Genome Biology最新文献_第2页

ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development 在小鼠卵母细胞发育过程中，ZAR1和ZAR2调控母体mRNA聚腺苷化的动态

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-08 DOI: 10.1186/s13059-025-03593-8

Yu-Ke Wu, Ruibao Su, Zhi-Yan Jiang, Yun-Wen Wu, Yan Rong, Shu-Yan Ji, Jingwen Liu, Zhuoyue Niu, Zhiyi Li, Yuanchao Xue, Falong Lu, Heng-Yu Fan

{"title":"ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development","authors":"Yu-Ke Wu, Ruibao Su, Zhi-Yan Jiang, Yun-Wen Wu, Yan Rong, Shu-Yan Ji, Jingwen Liu, Zhuoyue Niu, Zhiyi Li, Yuanchao Xue, Falong Lu, Heng-Yu Fan","doi":"10.1186/s13059-025-03593-8","DOIUrl":"https://doi.org/10.1186/s13059-025-03593-8","url":null,"abstract":"During meiosis, the oocyte genome keeps dormant for a long time until zygotic genome activation. The dynamics and homeostasis of the maternal transcriptome are essential for maternal-to-zygotic transition. Zygotic arrest 1 (ZAR1) and its homolog, ZAR2, are RNA-binding proteins that are important for the regulation of maternal mRNA stability. Smart-seq2 analysis reveals drastically downregulated maternal transcripts. However, the detection of transcript levels by Smart-seq2 may be biased by the polyadenylated tail length of the mRNAs. Similarly, differential expression of maternal transcripts in oocytes with or without Zar1/2 differs when analyzed using total RNA-seq and Smart-seq2, suggesting an influence of polyadenylation. Combined analyses using total RNA-seq, LACE-seq, PAIso-seq2, and immunoprecipitation-mass spectrometry reveals that ZAR1 may target the 3’-untranslated regions of maternal transcripts, regulates their stability in germinal vesicle stage oocytes, and interacts with other proteins to control the polyadenylation of mRNAs. The jointly analyzed multi-omics data highlight the limitations of Smart-seq2 in oocytes, clarify the dynamics of the maternal transcriptome, and uncover new roles of ZAR1 in regulating the maternal transcriptome.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"48 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920831","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

Predicting adenine base editing efficiencies in different cellular contexts by deep learning 通过深度学习预测不同细胞环境下腺嘌呤碱基编辑效率

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-08 DOI: 10.1186/s13059-025-03586-7

Lucas Kissling, Amina Mollaysa, Sharan Janjuha, Nicolas Mathis, Kim F. Marquart, Yanik Weber, Woohyun J. Moon, Paulo J. C. Lin, Steven H. Y. Fan, Hiromi Muramatsu, Máté Vadovics, Ahmed Allam, Norbert Pardi, Ying K. Tam, Michael Krauthammer, Gerald Schwank

{"title":"Predicting adenine base editing efficiencies in different cellular contexts by deep learning","authors":"Lucas Kissling, Amina Mollaysa, Sharan Janjuha, Nicolas Mathis, Kim F. Marquart, Yanik Weber, Woohyun J. Moon, Paulo J. C. Lin, Steven H. Y. Fan, Hiromi Muramatsu, Máté Vadovics, Ahmed Allam, Norbert Pardi, Ying K. Tam, Michael Krauthammer, Gerald Schwank","doi":"10.1186/s13059-025-03586-7","DOIUrl":"https://doi.org/10.1186/s13059-025-03586-7","url":null,"abstract":"Adenine base editors (ABEs) enable the conversion of A•T to G•C base pairs. Since the sequence of the target locus influences base editing efficiency, efforts have been made to develop computational models that can predict base editing outcomes based on the targeted sequence. However, these models were trained on base editing datasets generated in cell lines and their predictive power for base editing in primary cells in vivo remains uncertain. In this study, we conduct base editing screens using SpRY-ABEmax and SpRY-ABE8e to target 2,195 pathogenic mutations with a total of 12,000 guide RNAs in cell lines and in the murine liver. We observe strong correlations between in vitro datasets generated by ABE-mRNA electroporation into HEK293T cells and in vivo datasets generated by adeno-associated virus (AAV)- or lipid nanoparticle (LNP)-mediated nucleoside-modified mRNA delivery (Spearman R = 0.83–0.92). We subsequently develop BEDICT2.0, a deep learning model that predicts adenine base editing efficiencies with high accuracy in cell lines (R = 0.60–0.94) and in the liver (R = 0.62–0.81). In conclusion, our work confirms that adenine base editing holds considerable potential for correcting a large fraction of pathogenic mutations. We also provide BEDICT2.0 – a robust computational model that helps identify sgRNA-ABE combinations capable of achieving high on-target editing with minimal bystander effects in both in vitro and in vivo settings.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"20 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920837","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

Development of a whole-exome sequencing kit to facilitate porcine biomedical research 开发全外显子组测序试剂盒以促进猪生物医学研究

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-08 DOI: 10.1186/s13059-025-03589-4

Vishwaarth Vijayakumar, Tanvi Joshi, Lobna Elkhadragy, Lawrence B. Schook, Ron C. Gaba, Mohammed El-Kebir, Kyle M. Schachtschneider

{"title":"Development of a whole-exome sequencing kit to facilitate porcine biomedical research","authors":"Vishwaarth Vijayakumar, Tanvi Joshi, Lobna Elkhadragy, Lawrence B. Schook, Ron C. Gaba, Mohammed El-Kebir, Kyle M. Schachtschneider","doi":"10.1186/s13059-025-03589-4","DOIUrl":"https://doi.org/10.1186/s13059-025-03589-4","url":null,"abstract":"It is important for porcine models to replicate gene mutations present in human diseases to improve the translatability of animal studies. In this study, the high efficacy of a whole exome sequencing kit was demonstrated for the improved pig reference genome (Sus scrofa 11.1) to profile biomedically relevant swine breeds and enable high-depth sequencing required for intratumor heterogeneity profiling. We identify a total of 751,624 single nucleotide variants (SNVs) and 113,597 insertions and deletions (INDELs) across 93 samples from 12 porcine breeds. The identified mutations and affected pathways are correlated to muscle-to-fat ratios between different porcine breeds and further inform their utility as models of obesity and cardiovascular disease. Finally, 7935 SNVs and 358 INDELs are present in an Oncopig hepatocellular carcinoma (HCC) cell line and samples from a single Oncopig HCC tumor, with pathways related to hepatic fibrosis, WNT/B-catenin, ATM signaling, and p53 signaling enriched. These results demonstrate the kit’s high efficacy and utility for identifying mutations in the context of obesity, cardiovascular disease, and cancer across a range of pig models used in biomedical research.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"287 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920749","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

Peak analysis of cell-free RNA finds recurrently protected narrow regions with clinical potential 无细胞RNA的峰值分析发现具有临床潜力的反复受保护的狭窄区域

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-08 DOI: 10.1186/s13059-025-03590-x

Pengfei Bao, Taiwei Wang, Xiaofan Liu, Shaozhen Xing, Hanjin Ruan, Hongli Ma, Yuhuan Tao, Qing Zhan, Efres Belmonte-Reche, Lizheng Qin, Zhengxue Han, Minghui Mao, Mengtao Li, Zhi John Lu

{"title":"Peak analysis of cell-free RNA finds recurrently protected narrow regions with clinical potential","authors":"Pengfei Bao, Taiwei Wang, Xiaofan Liu, Shaozhen Xing, Hanjin Ruan, Hongli Ma, Yuhuan Tao, Qing Zhan, Efres Belmonte-Reche, Lizheng Qin, Zhengxue Han, Minghui Mao, Mengtao Li, Zhi John Lu","doi":"10.1186/s13059-025-03590-x","DOIUrl":"https://doi.org/10.1186/s13059-025-03590-x","url":null,"abstract":"Cell-free RNAs (cfRNAs) can be detected in biofluids and have emerged as valuable disease biomarkers. Accurate identification of the fragmented cfRNA signals, especially those originating from pathological cells, is crucial for understanding their biological functions and clinical value. However, many challenges still need to be addressed for their application, including developing specific analysis methods and translating cfRNA fragments with biological support into clinical applications. We present cfPeak, a novel method combining statistics and machine learning models to detect the fragmented cfRNA signals effectively. When test in real and artificial cfRNA sequencing (cfRNA-seq) data, cfPeak shows an improved performance compared with other applicable methods. We reveal that narrow cfRNA peaks preferentially overlap with protein binding sites, vesicle-sorting sites, structural sites, and novel small non-coding RNAs (sncRNAs). When applied in clinical cohorts, cfPeak identified cfRNA peaks in patients’ plasma that enable cancer detection and are informative of cancer types and metastasis. Our study fills the gap in the current small cfRNA-seq analysis at fragment-scale and builds a bridge to the scientific discovery in cfRNA fragmentomics. We demonstrate the significance of finding low abundant tissue-derived signals in small cfRNA and prove the feasibility for application in liquid biopsy. ","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"19 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920832","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

Polygraph: a software framework for the systematic assessment of synthetic regulatory DNA elements 测谎仪：用于系统评估合成调控DNA元件的软件框架

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-06 DOI: 10.1186/s13059-025-03584-9

Avantika Lal, Laura Gunsalus, Anay Gupta, Tommaso Biancalani, Gokcen Eraslan

引用次数: 0

PRESCOTT: a population aware, epistatic, and structural model accurately predicts missense effects 普雷斯科特：人口意识、上位性和结构模型准确地预测了误义效应

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-06 DOI: 10.1186/s13059-025-03581-y

Mustafa Tekpinar, Laurent David, Thomas Henry, Alessandra Carbone

引用次数: 0

SlideCNA: spatial copy number alteration detection from Slide-seq-like spatial transcriptomics data SlideCNA：从类似slide -seq的空间转录组学数据中检测空间拷贝数改变

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-02 DOI: 10.1186/s13059-025-03573-y

Diane Zhang, Åsa Segerstolpe, Michal Slyper, Julia Waldman, Evan Murray, Robert Strasser, Jan Watter, Ofir Cohen, Orr Ashenberg, Daniel Abravanel, Judit Jané-Valbuena, Simon Mages, Ana Lako, Karla Helvie, Orit Rozenblatt-Rosen, Scott Rodig, Fei Chen, Nikhil Wagle, Aviv Regev, Johanna Klughammer

引用次数: 0

Four near-complete genome assemblies reveal the landscape and evolution of centromeres in Salicaceae 四个接近完整的基因组组合揭示了水杨科着丝粒的景观和进化

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-05-02 DOI: 10.1186/s13059-025-03578-7

Yubo Wang, Lulu Zhao, Deyan Wang, Kai Chen, Tiannan Luo, Jianglin Luo, Chengzhi Jiang, Zhoujian He, Heng Huang, Jiaxiao Xie, Yuanzhong Jiang, Jianquan Liu, Tao Ma

{"title":"Four near-complete genome assemblies reveal the landscape and evolution of centromeres in Salicaceae","authors":"Yubo Wang, Lulu Zhao, Deyan Wang, Kai Chen, Tiannan Luo, Jianglin Luo, Chengzhi Jiang, Zhoujian He, Heng Huang, Jiaxiao Xie, Yuanzhong Jiang, Jianquan Liu, Tao Ma","doi":"10.1186/s13059-025-03578-7","DOIUrl":"https://doi.org/10.1186/s13059-025-03578-7","url":null,"abstract":"Centromeres play a crucial role in maintaining genomic stability during cell division. They are typically composed of large arrays of tandem satellite repeats, which hinder high-quality assembly and complicate our efforts to understand their evolution across species. Here, we use long-read sequencing to generate near-complete genome assemblies for two Populus and two Salix species belonging to the Salicaceae family and characterize the genetic and epigenetic landscapes of their centromeres. The results show that only limited satellite repeats are present as centromeric components in these species, while most of them are located outside the centromere but exhibit a homogenized structure similar to that of the Arabidopsis centromeres. Instead, the Salicaceae centromeres are mainly composed of abundant transposable elements, including CRM and ATHILA, while LINE elements are exclusively discovered in the poplar centromeres. Comparative analysis reveals that these centromeric repeats are extensively expanded and interspersed with satellite arrays in a species-specific and chromosome-specific manner, driving rapid turnover of centromeres both in sequence compositions and genomic locations in the Salicaceae. Our results highlight the dynamic evolution of diverse centromeric landscapes among closely related species mediated by satellite homogenization and widespread invasions of transposable elements and shed further light on the role of centromere in genome evolution and species diversification.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"13 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897478","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

SpaNorm: spatially-aware normalization for spatial transcriptomics data 空间转录组学数据的空间感知规范化

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-04-29 DOI: 10.1186/s13059-025-03565-y

Agus Salim, Dharmesh D. Bhuva, Carissa Chen, Chin Wee Tan, Pengyi Yang, Melissa J. Davis, Jean Y. H. Yang

引用次数: 0

Multi-ancestry whole genome sequencing analysis of lean body mass 瘦体重的多祖先全基因组测序分析

IF 12.3 1区生物学

Genome Biology Pub Date : 2025-04-28 DOI: 10.1186/s13059-025-03520-x

Xiaoyu Zhang, Kuan-Jui Su, Bodhisattwa Banerjee, Ittai Eres, Yi-Hsiang Hsu, Carolyn J. Crandall, Rajashekar Donaka, Zhe Han, Rebecca D. Jackson, Hanhan Liu, Zhe Luo, Braxton D. Mitchell, Chuan Qiu, Qing Tian, Hui Shen, Ming-Ju Tsai, Kerri L. Wiggins, Hanfei Xu, Michelle Yau, Lan-Juan Zhao, Xiao Zhang, May E. Montasser, Douglas P. Kiel, Hong-Wen Deng, Ching-Ti Liu, David Karasik

{"title":"Multi-ancestry whole genome sequencing analysis of lean body mass","authors":"Xiaoyu Zhang, Kuan-Jui Su, Bodhisattwa Banerjee, Ittai Eres, Yi-Hsiang Hsu, Carolyn J. Crandall, Rajashekar Donaka, Zhe Han, Rebecca D. Jackson, Hanhan Liu, Zhe Luo, Braxton D. Mitchell, Chuan Qiu, Qing Tian, Hui Shen, Ming-Ju Tsai, Kerri L. Wiggins, Hanfei Xu, Michelle Yau, Lan-Juan Zhao, Xiao Zhang, May E. Montasser, Douglas P. Kiel, Hong-Wen Deng, Ching-Ti Liu, David Karasik","doi":"10.1186/s13059-025-03520-x","DOIUrl":"https://doi.org/10.1186/s13059-025-03520-x","url":null,"abstract":"Lean body mass is a crucial physiological component of body composition. Although lean body mass has a high heritability, studies evaluating the genetic determinants of lean mass (LM) have to date been limited largely to genome-wide association studies (GWAS) and common variants. Using whole genome sequencing (WGS)-based studies, we aimed to discover novel genetic variants associated with LM in population-based cohorts with multiple ancestries. We describe the largest WGS-based meta-analysis of lean body mass to date, encompassing 10,729 WGS samples from six TOPMed cohorts and the Louisiana Osteoporosis Study (LOS) cohort, measured with dual-energy X-ray absorptiometry. We identify seven genome-wide loci significantly associated with LM not reported by previous GWAS. We partially replicate these associations in UK Biobank samples. In rare variant analysis, we discover one novel protein-coding gene, DMAC1, associated with both whole-body LM and appendicular LM in females, and a long non-coding RNA gene linked to appendicular LM in males. Both genes exhibit notably high expression levels in skeletal muscle tissue. We investigate the functional roles of two novel lean-mass-related genes, EMP2 and SSUH2, in animal models. EMP2 deficiency in Drosophila leads to significantly reduced mobility without altering muscle tissue or body fat morphology, whereas an SSUH2 gene mutation in zebrafish stimulates muscle fiber growth. Our comprehensive analysis, encompassing a large-scale WGS meta-analysis and functional investigations, reveals novel genomic loci and genes associated with lean mass traits, shedding new insights into pathways influencing muscle metabolism and muscle mass regulation.\u0000","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"91 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880423","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