A. Possik, Kerrie L. Marie, David J. Adams
{"title":"Desmosome mutations in keratinocytes fuel melanoma development","authors":"Patricia A. Possik, Kerrie L. Marie, David J. Adams","doi":"10.1038/s41588-025-02133-1","DOIUrl":"10.1038/s41588-025-02133-1","url":null,"abstract":"In this study, somatic mutations in desmosome genes of keratinocytes were found to support melanoma growth. This work has fundamental implications for our understanding of the somatic landscape of cancer.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 5","pages":"1064-1065"},"PeriodicalIF":31.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837081","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}
Nature geneticsPub Date : 2025-04-14DOI: 10.1038/s41588-025-02156-8
Samvida S. Venkatesh, Laura B. L. Wittemans, Duncan S. Palmer, Nikolas A. Baya, Teresa Ferreira, Barney Hill, Frederik Heymann Lassen, Melody J. Parker, Saskia Reibe, Ahmed Elhakeem, Karina Banasik, Mie T. Bruun, Christian Erikstrup, Bitten Aagard Jensen, Anders Juul, Christina Mikkelsen, Henriette S. Nielsen, Sisse R. Ostrowski, Ole B. Pedersen, Palle Duun Rohde, Erik Sørensen, Henrik Ullum, David Westergaard, Asgeir Haraldsson, Hilma Holm, Ingileif Jonsdottir, Isleifur Olafsson, Thora Steingrimsdottir, Valgerdur Steinthorsdottir, Gudmar Thorleifsson, Jessica Figueredo, Minna K. Karjalainen, Anu Pasanen, Benjamin M. Jacobs, Georgios Kalantzis, Nikki Hubers, Genes & Health Research Team, Estonian Biobank Research Team, Estonian Health Informatics Research Team, DBDS Genomic Consortium, FinnGen, Margaret Lippincott, Abigail Fraser, Deborah A. Lawlor, Nicholas J. Timpson, Mette Nyegaard, Kari Stefansson, Reedik Magi, Hannele Laivuori, David A. van Heel, Dorret I. Boomsma, Ravikumar Balasubramanian, Stephanie B. Seminara, Yee-Ming Chan, Triin Laisk, Cecilia M. Lindgren
{"title":"Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum","authors":"Samvida S. Venkatesh, Laura B. L. Wittemans, Duncan S. Palmer, Nikolas A. Baya, Teresa Ferreira, Barney Hill, Frederik Heymann Lassen, Melody J. Parker, Saskia Reibe, Ahmed Elhakeem, Karina Banasik, Mie T. Bruun, Christian Erikstrup, Bitten Aagard Jensen, Anders Juul, Christina Mikkelsen, Henriette S. Nielsen, Sisse R. Ostrowski, Ole B. Pedersen, Palle Duun Rohde, Erik Sørensen, Henrik Ullum, David Westergaard, Asgeir Haraldsson, Hilma Holm, Ingileif Jonsdottir, Isleifur Olafsson, Thora Steingrimsdottir, Valgerdur Steinthorsdottir, Gudmar Thorleifsson, Jessica Figueredo, Minna K. Karjalainen, Anu Pasanen, Benjamin M. Jacobs, Georgios Kalantzis, Nikki Hubers, Genes & Health Research Team, Estonian Biobank Research Team, Estonian Health Informatics Research Team, DBDS Genomic Consortium, FinnGen, Margaret Lippincott, Abigail Fraser, Deborah A. Lawlor, Nicholas J. Timpson, Mette Nyegaard, Kari Stefansson, Reedik Magi, Hannele Laivuori, David A. van Heel, Dorret I. Boomsma, Ravikumar Balasubramanian, Stephanie B. Seminara, Yee-Ming Chan, Triin Laisk, Cecilia M. Lindgren","doi":"10.1038/s41588-025-02156-8","DOIUrl":"10.1038/s41588-025-02156-8","url":null,"abstract":"Genome-wide association studies (GWASs) may help inform the etiology of infertility. Here, we perform GWAS meta-analyses across seven cohorts in up to 42,629 cases and 740,619 controls and identify 25 genetic risk loci for male and female infertility. We additionally identify up to 269 genetic loci associated with follicle-stimulating hormone, luteinizing hormone, estradiol and testosterone through sex-specific GWAS meta-analyses (n = 6,095–246,862). Exome sequencing analyses reveal that women carrying testosterone-lowering rare variants in some genes are at risk of infertility. However, we find no local or genome-wide genetic correlation between female infertility and reproductive hormones. While infertility is genetically correlated with endometriosis and polycystic ovary syndrome, we find limited genetic overlap between infertility and obesity. Finally, we show that the evolutionary persistence of infertility-risk alleles may be explained by directional selection. Taken together, we provide a comprehensive view of the genetic determinants of infertility across multiple diagnostic criteria. Genome-wide analyses identify variants associated with infertility and reproductive hormone levels but find limited polygenic overlap between reproductive hormone levels and infertility at the population level.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 5","pages":"1107-1118"},"PeriodicalIF":31.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-025-02156-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature geneticsPub Date : 2025-04-14DOI: 10.1038/s41588-025-02158-6
Wenbao Yu, Rumeysa Biyik-Sit, Yasin Uzun, Chia-Hui Chen, Anusha Thadi, Jonathan H. Sussman, Minxing Pang, Chi-Yun Wu, Liron D. Grossmann, Peng Gao, David W. Wu, Aliza Yousey, Mei Zhang, Christina S. Turn, Zhan Zhang, Shovik Bandyopadhyay, Jeffrey Huang, Tasleema Patel, Changya Chen, Daniel Martinez, Lea F. Surrey, Michael D. Hogarty, Kathrin Bernt, Nancy R. Zhang, John M. Maris, Kai Tan
{"title":"Longitudinal single-cell multiomic atlas of high-risk neuroblastoma reveals chemotherapy-induced tumor microenvironment rewiring","authors":"Wenbao Yu, Rumeysa Biyik-Sit, Yasin Uzun, Chia-Hui Chen, Anusha Thadi, Jonathan H. Sussman, Minxing Pang, Chi-Yun Wu, Liron D. Grossmann, Peng Gao, David W. Wu, Aliza Yousey, Mei Zhang, Christina S. Turn, Zhan Zhang, Shovik Bandyopadhyay, Jeffrey Huang, Tasleema Patel, Changya Chen, Daniel Martinez, Lea F. Surrey, Michael D. Hogarty, Kathrin Bernt, Nancy R. Zhang, John M. Maris, Kai Tan","doi":"10.1038/s41588-025-02158-6","DOIUrl":"10.1038/s41588-025-02158-6","url":null,"abstract":"High-risk neuroblastoma, a leading cause of pediatric cancer mortality, exhibits substantial intratumoral heterogeneity, contributing to therapeutic resistance. To understand tumor microenvironment evolution during therapy, we longitudinally profiled 22 patients with high-risk neuroblastoma before and after induction chemotherapy using single-nucleus RNA and ATAC sequencing and whole-genome sequencing. This revealed profound shifts in tumor and immune cell subpopulations after therapy and identified enhancer-driven transcriptional regulators of neuroblastoma neoplastic states. Poor outcome correlated with proliferative and metabolically active neoplastic states, whereas more differentiated neuronal-like states predicted better prognosis. Proportions of mesenchymal neoplastic cells increased after therapy and a high proportion correlated with a poorer chemotherapy response. Macrophages significantly expanded towards pro-angiogenic, immunosuppressive and metabolic phenotypes. We identified paracrine signaling networks and validated the HB-EGF–ERBB4 axis between macrophage and neoplastic subsets, which promoted tumor growth through the induction of ERK signaling. These findings collectively reveal intrinsic and extrinsic regulators of therapy response in high-risk neuroblastoma. Analysis of pre- and post-chemotherapy samples collected from 22 patients with high-risk neuroblastoma using single-nucleus RNA and ATAC sequencing and spatial omics characterizes therapy-related changes in cell composition and the tumor microenvironment.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 5","pages":"1142-1154"},"PeriodicalIF":31.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-025-02158-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Wheat tandem kinase RWT4 directly binds a fungal effector to activate defense","authors":"Yi-Chang Sung, Yinghui Li, Zoe Bernasconi, Suji Baik, Soichiro Asuke, Beat Keller, Tzion Fahima, Gitta Coaker","doi":"10.1038/s41588-025-02162-w","DOIUrl":"10.1038/s41588-025-02162-w","url":null,"abstract":"Plants have intricate innate immune receptors that detect pathogens. Research has intensely focused on two receptor classes recognizing external and internal threats. Recent research has identified a class of disease-resistance proteins called tandem kinase proteins (TKPs). We investigated RWT4, a wheat TKP that confers resistance to the devastating fungal pathogen Magnaporthe oryzae. We established a rice protoplast system, revealing RWT4 specifically recognizes the AvrPWT4 effector, leading to the transcription of defense genes and inducing cell death. RWT4 possesses both kinase and pseudokinase domains, with its kinase activity essential for defense. RWT4 directly interacts with and transphosphorylates AvrPWT4. Biolayer interferometry revealed both RWT4 kinase and pseudokinase regions bind the effector. Sequence similarity and structural modeling revealed a partial kinase duplication in RWT4’s kinase region as critical for effector interaction and defense activation. Collectively, these findings demonstrate that TKPs can directly bind a recognized effector, leading to downstream defense activation. This study shows that RWT4, a wheat tandem kinase, confers resistance to the fungal pathogen Magnaporthe oryzae by directly binding to the pathogen effector AvrPWT4 and activating host defense.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 5","pages":"1238-1249"},"PeriodicalIF":31.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827205","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}
Nature geneticsPub Date : 2025-04-10DOI: 10.1038/s41588-025-02181-7
Safia Danovi
{"title":"Somatic mutations in the stomach","authors":"Safia Danovi","doi":"10.1038/s41588-025-02181-7","DOIUrl":"10.1038/s41588-025-02181-7","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 4","pages":"774-774"},"PeriodicalIF":31.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813799","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}