Nature Communications最新文献

{"title":"The global spectrum of tree crown architecture","authors":"Tommaso Jucker, Fabian Jörg Fischer, Jérôme Chave, David A. Coomes, John Caspersen, Arshad Ali, Grace Jopaul Loubota Panzou, Ted R. Feldpausch, Daniel Falster, Vladimir A. Usoltsev, Toby D. Jackson, Stephen Adu-Bredu, Luciana F. Alves, Mohammad Aminpour, Bhely Angoboy Ilondea, Niels P. R. Anten, Cécile Antin, Yousef Askari, Narayanan Ayyappan, Lindsay F. Banin, Nicolas Barbier, John J. Battles, Hans Beeckman, Yannick E. Bocko, Ben Bond-Lamberty, Frans Bongers, Samuel Bowers, Michiel van Breugel, Arthur Chantrain, Rajeev Chaudhary, Jingyu Dai, Michele Dalponte, Kangbéni Dimobe, Jean-Christophe Domec, Jean-Louis Doucet, Juan Manuel Dupuy Rada, Remko A. Duursma, Moisés Enríquez, Karin Y. van Ewijk, William Farfán-Rios, Adeline Fayolle, Marco Ferretti, Eric Forni, David I. Forrester, Hammad Gilani, John L. Godlee, Matthias Haeni, Jefferson S. Hall, Jie-Kun He, Andreas Hemp, José L. Hernández-Stefanoni, Steven I. Higgins, Robert J. Holdaway, Kiramat Hussain, Lindsay B. Hutley, Tomoaki Ichie, Yoshiko Iida, Hai-Sheng Jiang, Puspa Raj Joshi, Hasan Kaboli, Maryam Kazempour Larsary, Tanaka Kenzo, Brian D. Kloeppel, Takashi S. Kohyama, Suwash Kunwar, Shem Kuyah, Jakub Kvasnica, Siliang Lin, Emily R. Lines, Hongyan Liu, Craig Lorimer, Jean-Joël Loumeto, Yadvinder Malhi, Peter L. Marshall, Eskil Mattsson, Radim Matula, Jorge A. Meave, Sylvanus Mensah, Xiangcheng Mi, Stéphane T. Momo, Glenn R. Moncrieff, Francisco Mora, Rodrigo Muñoz, Sarath P. Nissanka, Zamah Shari Nur Hajar, Kevin L. O’Hara, Steven Pearce, Raphaël Pelissier, Pablo L. Peri, Pierre Ploton, Lourens Poorter, Mohsen Javanmiri Pour, Hassan Pourbabaei, Sabina C. Ribeiro, Casey Ryan, Anvar Sanaei, Jennifer Sanger, Michael Schlund, Giacomo Sellan, Alexander Shenkin, Bonaventure Sonké, Frank J. Sterck, Martin Svátek, Kentaro Takagi, Anna T. Trugman, Matthew A. Vadeboncoeur, Ahmad Valipour, Mark C. Vanderwel, Alejandra G. Vovides, Peter Waldner, Weiwei Wang, Li-Qiu Wang, Christian Wirth, Murray Woods, Wenhua Xiang, Fabiano de Aquino Ximenes, Yaozhan Xu, Toshihiro Yamada, Miguel A. Zavala, Niklaus E. Zimmermann","doi":"10.1038/s41467-025-60262-x","DOIUrl":"https://doi.org/10.1038/s41467-025-60262-x","url":null,"abstract":"<p>Trees can differ enormously in their crown architectural traits, such as the scaling relationships between tree height, crown width and stem diameter. Yet despite the importance of crown architecture in shaping the structure and function of terrestrial ecosystems, we lack a complete picture of what drives this incredible diversity in crown shapes. Using data from 374,888 globally distributed trees, we explore how climate, disturbance, competition, functional traits, and evolutionary history constrain the height and crown width scaling relationships of 1914 tree species. We find that variation in height–diameter scaling relationships is primarily controlled by water availability and light competition. Conversely, crown width is predominantly shaped by exposure to wind and fire, while also covarying with functional traits related to mechanical stability and photosynthesis. Additionally, we identify several plant lineages with highly distinctive stem and crown forms, such as the exceedingly slender dipterocarps of Southeast Asia, or the extremely wide crowns of legume trees in African savannas. Our study charts the global spectrum of tree crown architecture and pinpoints the processes that shape the 3D structure of woody ecosystems.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"24 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global land and carbon consequences of mass timber products","authors":"Kai Lan, Alice Favero, Yuan Yao, Robert O. Mendelsohn, Hannah Szu-Han Wang","doi":"10.1038/s41467-025-60245-y","DOIUrl":"https://doi.org/10.1038/s41467-025-60245-y","url":null,"abstract":"<p>Mass timber products can reduce greenhouse gas emissions by replacing steel and cement. However, the increase in wood demand raises wood prices, and the environmental consequences of these market changes are unclear. Here we investigate the global carbon and land use impacts of adopting mass timber products, focusing on cross-laminated timber as a case study. Our results show that higher wood prices reduce the production of traditional wood products but expand productive forestland by 30.7–36.5 million hectares from 2020 to 2100 and lead to more intensive forest management. If the cumulative global cross-laminated timber production reaches 3.6 to 9.6 billion m³ by 2100, long-term carbon storage can increase by 20.3–25.2 GtCO₂e, primarily in forests (16.1–17.7 GtCO₂e) and in cross-laminated timber panels (4.1–8.1 GtCO₂e). Including emission reductions from steel, cement, and traditional wood products, the net reduction of life-cycle greenhouse gas emissions will be 25.6–39.0 GtCO₂e.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"34 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electron displacement polarization of high-dielectric constant fiber separators enhances interface stability","authors":"Tao Zhang, Xiaoqing Zhu, Jiyang Xiong, Zhixin Xue, Yunteng Cao, Keith C. Gordon, Guiyin Xu, Meifang Zhu","doi":"10.1038/s41467-025-60256-9","DOIUrl":"https://doi.org/10.1038/s41467-025-60256-9","url":null,"abstract":"<p>The electrostatic effects of separators under the internal electric field are often overlooked, leading to the unreliability of traditional theoretical models. Here we introduce the dielectric constant as a descriptor and develop a high dielectric constant fiber separator primarily composed of phosphorylated cellulose. Under the internal electric field, the intense electron displacement polarization within the high dielectric constant separator enhances the charge transfer kinetics and optimizes the solvation structure, thus mitigating the formation of amorphous organic oligomers at the solid-electrolyte interphase. Furthermore, the separator induces the formation of LiF, thereby forming a robust and low-resistance solid-electrolyte interphase. The separator exhibits high ionic conductivity (0.76 mS cm⁻¹ at 25 °C) and Li⁺ transference number (0.68). Consequently, the Li||LiFePO₄ pouch cell with the prepared separator achieve high specific energy exceeding 350 Wh kg⁻¹ (relative to the mass of pouch cells) under practical quantities of active materials and electrolyte.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"34 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boosted charge and proton transfer over ternary Co/Co3O4/CoB for electrochemical nitric oxide reduction to ammonia","authors":"Xiaoxuan Fan, Zhenyuan Teng, Lupeng Han, Yongjie Shen, Xiyang Wang, Wenqiang Qu, Jialing Song, Zhenlin Wang, Haiyan Duan, Yimin A. Wu, Bin Liu, Dengsong Zhang","doi":"10.1038/s41467-025-60043-6","DOIUrl":"https://doi.org/10.1038/s41467-025-60043-6","url":null,"abstract":"<p>The electrochemical nitric oxide reduction reaction (NORR) holds a great potential for removing environmental pollutant NO and meanwhile generating high value-added ammonia (NH₃). Herein, we tactfully design and synthesize a ternary Co/Co₃O₄/CoB heterostructure that displays a high NH₃ Faradaic efficiency of 98.8% in NORR with an NH₃ yield rate of 462.18 µmol cm⁻² h⁻¹ (2.31 mol h⁻¹ g_cat⁻¹) at −0.5 V versus reversible hydrogen electrode, outperforming most of the reported NORR electrocatalysts to date. The superior NORR performance is attributed to the enhanced charge and proton transfer over the ternary Co/Co₃O₄/CoB heterostructure. The charge transfer between CoB and Co/Co₃O₄ yields electron-deficient Co and electron-rich Co₃O₄. The electron-deficient Co sites boost H₂O dissociation to generate *H while the electron-rich low-coordination Co₃O₄ sites promote NO adsorption. The *H formed on electron-deficient Co sites is more favorable to transfer to electron-rich Co₃O₄ sites adsorbed with NO, facilitating the selective hydrogenation of NO. This study paves the way for designing and developing highly efficient electrocatalysts for electrochemical reduction of NO to NH₃.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"56 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-hospital, clinician-initiated bacterial genomics programme to investigate treatment failure in severe Staphylococcus aureus infections","authors":"Stefano G. Giulieri, Marcel Leroi, Diane Daniel, Roy Chean, Katherine Bond, Harry Walker, Natasha E. Holmes, Nomvuyo Mothobi, Adrian Alexander, Adam Jenney, Carolyn Beckett, Andrew Mahony, Kerrie Stevens, Norelle L. Sherry, Benjamin P. Howden","doi":"10.1038/s41467-025-60045-4","DOIUrl":"https://doi.org/10.1038/s41467-025-60045-4","url":null,"abstract":"<p>Bacterial genomics is increasingly used for infectious diseases surveillance, outbreak detection and prediction of antibiotic resistance. With expanding availability of rapid whole-genome sequencing, bacterial genomics data could become a valuable tool for clinicians managing bacterial infections, driving precision medicine strategies. Here, we present a clinician-driven bacterial genomics framework that applies within-patient evolutionary analysis to identify in real-time microbial genetic changes that have an impact on treatment outcomes of severe <i>Staphylococcus aureus</i> infections, a strategy that is increasingly used in cancer genomics. Our approach uses a combination of bacterial genomics and antibiotic susceptibility testing to identify and track bacterial adaptive mutations that underlie microbiologically documented treatment failure (i.e. ongoing positive cultures [persistent infection] or new positive cultures after initial response [recurrent infection]). We show the potential added value of our approach to clinicians and propose a roadmap for the use of bacterial genomics to advance the management of severe bacterial infections.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"14 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-organ metabolome biological age implicates cardiometabolic conditions and mortality risk.","authors":"Filippos Anagnostakis, Sarah Ko, Mehrshad Saadatinia, Jingyue Wang, Christos Davatzikos, Junhao Wen","doi":"10.1038/s41467-025-59964-z","DOIUrl":"https://doi.org/10.1038/s41467-025-59964-z","url":null,"abstract":"<p><p>Multi-organ biological aging clocks across different organ systems have been shown to predict human disease and mortality. Here, we extend this multi-organ framework to plasma metabolomics, developing five organ-specific metabolome-based biological age gaps (MetBAGs) using 107 plasma non-derivatized metabolites from 274,247 UK Biobank participants. Our age prediction models achieve a mean absolute error of approximately 6 years (0.25<r < 0.42). Crucially, including composite metabolites (e.g. sums or ratios of raw metabolites) results in poor generalizability to independent test data due to multicollinearity. Genome-wide associations identify 405 MetBAG-locus pairs (P < 5 × 10^-8/5). Using SBayesS, we estimate the SNP-based heritability (0.09< <math> <msubsup><mrow><mi>h</mi></mrow> <mrow><mi>S</mi> <mi>N</mi> <mi>P</mi></mrow> <mrow><mn>2</mn></mrow> </msubsup> </math>  < 0.18), negative selection signatures (-0.93 < S < -0.76), and polygenicity (0.001<Pi < 0.003) for the 5 MetBAGs. Genetic correlation and Mendelian randomization analyses reveal potential causal links between the 5 MetBAGs and cardiometabolic conditions (e.g., metabolic disorders and hypertension). Integrating multi-organ and multi-omics features improves disease category and mortality predictions. The 5 MetBAGs extend existing biological aging clocks to study human aging and disease across multiple biological scales. All results are publicly available at https://labs-laboratory.com/medicine/ .</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"16 1","pages":"4871"},"PeriodicalIF":14.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anharmonic effects control interaction of carbyne confined in carbon nanotubes shaping their vibrational properties","authors":"Emil Parth, Andrea Corradini, Weili Cui, Davide Romanin, Christin Schuster, Clara Freytag, Lei Shi, Kazuhiro Yanagi, Matteo Calandra, Thomas Pichler","doi":"10.1038/s41467-025-59863-3","DOIUrl":"https://doi.org/10.1038/s41467-025-59863-3","url":null,"abstract":"<p>The resonant Raman response is due to electronic and vibrational excitations. Confined carbyne is a novel one dimensional heterostructure consisting of the linear carbon chain and a hosting carbon nanotube in the bulk limit. The resonant Raman fingerprint of confined carbyne comes concomitant with several new features which can neither be assigned to the hosting tube, nor to the linear carbon chain. This identifies the tube-chain system as a true hybrid structure in which the spectrum is usually driven by modifications in the electronic excitations via charge transfer. We show that the electronic structure results from those of the two isolated systems and the spectral modifications are solely due to the anharmonic interactions between the tube and the chain. Our work establishes confined carbyne as the ideal test system to probe anharmonicity in one dimension and its implications on the resonant Raman response.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"24 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCR4+ mammary gland macrophageal niche promotes tumor initiating cell activity and immune suppression during tumorigenesis","authors":"Eunmi Lee, Jason J. Hong, Gabriel Samcam Vargas, Natalie Sauerwald, Yong Wei, Xiang Hang, Chandra L. Theesfeld, Jean Arly A. Volmar, Jennifer M. Miller, Wei Wang, Sha Wang, Gary Laevsky, Christina J. DeCoste, Yibin Kang","doi":"10.1038/s41467-025-59972-z","DOIUrl":"https://doi.org/10.1038/s41467-025-59972-z","url":null,"abstract":"<p>Tumor-initiating cells (TICs) share features and regulatory pathways with normal stem cells, yet how the stem cell niche contributes to tumorigenesis remains unclear. Here, we identify CXCR4⁺ macrophages as a niche population enriched in normal mammary ducts, where they promote the regenerative activity of basal cells in response to luminal cell-derived CXCL12. CXCL12 triggers AKT-mediated stabilization of β-catenin, which induces Wnt ligands and pro-migratory genes, enabling intraductal macrophage infiltration and supporting regenerative activity of basal cells. Notably, these same CXCR4⁺ niche macrophages regulate the tumor-initiating activity of various breast cancer subtypes by enhancing TIC survival and tumor-forming capacity, while promoting early immune evasion through regulatory T cell induction. Furthermore, a CXCR4⁺ niche macrophage gene signature correlates with poor prognosis in human breast cancer. These findings highlight the pivotal role of the CXCL12-CXCR4 axis in orchestrating interactions between niche macrophages, mammary epithelial cells, and immune cells, thereby establishing a supportive niche for both normal tissue regeneration and mammary tumor initiation.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"56 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ampere-level co-electrosynthesis of formate from CO2 reduction paired with formaldehyde dehydrogenation reactions","authors":"Zhengyuan Li, Peng Wang, Guanqun Han, Shize Yang, Soumyabrata Roy, Shuting Xiang, Juan D. Jimenez, Vamsi Krishna Reddy Kondapalli, Xiang Lyu, Jianlin Li, Alexey Serov, Ruizhi Li, Vesselin Shanov, Sanjaya D. Senanayake, Anatoly I. Frenkel, Pulickel M. Ajayan, Yujie Sun, Thomas P. Senftle, Jingjie Wu","doi":"10.1038/s41467-025-60008-9","DOIUrl":"https://doi.org/10.1038/s41467-025-60008-9","url":null,"abstract":"<p>Current catalysts face challenges with low formate selectivity at high current densities during the CO₂ electroreduction. Here, we showcase a versatile strategy to enhance the formate production on <i>p</i>-block metal-based catalysts by incorporating noble metal atoms on their surface, refining oxygen affinity, and tuning adsorption of the critical oxygen-bound *OCHO intermediate. The formate yield is observed to afford a volcano-like dependence on the *OCHO binding strength across a series of modified catalysts. The rhodium-dispersed indium oxide (Rh/In₂O₃) catalyst exhibits impressive performances, achieving Faradaic efficiencies (FEs) of formate exceeding 90% across a broad current density range of 0.20 to 1.21 A cm⁻². In situ Raman spectroscopy and theoretical calculations reveal that the oxophilic Rh site facilitates *OCHO formation by optimizing its adsorption energy, placing Rh/In₂O₃ near the volcano-shaped apex. A bipolar electrosynthesis system, coupling the CO₂ reduction at the cathode with the formaldehyde oxidative dehydrogenation at the anode, further boosts the FE of formate to nearly 190% with pure hydrogen generation under an ampere-level current density and a low cell voltage of 2.5 V in a membrane electrode assembly cell.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"158 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of more than 400,000 women provides case-control evidence for BRCA1 and BRCA2 variant classification","authors":"Maria Zanti, Denise G. O’Mahony, Michael T. Parsons, Leila Dorling, Joe Dennis, Nicholas J. Boddicker, Wenan Chen, Chunling Hu, Marc Naven, Kristia Yiangou, Thomas U. Ahearn, Christine B. Ambrosone, Irene L. Andrulis, Antonis C. Antoniou, Paul L. Auer, Caroline Baynes, Clara Bodelon, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Kristen D. Brantley, Nicola J. Camp, Archie Campbell, Jose E. Castelao, Melissa H. Cessna, Jenny Chang-Claude, Fei Chen, Georgia Chenevix-Trench, Don M. Conroy, Kamila Czene, Arcangela De Nicolo, Susan M. Domchek, Thilo Dörk, Alison M. Dunning, A. Heather Eliassen, D. Gareth Evans, Peter A. Fasching, Jonine D. Figueroa, Henrik Flyger, Manuela Gago-Dominguez, Montserrat García-Closas, Gord Glendon, Anna González-Neira, Felix Grassmann, Andreas Hadjisavvas, Christopher A. Haiman, Ute Hamann, Steven N. Hart, Mikael B. A. Hartman, Weang-Kee Ho, James M. Hodge, Reiner Hoppe, Sacha J. Howell, Anna Jakubowska, Elza K. Khusnutdinova, Yon-Dschun Ko, Peter Kraft, Vessela N. Kristensen, James V. Lacey, Jingmei Li, Geok Hoon Lim, Sara Lindström, Artitaya Lophatananon, Craig Luccarini, Arto Mannermaa, Maria Elena Martinez, Dimitrios Mavroudis, Roger L. Milne, Kenneth Muir, Katherine L. Nathanson, Rocio Nuñez-Torres, Nadia Obi, Janet E. Olson, Julie R. Palmer, Mihalis I. Panayiotidis, Alpa V. Patel, Paul D. P. Pharoah, Eric C. Polley, Muhammad U. Rashid, Kathryn J. Ruddy, Emmanouil Saloustros, Elinor J. Sawyer, Marjanka K. Schmidt, Melissa C. Southey, Veronique Kiak-Mien Tan, Soo Hwang Teo, Lauren R. Teras, Diana Torres, Amy Trentham-Dietz, Thérèse Truong, Celine M. Vachon, Qin Wang, Jeffrey N. Weitzel, Siddhartha Yadav, Song Yao, Gary R. Zirpoli, Melissa S. Cline, Peter Devilee, Sean V. Tavtigian, David E. Goldgar, Fergus J. Couch, Douglas F. Easton, Amanda B. Spurdle, Kyriaki Michailidou","doi":"10.1038/s41467-025-59979-6","DOIUrl":"https://doi.org/10.1038/s41467-025-59979-6","url":null,"abstract":"<p>Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS. As an initiative of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Analytical Working Group we analyze germline sequencing data of <i>BRCA1</i> and <i>BRCA2</i> from 96,691 female breast cancer cases and 302,116 controls from three studies: the BRIDGES study of the Breast Cancer Association Consortium, the Cancer Risk Estimates Related to Susceptibility consortium, and the UK Biobank. We observe 11,207 <i>BRCA1</i> and <i>BRCA2</i> variants, with 6909 being coding, covering 23.4% of <i>BRCA1</i> and <i>BRCA2</i> VUS in ClinVar and 19.2% of ClinVar curated (likely) benign or pathogenic variants. Case-control likelihood ratio (ccLR) evidence is highly consistent with ClinVar assertions for (likely) benign or pathogenic variants; exhibiting 99.1% sensitivity and 95.3% specificity for <i>BRCA1</i> and 93.3% sensitivity and 86.6% specificity for <i>BRCA2</i>. This approach provides case-control evidence for 787 unclassified variants; these include 579 with strong or moderate benign evidence and 10 with strong pathogenic evidence for which ccLR evidence is sufficient to alter clinical classification.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"23 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}