Genome BiologyPub Date : 2025-08-12DOI: 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}
Genome BiologyPub Date : 2025-08-11DOI: 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}
{"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}
Genome BiologyPub Date : 2025-08-08DOI: 10.1186/s13059-025-03716-1
Qingnan Liang, Luisa Solis Soto, Cara Haymaker, Ken Chen
{"title":"LSGI: interpretable spatial gradient analysis for spatial transcriptomics data","authors":"Qingnan Liang, Luisa Solis Soto, Cara Haymaker, Ken Chen","doi":"10.1186/s13059-025-03716-1","DOIUrl":"https://doi.org/10.1186/s13059-025-03716-1","url":null,"abstract":"Cellular anatomy and signaling vary across niches, which can induce gradated gene expressions in subpopulations of cells. Such spatial transcriptomic gradient (STG) makes a significant source of intra-tumor heterogeneity. We present Local Spatial Gradient Inference (LSGI), a computational framework that systematically identifies spatial locations with prominent, interpretable STGs from spatial transcriptomic (ST) data. We demonstrate LSGI in tumor ST datasets and identify pan-cancer and tumor-type specific pathways with gradated patterns, highlighting the ones related to spatial transcriptional intratumoral heterogeneity. LSGI enables interpretable STG analysis, which can reveal novel insights in tumor biology from the increasingly reported tumor ST datasets.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"27 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797233","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}
Genome BiologyPub Date : 2025-08-07DOI: 10.1186/s13059-025-03710-7
Ruiyan Hou, Yuanhua Huang
{"title":"scTail: precise polyadenylation site detection and its alternative usage analysis from reads 1 preserved 3′ scRNA-seq data","authors":"Ruiyan Hou, Yuanhua Huang","doi":"10.1186/s13059-025-03710-7","DOIUrl":"https://doi.org/10.1186/s13059-025-03710-7","url":null,"abstract":"The first-strand reads (often reads 1) of three-prime single-cell RNA-seq (3′ scRNA-seq) can contain informative cDNA for analysis of polyadenylation sites (PAS), but are often overlooked or trimmed. Here, we describe a computational method, scTail, to identify PAS using first-strand reads and quantify its expression leveraging second-strand reads, consequently enabling detection of alternative PAS usage. Compared with other methods, scTail detects PAS more precisely and retains high sensitivity. Furthermore, we demonstrated that combining scTail and BRIE2 can discover differential alternative PAS usage in various biological processes including cancers and time-series development, giving critical insight into PAS regulation.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"21 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792837","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}
Genome BiologyPub Date : 2025-08-06DOI: 10.1186/s13059-025-03683-7
Lingling Wu, Xiang Zhu, Yanxia Liu, Dehua Zhao, Betty Chentzu Yu, Zheng Wei, Xueqiu Lin, Lei S. Qi
{"title":"Identification of replicative aging and inflammatory aging signatures via whole-genome CRISPRi screens","authors":"Lingling Wu, Xiang Zhu, Yanxia Liu, Dehua Zhao, Betty Chentzu Yu, Zheng Wei, Xueqiu Lin, Lei S. Qi","doi":"10.1186/s13059-025-03683-7","DOIUrl":"https://doi.org/10.1186/s13059-025-03683-7","url":null,"abstract":"Aging is a major risk factor for chronic diseases and cancer. Cellular aging, particularly in adult stem cells, offers a high-throughput framework for dissecting the molecular mechanisms of aging. We perform multiple genome-wide CRISPR interference (CRISPRi) screenings in human primary mesenchymal stem cells derived from adipose tissue during either replicative senescence or inflammation-induced senescence. These screens reveal distinct sets of potential novel regulators specific to each senescence pathway. Combining our perturbation-based functional genomic data with 405 genome-wide association study datasets, including 50 aging-related studies, we find that the inflammatory aging signatures identified from CRISPRi screenings are significantly associated with diverse aging processes, suggesting novel molecular signatures for analyzing and predicting aging status and aging-related disease. The signatures verified through comprehensive functional genomics and genetic analyses may provide new targets for modulating the aging process and enhancing the quality of cell therapy products.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"14 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786793","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}
Genome BiologyPub Date : 2025-07-30DOI: 10.1186/s13059-025-03691-7
Andrea Movilli, Svitlana Sushko, Fernando A. Rabanal, Detlef Weigel
{"title":"Long-read detection of transposable element mobilization in the soma of hypomethylated Arabidopsis thaliana individuals","authors":"Andrea Movilli, Svitlana Sushko, Fernando A. Rabanal, Detlef Weigel","doi":"10.1186/s13059-025-03691-7","DOIUrl":"https://doi.org/10.1186/s13059-025-03691-7","url":null,"abstract":"Because transposable elements (TEs) can cause heritable genetic changes, past work on TE mobility in Arabidopsis thaliana has mostly focused on new TE insertions in the germline of hypomethylated plants. It is, however, well-known that TEs can also be active in the soma, although the high-confidence detection of somatic events has been challenging. Here, we leverage the high accuracy of PacBio HiFi long reads to evaluate the somatic mobility of TEs in individuals of an A. thaliana non-reference strain lacking activity of METHYLTRANSFERASE1 (MET1), a major component of the DNA methylation maintenance machinery. Most somatically mobile families coincide with those found in germline studies of hypomethylated genotypes, although the exact TE copies differ. We also discover mobile elements that had been missed by standard TE annotation methods. Somatic TE activity is variable among individual plants, but also within TE families. Finally, our approach points to the possible involvement of alternative transposition as a cause for somatic hypermutability in a region that contains two closely spaced VANDAL21 elements. Long-read sequencing reveals widespread TE transposition in the soma of A. thaliana hypomethylated mutants. Assessing somatic instead of germline mobilization is a fast and reliable method to investigate different aspects of TE mobility at the single plant level.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"27 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747319","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":"Artificial chromosome reorganization reveals high plasticity of the budding and fission yeast genomes","authors":"Xueting Zhu, Shaochun Liu, Tiantian Ye, Xin Gu, Feiyu Pu, Zhen Zhou, Zhi-Jing Wu, Jin-Qiu Zhou","doi":"10.1186/s13059-025-03689-1","DOIUrl":"https://doi.org/10.1186/s13059-025-03689-1","url":null,"abstract":"The genome of a eukaryotic cell is usually organized on a set of chromosomes. Recently, karyotype engineering has been applied to various organisms, but whether and to what extent a naturally evolved genome can resist or tolerate massive artificial manipulations remains unexplored. Using unicellular yeast models of both Saccharomyces cerevisiae and Schizosaccharomyces pombe, we deliberately construct dozens of single-chromosome strains with different chromosome architectures. Three S. cerevisiae strains have the individual chromosomes fused into a single chromosome, but with the individual chromosomes in different orders. Eighteen S. cerevisiae strains have a single chromosome but with different centromeric sequences. Fifteen S. cerevisiae strains have a single chromosome with the centromere at different distances relative to the telomeres. Two S. pombe strains have a single, circular chromosome, and three strains have a single, linear chromosome with the centromere at different distances relative to the telomeres. All of these single-chromosome strains are viable, but the strains with an acrocentric or a telocentric chromosome have abnormal cell morphologies, and grow more slowly than those with a metacentric or sub-metacentric chromosome, and show increased genome instability with chromosome segregation abnormalities or genome diploidization. The functional genomes of both the evolutionarily distant yeasts S. cerevisiae and S. pombe are highly tolerant of diversified genome organizations. The phenotypic abnormalities and increased genome instability of the acrocentric/telocentric single-chromosome yeasts suggest that yeasts with metacentric chromosomes have an evolutionary advantage.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"24 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719696","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}
Genome BiologyPub Date : 2025-07-29DOI: 10.1186/s13059-025-03673-9
Björn E. Langer, Andreia Amaral, Marie-Odile Baudement, Franziska Bonath, Mathieu Charles, Praveen Krishna Chitneedi, Emily L. Clark, Paolo Di Tommaso, Sarah Djebali, Philip A. Ewels, Sonia Eynard, James A. Fellows Yates, Daniel Fischer, Evan W. Floden, Sylvain Foissac, Gisela Gabernet, Maxime U. Garcia, Gareth Gillard, Manu Kumar Gundappa, Cervin Guyomar, Christopher Hakkaart, Friederike Hanssen, Peter W. Harrison, Matthias Hörtenhuber, Cyril Kurylo, Christa Kühn, Sandrine Lagarrigue, Delphine Lallias, Daniel J. Macqueen, Edmund Miller, Júlia Mir-Pedrol, Gabriel Costa Monteiro Moreira, Sven Nahnsen, Harshil Patel, Alexander Peltzer, Frederique Pitel, Yuliaxis Ramayo-Caldas, Marcel da Câmara Ribeiro-Dantas, Dominique Rocha, Mazdak Salavati, Alexey Sokolov, Jose Espinosa-Carrasco, Cedric Notredame, the nf-core community
{"title":"Empowering bioinformatics communities with Nextflow and nf-core","authors":"Björn E. Langer, Andreia Amaral, Marie-Odile Baudement, Franziska Bonath, Mathieu Charles, Praveen Krishna Chitneedi, Emily L. Clark, Paolo Di Tommaso, Sarah Djebali, Philip A. Ewels, Sonia Eynard, James A. Fellows Yates, Daniel Fischer, Evan W. Floden, Sylvain Foissac, Gisela Gabernet, Maxime U. Garcia, Gareth Gillard, Manu Kumar Gundappa, Cervin Guyomar, Christopher Hakkaart, Friederike Hanssen, Peter W. Harrison, Matthias Hörtenhuber, Cyril Kurylo, Christa Kühn, Sandrine Lagarrigue, Delphine Lallias, Daniel J. Macqueen, Edmund Miller, Júlia Mir-Pedrol, Gabriel Costa Monteiro Moreira, Sven Nahnsen, Harshil Patel, Alexander Peltzer, Frederique Pitel, Yuliaxis Ramayo-Caldas, Marcel da Câmara Ribeiro-Dantas, Dominique Rocha, Mazdak Salavati, Alexey Sokolov, Jose Espinosa-Carrasco, Cedric Notredame, the nf-core community","doi":"10.1186/s13059-025-03673-9","DOIUrl":"https://doi.org/10.1186/s13059-025-03673-9","url":null,"abstract":"Standardized analysis pipelines contribute to making data bioinformatics research compliant with the paradigm of Findability, Accessibility, Interoperability, and Reusability (FAIR), and facilitate collaboration. Nextflow and Snakemake, two popular command-line solutions, are increasingly adopted by users, complementing GUI-based platforms such as Galaxy. We report recent developments of the nf-core framework with the new Nextflow Domain-Specific Language (DSL2). An extensive library of modules and subworkflows enables research communities to adopt common standards progressively, as resources and needs allow. We present an overview of some of the research communities built around nf-core and showcase its adoption by six EuroFAANG farmed animal research consortia.\u0000","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"27 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719697","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":"SpaSEG: unsupervised deep learning for multi-task analysis of spatially resolved transcriptomics","authors":"Yong Bai, Xiangyu Guo, Keyin Liu, Bingjie Zheng, Yilin Wei, Yingyue Wang, Wenxi Zhang, Qiuhong Luo, Jianhua Yin, Liang Wu, Yuxiang Li, Yong Zhang, Ao Chen, Xiangdong Wang, Xun Xu, Chuanyu Liu, Xin Jin","doi":"10.1186/s13059-025-03697-1","DOIUrl":"https://doi.org/10.1186/s13059-025-03697-1","url":null,"abstract":"Spatially resolved transcriptomics (SRT) for characterizing spatial cellular heterogeneities in tissue environments requires systematic analytical approaches to elucidate gene expression variations within their physiological context. Here, we introduce SpaSEG, an unsupervised deep learning model utilizing convolutional neural networks for multiple SRT analysis tasks. Extensive evaluations across diverse SRT datasets generated by various platforms demonstrate SpaSEG’s superior robustness and efficiency compared to existing methods. In the application analysis of invasive ductal carcinoma, SpaSEG successfully unravels intratumoral heterogeneity and delivers insights into immunoregulatory mechanisms. These results highlight SpaSEG’s substantial potential for exploring tissue architectures and pathological biology.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"25 1","pages":"230"},"PeriodicalIF":12.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737463","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}