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DelSIEVE: cell phylogeny modeling of single nucleotide variants and deletions from single-cell DNA sequencing data DelSIEVE：单细胞DNA测序数据中单核苷酸变异和缺失的细胞系统发育模型
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-08-25 DOI: 10.1186/s13059-025-03738-9
Senbai Kang, Nico Borgsmüller, Monica Valecha, Magda Markowska, Jack Kuipers, Niko Beerenwinkel, David Posada, Ewa Szczurek
{"title":"DelSIEVE: cell phylogeny modeling of single nucleotide variants and deletions from single-cell DNA sequencing data","authors":"Senbai Kang, Nico Borgsmüller, Monica Valecha, Magda Markowska, Jack Kuipers, Niko Beerenwinkel, David Posada, Ewa Szczurek","doi":"10.1186/s13059-025-03738-9","DOIUrl":"https://doi.org/10.1186/s13059-025-03738-9","url":null,"abstract":"With rapid advancements in single-cell DNA sequencing (scDNA-seq), various computational methods have been developed to study evolution and call variants on single-cell level. However, modeling deletions remains challenging because they affect total coverage in ways that are difficult to distinguish from technical artifacts. We present DelSIEVE, a statistical method that infers cell phylogeny and single-nucleotide variants, accounting for deletions, from scDNA-seq data. DelSIEVE distinguishes deletions from mutations and artifacts, detecting more evolutionary events than previous methods. Simulations show high performance, and application to cancer samples reveals varying amounts of deletions and double mutants in different tumors.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"18 4 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898385","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
Highly accurate prophage island detection with PIDE 用PIDE进行高精度的噬菌体岛检测
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-08-20 DOI: 10.1186/s13059-025-03733-0
Hongyan Gao, Bowen Li, Zihan Guo, Lei Zheng, Junnan Chen, Guanxiang Liang
{"title":"Highly accurate prophage island detection with PIDE","authors":"Hongyan Gao, Bowen Li, Zihan Guo, Lei Zheng, Junnan Chen, Guanxiang Liang","doi":"10.1186/s13059-025-03733-0","DOIUrl":"https://doi.org/10.1186/s13059-025-03733-0","url":null,"abstract":"As important mobile elements in prokaryotes, prophages shape the genomic context of their hosts and regulate the structure of bacterial populations. However, it is challenging to precisely identify prophages through computational methods. Here, we introduce PIDE for identifying prophages from bacterial genomes or metagenome-assembled genomes. PIDE integrates a pre-trained protein language model and gene density clustering algorithm to distinguish prophages. Benchmarking with induced prophage sequencing datasets demonstrates that PIDE pinpoints prophages with precise boundaries. Applying PIDE to 4744 human gut representative genomes reveals 24,467 prophages with widespread functional capacity. PIDE is available at https://github.com/chyghy/PIDE , with model training code at https://zenodo.org/records/16457629 .","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"31 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898191","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
TRsv: simultaneous detection of tandem repeat variations, structural variations, and short indels using long read sequencing data. TRsv：利用长读测序数据同时检测串联重复序列变异、结构变异和短索引。
IF 10.1 1区 生物学
Genome Biology Pub Date : 2025-08-20 DOI: 10.1186/s13059-025-03718-z
Shunichi Kosugi, Chikashi Terao
{"title":"TRsv: simultaneous detection of tandem repeat variations, structural variations, and short indels using long read sequencing data.","authors":"Shunichi Kosugi, Chikashi Terao","doi":"10.1186/s13059-025-03718-z","DOIUrl":"10.1186/s13059-025-03718-z","url":null,"abstract":"<p><p>Tandem repeat copy number variations (TR-CNVs), structural variations (SVs), and short indels have been responsible for many diseases and traits, but no tools exist to distinguish and detect these variants. In this study, we developed a computational tool, TRsv, to distinguish and detect TR-CNVs, SVs, and short indels using long reads. In evaluation with simulated and real datasets, TRsv outperformed existing tools for detection of TR-CNVs and indels and performed equally well for detection of SVs. We demonstrated genome-wide detection of TR-CNVs, including variants associated with gene expression, disease, and quantitative traits, using 160 long-read whole genome sequencing data and TRsv.</p>","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"26 1","pages":"246"},"PeriodicalIF":10.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882625","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
A message passing framework for precise cell state identification with scClassify2. 一个消息传递框架，用于使用scClassify2进行精确的单元状态识别。
IF 10.1 1区 生物学
Genome Biology Pub Date : 2025-08-19 DOI: 10.1186/s13059-025-03722-3
Wenze Ding, Yue Cao, Xiaohang Fu, Marni Torkel, Jean Yee Hwa Yang
{"title":"A message passing framework for precise cell state identification with scClassify2.","authors":"Wenze Ding, Yue Cao, Xiaohang Fu, Marni Torkel, Jean Yee Hwa Yang","doi":"10.1186/s13059-025-03722-3","DOIUrl":"10.1186/s13059-025-03722-3","url":null,"abstract":"<p><p>Cell annotation is crucial for downstream exploration. Although many approaches, spanning from classic statistics to large language models, have been developed, most of their focus is on distinct cell types and overlook sequential cell populations. Here, we propose an annotation method, scClassify2, to specifically focus on adjacent cell state identification. By incorporating prior biological knowledge through a novel dual-layer architecture and ordinal regression, scClassify2 achieves competitive performance compared to other state-of-the-art methods. Besides single-cell RNA-sequencing data, scClassify2 is generalizable from different platforms including subcellular spatial transcriptomics data. We also develop a web server for academic uses.</p>","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"26 1","pages":"252"},"PeriodicalIF":10.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882623","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
KAT6A chimeras form a self-reinforcing epigenetic module with NURF and MLL/COMPASS to sustain AML. KAT6A嵌合体与NURF和MLL/COMPASS形成自我强化的表观遗传模块，以维持AML。
IF 10.1 1区 生物学
Genome Biology Pub Date : 2025-08-19 DOI: 10.1186/s13059-025-03743-y
Junhui Lv, Zhinang Yin, Conghui Li, Honglin Wen, Jian Ni, Peiyuan Yang, Zemin Song, Ying Xiang, Honghong Wang, Rui Lu, Li Huang, Ying Zhou, Hai-Bing Zhou, Ruijing Xiao, Pingping Fang, Kaiwei Liang
{"title":"KAT6A chimeras form a self-reinforcing epigenetic module with NURF and MLL/COMPASS to sustain AML.","authors":"Junhui Lv, Zhinang Yin, Conghui Li, Honglin Wen, Jian Ni, Peiyuan Yang, Zemin Song, Ying Xiang, Honghong Wang, Rui Lu, Li Huang, Ying Zhou, Hai-Bing Zhou, Ruijing Xiao, Pingping Fang, Kaiwei Liang","doi":"10.1186/s13059-025-03743-y","DOIUrl":"10.1186/s13059-025-03743-y","url":null,"abstract":"<p><strong>Background: </strong>KAT6A-CBP (K/C) and KAT6A-P300 (K/P) fusions are recurrent genetic alterations in acute myeloid leukemia (AML) associated with poor prognosis. Despite their strong oncogenic potential, the mechanisms underlying their genomic targeting and leukemogenic function remain unclear. A major challenge has been their large size, which has impeded preclinical model development and mechanistic studies.</p><p><strong>Results: </strong>We employ a domain-focused truncation strategy to generate de novo murine models of K/C and K/P fusions, which faithfully recapitulate the morphological, immunophenotypic, and transcriptomic features of KAT6A-rearranged AML. Genomic profiling reveals that KAT6A fusions preferentially localize to H3K4me2/3-marked regions, while biochemical analyses uncover that KAT6A interacts with the Nucleosome Remodeling Factor (NURF), a key H3K4me2/3 reader. Disrupting NURF-chromatin interactions via depletion or small-molecule inhibition of its subunit, Bromodomain PHD Finger Transcription Factor (BPTF), impairs K/C recruitment and disrupts MLL/COMPASS-mediated H3K4me2 deposition, defining a functional epigenetic module involving KAT6A chimeras, NURF, and MLL/COMPASS. Notably, CBP/P300 inhibition reduces histone acetylation and chromatin accessibility, further impairing the recruitment of this epigenetic module. Targeting this module via NURF or CBP/P300 inhibition demonstrates efficacy in K/C leukemia models, with enhanced therapeutic effects observed when combined.</p><p><strong>Conclusions: </strong>Our study identifies a self-reinforcing epigenetic module of histone modifiers and readers in KAT6A-rearranged AML, providing mechanistic insights into the genomic targeting of KAT6A chimeras and highlighting promising combinatorial therapeutic strategies.</p>","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"26 1","pages":"253"},"PeriodicalIF":10.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882624","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
Mutations of short tandem repeats explain abundant trait heritability in Arabidopsis 短串联重复序列的突变解释了拟南芥丰富的性状遗传力
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-08-12 DOI: 10.1186/s13059-025-03720-5
Zhi-Qin Zhang, Juan Jiang, Yong-Chao Xu, Craig Dent, Sridevi Sureshkumar, Sureshkumar Balasubramanian, Ya-Long Guo
{"title":"Mutations of short tandem repeats explain abundant trait heritability in Arabidopsis","authors":"Zhi-Qin Zhang, Juan Jiang, Yong-Chao Xu, Craig Dent, Sridevi Sureshkumar, Sureshkumar Balasubramanian, Ya-Long Guo","doi":"10.1186/s13059-025-03720-5","DOIUrl":"https://doi.org/10.1186/s13059-025-03720-5","url":null,"abstract":"Short tandem repeat (STR) mutations are major drivers of genetic variation and deeply influence phenotypic diversity and evolution, they are often overlooked despite their significant effects. Here, we leverage mutation accumulation lines descended from Col-0 accession of Arabidopsis thaliana to assess the variation in the repeat length of STRs (STR mutation rate). We find that STR mutation rate far exceeds single nucleotide polymorphisms rates. Interspecific comparison between A. thaliana and Arabidopsis lyrata reveals rapid STR turnover, with the most majority of the loci occurring only in A. thaliana. Intraspecific comparison of ten assembled A. thaliana genomes reveals that 29.3% of STRs display presence/absence variations, 36.5% show length variation, 21.2% have both types of variations, while only a small proportion have no variation. By association analysis, we find several STRs are associated with diverse phenotypes. Further analysis based on RNA-seq dataset from 413 accessions, we identify 3,871 expression-associated STRs and 651 splicing-associated STRs, of which over one thousand co-localized with known signals for diverse traits detected by genome-wide association studies. Notably, based on analysis of the expression levels of 24,175 genes and splice site strength values of 12,784 splice sites, as well as 16 phenotypes of natural A. thaliana populations, we determine the similar average heritability of these three trait sets explained by STR variation. Our results reveal the evolutionary dynamics of STRs, and highlight the importance of STR variation as an important contributor to missing heritability in regulating complex traits.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"69 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819912","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
Y-mer: a k-mer based method for determining human Y chromosome haplogroups from ultra-low sequencing depth data Y-mer：一种基于k-mer的方法，用于从超低测序深度数据中确定人类Y染色体单倍群
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-08-12 DOI: 10.1186/s13059-025-03714-3
Tarmo Puurand, Märt Möls, Lauris Kaplinski, Kadri Maal, Kaarel Krjutskov, Andres Salumets, Toomas Kivisild, Maido Remm
{"title":"Y-mer: a k-mer based method for determining human Y chromosome haplogroups from ultra-low sequencing depth data","authors":"Tarmo Puurand, Märt Möls, Lauris Kaplinski, Kadri Maal, Kaarel Krjutskov, Andres Salumets, Toomas Kivisild, Maido Remm","doi":"10.1186/s13059-025-03714-3","DOIUrl":"https://doi.org/10.1186/s13059-025-03714-3","url":null,"abstract":"Determining genetic ancestry of an individual is challenging from poorly preserved or mixed samples that permit only ultra-low coverage sequence at depths less than 0.1 × at target loci. Leveraging recent advances in telomere-to-telomere sequencing of whole genomes with long reads, we develop a new k-mer based method, Y-mer, and show how information from hundreds of thousands of k-mers in distance-based models enables accurate inference of chrY haplogroup from whole-genome sequence at depth less than 0.01x. We test the performance of Y-mer on ancient DNA and prenatal screening data, showing its potential for genetic ancestry inference for cell-free, forensic and ancient DNA research.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"27 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819947","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
Common cell lysis procedures distort ribosome profiling analyses of gene expression 普通的细胞裂解程序扭曲了基因表达的核糖体谱分析
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-08-11 DOI: 10.1186/s13059-025-03651-1
Aoife O’Connell, Alla D. Fedorova, Patrick B. F. O’Connor, Alexander V. Zhdanov, Pavel V. Baranov, Gary Loughran, Dmitry E. Andreev
{"title":"Common cell lysis procedures distort ribosome profiling analyses of gene expression","authors":"Aoife O’Connell, Alla D. Fedorova, Patrick B. F. O’Connor, Alexander V. Zhdanov, Pavel V. Baranov, Gary Loughran, Dmitry E. Andreev","doi":"10.1186/s13059-025-03651-1","DOIUrl":"https://doi.org/10.1186/s13059-025-03651-1","url":null,"abstract":"Ribosome profiling is a powerful technique used to study gene expression on a transcriptome-wide scale. It involves sequencing of mRNA fragments protected by ribosomes from ribonuclease digestion. The initial steps commonly involve cell lysis followed by centrifugation and ribonuclease digestion. We find that centrifugation depletes 329 translated mRNAs in HEK293T cells. Many of these mRNAs encode cytoskeleton proteins. This suggests that the expression of a subset of mRNAs may be significantly underestimated in most ribosome profiling experiments. We show that omitting the centrifugation step after cell lysis can resolve this issue.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"109 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819309","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
The evolutionary dynamics of organellar pan-genomes in Arabidopsis thaliana 拟南芥细胞器泛基因组的进化动力学
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-08-11 DOI: 10.1186/s13059-025-03717-0
Yi Zou, Weidong Zhu, Yingke Hou, Daniel B. Sloan, Zhiqiang Wu
{"title":"The evolutionary dynamics of organellar pan-genomes in Arabidopsis thaliana","authors":"Yi Zou, Weidong Zhu, Yingke Hou, Daniel B. Sloan, Zhiqiang Wu","doi":"10.1186/s13059-025-03717-0","DOIUrl":"https://doi.org/10.1186/s13059-025-03717-0","url":null,"abstract":"In plants, comparative analyses of organellar genomes are often based on draft assemblies. Large-scale investigations into the complex structural rearrangements of mitochondrial genomes remain scarce. Here, we perform a comprehensive analysis of the dominant conformations and dynamic heteroplasmic variants of organellar genomes in the model plant Arabidopsis thaliana, utilizing high-quality long-read assemblies validated at high resolution from 149 samples. We find that mitochondrial and plastid genomes share common types of structural and small-scale variants driven by similar DNA sequence features. However, rearrangements mediated by repetitive sequences in mitochondrial genomes evolve so rapidly that they are often decoupled from other types of variants. Rare complex events involving elongation and fusion of existing repeats are also observed, contributing to the unalignable regions commonly found at the interspecies level. Additionally, we demonstrate that disrupting and rescuing organellar DNA maintenance could drive the rapid evolution of dominant mitochondrial genome conformations. Our study provides an unprecedentedly detailed view of the dynamics of organellar genomes at pan-genome scale in Arabidopsis thaliana, paving the way to unlock the full potential of organellar genetic resources.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"27 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819318","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
spVelo: RNA velocity inference for multi-batch spatial transcriptomics data 多批空间转录组学数据的RNA速度推断
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-08-11 DOI: 10.1186/s13059-025-03701-8
Wenxin Long, Tianyu Liu, Lingzhou Xue, Hongyu Zhao
{"title":"spVelo: RNA velocity inference for multi-batch spatial transcriptomics data","authors":"Wenxin Long, Tianyu Liu, Lingzhou Xue, Hongyu Zhao","doi":"10.1186/s13059-025-03701-8","DOIUrl":"https://doi.org/10.1186/s13059-025-03701-8","url":null,"abstract":"RNA velocity has emerged as a powerful tool to interpret transcriptional dynamics and infer trajectory from snapshot datasets. However, current methods fail to utilize the spatial information inherent in spatial transcriptomics and lack scalability in multi-batch datasets. Here, we introduce spVelo, a scalable framework for RNA velocity inference of multi-batch spatial transcriptomics data. spVelo supports several downstream applications, including uncertainty quantification, complex trajectory pattern discovery, driver marker identification, gene regulatory network inference, and temporal cell-cell communication inference. spVelo has the potential to provide deeper insights into complex tissue organization and underscore biological mechanisms based on spatially resolved patterns.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"46 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819179","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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