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Long-read sequencing identifies aberrant fragmentation patterns linked to elevated cell-free DNA levels in cancer. 长读测序确定了癌症中与游离DNA水平升高相关的异常片段模式。
IF 12.3 1区 生物学
Genome Biology Pub Date : 2026-04-10 DOI: 10.1186/s13059-026-04060-8
Benjamin P Berman, Sarah A Erdman, Christina Wheeler, Justin Cayford, Jean-Valery Turatsinze, Maria Ouzounova, Marie Piecyk, Marielle Herzog, Léa Payen-Gay, Thomas Walter, Theresa K Kelly
{"title":"Long-read sequencing identifies aberrant fragmentation patterns linked to elevated cell-free DNA levels in cancer.","authors":"Benjamin P Berman, Sarah A Erdman, Christina Wheeler, Justin Cayford, Jean-Valery Turatsinze, Maria Ouzounova, Marie Piecyk, Marielle Herzog, Léa Payen-Gay, Thomas Walter, Theresa K Kelly","doi":"10.1186/s13059-026-04060-8","DOIUrl":"https://doi.org/10.1186/s13059-026-04060-8","url":null,"abstract":"<p><strong>Background: </strong>Altered circulating cell-free DNA (cfDNA) fragmentation patterns serve as cancer biomarkers, yet standard short-read sequencing fails to capture the full fragment-length spectrum. Although cancer patients often exhibit elevated cfDNA, the relationship between high cfDNA concentration and altered fragmentation remains poorly defined. To address this question, we leverage Oxford Nanopore (ONT) sequencing, which captures the full fragment-length spectrum and enables cell type inference via DNA methylation markers.</p><p><strong>Results: </strong>We perform ONT whole-genome sequencing on a pan-cancer cohort and a neuroendocrine cancer cohort, both with elevated cfDNA levels. In both cohorts, the highest cfDNA levels are characterized by either hypofragmentation or hyperfragmentation. Hypofragmented samples (characterized by 1-4 kb fragments) exhibit hallmarks of DNASE1L3-mediated fragmentation due to blood-derived DNA release during delayed blood processing, while samples with ultra-long fragments (> 7.5 kb) indicate release due to cell lysis during plasma processing. In contrast, the short (<145 bp) fragments of hyperfragmented cancer samples are not artifactual, and they are characterized by elevated levels of both cancer- and blood-derived DNA, suggesting an inflammatory or other systemic response as opposed to a cancer-specific fragmentation mechanism.</p><p><strong>Conclusions: </strong>These findings differentiate biological from artifactual fragmentation, broaden our understanding of high cfDNA levels and hyperfragmentation in cancer, and establish long-read sequencing as a robust tool for biomarker discovery.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":" ","pages":""},"PeriodicalIF":12.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647337","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}
引用次数: 0
Transposable element-mediated evolutionary expansion of Sox2- and Brn2-binding regulatory modules for mammalian neural-cell differentiation. 转座元件介导的Sox2-和brn2结合调节模块在哺乳动物神经细胞分化中的进化扩展。
IF 12.3 1区 生物学
Genome Biology Pub Date : 2026-04-09 DOI: 10.1186/s13059-026-04050-w
Hidenori Nishihara, Atsushi Komiya
{"title":"Transposable element-mediated evolutionary expansion of Sox2- and Brn2-binding regulatory modules for mammalian neural-cell differentiation.","authors":"Hidenori Nishihara, Atsushi Komiya","doi":"10.1186/s13059-026-04050-w","DOIUrl":"10.1186/s13059-026-04050-w","url":null,"abstract":"<p><strong>Background: </strong>In mammalian genomes, at least several thousand copies of transposable elements (TEs) may function as enhancers or promoters that regulate gene expression, cellular processes, and development. However, it is still largely unknown how many TEs have been co-opted into regulatory processes and under which cellular situations they are functional. In particular, few studies have addressed how TE functions change during cell differentiation.</p><p><strong>Results: </strong>We analyze human TEs bound by the transcription factor Sox2 and by the neuronal transcription factor Brn2 during differentiation of embryonic stem cells into neural progenitor cells (NPC). We identify more than 20,000 copies of Sox2- or Brn2-binding TEs, including ancient SINEs/LINEs and simian-specific endogenous retroviruses, which represents two-wave evolutionary acquisition. Our results suggest that retrotransposition of the endogenous retroviruses including MER51 and MER49 has expanded the genomic prevalence of the simian-specific binding sites for Sox2 and Brn2, respectively. Epigenetics profiling suggests that approximately half of the Sox2- or Brn2-binding TEs function as potential cis-regulatory sequences, with a subset exhibiting clear functional transitions associated with Sox2 binding and release dynamics during neural cell differentiation. The nearest genes of NPC-specific Sox2 binding TEs are upregulated and enrich for neurogenesis-related gene ontology terms.</p><p><strong>Conclusions: </strong>The accumulation of TE-derived cis-regulatory elements during mammalian evolution may have contributed to the diversification and refinement of gene regulatory dynamics underlying neuronal development.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":"27 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147640348","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}
引用次数: 0
Allelic structural variation at the NLR25-1 locus enhances defense against Pseudomonas syringae in kiwifruit. NLR25-1位点的等位基因结构变异增强了猕猴桃对丁香假单胞菌的防御能力。
IF 12.3 1区 生物学
Genome Biology Pub Date : 2026-04-09 DOI: 10.1186/s13059-026-04068-0
Ying Wu, Yingzhen Wang, Yunzhi Lin, Meng Zhao, Yuyu Huo, Tao Zhang, Hongtao Wang, Yanyan Zhu, Lihuan Wang, Pengpeng Zheng, Junyang Yue, Songhu Wang, Yongsheng Liu
{"title":"Allelic structural variation at the NLR25-1 locus enhances defense against Pseudomonas syringae in kiwifruit.","authors":"Ying Wu, Yingzhen Wang, Yunzhi Lin, Meng Zhao, Yuyu Huo, Tao Zhang, Hongtao Wang, Yanyan Zhu, Lihuan Wang, Pengpeng Zheng, Junyang Yue, Songhu Wang, Yongsheng Liu","doi":"10.1186/s13059-026-04068-0","DOIUrl":"https://doi.org/10.1186/s13059-026-04068-0","url":null,"abstract":"<p><strong>Background: </strong>Canker disease caused by Pseudomonas syringae pv. actinidiae (Psa) poses a major threat to cultivated kiwifruit, and utilization of wild relatives are key to improve resistance. However, comprehensive comparative genomic analyses between cultivated kiwifruit and their wild relatives with enhanced resistance to Psa remain limited.</p><p><strong>Results: </strong>Here we generate chromosome-scale genome assemblies for eleven wild Actinidia eriantha accessions and one interspecific hybrid between Actinidia eriantha and cultivated Actinidia chinensis var. chinensis. Integrating these with twelve previously released genomes including three Actinidia eriantha and nine Actinidia chinensis var. chinensis, we construct a reference-unbiased graph-based pangenome. These datasets reveal extensive genomic variation, including 31,790,044 SNPs, 13,512,079 InDels and 623,478 structural variations, and provide a landscape of structural variations within and between the two species. Leveraging these datasets, we identify a wild allele showing allele-specific expression, AeNLR25-1, which enhances Psa resistance in cultivated kiwifruit. Genetic and molecular analyses demonstrate that a transposable element-induced structural variation in the AeNLR25-1 promoter introduces a species-specific WRKY binding site, conferring enhanced defense against Psa.</p><p><strong>Conclusions: </strong>Pangenome across cultivated species and wild relatives provides a theoretical framework for accelerating kiwifruit genetic improvement through pangenome-enabled identification of favorable wild alleles.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":" ","pages":""},"PeriodicalIF":12.3,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647292","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}
引用次数: 0
Benchmarking tools for deciphering cellular crosstalk in spatially-resolved transcriptomics. 在空间分辨转录组学中破译细胞串扰的基准工具。
IF 12.3 1区 生物学
Genome Biology Pub Date : 2026-04-08 DOI: 10.1186/s13059-026-04063-5
Li-Ting Ku, Vincent Bernard, Jimin Min, Ying Yuan, Eugene Jon Koay, Anirban Maitra, Liang Li, Ziyi Li
{"title":"Benchmarking tools for deciphering cellular crosstalk in spatially-resolved transcriptomics.","authors":"Li-Ting Ku, Vincent Bernard, Jimin Min, Ying Yuan, Eugene Jon Koay, Anirban Maitra, Liang Li, Ziyi Li","doi":"10.1186/s13059-026-04063-5","DOIUrl":"10.1186/s13059-026-04063-5","url":null,"abstract":"<p><strong>Background: </strong>Cell-cell communication via ligand-receptor signaling is a fundamental mechanism shaping multicellular organization and functional heterogeneity within tissue microenvironments. Recent advances in spatial transcriptomics (ST) have enabled unprecedented opportunities to systematically infer such interactions under the native spatial context. While prior studies have summarized or compared existing cell-cell interaction (CCI) inference methods, comprehensive benchmarking of tools specifically developed for ST applications remains limited.</p><p><strong>Results: </strong>Here, we present a comprehensive evaluation of nine computational CCI inference methods on a series of realistic simulation settings and nine real ST datasets from three independent studies, spanning Visium, Stereo-seq, and Xenium platforms. Method performance was assessed based on ligand-receptor prediction accuracy, spatial coherence of interactions, biological relevance via pathway enrichment, and computational efficiency.</p><p><strong>Conclusions: </strong>Our results demonstrate substantial variability in tool performance across spatial resolutions, tissue contexts, and platforms, offering practical guidance for tool selection. This study also highlights key challenges in applying existing tools to real ST data and provides insights to inform future advances in spatially resolved cell-cell interaction analysis.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":" ","pages":""},"PeriodicalIF":12.3,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147640332","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}
引用次数: 0
Benchmarking of sequencing technologies defines optimal strategies for genetic variants detection in a human genome. 对标测序技术定义了人类基因组中遗传变异检测的最佳策略。
IF 12.3 1区 生物学
Genome Biology Pub Date : 2026-04-08 DOI: 10.1186/s13059-026-04048-4
Robert J M Eveleigh, Sarah J Reiling, Jose Hector Galvez, Mathieu Bourgey, Jiannis Ragoussis, Guillaume Bourque
{"title":"Benchmarking of sequencing technologies defines optimal strategies for genetic variants detection in a human genome.","authors":"Robert J M Eveleigh, Sarah J Reiling, Jose Hector Galvez, Mathieu Bourgey, Jiannis Ragoussis, Guillaume Bourque","doi":"10.1186/s13059-026-04048-4","DOIUrl":"10.1186/s13059-026-04048-4","url":null,"abstract":"<p><strong>Background: </strong>Advances in sequencing technologies continue to improve the resolution and completeness with which human genetic variation can be characterized. Short-read sequencing remains widely used due to its high base accuracy, throughput, and cost efficiency; however, its limited ability to resolve repetitive and structurally complex regions has accelerated adoption of long-read sequencing platforms, including those from Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT).</p><p><strong>Results: </strong>We systematically compared sequencing technologies and variant calling pipelines for small variants and structural variants across diverse genomic contexts and sequencing depths. Short-read sequencing combined with DRAGEN achieved high accuracy for single-nucleotide variants (SNVs) and indels in well-mapped and moderately complex regions but showed reduced sensitivity and completeness for structural variant detection. In contrast, long-read sequencing platforms demonstrated clear advantages in detecting structural variants and resolving small variants in difficult genomic regions, although challenges remain in specific indel-prone sequence contexts. Among long-read pipelines, PacBio Revio with DeepVariant achieved the highest SNV and indel accuracy genome-wide, while ONT R10 with DeepVariant performed particularly well in clinically relevant loci. Structural variant detection was dominated by long-read optimized callers, with SVIM and Sawfish performing best for PacBio, and Sniffles2 and CuteSV2 for ONT, consistently outperforming short-read-based methods across variant classes and sizes. Coverage analyses indicated that long-read sequencing reached accuracy saturation between 20 × and 45 × , whereas short-read sequencing required more than 60 × coverage to approach maximal genome completeness.</p><p><strong>Conclusions: </strong>These results provide practical guidance for platform and pipeline selection. Long-read sequencing enables more comprehensive detection and resolution of structural variants and variation in complex genomic regions, while short-read sequencing remains a cost-effective and scalable solution for high-throughput genotyping and clinically focused applications.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":" ","pages":""},"PeriodicalIF":12.3,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13072666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147640352","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}
引用次数: 0
Cis-regulatory architecture downstream of FLOWERING LOCUS T underlies quantitative control of flowering in Arabidopsis thaliana. 开花位点T下游的顺式调控结构是拟南芥开花数量控制的基础。
IF 12.3 1区 生物学
Genome Biology Pub Date : 2026-04-06 DOI: 10.1186/s13059-026-04064-4
Hao-Ran Zhou, Duong Thi Hai Doan, Thomas Hartwig, Franziska Turck
{"title":"Cis-regulatory architecture downstream of FLOWERING LOCUS T underlies quantitative control of flowering in Arabidopsis thaliana.","authors":"Hao-Ran Zhou, Duong Thi Hai Doan, Thomas Hartwig, Franziska Turck","doi":"10.1186/s13059-026-04064-4","DOIUrl":"10.1186/s13059-026-04064-4","url":null,"abstract":"<p><strong>Background: </strong>The FLOWERING LOCUS T (FT) gene is a central integrator of floral induction in Arabidopsis thaliana, with its precise expression controlled by complex transcriptional networks. While upstream regulatory regions are well-studied, the role of downstream cis-regulatory elements in modulating FT expression remains poorly characterized.</p><p><strong>Results: </strong>Systematic dissection of the FT downstream region in its native chromosomal context using CRISPR/Cas9-mediated genome editing provides genetic evidence that a 2.3-kb sequence, encompassing the Block E enhancer immediately adjacent to the FT coding sequence, is essential for proper FT expression and timely flowering. Fine-scale deletions within Block E reveal that a 63-bp sequence containing one CCAAT-box and one G-box, both closely spaced, forms a core functional module, whereas other conserved motifs contribute modestly in a context-dependent manner. Strikingly, a cryptic CCAAT-box module downstream of Block E that becomes active when repositioned. This coincides with increased transcription factor occupancy and local chromatin accessibility.</p><p><strong>Conclusions: </strong>Our work reveals that quantitative FT expression and flowering time are governed by the spatial organization and chromatin context of downstream cis-regulatory elements. The positional sensitivity and modular logic of these elements provide framework for understanding and engineering quantitative gene regulation through targeted cis-regulatory design, a concept broadly applicable across diverse developmental systems.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":" ","pages":""},"PeriodicalIF":12.3,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147624539","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}
引用次数: 0
An integrative single-nucleus multiomic atlas of the human left ventricle identifies gene regulatory network dynamics across cardiac development, aging, and disease. 人类左心室的综合单核多组图谱确定了心脏发育,衰老和疾病的基因调控网络动力学。
IF 12.3 1区 生物学
Genome Biology Pub Date : 2026-04-06 DOI: 10.1186/s13059-026-04061-7
William Gao, Peng Hu, Brittney Wick, Qi Qiu, Hongjie Zhang, Ying Li, Xiangjin Kang, Kenneth Bedi, Maximilian Haeussler, Kotaro Sasaki, Kenneth Margulies, Hao Wu
{"title":"An integrative single-nucleus multiomic atlas of the human left ventricle identifies gene regulatory network dynamics across cardiac development, aging, and disease.","authors":"William Gao, Peng Hu, Brittney Wick, Qi Qiu, Hongjie Zhang, Ying Li, Xiangjin Kang, Kenneth Bedi, Maximilian Haeussler, Kotaro Sasaki, Kenneth Margulies, Hao Wu","doi":"10.1186/s13059-026-04061-7","DOIUrl":"10.1186/s13059-026-04061-7","url":null,"abstract":"<p><strong>Background: </strong>As the first organ to develop in utero, the human heart undergoes extensive molecular, structural and metabolic remodeling during development and must sustain its function throughout life.</p><p><strong>Results: </strong>We generate an integrated multiomic atlas of human cardiac cells, combining newly generated and publicly available single-nucleus RNA sequencing datasets from 299 donors and single nucleus ATAC-seq datasets from 106 donors. Developmental and disease-associated processes drive far more extensive molecular remodeling than sex-associated or aging-dependent effects. Across nearly all cardiac cell types, developmental and disease-driven changes exhibit strong overlap at both the transcriptomic and epigenomic levels, revealing widespread reactivation of fetal-associated gene programs beyond cardiomyocytes. Both cardiac development and disease show convergent shifts in intercellular communication, including increased TGFβ signaling. Integration of gene expression and chromatin accessibility data reveals putative cell-type-specific transcriptional factors driving fetal reactivation in major cardiac diseases. Spatial transcriptomics data orthogonally identifies localization of this fetal reactivation signature within spatially distinct niches in ischemic and fibrotic zones of acute myocardial infarction. Finally, we construct a cell-type-resolved enhancer-to-gene linkage map that refines the association of dilated and hypertrophic cardiomyopathy genetic risk loci to downstream target genes.</p><p><strong>Conclusions: </strong>This study presents a comprehensive multimodal, cell-type-resolved atlas of the human heart, providing a foundation for understanding human cardiac gene regulation across the human lifespan and in cardiac diseases.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":" ","pages":""},"PeriodicalIF":12.3,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147624472","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}
引用次数: 0
Benchmarking single-cell tumor immune atlases and application for uncovering cell states related to immunotherapy response. 对标单细胞肿瘤免疫图谱及其在揭示与免疫治疗反应相关的细胞状态中的应用。
IF 12.3 1区 生物学
Genome Biology Pub Date : 2026-03-31 DOI: 10.1186/s13059-026-04055-5
Jing Yang, Yu Shyr, Qi Liu
{"title":"Benchmarking single-cell tumor immune atlases and application for uncovering cell states related to immunotherapy response.","authors":"Jing Yang, Yu Shyr, Qi Liu","doi":"10.1186/s13059-026-04055-5","DOIUrl":"10.1186/s13059-026-04055-5","url":null,"abstract":"<p><strong>Background: </strong>The tumor immune microenvironment, containing a variety of immune cells with both tumor-promoting and anti-tumoral functions, plays a significant role in tumor immune surveillance and immunological evasion. Characterizing the landscape of the tumor immune microenvironment at the single-cell level is crucial for both cancer diagnosis and treatment strategy design. While current efforts to develop single-cell tumor immune atlases have laid a foundation for understanding the complexity and heterogeneity of the tumor immune microenvironment, existing atlases vary in their data sources, integration and annotation strategies, and the number and definition of cell types, posing challenges in selection.</p><p><strong>Results: </strong>We systematically benchmarked five single-cell tumor immune atlases, comprising two pan-cancer and three cancer-specific ones. We first assessed their similarities and distinct characteristics of major immune cell subpopulations, including T, NK, B, macrophage, and dendritic cells. Next, we utilized each atlas as a reference to perform supervised annotation of six single-cell immuno-transcriptomics datasets, two with expert manual labels and four without. We evaluated annotation performance based on agreement with manual labels, mapping success, accuracy, clusterability, annotatability, and stability. Notably, supervised annotations consistently outperformed unsupervised clustering in identifying cell states related to immunotherapy response.</p><p><strong>Conclusions: </strong>Our study provides insights into the characteristics and quality of existing atlases, demonstrating their utility in delivering harmonized annotations across datasets and uncovering crucial immune components associated with immunotherapy response. It also highlights key requirements and directions for the development of future atlases.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":" ","pages":""},"PeriodicalIF":12.3,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582837","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}
引用次数: 0
MRBEE-TL: improving causal effect estimation in multi-ancestry multivariable Mendelian randomization with transfer learning. 用迁移学习改进多祖先多变量孟德尔随机化的因果效应估计。
IF 12.3 1区 生物学
Genome Biology Pub Date : 2026-03-31 DOI: 10.1186/s13059-026-04051-9
Yihe Yang, Xiaofeng Zhu
{"title":"MRBEE-TL: improving causal effect estimation in multi-ancestry multivariable Mendelian randomization with transfer learning.","authors":"Yihe Yang, Xiaofeng Zhu","doi":"10.1186/s13059-026-04051-9","DOIUrl":"10.1186/s13059-026-04051-9","url":null,"abstract":"<p><p>Multivariable Mendelian randomization has been largely applied to individuals of European ancestry, due to the larger sample sizes available in European GWAS. We introduce MRBEE-TL, one of the first multi-ancestry multivariable Mendelian randomization methods, which combines transfer learning with bias-corrected estimating equations to improve power in underpowered ancestries and to assess cross-ancestry heterogeneity of disease risk factors. In simulations, MRBEE-TL consistently outperforms MR methods that rely solely on ancestry-specific GWAS data. In real data analyses, MRBEE-TL not only identifies ancestry-consistent and ancestry-specific causal effects missed by conventional methods, but also improves power in underpowered ancestries.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":" ","pages":""},"PeriodicalIF":12.3,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582842","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}
引用次数: 0
A H3K27me3 reader complex couples H3K27me3 accumulation to nascent transcription of transposable elements in Paramecium. 草履虫中H3K27me3读取器复合体将H3K27me3积累与转座因子的新生转录结合起来。
IF 12.3 1区 生物学
Genome Biology Pub Date : 2026-03-30 DOI: 10.1186/s13059-026-04045-7
Thomas Balan, Ambre Petitalot, Julien Richard Albert, Louise Abbou, Guillaume Chevreux, Bassem Al-Sady, Bihter Özdemir Aygenli, Till Bartke, Raphaël Margueron, Sandra Duharcourt
{"title":"A H3K27me3 reader complex couples H3K27me3 accumulation to nascent transcription of transposable elements in Paramecium.","authors":"Thomas Balan, Ambre Petitalot, Julien Richard Albert, Louise Abbou, Guillaume Chevreux, Bassem Al-Sady, Bihter Özdemir Aygenli, Till Bartke, Raphaël Margueron, Sandra Duharcourt","doi":"10.1186/s13059-026-04045-7","DOIUrl":"https://doi.org/10.1186/s13059-026-04045-7","url":null,"abstract":"<p><strong>Background: </strong>The ability to deposit histone H3K27-trimethyl (me3) marks is essential for transcriptional repression by Polycomb Repressive Complex 2 (PRC2). This is largely attributed to Polycomb repressive complex 1 (PRC1), whose recruitment is H3K27me3-dependent. Yet it is unclear how H3K27me3 contributes to transcription regulation independently of PRC1.</p><p><strong>Results: </strong>To address this question, we identified H3K27me3-binding proteins in the unicellular eukaryote Paramecium where PRC2 targets transposable elements (TEs) and PRC1 is absent. We show that the chromodomain protein Firefly is a H3K27me3 reader in vitro and accumulates onto TEs in a H3K27me3-dependent manner. We also identify Firefly interactors: Sleepy, a coiled-coil containing protein and TfIIs4, a transcription elongation factor. We show that Firefly, Sleepy and TfIIs4 are jointly required in vivo for correct H3K27me3 accumulation and nascent transcription at TEs.</p><p><strong>Conclusions: </strong>This positive feedback loop to enrich H3K27me3 at TEs is analogous to self-reinforcing loops leading to H3K9 methylation at repeats in fungi, plants and animals. Our work reveals a unique association between H3K27me3 readers and active transcription.</p>","PeriodicalId":48922,"journal":{"name":"Genome Biology","volume":" ","pages":""},"PeriodicalIF":12.3,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582847","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}
引用次数: 0
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