Genome Biology最新文献

{"title":"Incorporating scale uncertainty in microbiome and gene expression analysis as an extension of normalization","authors":"Michelle Pistner Nixon, Gregory B. Gloor, Justin D. Silverman","doi":"10.1186/s13059-025-03609-3","DOIUrl":"https://doi.org/10.1186/s13059-025-03609-3","url":null,"abstract":"Statistical normalizations are used in differential analyses to address sample-to-sample variation in sequencing depth. Yet normalizations make strong, implicit assumptions about the scale of biological systems, such as microbial load, leading to false positives and negatives. We introduce scale models as a generalization of normalizations, which allows researchers to model potential errors in these modeling assumptions, thereby enhancing the transparency and robustness of data analyses. In practice, scale models can drastically reduce false positives and false negatives rates. We introduce updates to the popular ALDEx2 software package, available on Bioconductor, facilitating scale model analysis.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"44 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114080","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":"H3K4me3 binding ALFIN-LIKE proteins recruit SWR1 for gene-body deposition of H2A.Z","authors":"Linhao Xu, Yafei Wang, Xueying Li, Qin Hu, Vanda Adamkova, Junjie Xu, C. Jake Harris, Israel Ausin","doi":"10.1186/s13059-025-03605-7","DOIUrl":"https://doi.org/10.1186/s13059-025-03605-7","url":null,"abstract":"The H2A.Z histone variant is highly enriched over gene bodies, playing an essential role in several genome-templated processes, including transcriptional regulation and epigenetic patterning across eukaryotes. Deposition of H2A.Z is mediated by the SWR1 remodeling complex. How SWR1 is directed to gene bodies is largely unknown. Here, we show that ALFIN-LIKE (AL) proteins are responsible for H2A.Z gene body patterning in Arabidopsis. AL proteins encode H3K4me3-binding PHD domains, and by ChIP-seq, we confirm preferential binding of AL5 to H3K4me3 over H3K4me1/2 in planta. We observe a global reduction in H2A.Z in al septuple mutants (al7m), especially over H3K4me3-enriched genic regions. While MBD9 recruits SWR1 to nucleosome-free regions, ALs act non-redundantly with MBD9 for deposition of H2A.Z. Notably, al7m mutants show severe developmental abnormalities and upregulation of H2A.Z gene body-enriched responsive genes. Therefore, we propose a model whereby AL proteins direct gene body enrichment of H2A.Z by recruiting SWR1 to H3K4me3-containing responsive genes.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"133 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113818","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":"Revealing long-range heterogeneous organization of nucleoproteins with 6mA footprinting by ipdTrimming","authors":"Wentao Yang, Xue Qing Wang, Fan Wei, Jingqi Yu, Yifan Liu, Yali Dou","doi":"10.1186/s13059-025-03592-9","DOIUrl":"https://doi.org/10.1186/s13059-025-03592-9","url":null,"abstract":"Enabled by long-read sequencing technologies, particularly Single Molecule, Real-Time sequencing, N6-methyladenine (6mA) footprinting is a transformative methodology for revealing the heterogenous and dynamic distribution of nucleosomes and other DNA-binding proteins. Here, we present ipdTrimming, a novel 6mA-calling pipeline that outperforms existing tools in both computational efficiency and accuracy. Utilizing this optimized experimental and computational framework, we are able to map nucleosome positioning and transcription factor occupancy in nuclear DNA and establish high-resolution, long-range binding events in mitochondrial DNA. Our study highlights the potential of 6mA footprinting to capture coordinated nucleoprotein binding and to unravel epigenetic heterogeneity.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"2 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113988","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":"SMOPCA: spatially aware dimension reduction integrating multi-omics improves the efficiency of spatial domain detection","authors":"Mo Chen, Ruihua Cheng, Jianuo He, Jun Chen, Jie Zhang","doi":"10.1186/s13059-025-03576-9","DOIUrl":"https://doi.org/10.1186/s13059-025-03576-9","url":null,"abstract":"Technological advances have enabled us to profile multiple omics layers with spatial information, significantly enhancing spatial domain detection and advancing a variety of biomedical research fields. Despite these advancements, there is a notable lack of effective methods for modeling spatial multi-omics data. We introduce SMOPCA, a Spatial Multi-Omics Principal Component Analysis method designed to perform joint dimension reduction on multimodal data while preserving spatial dependencies. Extensive experiments reveal that SMOPCA outperforms existing single-modal and multimodal dimension reduction and clustering methods, across both single-cell and spatial multi-omics datasets derived from diverse technologies and tissue structures.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"11 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113989","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":"CMImpute: cross-species and tissue imputation of species-level DNA methylation samples across mammalian species","authors":"Emily Maciejewski, Steve Horvath, Jason Ernst","doi":"10.1186/s13059-025-03561-2","DOIUrl":"https://doi.org/10.1186/s13059-025-03561-2","url":null,"abstract":"The large-scale application of the mammalian methylation array has substantially expanded the availability of DNA methylation data in mammalian species. However, this data captures only a small portion of species-tissue combinations. To address this, we develop CMImpute (Cross-species Methylation Imputation), a method based on a conditional variational autoencoder, to impute DNA methylation representing species-tissue combinations. We demonstrate that CMImpute achieves strong sample-wise correlation between imputed and observed values. Using CMImpute and data from 348 species and 59 tissue types, we impute methylation data for 19,786 new species-tissue combinations. We expect CMImpute will be a useful resource for DNA methylation analyses.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"1 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097508","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":"CloseRead: a tool for assessing assembly errors in immunoglobulin loci applied to vertebrate long-read genome assemblies","authors":"Yixin Zhu, Corey Watson, Yana Safonova, Matt Pennell, Anton Bankevich","doi":"10.1186/s13059-025-03594-7","DOIUrl":"https://doi.org/10.1186/s13059-025-03594-7","url":null,"abstract":"Despite tremendous advances in long-read sequencing, some structurally complex and repeat-rich genomic regions remain challenging to assemble. Furthermore, we lack tools to assess local assembly quality, making it hard to identify problems and assess progress. Here we develop a new approach “CloseRead” for visualizing local assembly quality and diagnosing errors using multiple metrics. We apply CloseRead to evaluate how well immunoglobulin loci, paradigmatic cases of structurally complex regions, are assembled in 74 state-of-the-art vertebrate genomes. We then show that targeted, local re-assembly can correct the specific errors identified by CloseRead, highlighting the value of an iterative approach to genome assembly.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"80 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097674","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":"Evaluating topography of mutational signatures with SigProfilerTopography","authors":"Burçak Otlu, Ludmil B. Alexandrov","doi":"10.1186/s13059-025-03612-8","DOIUrl":"https://doi.org/10.1186/s13059-025-03612-8","url":null,"abstract":"The mutations found in a cancer genome are shaped by diverse processes, each displaying a characteristic mutational signature that may be influenced by the genome’s architecture. While prior analyses have evaluated the effect of topographical genomic features on mutational signatures, there has been no computational tool that can comprehensively examine this interplay. Here, we present SigProfilerTopography, a Python package that allows evaluating the effect of chromatin organization, histone modifications, transcription factor binding, DNA replication, and DNA transcription on the activities of different mutational processes. SigProfilerTopography elucidates the unique topographical characteristics of mutational signatures, unveiling their underlying biological and molecular mechanisms.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"234 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097507","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":"Urbanization and genetic homogenization in the medieval Low Countries revealed through a ten-century paleogenomic study of the city of Sint-Truiden","authors":"Owyn Beneker, Ludovica Molinaro, Meriam Guellil, Stefania Sasso, Helja Kabral, Biancamaria Bonucci, Noah Gaens, Eugenia D’Atanasio, Massimo Mezzavilla, Hélios Delbrassine, Linde Braet, Bart Lambert, Pieterjan Deckers, Simone Andrea Biagini, Ruoyun Hui, Sara Becelaere, Jan Geypen, Maxim Hoebreckx, Birgit Berk, Petra Driesen, April Pijpelink, Philip van Damme, Sofie Vanhoutte, Natasja De Winter, Lehti Saag, Luca Pagani, Kristiina Tambets, Christiana L. Scheib, Maarten H. D. Larmuseau, Toomas Kivisild","doi":"10.1186/s13059-025-03580-z","DOIUrl":"https://doi.org/10.1186/s13059-025-03580-z","url":null,"abstract":"Processes shaping the formation of the present-day population structure in highly urbanized Northern Europe are still poorly understood. Gaps remain in our understanding of when and how currently observable regional differences emerged and what impact city growth, migration, and disease pandemics during and after the Middle Ages had on these processes. We perform low-coverage sequencing of the genomes of 338 individuals spanning the eighth to the eighteenth centuries in the city of Sint-Truiden in Flanders, in the northern part of Belgium. The early/high medieval Sint-Truiden population was more heterogeneous, having received migrants from Scotland or Ireland, and displayed less genetic relatedness than observed today between individuals in present-day Flanders. We find differences in gene variants associated with high vitamin D blood levels between individuals with Gaulish or Germanic ancestry. Although we find evidence of a Yersinia pestis infection in 5 of the 58 late medieval burials, we were unable to detect a major population-scale impact of the second plague pandemic on genetic diversity or on the elevated differentiation of immunity genes. This study reveals that the genetic homogenization process in a medieval city population in the Low Countries was protracted for centuries. Over time, the Sint-Truiden population became more similar to the current population of the surrounding Limburg province, likely as a result of reduced long-distance migration after the high medieval period, and the continuous process of local admixture of Germanic and Gaulish ancestries which formed the genetic cline observable today in the Low Countries.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"10 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097511","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":"Tumor ploidy determination in low-pass whole genome sequencing and allelic copy number visualization using the Constellation Plot","authors":"Sarah H. Johnson, James B. Smadbeck, Roman M. Zenka, Michael T. Barrett, Athanasios Gaitatzes, Arnav Solanki, Angela B. Florio, Mitesh J. Borad, John C. Cheville, George Vasmatzis","doi":"10.1186/s13059-025-03599-2","DOIUrl":"https://doi.org/10.1186/s13059-025-03599-2","url":null,"abstract":"Ploidy determination across the genome has been challenging for low-pass-WGS tumor-only samples. We present BACDAC, a method that calculates tumor ploidy down to 1.2X effective tumor coverage. Allele fraction patterns displayed in the Constellation Plot verify tumor ploidy and reveal subclonal populations. BACDAC outputs a metric, 2N+LOH, that when combined with ploidy better distinguishes near-diploid from high-ploidy tumors. Validated using TCGA, BACDAC had good agreement with other methods and 88% agreement with experimental methods. Discrepancies occur mainly when BACDAC predicts diploidy with subclones rather than high-ploidy. Applied to 653 low-pass-WGS samples spanning 12 cancer subtypes, BACDAC calls 40% as high-ploidy.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"131 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097509","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":"RobusTAD: reference panel based annotation of nested topologically associating domains","authors":"Yanlin Zhang, Rola Dali, Mathieu Blanchette","doi":"10.1186/s13059-025-03568-9","DOIUrl":"https://doi.org/10.1186/s13059-025-03568-9","url":null,"abstract":"Topologically associating domains (TADs) are fundamental units of 3D genomes and play essential roles in gene regulation. Hi-C data suggests a hierarchical organization of TADs. Accurately annotating nested TADs from Hi-C data remains challenging, both in terms of the precise identification of boundaries and the correct inference of hierarchies. While domain boundary is relatively well conserved across cells, few approaches have taken advantage of this fact. Here, we present RobusTAD to annotate TAD hierarchies. It incorporates additional Hi-C data to refine boundaries annotated from the study sample. RobusTAD outperforms existing tools at boundary and domain annotation across several benchmarking tasks.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"55 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088313","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}