2026-09-21
Savandara Besse, Tatsuya Sakaguchi, Louis Gauthier, Zahra Sahaf, Rini Ravindran, Lidice Gonzalez, Xavier Castellanos-Girouard, Cassandre Clermont, Nazli Koçatug, Olivier Péloquin, Chloé Matta, Julie G. Hussin, Stephen W. Michnick, Adrian W. R. Serohijos
This study uses budding yeast as a model system to link genetic variants with quantitative changes in protein–protein interaction strength under different environmental perturbations by leveraging a protein-fragment complementation assay targeting 61 pairs of interacting proteins.
DOI: 10.1038/s41588-026-02747-z2026-09-21
Michael T. Zimmermann, Raul Urrutia
This Perspective discusses computational structural genomics, a conceptual framework that links genetic variants to three-dimensional molecular structures and their dynamics and function in a cellular context, aiming to interpret their mechanisms.
DOI: 10.1038/s41588-026-02763-z2026-09-21
Jing Hou, Joseph Schacherer
A large-scale genetic screen in yeast identifies protein interaction quantitative trait loci (piQTLs), demonstrating that natural genetic variation acts extensively through protein interaction networks rather than solely through changes in gene expression.
DOI: 10.1038/s41588-026-02757-x2026-09-18
Zhuye Jie, Weiting Liang, Qiuxia Ding, Xiaomin Liu, Yunhong Zhang, Na Chen, Shenghui Li, Xin Tong, Hongqin Gao, Ruike Lu, Xincheng Huang, Ruochun Guo, Junhong Chen, Jie Zhu, Zhe Zhang, Na Liu, Zhangwei Xie, Xiaman Wang, Le Qi, Yumei Li, Liang Xiao, Shaoqiao Zhang, Xin Jin, Xun Xu, Huanming Yang, Jian Wang, Fangqing Zhao, Huijue Jia, Karsten Kristiansen, Tao Zhang, Lilan Hao, Lan Zhu, Chen Chen
DOI: 10.1038/s41588-026-02788-42026-09-16
Shanice Van Haeften, Stephanie M. Brunner, Ben J. Hayes, Michael Udvardi, Lee T. Hickey, Millicent R. Smith
Crops leave a legacy in the soil that shapes the next season’s harvest, and the size of that legacy depends on the variety’s genetics. This Perspective proposes breeding for entire rotations rather than single crops to build more sustainable farms.
DOI: 10.1038/s41588-026-02744-22026-09-15
Chhiring Lama, Danielle Isakov, Shira Rosenberg, Miguel Quijada-Álamo, Mirca S. Saurty-Seerunghen, Sara Moein, Mathis Nozais, Tsega-Ab Abera, Olivia Sakaguchi, Mansi Totwani, Grace Freed, Leila Zaydon, Chi-Lam Poon, Neelang Parghi, Andrea Kubas-Meyer, Amy X. Xie, Mohamed Omar, Daniel Choi, Franco Castillo-Tokumori, Ghaith Abu-Zeinah, Alicia Dillard, Saravanan Ganesan, Nathaniel D. Omans, Neville Dusaj, Paulina Chamely, Eleni Mimitou, Peter Smibert, Heidi E. Kosiorek, Amylou C. Dueck, Rona Weinberg, Ronan Chaligne, Bridget Marcellino, Luigi Marchionni, Sanjay Patel, Paul Simonson, Dan A. Landau, Elvin Wagenblast, Ronald Hoffman, Anna S. Nam
Single-cell multiomics of blood stem cells from patients with myeloproliferative neoplasms revealed that interferon-α normalizes blood counts by augmenting lymphoid differentiation and modulates clonal dynamics via inflammatory myeloid differentiation
DOI: 10.1038/s41588-026-02751-32026-09-15
Yiyang Liu, Weitao Li, Rongchong Li, Manish K. Pandey, Bo Bai, Yan Han, Guiying Tang, Lei Zhang, Annapurna Chitkineni, Yanjiao Li, Libing Li, Shulong Li, Vanika Garg, Fengping Du, Feng Cui, Liangqiong He, Lei Shan, Fangji Xu, Pingli Xu, Ronghua Tang, Reyazul R. Mir, Feng Guo, Xinguo Li, Jialei Zhang, Zheng Zhang, Kuldeep Singh, Qiang He, Guowei Li, Xinyou Zhang, Rajeev K. Varshney, Shubo Wan
Pan-genome analyses of cultivated peanut using 10 newly assembled genomes, along with whole-genome resequencing of 2,320 germplasm accessions, highlight structural variations and loci associated with agronomic traits such as flowering and dwarfism.
DOI: 10.1038/s41588-026-02765-x2026-09-15
Christophe O. Benoist, Diane Mathis, Patrick Schultz, László Tora
DOI: 10.1038/s41588-026-02771-z2026-09-14
Jesper Qvist Thomassen, Hampton Leonard, Brittany Ulms, Benjamin Grenier-Boley, Sami Heikkinen, Pablo Garcia-González, Atahualapa Castillo-Morales, Masataka Kikuchi, Jungsoo Gim, Han Cao, Fahri Küçükali, Najaf Amin, Dabin Yoon, Itziar de Rojas, Pilar Alvarez Jerez, Victoria Alvarez, Beatrice Arosio, Céline Bellenguez, Sverre Bergh, Kimberley Billingsley, Cornelis Blauwendraat, Merce Boada, Barbara Borroni, Paola Bossù, María J. Bullido, Antonio Daniele, Ángel Carracedo, Alexandre de Mendonça, Mark Cookson, Jürgen Deckert, Martin Dichgans, Srdjan Djurovic, Oriol Dols-Icardo, Carole Dufouil, Emrah Düzel, Valentina Escott-Price, Tormod Fladby, Laura Fratiglioni, Amy K. Y. Fu, Daniela Galimberti, Jose Maria García-Alberca, Vilmantas Giedraitis, Guillermo Garcia-Ribas, Caroline Graff, Timo Grimmer, Edna Grünblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Jakub Hort, Frank Jessen, Kendall Jensen, Caroline Jonson, Yoontae Kim, Nicole Kuznetsov, Ville Leinonen, Anssi Lipponen, Jiao Luo, Mary Makarious, Henna Martiskainen, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Pablo Mir, Akinori Miyashita, Susanne Moebus, Kin Y. Mok, Laura Molina Porcel, Fermin Moreno, Benedetta Nacmias, Lucilla Parnetti, Pau Pastor, Jordi Pérez-Tur, Oliver Peters, Yolande A. L. Pijnenburg, Gerard Piñol-Ripoll, Julius Popp, Innocenzo Rainero, Luis M. Real, Steffi Riedel-Heller, Eloy Rodriguez-Rodriguez, Arvid Rongve, Giacomina Rossi, Jose Luis Royo, Dan Rujescu, Ingvild Saltvedt, María Eugenia Sáez, Raquel Sánchez-Valle, Florentino Sanchez-Garcia, Nicolai Sandau, Nikolaos Scarmeas, Katja Scheffler, Norbert Scherbaum, Anja Schneider, Geir Selbæk, Davide Seripa, Vincenzo Solfrizzi, Marco Spallazzi, Alessio Squassina, Eystein Stordal, Niccoló Tesi, Lucio Tremolizzo, Kumar P. Tripathi, Wiesje M. van der Flier, Julie Williams, Jens Wiltfang, Dag Aarsland, Andrew B. Singleton, Philippe Amouyel, Stéphanie Debette, Magda Tsolaki, Gael Nicolas, Sven van der Lee, Henne Holstege, Maria Victoria Fernandez, Patrick Gavin Kehoe, Kristel Sleegers, Martin Ingelsson, Roberta Ghidoni, Ole A. Andreassen, Peter A. Holmans, Pascual Sánchez-Juan, Rebecca Sims, Nancy Y. Ip, Kun Ho Lee, Takeshi Ikeuchi, Alfredo Ramirez, Agustin Ruiz, Mikko Hiltunen, Jean-Charles Lambert, Cornelia van Duijn, Mike Nalls, Ruth Frikke-Schmidt
Genome-wide association analyses of Alzheimer’s disease stratified by APOE carrier status identify variants whose effects are attenuated or augmented by the ε4 risk allele.
DOI: 10.1038/s41588-026-02713-92026-09-14
Kristin Tsuo, Zhuozheng Shi, Tian Ge, Ravi Mandla, Kangcheng Hou, Yi Ding, Bogdan Pasaniuc, Ying Wang, Alicia R. Martin
Leveraging multiancestry and multi-biobank data from the All of Us Research Program and the UK Biobank improves polygenic prediction models for complex traits and diseases, especially for under-represented populations.
DOI: 10.1038/s41588-026-02734-42026-09-11
Short duration chemotherapy and/or radiation therapy before surgery selected mutations in DNA damage response, human leukocyte antigen and kinase genes in normal esophageal epithelium, despite leaving no detectable mutational signatures in the tissue. Thus, sequencing normal tissue from treated patients with cancer could identify genes and pathways conferring resistance to treatment.
DOI: 10.1038/s41588-026-02740-62026-07-22
Nature Genetics, Published online: 22 July 2026; doi:10.1038/s41588-026-02680-1 We constructed a tetraploid wheat pangenome from 12 genomes covering all 10 recognized subspecies. Combined with graph-based pangenome and population genomic analyses, we investigated untapped beneficial alleles, determined domestication trajectories, revealed convergent rachis non‑brittleness, and identified genomic loci that underlie agronomic trait variation.]]>
DOI: 10.1038/s41588-026-02680-12026-07-10
Arvind Iyer
Nature Genetics, Published online: 10 July 2026; doi:10.1038/s41588-026-02661-4 SelectSim uses cancer and healthy tissue sequencing datasets to identify co-mutations that occur more or less frequently than would be expected by chance. Differences in co-mutation patterns observed during different stages of tumor evolution are also explored.]]>
DOI: 10.1038/s41588-026-02661-42026-07-10
Nature Genetics, Published online: 10 July 2026; doi:10.1038/s41588-026-02690-z We launch a Focus on BRCA1 and BRCA2 to highlight the field’s evolution from the initial gene discoveries and functional dissection to the development of drugs to target BRCA1- and BRCA2-mutant cancers. We will also cover broader societal questions around the global health disparities preventing these discoveries from benefitting everyone in need.]]>
DOI: 10.1038/s41588-026-02690-z2026-07-10
Deborah Mascalzoni
Nature Genetics, Published online: 10 July 2026; doi:10.1038/s41588-026-02667-y As genomics infrastructure expands, current governance will determine whether it advances global health equity or entrenches disparities, locking biased data into future clinical tools. This Comment calls for inclusive, community-centered genomic systems, before biased data and extractive models becoming the default.]]>
DOI: 10.1038/s41588-026-02667-y2026-07-10
Ryan C. Chai
Nature Genetics, Published online: 10 July 2026; doi:10.1038/s41588-026-02640-9 The study integrates cross-species single-cell and genomic analyses with functional validations to map the endosteal bone compartment, revealing musculoskeletal-disease-relevant cell types and transcriptional programs.]]>
DOI: 10.1038/s41588-026-02640-92026-07-08
Liyuan Zhang
Nature Genetics, Published online: 08 July 2026; doi:10.1038/s41588-026-02660-5 This study implicates cross-talk between splenic CD8+ T cells and hepatic stellate cells in fibrosis associated with metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis.]]>
DOI: 10.1038/s41588-026-02660-52026-07-01
David M. Walter
Nature Genetics, Published online: 01 July 2026; doi:10.1038/s41588-026-02648-1 KRASG12S mutations generate potential docking sites for splicing factor U2AF1, which can lead to exon skipping and nonfunctional KRAS transcripts. This is mitigated by mutations in U2AF1, which rescue exon skipping, thereby restoring KRAS activity in lung adenocarcinoma cells.]]>
DOI: 10.1038/s41588-026-02648-12026-07-01
Nature Genetics, Published online: 01 July 2026; doi:10.1038/s41588-026-02647-2 By combining cell modeling and computational approaches, we identified a function for mutations in splicing factor genes in cancer. U2AF1 mutations are positively enriched in cancers with specific KRAS mutations and rescue splicing defects, leading to cascading selection of mutational events.]]>
DOI: 10.1038/s41588-026-02647-22026-07-01
Nature Genetics, Published online: 01 July 2026; doi:10.1038/s41588-026-02602-1 The immune system recognizes and destroys cancerous cells, but whether such immunosurveillance occurs in precancer cell expansions was unclear. Using data from the UK Biobank, we investigated the role of immunosurveillance in shaping clonal expansions in precancerous hematopoietic stem cells.]]>
DOI: 10.1038/s41588-026-02602-12026-06-30
Huan Zhu
Nature Genetics, Published online: 30 June 2026; doi:10.1038/s41588-026-02628-5 Lineage tracing reveals how a cell’s past shapes its fate in cancer, aging and heart disease. This Review presents tools, including refined recombinase systems, CRISPR barcodes and natural mutations that are enabling precision medicine by decoding cellular ancestry.]]>
DOI: 10.1038/s41588-026-02628-52026-06-29
Barbara Walkowiak
Nature Genetics, Published online: 29 June 2026; doi:10.1038/s41588-026-02594-y Analysis of the UK Biobank cohort demonstrates that there is no significant MHC-I- or MHC-II-driven negative selection against expansion of mutant clones in clonal hematopoiesis.]]>
DOI: 10.1038/s41588-026-02594-y2026-06-22
Nature Genetics, Published online: 22 June 2026; doi:10.1038/s41588-026-02618-7 By using deep learning sequence models, we predict non-coding variant effects across the allele frequency spectrum in over 100 fetal and adult cell types. Linking these data with evolutionary constraint helps prioritize variants across conditions, such as Alzheimer’s disease, autism spectrum disorder, congenital heart disease and schizophrenia.]]>
DOI: 10.1038/s41588-026-02618-72026-06-15
Monika Krzak
Nature Genetics, Published online: 15 June 2026; doi:10.1038/s41588-026-02634-7 IBDverse is a single-cell RNA atlas of terminal ileal biopsies comprising 1.1 million cells from 111 patients with Crohn’s disease and 232 healthy participants. Analysis of the data identifies genes, pathways and cell populations associated with the disease and implicates inflammatory monocytes and macrophages in disease susceptibility.]]>
DOI: 10.1038/s41588-026-02634-72026-06-12
Dan Sarni
Nature Genetics, Published online: 12 June 2026; doi:10.1038/s41588-026-02633-8 This study investigates the consequences of hypermethylation in a progeria syndrome caused by gain-of-function DNMT3A mutations, finding effects on adult stem cell function.]]>
DOI: 10.1038/s41588-026-02633-82026-06-12
Masayuki Fujii
Nature Genetics, Published online: 12 June 2026; doi:10.1038/s41588-026-02616-9 This study implicates recurrent in-frame deletions in COPA exon 13 in small intestinal tumorigenesis through activation of Wnt signaling in an R-spondin-independent but Wnt ligand-dependent manner.]]>
DOI: 10.1038/s41588-026-02616-92026-06-12
Margot Brandt
Nature Genetics, Published online: 12 June 2026; doi:10.1038/s41588-026-02652-5 Dynamic genetic effects on lifespan]]>
DOI: 10.1038/s41588-026-02652-52026-06-12
Chiara Anania
Nature Genetics, Published online: 12 June 2026; doi:10.1038/s41588-026-02651-6 Mitochondrial capsules mitigate mitochondrial dysfunction]]>
DOI: 10.1038/s41588-026-02651-62026-06-09
Alexander P. Landry
Nature Genetics, Published online: 09 June 2026; doi:10.1038/s41588-026-02615-w This paper presents a sizeable single-cell multi-omic analysis of meningiomas comprising more than seven million cells. The results highlight tumor-intrinsic heterogeneity within both malignant and stromal compartments.]]>
DOI: 10.1038/s41588-026-02615-w2026-06-03
Andrew P. Feinberg
Nature Genetics, Published online: 03 June 2026; doi:10.1038/s41588-026-02630-x Leveraging a national-scale long-read sequencing program and new methods for allele-specific epigenome analysis, the integrated health ecosystem of the United Arab Emirates has created a unique platform in which genomic, clinical and environmental insights can converge to enable adaptive, preventive healthcare.]]>
DOI: 10.1038/s41588-026-02630-x