Nature genetics最新文献

{"title":"Spatial biology captures the effects of neoadjuvant chemo-immunotherapy in lung cancer","authors":"Jonathan H. Chen, Justin F. Gainor","doi":"10.1038/s41588-024-01992-4","DOIUrl":"https://doi.org/10.1038/s41588-024-01992-4","url":null,"abstract":"PD-1 pathway blockade in combination with chemotherapy has emerged as a treatment paradigm for patients with resectable lung cancer, but insights into predictive biomarkers and mechanisms of immune responses are lacking. A study uses spatial transcriptomic methods to identify patterns within the tumor microenvironment associated with response.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"37 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796908","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":"Multi-omic profiling highlights factors associated with resistance to immuno-chemotherapy in non-small-cell lung cancer","authors":"Yilv Yan, Dongqing Sun, Junjie Hu, Yue Chen, Liangdong Sun, Huansha Yu, Yicheng Xiong, Zhida Huang, Haoran Xia, Xinsheng Zhu, Dongliang Bian, Fenghuan Sun, Likun Hou, Chunyan Wu, Orion R. Fan, Haiyang Hu, An Zeng, Lele Zhang, Yi Eve Sun, Chenfei Wang, Peng Zhang","doi":"10.1038/s41588-024-01998-y","DOIUrl":"https://doi.org/10.1038/s41588-024-01998-y","url":null,"abstract":"<p>Although immune checkpoint blockade (ICB) therapies have shifted the treatment paradigm for non-small-cell lung cancer (NSCLC), many patients remain resistant. Here we characterize the tumor cell states and spatial cellular compositions of the NSCLC tumor microenvironment (TME) by analyzing single-cell transcriptomes of 232,080 cells and spatially resolved transcriptomes of tumors from 19 patients before and after ICB–chemotherapy. We find that tumor cells and secreted phosphoprotein 1-positive macrophages interact with collagen type XI alpha 1 chain-positive cancer-associated fibroblasts to stimulate the deposition and entanglement of collagen fibers at tumor boundaries, obstructing T cell infiltration and leading to poor prognosis. We also reveal distinct states of tertiary lymphoid structures (TLSs) in the TME. Activated TLSs are associated with improved prognosis, whereas a hypoxic microenvironment appears to suppress TLS development and is associated with poor prognosis. Our study provides novel insights into different cellular and molecular components corresponding to NSCLC ICB–chemotherapeutic responsiveness, which will benefit future individualized immuno-chemotherapy.</p>","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"212 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797061","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":"Chromatin topology dynamics in gene activation","authors":"Petra Gross","doi":"10.1038/s41588-024-02041-w","DOIUrl":"10.1038/s41588-024-02041-w","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2589-2589"},"PeriodicalIF":31.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797064","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":"Functional genomics of height heritability","authors":"Tiago Faial","doi":"10.1038/s41588-024-02043-8","DOIUrl":"10.1038/s41588-024-02043-8","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2589-2589"},"PeriodicalIF":31.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797271","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":"DRAGEN optimizes genomic variant detection","authors":"Wei Li","doi":"10.1038/s41588-024-02042-9","DOIUrl":"10.1038/s41588-024-02042-9","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2589-2589"},"PeriodicalIF":31.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797062","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":"Improved tool for scRNA-seq analysis","authors":"Michael Fletcher","doi":"10.1038/s41588-024-02040-x","DOIUrl":"10.1038/s41588-024-02040-x","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2589-2589"},"PeriodicalIF":31.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797063","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":"Genetic control of alternative splicing across blood cell types from diverse Asian donors","authors":"","doi":"10.1038/s41588-024-02020-1","DOIUrl":"10.1038/s41588-024-02020-1","url":null,"abstract":"Existing functional genomics datasets are European-centric. The Asian Immune Diversity Atlas incorporated single-cell RNA-sequencing data from approximately 1 million peripheral blood mononuclear cells from around 500 donors of diverse Asian ancestries. Mapping of splicing quantitative trait loci revealed context-specific regulation of alternative splicing, as well as cell-type and ancestry-specific genetic effects on complex diseases.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2602-2603"},"PeriodicalIF":31.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763210","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":"Publisher Correction: Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience","authors":"Sean J. Jurgens,&nbsp;Joel T. Rämö,&nbsp;Daria R. Kramarenko,&nbsp;Leonoor F. J. M. Wijdeveld,&nbsp;Jan Haas,&nbsp;Mark D. Chaffin,&nbsp;Sophie Garnier,&nbsp;Liam Gaziano,&nbsp;Lu-Chen Weng,&nbsp;Alex Lipov,&nbsp;Sean L. Zheng,&nbsp;Albert Henry,&nbsp;Jennifer E. Huffman,&nbsp;Saketh Challa,&nbsp;Frank Rühle,&nbsp;Carmen Diaz Verdugo,&nbsp;Christian Krijger Juárez,&nbsp;Shinwan Kany,&nbsp;Constance A. van Orsouw,&nbsp;Kiran Biddinger,&nbsp;Edwin Poel,&nbsp;Amanda L. Elliott,&nbsp;Xin Wang,&nbsp;Catherine Francis,&nbsp;Richard Ruan,&nbsp;Satoshi Koyama,&nbsp;Leander Beekman,&nbsp;Dominic S. Zimmerman,&nbsp;Jean-François Deleuze,&nbsp;Eric Villard,&nbsp;David-Alexandre Trégouët,&nbsp;Richard Isnard,&nbsp;FinnGen,&nbsp;VA Million Veteran Program,&nbsp;HERMES Consortium,&nbsp;Dorret I. Boomsma,&nbsp;Eco J. C. de Geus,&nbsp;Rafik Tadros,&nbsp;Yigal M. Pinto,&nbsp;Arthur A. M. Wilde,&nbsp;Jouke-Jan Hottenga,&nbsp;Juha Sinisalo,&nbsp;Teemu Niiranen,&nbsp;Roddy Walsh,&nbsp;Amand F. Schmidt,&nbsp;Seung Hoan Choi,&nbsp;Kyong-Mi Chang,&nbsp;Philip S. Tsao,&nbsp;Paul M. Matthews,&nbsp;James S. Ware,&nbsp;R. Thomas Lumbers,&nbsp;Saskia van der Crabben,&nbsp;Jari Laukkanen,&nbsp;Aarno Palotie,&nbsp;Ahmad S. Amin,&nbsp;Philippe Charron,&nbsp;Benjamin Meder,&nbsp;Patrick T. Ellinor,&nbsp;Mark Daly,&nbsp;Krishna G. Aragam,&nbsp;Connie R. Bezzina","doi":"10.1038/s41588-024-02047-4","DOIUrl":"10.1038/s41588-024-02047-4","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2843-2843"},"PeriodicalIF":31.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-02047-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776908","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":"A blueprint to discovering synthetic lethal gene interactions for precision oncology","authors":"","doi":"10.1038/s41588-024-02024-x","DOIUrl":"https://doi.org/10.1038/s41588-024-02024-x","url":null,"abstract":"The SCHEMATIC resource combines CRISPR pairwise gene knockout experiments across tumor cell types with large-scale drug sensitivity assays to identify a core network of highly penetrant, synthetic lethal genetic interactions that can help to match individuals with cancer to targeted therapies.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"5 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760425","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":"Single-cell RNA sequencing of peripheral blood links cell-type-specific regulation of splicing to autoimmune and inflammatory diseases","authors":"Chi Tian,&nbsp;Yuntian Zhang,&nbsp;Yihan Tong,&nbsp;Kian Hong Kock,&nbsp;Donald Yuhui Sim,&nbsp;Fei Liu,&nbsp;Jiaqi Dong,&nbsp;Zhixuan Jing,&nbsp;Wenjing Wang,&nbsp;Junbin Gao,&nbsp;Le Min Tan,&nbsp;Kyung Yeon Han,&nbsp;Yoshihiko Tomofuji,&nbsp;Masahiro Nakano,&nbsp;Eliora Violain Buyamin,&nbsp;Radhika Sonthalia,&nbsp;Yoshinari Ando,&nbsp;Hiroaki Hatano,&nbsp;Kyuto Sonehara,&nbsp;Asian Immune Diversity Atlas Network,&nbsp;Xin Jin,&nbsp;Marie Loh,&nbsp;John Chambers,&nbsp;Chung-Chau Hon,&nbsp;Murim Choi,&nbsp;Jong-Eun Park,&nbsp;Kazuyoshi Ishigaki,&nbsp;Tomohisa Okamura,&nbsp;Keishi Fujio,&nbsp;Yukinori Okada,&nbsp;Woong-Yang Park,&nbsp;Jay W. Shin,&nbsp;Xavier Roca,&nbsp;Shyam Prabhakar,&nbsp;Boxiang Liu","doi":"10.1038/s41588-024-02019-8","DOIUrl":"10.1038/s41588-024-02019-8","url":null,"abstract":"Alternative splicing contributes to complex traits, but whether this differs in trait-relevant cell types across diverse genetic ancestries is unclear. Here we describe cell-type-specific, sex-biased and ancestry-biased alternative splicing in ~1 M peripheral blood mononuclear cells from 474 healthy donors from the Asian Immune Diversity Atlas. We identify widespread sex-biased and ancestry-biased differential splicing, most of which is cell-type-specific. We identify 11,577 independent cis-splicing quantitative trait loci (sQTLs), 607 trans-sGenes and 107 dynamic sQTLs. Colocalization between cis-eQTLs and trans-sQTLs revealed a cell-type-specific regulatory relationship between HNRNPLL and PTPRC. We observed an enrichment of cis-sQTL effects in autoimmune and inflammatory disease heritability. Specifically, we functionally validated an Asian-specific sQTL disrupting the 5′ splice site of TCHP exon 4 that putatively modulates the risk of Graves’ disease in East Asian populations. Our work highlights the impact of ancestral diversity on splicing and provides a roadmap to dissect its role in complex diseases at single-cell resolution. This analysis of single-cell RNA sequencing data from peripheral blood mononuclear cells for 474 individuals of diverse Asian ancestries in the Asian Immune Diversity Atlas links cell-type-specific splicing variation with autoimmune and inflammatory disease risk.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 12","pages":"2739-2752"},"PeriodicalIF":31.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-02019-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759931","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}