Genome Biology最新文献

{"title":"MaveDB 2024: a curated community database with over seven million variant effects from multiplexed functional assays","authors":"Alan F. Rubin, Jeremy Stone, Aisha Haley Bianchi, Benjamin J. Capodanno, Estelle Y. Da, Mafalda Dias, Daniel Esposito, Jonathan Frazer, Yunfan Fu, Sally B. Grindstaff, Matthew R. Harrington, Iris Li, Abbye E. McEwen, Joseph K. Min, Nick Moore, Olivia G. Moscatelli, Jesslyn Ong, Polina V. Polunina, Joshua E. Rollins, Nathan J. Rollins, Ashley E. Snyder, Amy Tam, Matthew J. Wakefield, Shenyi Sunny Ye, Lea M. Starita, Vanessa L. Bryant, Debora S. Marks, Douglas M. Fowler","doi":"10.1186/s13059-025-03476-y","DOIUrl":"https://doi.org/10.1186/s13059-025-03476-y","url":null,"abstract":"Multiplexed assays of variant effect (MAVEs) are a critical tool for researchers and clinicians to understand genetic variants. Here we describe the 2024 update to MaveDB ( https://www.mavedb.org/ ) with four key improvements to the MAVE community’s database of record: more available data including over 7 million variant effect measurements, an improved data model supporting assays such as saturation genome editing, new built-in exploration and visualization tools, and powerful APIs for data federation and streamlined submission and access. Together these changes support MaveDB’s role as a hub for the analysis and dissemination of MAVEs now and into the future.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"162 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990650","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":"Author Correction: Considerations in the search for epistasis","authors":"Marleen Balvert, Johnathan Cooper-Knock, Julian Stamp, Ross P. Byrne, Soufane Mourragui, Juami van Gils, Stefania Benonisdottir, Johannes Schlüter, Kevin Kenna, Sanne Abeln, Alfredo Iacoangeli, Joséphine T. Daub, Brian L. Browning, Gizem Taş, Jiajing Hu, Yan Wang, Elham Alhathli, Calum Harvey, Luna Pianesi, Sara C. Schulte, Jorge González-Domínguez, Erik Garrisson, Michael P. Snyder, Alexander Schönhuth, Letitia M. F. Sng, Natalie A. Twine","doi":"10.1186/s13059-025-03477-x","DOIUrl":"https://doi.org/10.1186/s13059-025-03477-x","url":null,"abstract":"<p><b>Correction: Genome Biol 25, 296 (2024)</b></p><p><b>https://doi.org/10.1186/s13059-024-03427-z</b></p><br/><p>Following publication of the original article [1], the authors identified that two author affiliations were incorrect.</p><p>Joséphine Daub is affiliated with Utrecht University (21) and not affiliation 9.</p><p>Sanne Abeln is affiliated with Utrecht University only (21) and not affiliation 1.</p><p>The original article [1] has been corrected.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1\"><p>Balvert M, Cooper-Knock J, Stamp J, et al. Considerations in the search for epistasis. Genome Biol. 2024;25:296. https://doi.org/10.1186/s13059-024-03427-z.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><span>Author notes</span><ol><li><p>Marleen Balvert and Johnathan Cooper-Knock contributed equally to this work.</p></li><li><p>Alexander Schönhuth, Letitia M. F. Sng, and Natalie A. Twine contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Tilburg University, Tilburg, The Netherlands</p><p>Marleen Balvert & Gizem Taş</p></li><li><p>SITraN, University of Sheffield, Sheffield, UK</p><p>Johnathan Cooper-Knock, Elham Alhathli & Calum Harvey</p></li><li><p>Brown University, Providence, USA</p><p>Julian Stamp</p></li><li><p>Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland</p><p>Ross P. Byrne</p></li><li><p>Hubrecht Institute, Utrecht, The Netherlands</p><p>Soufane Mourragui</p></li><li><p>Vrije Universiteit Amsterdam, Amsterdam, The Netherlands</p><p>Juami van Gils</p></li><li><p>University of Oxford, Oxford, UK</p><p>Stefania Benonisdottir</p></li><li><p>Bielefeld University, Bielefeld, Germany</p><p>Johannes Schlüter, Luna Pianesi & Alexander Schönhuth</p></li><li><p>UMC Utrecht, Utrecht, The Netherlands</p><p>Kevin Kenna, Gizem Taş & Yan Wang</p></li><li><p>Department of Biostatistics and Health Informatics, King’s College London, London, UK</p><p>Alfredo Iacoangeli & Jiajing Hu</p></li><li><p>Department of Basic and Clinical Neuroscience, King’s College London, London, UK</p><p>Alfredo Iacoangeli</p></li><li><p>NIHR BRC SLAM NHS Foundation Trust, London, UK</p><p>Alfredo Iacoangeli</p></li><li><p>University of Washington, Seattle, USA</p><p>Brian L. Browning</p></li><li><p>Algorithmic Bioinformatics and Center for Digital Medicine, Heinrich Heine University, Düsseldorf, Germany</p><p>Sara C. Schulte</p></li><li><p>CITIC, University of A Coruña, A Coruña, Spain</p><p>Jorge González-Domínguez</p></li><li><p>University of Tennessee, Knoxville, USA</p><p>Erik Garrisson</p></li><li><p>Department of Genetics, Stanford University, Stanford, USA</p><p>Michael P. Snyder</p></li><li><p>Commonwealt","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"31 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990080","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":"Alternative silencing states of transposable elements in Arabidopsis associated with H3K27me3","authors":"Valentin Hure, Florence Piron-Prunier, Tamara Yehouessi, Clémentine Vitte, Aleksandra E. Kornienko, Gabrielle Adam, Magnus Nordborg, Angélique Déléris","doi":"10.1186/s13059-024-03466-6","DOIUrl":"https://doi.org/10.1186/s13059-024-03466-6","url":null,"abstract":"The DNA/H3K9 methylation and Polycomb-group proteins (PcG)-H3K27me3 silencing pathways have long been considered mutually exclusive and specific to transposable elements (TEs) and genes, respectively in mammals, plants, and fungi. However, H3K27me3 can be recruited to many TEs in the absence of DNA/H3K9 methylation machinery and sometimes also co-occur with DNA methylation. In this study, we show that TEs can also be solely targeted and silenced by H3K27me3 in wild-type Arabidopsis plants. These H3K27me3-marked TEs not only comprise degenerate relics but also seemingly intact copies that display the epigenetic features of responsive PcG target genes as well as an active H3K27me3 regulation. We also show that H3K27me3 can be deposited on newly inserted transgenic TE sequences in a TE-specific manner indicating that silencing is determined in cis. Finally, a comparison of Arabidopsis natural accessions reveals the existence of a category of TEs—which we refer to as “bifrons”—that are marked by DNA methylation or H3K27me3 depending on the accession. This variation can be linked to intrinsic TE features and to trans-acting factors and reveals a change in epigenetic status across the TE lifespan. Our study sheds light on an alternative mode of TE silencing associated with H3K27me3 instead of DNA methylation in flowering plants. It also suggests dynamic switching between the two epigenetic marks at the species level, a new paradigm that might extend to other multicellular eukaryotes.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"56 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990078","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":"Enhancer regulatory networks globally connect non-coding breast cancer loci to cancer genes","authors":"Yihan Wang, Daniel A. Armendariz, Lei Wang, Huan Zhao, Shiqi Xie, Gary C. Hon","doi":"10.1186/s13059-025-03474-0","DOIUrl":"https://doi.org/10.1186/s13059-025-03474-0","url":null,"abstract":"Genetic studies have associated thousands of enhancers with breast cancer (BC). However, the vast majority have not been functionally characterized. Thus, it remains unclear how BC-associated enhancers contribute to cancer. Here, we perform single-cell CRISPRi screens of 3513 regulatory elements associated with breast cancer to measure the impact of these regions on transcriptional phenotypes. Analysis of > 500,000 single-cell transcriptomes in two breast cancer cell lines shows that perturbation of BC-associated enhancers disrupts breast cancer gene programs. We observe BC-associated enhancers that directly or indirectly regulate the expression of cancer genes. We also find one-to-multiple and multiple-to-one network motifs where enhancers indirectly regulate cancer genes. Notably, multiple BC-associated enhancers indirectly regulate TP53. Comparative studies illustrate subtype specific functions between enhancers in ER + and ER − cells. Finally, we develop the pySpade package to facilitate analysis of single-cell enhancer screens. Overall, we demonstrate that enhancers form regulatory networks that link cancer genes in the genome, providing a more comprehensive understanding of the contribution of enhancers to breast cancer development.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"30 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987508","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":"Pangenome mining of the Streptomyces genus redefines species’ biosynthetic potential","authors":"Omkar S. Mohite, Tue S. Jørgensen, Thomas J. Booth, Pep Charusanti, Patrick V. Phaneuf, Tilmann Weber, Bernhard O. Palsson","doi":"10.1186/s13059-024-03471-9","DOIUrl":"https://doi.org/10.1186/s13059-024-03471-9","url":null,"abstract":"Streptomyces is a highly diverse genus known for the production of secondary or specialized metabolites with a wide range of applications in the medical and agricultural industries. Several thousand complete or nearly complete Streptomyces genome sequences are now available, affording the opportunity to deeply investigate the biosynthetic potential within these organisms and to advance natural product discovery initiatives. We perform pangenome analysis on 2371 Streptomyces genomes, including approximately 1200 complete assemblies. Employing a data-driven approach based on genome similarities, the Streptomyces genus was classified into 7 primary and 42 secondary Mash-clusters, forming the basis for comprehensive pangenome mining. A refined workflow for grouping biosynthetic gene clusters (BGCs) redefines their diversity across different Mash-clusters. This workflow also reassigns 2729 known BGC families to only 440 families, a reduction caused by inaccuracies in BGC boundary detections. When the genomic location of BGCs is included in the analysis, a conserved genomic structure, or synteny, among BGCs becomes apparent within species and Mash-clusters. This synteny suggests that vertical inheritance is a major factor in the diversification of BGCs. Our analysis of a genomic dataset at a scale of thousands of genomes refines predictions of BGC diversity using Mash-clusters as a basis for pangenome analysis. The observed conservation in the order of BGCs’ genomic locations shows that the BGCs are vertically inherited. The presented workflow and the in-depth analysis pave the way for large-scale pangenome investigations and enhance our understanding of the biosynthetic potential of the Streptomyces genus.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"90 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974549","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":"Relating ecological diversity to genetic discontinuity across bacterial species","authors":"Hemanoel Passarelli-Araujo, Thiago M. Venancio, William P. Hanage","doi":"10.1186/s13059-024-03443-z","DOIUrl":"https://doi.org/10.1186/s13059-024-03443-z","url":null,"abstract":"Genetic discontinuity represents abrupt breaks in genomic identity among species. Advances in genome sequencing have enhanced our ability to track and characterize genetic discontinuity in bacterial populations. However, exploring the degree to which bacterial diversity exists as a continuum or sorted into discrete and readily defined species remains a challenge in microbial ecology. Here, we aim to quantify the genetic discontinuity ( $$delta$$ ) and investigate how this metric is related to ecology. We harness a dataset comprising 210,129 genomes to systematically explore genetic discontinuity patterns across several distantly related species, finding clear breakpoints which vary depending on the taxa in question. By delving into pangenome characteristics, we uncover a significant association between pangenome saturation and genetic discontinuity. Closed pangenomes are associated with more pronounced breaks, exemplified by Mycobacterium tuberculosis. Additionally, through a machine learning approach, we detect key features such as gene conservation patterns and functional annotations that significantly impact genetic discontinuity prediction. Our study clarifies bacterial genetic patterns and their ecological impacts, enhancing the delineation of species boundaries and deepening our understanding of microbial diversity.\u0000","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"16 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940149","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":"Graph pangenome reveals the regulation of malate content in blood-fleshed peach by NAC transcription factors","authors":"Wenbo Chen, Qi Xie, Jia Fu, Shaojia Li, Yanna Shi, Jiao Lu, Yuanyuan Zhang, Yingjie Zhao, Ruijuan Ma, Baijun Li, Bo Zhang, Donald Grierson, Mingliang Yu, Zhangjun Fei, Kunsong Chen","doi":"10.1186/s13059-024-03470-w","DOIUrl":"https://doi.org/10.1186/s13059-024-03470-w","url":null,"abstract":"Fruit acidity and color are important quality attributes in peaches. Although there are some exceptions, blood-fleshed peaches typically have a sour taste. However, little is known about the genetic variations linking organic acid and color regulation in peaches. Here, we report a peach graph-based pangenome constructed from sixteen individual genome assemblies, capturing abundant structural variations and 82.3 Mb of sequences absent in the reference genome. Pangenome analysis reveals a long terminal repeat retrotransposon insertion in the promoter of the NAC transcription factor (TF) PpBL in blood-fleshed peaches, which enhances PpBL expression. Genome-wide association study identifies a significant association between PpBL and malate content. Silencing PpBL in peach fruit and ectopic overexpression of PpBL in tomatoes confirm that PpBL is a positive regulator of malate accumulation. Furthermore, we demonstrate that PpBL works synergistically with another NAC TF, PpNAC1, to activate the transcription of the aluminum-activated malate transporter PpALMT4, leading to increased malate content. These findings, along with previous research showing that PpBL and PpNAC1 also regulate anthocyanin accumulation, explain the red coloration and sour taste in blood-fleshed peach fruits.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"39 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937668","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":"Pre-processing of paleogenomes: mitigating reference bias and postmortem damage in ancient genome data","authors":"Dilek Koptekin, Etka Yapar, Kıvılcım Başak Vural, Ekin Sağlıcan, N. Ezgi Altınışık, Anna-Sapfo Malaspinas, Can Alkan, Mehmet Somel","doi":"10.1186/s13059-024-03462-w","DOIUrl":"https://doi.org/10.1186/s13059-024-03462-w","url":null,"abstract":"We investigate alternative strategies against reference bias and postmortem damage in low coverage paleogenomes. Compared to alignment to the linear reference genome, we show that masking known polymorphic sites and graph alignment effectively remove reference bias, but only starting from raw read files. We next study approaches to overcome postmortem damage: trimming, rescaling, and our newly developed algorithm, bamRefine (github.com/etkayapar/bamRefine and zenodo.org/records/14234666), masking reads only at positions possibly affected by PMD. We propose graph alignment coupled with bamRefine as a simple strategy to minimize data loss and bias, and urge the community to publish FASTQ files.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"45 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936961","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":"Marsilea: an intuitive generalized paradigm for composable visualizations","authors":"Yimin Zheng, Zhihang Zheng, André F. Rendeiro, Edwin Cheung","doi":"10.1186/s13059-024-03469-3","DOIUrl":"https://doi.org/10.1186/s13059-024-03469-3","url":null,"abstract":"Biological data visualization is challenged by the growing complexity of datasets. Traditional single-data plots or simple juxtapositions often fail to fully capture dataset intricacies and interrelations. To address this, we introduce “cross-layout,” a novel visualization paradigm that integrates multiple plot types in a cross-like structure, with a central main plot surrounded by secondary plots for enhanced contextualization and interrelation insights. We also introduce “Marsilea,” a Python-based implementation of cross-layout visualizations, available in both programmatic and web-based interfaces to support users of all experience levels. This paradigm and its implementation offer a customizable, intuitive approach to advance biological data visualization.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"24 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928985","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":"Resolving the source of branch length variation in the Y chromosome phylogeny","authors":"Yaniv Swiel, Janet Kelso, Stéphane Peyrégne","doi":"10.1186/s13059-024-03468-4","DOIUrl":"https://doi.org/10.1186/s13059-024-03468-4","url":null,"abstract":"Genetic variation in the non-recombining part of the human Y chromosome has provided important insight into the paternal history of human populations. However, a significant and yet unexplained branch length variation of Y chromosome lineages has been observed, notably amongst those that are highly diverged from the human reference Y chromosome. Understanding the origin of this variation, which has previously been attributed to changes in generation time, mutation rate, or efficacy of selection, is important for accurately reconstructing human evolutionary and demographic history. Here, we analyze Y chromosomes from present-day and ancient modern humans, as well as Neandertals, and show that branch length variation amongst human Y chromosomes cannot solely be explained by differences in demographic or biological processes. Instead, reference bias results in mutations being missed on Y chromosomes that are highly diverged from the reference used for alignment. We show that masking fast-evolving, highly divergent regions of the human Y chromosome mitigates the effect of this bias and enables more accurate determination of branch lengths in the Y chromosome phylogeny. We show that our approach allows us to estimate the age of ancient samples from Y chromosome sequence data and provide updated estimates for the time to the most recent common ancestor using the portion of the Y chromosome where the effect of reference bias is minimized.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"12 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929158","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}