Nature geneticsPub Date : 2026-04-28DOI: 10.1038/s41588-026-02562-6
Dina MemarMoshrefi,Olivia L Johnson,Christian D Huber
{"title":"Insights into human adaptation from ancient DNA.","authors":"Dina MemarMoshrefi,Olivia L Johnson,Christian D Huber","doi":"10.1038/s41588-026-02562-6","DOIUrl":"https://doi.org/10.1038/s41588-026-02562-6","url":null,"abstract":"Ancient DNA (aDNA) has revolutionized our ability to study human evolution by enabling the direct observation of genetic changes through time. This has reshaped our understanding of human adaptation and its relevance for modern health and disease. In recent years, high-quality ancient genomes and large datasets have made it possible to track allele frequency dynamics and identify episodes of natural selection with unprecedented resolution. Here, we synthesize insights from recent studies that have systematically investigated how humans adapted to shifts in diet, mobility, pathogen exposure and environment. We summarize the approaches used to detect selection in aDNA, examine the role of major migration and admixture events and connect results across time periods and archaeological contexts. Finally, we outline future challenges and opportunities that need to be addressed for aDNA studies to provide new insights into human adaptation that could not be inferred from present-day genomes alone.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"21 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754559","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 : 2026-04-28DOI: 10.1038/s41588-026-02608-9
Marlena Fejzo,Xinran Wang,Qing Tan,Julia Zöllner,Natàlia Pujol-Gualdo,Triin Laisk, ,Sarah Finer,David A van Heel, ,Ben Brumpton,Laxmi Bhatta,Kristian Hveem,Elizabeth A Jasper,Digna R Velez Edwards,Jacklyn N Hellwege,Todd Edwards,Gail P Jarvik,Yuan Luo,Atlas Khan,Kimber MacGibbon,Yuan Gao,Gaoxiang Ge,Inna Averbukh,Erin Soon,Michael Angelo,Per Magnus,Stefan Johansson,Pål R Njølstad,Artem Kim,Steven Gazal,Marc Vaudel,Chang April Shu,Nicholas Mancuso
{"title":"Publisher Correction: Multi-ancestry genome-wide association study of severe pregnancy nausea and vomiting.","authors":"Marlena Fejzo,Xinran Wang,Qing Tan,Julia Zöllner,Natàlia Pujol-Gualdo,Triin Laisk, ,Sarah Finer,David A van Heel, ,Ben Brumpton,Laxmi Bhatta,Kristian Hveem,Elizabeth A Jasper,Digna R Velez Edwards,Jacklyn N Hellwege,Todd Edwards,Gail P Jarvik,Yuan Luo,Atlas Khan,Kimber MacGibbon,Yuan Gao,Gaoxiang Ge,Inna Averbukh,Erin Soon,Michael Angelo,Per Magnus,Stefan Johansson,Pål R Njølstad,Artem Kim,Steven Gazal,Marc Vaudel,Chang April Shu,Nicholas Mancuso","doi":"10.1038/s41588-026-02608-9","DOIUrl":"https://doi.org/10.1038/s41588-026-02608-9","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"21 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754508","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 : 2026-04-27DOI: 10.1038/s41588-026-02580-4
Luana Calabrò, Francesca P. Caruso, Alessia Covre, Teresa M. R. Noviello, Maria F. Lofiego, Rossella Tufano, Luigi Ferraro, Piera Grisolia, Antonio De Falco, Vincenzo Lagano, Francesco Sgambelluri, Giovanna Sabella, Giulia Rossi, Giulia Gibilisco, Francesco Marzani, Emma Bello, Elena Simonetti, Vincenzo D’Alonzo, Michele Caraglia, Sandra Coral, Antonina De Angelis, Luigi Cerbone, Sara Delfanti, Diana Giannarelli, Federica Grosso, Anna Maria Di Giacomo, Massimo Milione, Roberta Mortarini, Andrea Anichini, Michele Ceccarelli, Michele Maio
{"title":"Tumor DNA methylation subtypes predict immunotherapy outcomes in pleural mesothelioma patients in the NIBIT-EPI-MESO study","authors":"Luana Calabrò, Francesca P. Caruso, Alessia Covre, Teresa M. R. Noviello, Maria F. Lofiego, Rossella Tufano, Luigi Ferraro, Piera Grisolia, Antonio De Falco, Vincenzo Lagano, Francesco Sgambelluri, Giovanna Sabella, Giulia Rossi, Giulia Gibilisco, Francesco Marzani, Emma Bello, Elena Simonetti, Vincenzo D’Alonzo, Michele Caraglia, Sandra Coral, Antonina De Angelis, Luigi Cerbone, Sara Delfanti, Diana Giannarelli, Federica Grosso, Anna Maria Di Giacomo, Massimo Milione, Roberta Mortarini, Andrea Anichini, Michele Ceccarelli, Michele Maio","doi":"10.1038/s41588-026-02580-4","DOIUrl":"https://doi.org/10.1038/s41588-026-02580-4","url":null,"abstract":"Pleural mesothelioma (PM) has a poor prognosis and standard therapy with immune checkpoint inhibitors (ICIs) CTLA-4 and PD-1 is still clinically unsatisfying. No predictive biomarkers of ICI efficacy in PM are available yet. In the retrospective multicenter NIBIT-EPI-MESO study, multi-omics analysis of pre-ICI therapy tumor lesions from 91 patients with PM treated in earlier clinical trials or in daily practice identified four PM subsets with progressively increasing global DNA methylation profiles—demethylated, LOW, intermediate and CpG island methylator phenotype (CIMP). These methylation subsets predicted response and survival to ICI therapy. The LOW subset was enriched in responder patients, who had the longest median overall survival and the highest 3-year overall survival rate, and showed a T cell- and B cell-rich immune microenvironment. Conversely, the CIMP subtype was enriched in nonresponder patients with the shortest median overall survival and overall survival, along with a depleted immune microenvironment. A methylation-based probabilistic decision-making classification tool to predict the outcome of ICI treatment in patients with PM was developed.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"3 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751840","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}
{"title":"Interpretable, flexible and spatially aware integration of multiple spatial transcriptomics datasets from diverse sources","authors":"Jia Zhao, Xiangyu Zhang, Gefei Wang, Yingxin Lin, Tianyu Liu, Rui B. Chang, Hongyu Zhao","doi":"10.1038/s41588-026-02579-x","DOIUrl":"https://doi.org/10.1038/s41588-026-02579-x","url":null,"abstract":"Recent advances in spatial transcriptomics (ST) have generated an expanding collection of heterogeneous datasets, offering unprecedented opportunities to investigate tissue organizations and functions. However, effective interpretation and integration of data originating from diverse sources and conditions remain a major challenge. We present INSPIRE, a deep-learning method for interpretable, integrative analysis of multiple ST datasets. INSPIRE adopts an adversarial learning strategy with graph neural networks to achieve spatially informed and adaptive data integration. By incorporating non-negative matrix factorization, INSPIRE identifies interpretable spatial factors and associated gene programs that characterize tissue architecture, cell-type organization and biological processes. Across a broad range of applications, INSPIRE demonstrates superior performance in resolving fine-grained biological signals, integrating complementary strengths across technologies, capturing condition-specific variation, uncovering tumor microenvironment heterogeneity, elucidating developmental dynamics and facilitating three-dimensional tissue reconstruction. INSPIRE also scales to extremely large datasets, as demonstrated by applications to Xenium-profiled human breast cancer and Stereo-seq mouse organogenesis datasets.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"27 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751848","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 : 2026-04-24DOI: 10.1038/s41588-026-02577-z
Jianxin Bian,Yilin Zhang,Shuai Ding,Haosong Guo,Kui Li,Yu Guan,Guoliang Zhou,Jihua Li,Vanika Garg,Yuanyuan Cui,Yuan Lv,Annapurna Chitikineni,Qingjing Meng,Tianyu Li,Liangqiong He,Chuanzhi Zhao,Xingjun Wang,Ronghua Tang,Liangsheng Zhang,Xing Wang Deng,Rajeev K Varshney,Hang He,Xiaoqin Liu
{"title":"Telomere-to-telomere genome assemblies and population resequencing of diploid and allotetraploid peanut varieties.","authors":"Jianxin Bian,Yilin Zhang,Shuai Ding,Haosong Guo,Kui Li,Yu Guan,Guoliang Zhou,Jihua Li,Vanika Garg,Yuanyuan Cui,Yuan Lv,Annapurna Chitikineni,Qingjing Meng,Tianyu Li,Liangqiong He,Chuanzhi Zhao,Xingjun Wang,Ronghua Tang,Liangsheng Zhang,Xing Wang Deng,Rajeev K Varshney,Hang He,Xiaoqin Liu","doi":"10.1038/s41588-026-02577-z","DOIUrl":"https://doi.org/10.1038/s41588-026-02577-z","url":null,"abstract":"Peanut (Arachis hypogaea L.) is a globally significant leguminous oil crop. Here we present telomere-to-telomere genome assemblies for two diploid and four tetraploid peanut varieties, resulting in high-quality reference genomes, showing that the complex activities of transposable elements, chromosomal rearrangements and centromere expansions within subgenomes collectively contribute to the asymmetrical evolution of the tetraploid genome, and unique structural variants in the four tetraploid peanut varieties provide clear evidence of domestication. Population analyses of 521 peanut accessions revealed asymmetric selection events between subgenomes during breeding, and genome-wide association studies identified candidate genes linked to oil content, seed size and weight, kernel dehydration rate, and arachidic acid content. In addition, transcriptomic and metabolomic analyses revealed enhanced activity in lipidomic and anthocyanin biosynthetic pathways during seed development. These comprehensive findings provide insights into genome organization, evolutionary dynamics and phenotypic differentiation across peanut varieties that could inform future peanut breeding and improvement strategies.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"28 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738985","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 : 2026-04-24DOI: 10.1038/s41588-026-02573-3
Xuhua Yan, Zhaoyu Fang, Kok Siong Ang, Lynn van Olst, Alex Edwards, Thomas Watson, Ruiqing Zheng, Di Zhang, Rong Fan, Min Li, David Gate, Jinmiao Chen
{"title":"Mosaic integration of spatial multi-omics with SpaMosaic","authors":"Xuhua Yan, Zhaoyu Fang, Kok Siong Ang, Lynn van Olst, Alex Edwards, Thomas Watson, Ruiqing Zheng, Di Zhang, Rong Fan, Min Li, David Gate, Jinmiao Chen","doi":"10.1038/s41588-026-02573-3","DOIUrl":"https://doi.org/10.1038/s41588-026-02573-3","url":null,"abstract":"With the advent of spatial multi-omics, mosaic integration of diverse datasets with partially overlapping modalities enables the construction of comprehensive multimodal spatial atlases from heterogeneous sources. Here we present SpaMosaic, a tool that uses contrastive learning and graph neural networks to build a modality-agnostic, batch-corrected latent space for spatial domain identification and missing-modality imputation. We systematically benchmarked SpaMosaic against existing integration methods using simulated data and experimentally acquired datasets spanning RNA and protein abundance, chromatin accessibility and histone modifications from brain, embryo, tonsil and lymph node tissues. SpaMosaic consistently outperformed other methods in identifying coherent spatial domains by reducing noise and mitigating batch effects. We further challenged SpaMosaic with heterogeneous real-world datasets spanning different technologies, developmental stages, resolutions and modality compositions, where it consistently resolved fine anatomical structures and enabled comprehensive mouse embryo atlasing. Beyond integration, SpaMosaic enables accurate imputation of missing modalities. In a mosaic mouse brain dataset, the imputed histone modifications not only recapitulated expected transcriptome–epigenome correlations but also uncovered more region-specific regulatory links compared to the measured chromatin accessibility data, demonstrating the ability to infer relationships across modalities without coprofiling. Computationally, SpaMosaic is highly scalable, capable of integrating over 100 sections and processing a single section with more than 800,000 spots. In summary, SpaMosaic provides a versatile framework for unifying the rapidly accumulating heterogeneous spatial omics data into comprehensive biological atlases.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"152 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751844","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 : 2026-04-23DOI: 10.1038/s41588-026-02605-y
Daniel Greene, Rodrigo Mendez, Jon Lees, Mafalda Barbosa, Alessandro Bruselles, Luigi Chiriatti, Federico Ferraro, Cecilia Mancini, Rachel Schot, Frank Sleutels, Enrico Bertini, Devon E Bonner, Arjan Bouman, Alice S Brooks, T Homas A Cassini, Kimberly M Ezell, Natalia Gomez-Ospina, Tjitske Kleefstra, Michael O'Donoghue, Lynette Rives, Vandana Shashi, Rebecca C Spillmann, Mohamed Wafik, Kathleen Freson, Tahsin Stefan Barakat, Marco Tartaglia, Jonathan A Bernstein, Andrew D Mumford, Matthew T Wheeler, Ernest Turro
{"title":"Publisher Correction: Biallelic variants in RNU2-2 cause the most prevalent known recessive neurodevelopmental disorder.","authors":"Daniel Greene, Rodrigo Mendez, Jon Lees, Mafalda Barbosa, Alessandro Bruselles, Luigi Chiriatti, Federico Ferraro, Cecilia Mancini, Rachel Schot, Frank Sleutels, Enrico Bertini, Devon E Bonner, Arjan Bouman, Alice S Brooks, T Homas A Cassini, Kimberly M Ezell, Natalia Gomez-Ospina, Tjitske Kleefstra, Michael O'Donoghue, Lynette Rives, Vandana Shashi, Rebecca C Spillmann, Mohamed Wafik, Kathleen Freson, Tahsin Stefan Barakat, Marco Tartaglia, Jonathan A Bernstein, Andrew D Mumford, Matthew T Wheeler, Ernest Turro","doi":"10.1038/s41588-026-02605-y","DOIUrl":"10.1038/s41588-026-02605-y","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":" ","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776454","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 : 2026-04-23DOI: 10.1038/s41588-026-02543-9
Loes M. E. Moolhuijsen, Jia Zhu, Benjamin H. Mullin, Natàlia Pujol-Gualdo, Ky’Era V. Actkins, Jasmine A. Mack, Hridya Rao, Bhavi Trivedi, Katherine A. Kentistou, Yajie Zhao, David Westergaard, Jaakko S. Tyrmi, Gudmar Thorleifsson, Yanfei Zhang, Laura Wittemans, Amber DeVries, Kelly Brewer, Ryan Sisk, Rebecca Danning, Michael H. Preuss, Michelle R. Jones, Katherine S. Ruth, Marianne Andersen, Ricardo Azziz, Karina Banasik, Michael Boehnke, Linda Broer, Søren Brunak, Yee-Ming Chan, Daniel I. Chasman, Mark Daly, David A. Ehrmann, Bart C. Fauser, Lars G. Fritsche, M. Geoffrey Hayes, Chunyan He, Hongyan Huang, Irina Kowalska, Peter Kraft, Richard S. Legro, Nan Lin, Ruth J. Loos, Yvonne V. Louwers, Reedik Magi, Mark I. McCarthy, Laure Morin-Papunen, Jean V. Morrison, Cynthia Morton
{"title":"Genomic analyses implicate hormonal and metabolic dysregulation in polycystic ovary syndrome","authors":"Loes M. E. Moolhuijsen, Jia Zhu, Benjamin H. Mullin, Natàlia Pujol-Gualdo, Ky’Era V. Actkins, Jasmine A. Mack, Hridya Rao, Bhavi Trivedi, Katherine A. Kentistou, Yajie Zhao, David Westergaard, Jaakko S. Tyrmi, Gudmar Thorleifsson, Yanfei Zhang, Laura Wittemans, Amber DeVries, Kelly Brewer, Ryan Sisk, Rebecca Danning, Michael H. Preuss, Michelle R. Jones, Katherine S. Ruth, Marianne Andersen, Ricardo Azziz, Karina Banasik, Michael Boehnke, Linda Broer, Søren Brunak, Yee-Ming Chan, Daniel I. Chasman, Mark Daly, David A. Ehrmann, Bart C. Fauser, Lars G. Fritsche, M. Geoffrey Hayes, Chunyan He, Hongyan Huang, Irina Kowalska, Peter Kraft, Richard S. Legro, Nan Lin, Ruth J. Loos, Yvonne V. Louwers, Reedik Magi, Mark I. McCarthy, Laure Morin-Papunen, Jean V. Morrison, Cynthia Morton","doi":"10.1038/s41588-026-02543-9","DOIUrl":"https://doi.org/10.1038/s41588-026-02543-9","url":null,"abstract":"Polycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic study (n = 544,513), we expand the number of genetic loci from 16 to 29, and additionally identify 31 associated plasma proteins. Many risk-increasing loci were associated with later age at menopause, underscoring the reproductive longevity related to an increased oocyte number and/or availability across the lifespan. Hormonal regulation in the etiology of this condition, through metabolic and reproductive features, was emphasized. The proteomic analysis highlighted metabolic biology known to be related to PCOS. A polygenic risk score (PRS) was associated with adverse cardiometabolic outcomes, with differing relevance of testosterone and body mass index in women and men. Finally, while oligo-anovulation and anovulatory infertility are features of PCOS, we observed no impact of PCOS susceptibility on childlessness. We suggest that PCOS susceptibility confers balanced pleiotropic influences on fertility in women, and life-long adverse metabolic consequences in both sexes.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"120 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147734060","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 : 2026-04-22DOI: 10.1038/s41588-026-02572-4
{"title":"Somatic mutations link focal onset to widespread neurodegeneration in ALS and FTD.","authors":"","doi":"10.1038/s41588-026-02572-4","DOIUrl":"https://doi.org/10.1038/s41588-026-02572-4","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"24 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733956","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
