Genome research最新文献_第8页

Mitotic chromosomes harbor cell type and species-specific structural features within a universal loop array conformation 有丝分裂染色体在一个普遍的环状阵列构象中包含细胞类型和物种特异性的结构特征

IF 7 2区生物学

Genome research Pub Date : 2025-06-06 DOI: 10.1101/gr.280648.125

Marlies E. Oomen, A. Nicole Fox, Inma Gonzalez, Amandine Molliex, Thaleia Papadopoulou, Pablo Navarro, Job Dekker

{"title":"Mitotic chromosomes harbor cell type and species-specific structural features within a universal loop array conformation","authors":"Marlies E. Oomen, A. Nicole Fox, Inma Gonzalez, Amandine Molliex, Thaleia Papadopoulou, Pablo Navarro, Job Dekker","doi":"10.1101/gr.280648.125","DOIUrl":"https://doi.org/10.1101/gr.280648.125","url":null,"abstract":"Mitotic chromosomes are considered to be universally folded as loop arrays across species and cell types. However, some studies suggest that features of mitotic chromosomes might be cell type or species specific. We previously reported that CTCF binding in human differentiated cell lines is lost in mitosis, whereas mitotic mouse embryonic stem cells (mESC) display prominent binding at a subset of CTCF sites. Here, we perform footprint ATAC-seq analyses of mESCs and somatic mouse and human cells confirming these findings. We then investigate roles of mitotically bookmarked CTCF in prometaphase chromosome organization by Hi-C. We do not find any remaining interphase structures such as TADs or loops at bookmarked CTCF sites in mESCs. This suggests that mitotic loop extruders condensin I and II are not blocked by CTCF, and thus that maintained CTCF binding does not alter mitotic chromosome folding. Lastly, we compare mitotic Hi-C data generated in this study in mouse with public data in human and chicken. We do not find any cell type-specific differences; however, we find a difference between species. The average genomic size of mitotic loops is smaller in chicken (200-300 kb), compared to human (400-600 kb) and especially mouse (1-1.5 mb). Interestingly, we find that this difference is correlated with the genomic length of q-arms in these species, a finding we confirm by microscopy measurements of chromosome compaction. This suggests that the dimensions of mitotic chromosomes can be modulated through control of loop size by condensins to facilitate species-appropriate shortening of chromosome arms.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"5 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Functional assays in Drosophila facilitate classification of variants of uncertain significance associated with rare diseases 果蝇的功能分析有助于分类与罕见疾病相关的不确定意义的变异

IF 7 2区生物学

Genome research Pub Date : 2025-06-04 DOI: 10.1101/gr.278291.123

Jung-Wan Mok, Shelley B. Gibson, Haley A. Dostalik, Shinya Yamamoto

{"title":"Functional assays in Drosophila facilitate classification of variants of uncertain significance associated with rare diseases","authors":"Jung-Wan Mok, Shelley B. Gibson, Haley A. Dostalik, Shinya Yamamoto","doi":"10.1101/gr.278291.123","DOIUrl":"https://doi.org/10.1101/gr.278291.123","url":null,"abstract":"Individuals living with rare diseases often undergo a frustrating and expensive diagnostic odyssey. Clinical geneticists who analyze exome or genome sequencing data from rare disease patients often encounter a list of variants of uncertain significance (VUS) in known disease-causing genes or rare variants in genes of uncertain significance (GUS) that are difficult to interpret, even with the integration of the latest bioinformatic tools. In this Perspective, we review how studies using the fruit fly Drosophila melanogaster have facilitated rare disease diagnosis by uncovering the clinical relevance of GUS and classifying rare variants into specific allelic categories (loss-of-function or gain-of-function, Muller's morphs). We showcase how fly researchers have been collaboratively studying the loss-of-function of orthologous fly genes, assessing the ability of the human genes to rescue the fly mutant phenotypes, determining the effect of overexpressing human proteins, and testing functional consequences of rare variants of interest by generating analogous fly mutants to contribute to rare disease diagnosis. We argue that data obtained using Drosophila can be leveraged to design effective multiplexed assays for variant effects (MAVEs) to decipher the vast human variome.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"11 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144219029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Androgen receptor-mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells 雄激素受体介导的糖皮质激素受体的辅助负载调节前列腺癌细胞的转录反应

IF 7 2区生物学

Genome research Pub Date : 2025-06-02 DOI: 10.1101/gr.280224.124

Johannes Hiltunen, Laura Helminen, Niina Aaltonen, Kaisa-Mari Launonen, Hanna Laakso, Marjo Malinen, Einari A Niskanen, Jorma J Palvimo, Ville Paakinaho

{"title":"Androgen receptor-mediated assisted loading of the glucocorticoid receptor modulates transcriptional responses in prostate cancer cells","authors":"Johannes Hiltunen, Laura Helminen, Niina Aaltonen, Kaisa-Mari Launonen, Hanna Laakso, Marjo Malinen, Einari A Niskanen, Jorma J Palvimo, Ville Paakinaho","doi":"10.1101/gr.280224.124","DOIUrl":"https://doi.org/10.1101/gr.280224.124","url":null,"abstract":"Steroid receptors are involved in a wide array of crosstalk mechanisms that regulate diverse biological processes, with significant implications in diseases, particularly in cancers. In prostate cancer, indirect crosstalk between androgen receptor (AR) and glucocorticoid receptor NR3C1 (also known as GR) is well-documented, wherein AR suppression by antiandrogen therapy leads to elevated GR levels, enabling GR to compensate for and replace AR signaling. However, the existence and impact of direct chromatin crosstalk between AR and GR in prostate cancer remain elusive. Our genome-wide investigations reveal that AR activation significantly expands GR chromatin binding. Mechanistically, AR induces remodeling of closed chromatin sites, facilitating GR binding to inaccessible sites. Importantly, coactivation of AR and GR results in distinct transcriptional responses at both the cell population and single-cell levels. Pathways affected by these transcriptional changes are generally associated with improved patient survival. Thus, the direct crosstalk between AR and GR yields markedly different outcomes from the known role of GR in circumventing AR blockade by antiandrogens.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"4 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Oxygen-induced stress reveals context-specific gene regulatory effects in human brain organoids 氧诱导应激揭示了人类大脑类器官中特定环境的基因调控作用

IF 7 2区生物学

Genome research Pub Date : 2025-06-02 DOI: 10.1101/gr.280219.124

Benjamin D Umans, Yoav Gilad

引用次数: 0

Overcoming limitations to customize DeepVariant for domesticated animals with TrioTrain 克服限制，自定义DeepVariant家养动物与TrioTrain

IF 7 2区生物学

Genome research Pub Date : 2025-06-02 DOI: 10.1101/gr.279542.124

Jenna Kalleberg, Jacob Rissman, Robert D Schnabel

{"title":"Overcoming limitations to customize DeepVariant for domesticated animals with TrioTrain","authors":"Jenna Kalleberg, Jacob Rissman, Robert D Schnabel","doi":"10.1101/gr.279542.124","DOIUrl":"https://doi.org/10.1101/gr.279542.124","url":null,"abstract":"Generating high-quality variant callsets across diverse species remains challenging as most bioinformatics tools default to assumptions based on human genomes. DeepVariant (DV) excels without joint genotyping while offering fewer implementation barriers. However, the growing appeal of a \"universal\" algorithm has magnified the unknown impacts when used with non-human species. We use bovine genomes to assess the limits of using human-genome-trained variant callers, including the allele frequency channel (DV-AF) and joint-caller DeepTrio (DT). Our novel approach, TrioTrain, automates extending DV for diploid species lacking Genome-in-a-Bottle (GIAB) resources, using a region shuffling approach to mitigate barriers for SLURM-based clusters. Imperfect animal truth labels are curated to remove Mendelian discordant sites before training DV to genotype the offspring correctly. With TrioTrain, we use cattle, yak, and bison trios to create the first multi-species-trained DV-AF checkpoint. Although incomplete bovine truth sets constrain recall within challenging repetitive regions, we observe a mean SNV F1 score >0.990 across new checkpoints during GIAB benchmarking. With HG002, a bovine-trained checkpoint (28) decreased the Mendelian Inheritance Error (MIE) rate by a factor of two compared to the default (DV). Checkpoint 28 has a mean MIE rate of 0.03 percent in three bovine interspecies cross genomes. These results illustrate that a multi-species, trio-based training strategy reduces inheritance errors during single-sample variant calling. While exclusively training with human genomes deters transferring deep-learning-based variant calling to new species, we use the diverse ancestry within bovids to illustrate the need for advanced tools designed for comparative genomics.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"64 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Regeneration alters open chromatin and cis-regulatory landscape of erythroid precursors 再生改变了红系前体的开放染色质和顺式调控景观

IF 7 2区生物学

Genome research Pub Date : 2025-06-02 DOI: 10.1101/gr.279949.124

Yichao Zhou, Venkatasai Rahul Dogiparthi, Hannah L. Harris, Suhita Ray, Avik Choudhuri, Song Yang, Yi Zhou, Leonard I. Zon, M. Jordan Rowley, Kyle J. Hewitt

{"title":"Regeneration alters open chromatin and cis-regulatory landscape of erythroid precursors","authors":"Yichao Zhou, Venkatasai Rahul Dogiparthi, Hannah L. Harris, Suhita Ray, Avik Choudhuri, Song Yang, Yi Zhou, Leonard I. Zon, M. Jordan Rowley, Kyle J. Hewitt","doi":"10.1101/gr.279949.124","DOIUrl":"https://doi.org/10.1101/gr.279949.124","url":null,"abstract":"Stress erythropoiesis elevates the rate of red blood cell (RBC) production as a physiological response to stressors such as anemia or hypoxia. In acute anemia, RBC progenitors and precursors temporarily rewire their transcriptome, up- and downregulating hundreds of genes to accelerate the production of mature RBCs. Effective regeneration requires communication between critical cytokine signals (e.g., BMP4) and cis-regulatory elements on chromatin which coordinate transcriptional changes. To identify cis-regulatory changes that underlie anemia-specific gene expression and cellular responses, we analyzed chromatin accessibility in populations of cells enriched for red blood cell precursors isolated from mice at a range of time points after anemia induction. Early in the anemia response, chromatin is transiently open at AP-1-containing regions, correlated with increased Jun and Fos transcript/protein levels. Jun knockdown ex vivo decreases the percentage of KIT+ erythroid precursors after anemia induction. We observe a second rewiring event at time points consistent with anemia resolution, involving repression of GATA factor-accessible regions and activation of ETS factor-accessible regions. In both mouse in vivo models and human CD34+ cells stimulated with BMP4, accessibility changes at regions with prior associations to human blood phenotypes. Dozens of BMP4- and anemia-activated loci are sensitive to natural human variation. The representation of red blood cell trait–associated loci in ATAC-seq data remains durably elevated more than 1 month after anemia resolution. Together, these findings provide a framework to understand the early establishment and late resolution of a regeneration-dependent transcriptome in RBC precursors.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"20 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Accurate genotyping of three major respiratory bacterial pathogens with ONT R10.4.1 long-read sequencing ONT R10.4.1长读测序对三种主要呼吸道细菌病原体的准确基因分型

IF 7 2区生物学

Genome research Pub Date : 2025-06-02 DOI: 10.1101/gr.279829.124

Nora Zidane, Carla Rodrigues, Valerie Bouchez, Martin Rethoret-Pasty, Virginie Passet, Sylvain Brisse, Chiara Crestani

{"title":"Accurate genotyping of three major respiratory bacterial pathogens with ONT R10.4.1 long-read sequencing","authors":"Nora Zidane, Carla Rodrigues, Valerie Bouchez, Martin Rethoret-Pasty, Virginie Passet, Sylvain Brisse, Chiara Crestani","doi":"10.1101/gr.279829.124","DOIUrl":"https://doi.org/10.1101/gr.279829.124","url":null,"abstract":"High-throughput massive parallel sequencing has significantly improved bacterial pathogen genomics, diagnostics, and epidemiology. Despite its high accuracy, short-read sequencing struggles with complete genome reconstruction and assembly of extrachromosomal elements such as plasmids. Long-read sequencing with Oxford Nanopore Technologies (ONT) presents an alternative that offers benefits including real-time sequencing and cost-efficiency, particularly useful in resource-limited settings. However, the historically higher error rates of ONT data have so far limited its application in high-precision genomic typing. The recent release of ONT's R10.4.1 chemistry, with significantly improved raw read accuracy (Q20+), offers a potential solution to this problem. The aim of this study was to evaluate the performance of ONT's latest chemistry for bacterial genomic typing against the gold standard Illumina technology, focusing on three respiratory pathogens of public health importance, Klebsiella pneumoniae, Bordetella pertussis, and Corynebacterium diphtheriae, and their related species. Using the Rapid Barcoding Kit V14, we generated and analyzed genome assemblies with different basecalling models, at different simulated depths of coverage. ONT assemblies were compared to the Illumina reference for completeness and core genome multilocus sequence typing (cgMLST) accuracy (number of allelic mismatches). Our results show that genomes obtained from raw ONT data basecalled with Dorado SUP v0.9.0, assembled with Flye, and with a minimum coverage depth of 35×, optimized accuracy for all bacterial species tested. Error rates were consistently below 0.5% for each cgMLST scheme, indicating that ONT R10.4.1 data is suitable for high-resolution genomic typing applied to outbreak investigations and public health surveillance.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"136 1","pages":"gr.279829.124"},"PeriodicalIF":7.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Revisiting models of enhancer–promoter communication in gene regulation 基因调控中增强子-启动子通讯模型的回顾

IF 7 2区生物学

Genome research Pub Date : 2025-06-01 DOI: 10.1101/gr.278389.123

Gilad Barshad, Charles G. Danko

引用次数: 0

Corrigendum: Cre-dependent Cas9-expressing pigs enable efficient in vivo genome editing 更正：cre依赖性cas9表达猪能够有效地进行体内基因组编辑

IF 7 2区生物学

Genome research Pub Date : 2025-06-01 DOI: 10.1101/gr.280849.125

Kepin Wang, Qin Jin, Degong Ruan, Yi Yang, Qishuai Liu, Han Wu, Zhiwei Zhou, Zhen Ouyang, Zhaoming Liu, Yu Zhao, Bentian Zhao, Quanjun Zhang, Jiangyun Peng, Chengdan Lai, Nana Fan, Yanhui Liang, Ting Lan, Nan Li, Xiaoshan Wang, Xinlu Wang, Yong Fan, Pieter A. Doevendans, Joost P.G. Sluijter, Pentao Liu, Xiaoping Li, Liangxue Lai

引用次数: 0

Corrigendum: Characterization of DNA methylation reader proteins in Arabidopsis thaliana 勘误：拟南芥DNA甲基化解读蛋白的表征

IF 7 2区生物学

Genome research Pub Date : 2025-06-01 DOI: 10.1101/gr.280860.125

Jonathan Cahn, James P.B. Lloyd, Ino D. Karemaker, Pascal W.T.C. Jansen, Jahnvi Pflueger, Owen Duncan, Jakob Petereit, Ozren Bogdanovic, A. Harvey Millar, Michiel Vermeulen, Ryan Lister

引用次数: 0