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Hmgb2 improves astrocyte to neuron conversion by increasing the chromatin accessibility of genes associated with neuronal maturation in a proneuronal factor-dependent manner Genome Biol. (IF 10.1) Pub Date : 2025-04-17 Priya Maddhesiya, Tjasa Lepko, Andrea Steiner-Mezzardi, Julia Schneider, Veronika Schwarz, Juliane Merl-Pham, Finja Berger, Stefanie M. Hauck, Lorenza Ronfani, Marco Bianchi, Tatiana Simon, Anthodesmi Krontira, Giacomo Masserdotti, Magdalena Götz, Jovica Ninkovic
Direct conversion of reactive glial cells to neurons is a promising avenue for neuronal replacement therapies after brain injury or neurodegeneration. The overexpression of neurogenic fate determinants in glial cells results in conversion to neurons. For repair purposes, the conversion should ideally be induced in the pathology-induced neuroinflammatory environment. However, very little is known regarding
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DNA methylation dynamics play crucial roles in shaping the distinct transcriptomic profiles for different root-type initiation in rice Genome Biol. (IF 10.1) Pub Date : 2025-04-17 Wei Jiang, Zhou Zhou, Xiaoying Li, Yu Zhao, Shaoli Zhou
Monocots possess a fibrous root system comprising an embryonic root, crown roots, and lateral roots. The distinct cellular origins highlight the diversity of the initiation mechanism. To date, the distinct initiation mechanisms have been poorly studied. In this study, we conduct a comprehensive transcriptome and DNA methylome assay of these root types during their initiation. Our findings indicate
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Bayesian multi-study non-negative matrix factorization for mutational signatures Genome Biol. (IF 10.1) Pub Date : 2025-04-16 Isabella N. Grabski, Lorenzo Trippa, Giovanni Parmigiani
Mutational signatures are typically identified from tumor genome sequencing data using non-negative matrix factorization (NMF). However, existing NMF techniques only decompose a single dataset, limiting rigorous comparisons of signatures across conditions. We propose a Bayesian NMF method that jointly decomposes multiple datasets to identify signatures and their sharing pattern across conditions. We
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Guidelines for releasing a variant effect predictor Genome Biol. (IF 10.1) Pub Date : 2025-04-15 Benjamin J. Livesey, Mihaly Badonyi, Mafalda Dias, Jonathan Frazer, Sushant Kumar, Kresten Lindorff-Larsen, David M. McCandlish, Rose Orenbuch, Courtney A. Shearer, Lara Muffley, Julia Foreman, Andrew M. Glazer, Ben Lehner, Debora S. Marks, Frederick P. Roth, Alan F. Rubin, Lea M. Starita, Joseph A. Marsh
Computational methods for assessing the likely impacts of mutations, known as variant effect predictors (VEPs), are widely used in the assessment and interpretation of human genetic variation, as well as in other applications like protein engineering. Many different VEPs have been released, and there is tremendous variability in their underlying algorithms, outputs, and the ways in which the methodologies
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Post-cleavage target residence determines asymmetry in non-homologous end joining of Cas12a-induced DNA double strand breaks Genome Biol. (IF 10.1) Pub Date : 2025-04-14 Ruo-Dan Chen, Yi Yang, Kun-Ming Liu, Jing-Zhen Hu, Yi-Li Feng, Chun-Yi Yang, Rui-Rui Jiang, Si-Cheng Liu, Yue Wang, Ping-An Han, Ru-Gang Tian, Yu-Long Wang, Shi-Ming Xu, An-Yong Xie
After Cas12a cleaves its DNA target, it generates a DNA double strand break (DSB) with two compatible 5′-staggered ends. The Cas12a-gRNA complex remains at the protospacer adjacent motif (PAM)-proximal end (PPE) while releasing the PAM-distal end (PDE). The effects of this asymmetric retention on DSB repair are currently unknown. Post-cleavage retention of LbCas12a at PPEs suppresses the recruitment
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Extracellular vesicle-derived miRNA-mediated cell–cell communication inference for single-cell transcriptomic data with miRTalk Genome Biol. (IF 10.1) Pub Date : 2025-04-14 Xin Shao, Lingqi Yu, Chengyu Li, Jingyang Qian, Xinyu Yang, Haihong Yang, Jie Liao, Xueru Fan, Xiao Xu, Xiaohui Fan
MicroRNAs are released from cells in extracellular vesicles (EVs), representing an essential mode of cell–cell communication (CCC) via a regulatory effect on gene expression. Single-cell RNA-sequencing technologies have ushered in an era of elucidating CCC at single-cell resolution. Herein, we present miRTalk, a pioneering approach for inferring CCC mediated by EV-derived miRNA-target interactions
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Genomic evidence for low genetic diversity but purging of strong deleterious variants in snow leopards Genome Biol. (IF 10.1) Pub Date : 2025-04-14 Lin Yang, Hong Jin, Qien Yang, Andrey Poyarkov, Miroslav Korablev, Viatcheslav Rozhnov, Junjie Shao, Qiaomei Fu, Jose Antonio Hernandez-Blanco, Xiangjiang Zhan, Li Yu, Dmitry Alexandrov, Qingyan Dai, Bariushaa Munkhtsog, Xin Du, Bayaraa Munkhtsog, Liqing Ma, Wanlin Chen, Sergei Malykh, Yipeng Jin, Shunfu He, Tongzuo Zhang, Guosheng Wu, Yonghong Shi, Fuwen Wei, Yibo Hu
Long-term persistence of species with low genetic diversity is the focus of widespread attention in conservation biology. The snow leopard, Panthera uncia, is a big cat from high-alpine regions of Asia. However, its subspecies taxonomy, evolutionary history, evolutionary potential, and survival strategy remain unclear, which greatly hampers their conservation. We sequence a high-quality chromosome-level
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Spatiotemporal transcriptomics reveals key gene regulation for grain yield and quality in wheat Genome Biol. (IF 10.1) Pub Date : 2025-04-11 Xiaohui Li, Yiman Wan, Dongzhi Wang, Xingguo Li, Jiajie Wu, Jun Xiao, Kunming Chen, Xue Han, Yuan Chen
Cereal grain size and quality are critical agronomic traits in crop production. Wheat grain development is governed by intricate regulatory networks that require precise spatiotemporal coordination of gene expression to establish functional compartments in different cell types. Here, we perform a spatial transcriptomics study covering the early stages of wheat grain development, from 4 to 12 days after
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TF Profiler: a transcription factor inference method that broadly measures transcription factor activity and identifies mechanistically distinct networks Genome Biol. (IF 10.1) Pub Date : 2025-04-09 Taylor Jones, Rutendo F. Sigauke, Lynn Sanford, Dylan J. Taatjes, Mary A. Allen, Robin D. Dowell
TF Profiler is a method of inferring transcription factor (TF) regulatory activity, i.e., when a TF is present and actively participating in the regulation of transcription, directly from nascent sequencing assays such as PRO-seq and GRO-seq. While ChIP assays have measured DNA localization, they fall short of identifying when and where the effector domain of a transcription factor is active. Our method
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Filtering cells with high mitochondrial content depletes viable metabolically altered malignant cell populations in cancer single-cell studies Genome Biol. (IF 10.1) Pub Date : 2025-04-09 Josephine Yates, Agnieszka Kraft, Valentina Boeva
Single-cell transcriptomics has transformed our understanding of cellular diversity, yet noise from technical artifacts and low-quality cells can obscure key biological signals. A common practice is filtering out cells with a high percentage of mitochondrial RNA counts (pctMT), typically indicative of cell death. However, commonly used filtering thresholds, primarily derived from studies on healthy
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MIDAA: deep archetypal analysis for interpretable multi-omic data integration based on biological principles Genome Biol. (IF 10.1) Pub Date : 2025-04-08 Salvatore Milite, Giulio Caravagna, Andrea Sottoriva
High-throughput multi-omic molecular profiling allows the probing of biological systems at unprecedented resolution. However, integrating and interpreting high-dimensional, sparse, and noisy multimodal datasets remains challenging. Deriving new biological insights with current methods is difficult because they are not rooted in biological principles but prioritise tasks like dimensionality reduction
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The histone acetyltransferase CBP participates in regulating the DNA damage response through ATM after double-strand breaks Genome Biol. (IF 10.1) Pub Date : 2025-04-08 Wafaa S. Ramadan, Samrein B. M. Ahmed, Iman M. Talaat, Lama Lozon, Soraya Mouffak, Timo Gemoll, Wael Y. Mansour, Raafat El-Awady
Spatial and temporal control of DNA damage response pathways after DNA damage is crucial for maintenance of genomic stability. Ataxia telangiectasia mutated (ATM) protein plays a central role in DNA damage response pathways. The chain of events following induction of DNA damage that results in full activation of ATM is still evolving. Here we set out to explore the role of CREB-binding protein (CBP)
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Benchmark of cellular deconvolution methods using a multi-assay dataset from postmortem human prefrontal cortex Genome Biol. (IF 10.1) Pub Date : 2025-04-07 Louise A. Huuki-Myers, Kelsey D. Montgomery, Sang Ho Kwon, Sophia Cinquemani, Nicholas J. Eagles, Daianna Gonzalez-Padilla, Sean K. Maden, Joel E. Kleinman, Thomas M. Hyde, Stephanie C. Hicks, Kristen R. Maynard, Leonardo Collado-Torres
Cellular deconvolution of bulk RNA-sequencing data using single cell/nuclei RNA-seq reference data is an important strategy for estimating cell type composition in heterogeneous tissues, such as the human brain. Here, we generate a multi-assay dataset in postmortem human dorsolateral prefrontal cortex from 22 tissue blocks, including bulk RNA-seq, reference snRNA-seq, and orthogonal measurement of
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CNRein: an evolution-aware deep reinforcement learning algorithm for single-cell DNA copy number calling Genome Biol. (IF 10.1) Pub Date : 2025-04-07 Stefan Ivanovic, Mohammed El-Kebir
Low-pass single-cell DNA sequencing technologies and algorithmic advancements have enabled haplotype-specific copy number calling on thousands of cells within tumors. However, measurement uncertainty may result in spurious CNAs inconsistent with realistic evolutionary constraints. We introduce evolution-aware copy number calling via deep reinforcement learning (CNRein). Our simulations demonstrate
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Missing cell types in single-cell references impact deconvolution of bulk data but are detectable Genome Biol. (IF 10.1) Pub Date : 2025-04-07 Adriana Ivich, Natalie R. Davidson, Laurie Grieshober, Weishan Li, Stephanie C. Hicks, Jennifer A. Doherty, Casey S. Greene
Advancements in RNA sequencing have expanded our ability to study gene expression profiles of biological samples in bulk tissue and single cells. Deconvolution of bulk data with single-cell references provides the ability to study relative cell-type proportions, but most methods assume a reference is present for every cell type in bulk data. This is not true in all circumstances—cell types can be missing
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Systematic optimization and prediction of cre recombinase for precise genome editing in mice Genome Biol. (IF 10.1) Pub Date : 2025-04-04 Valerie Erhardt, Elli Hartig, Kristian Lorenzo, Hannah R. Megathlin, Basile Tarchini, Vishnu Hosur
The Cre-Lox system is a powerful tool in mouse genetics, enabling precise spatiotemporal control of gene expression and conditional knockout models. Since its development, it has transformed genome editing by facilitating targeted deletions, translocations, inversions, and complex modifications—double-floxed inverse orientation. Its utility extends beyond mice to rats, pigs, and zebrafish. However
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Genomic prediction with kinship-based multiple kernel learning produces hypothesis on the underlying inheritance mechanisms of phenotypic traits Genome Biol. (IF 10.1) Pub Date : 2025-04-04 Daniele Raimondi, Nora Verplaetse, Antoine Passemiers, Deborah Sarah Jans, Isabelle Cleynen, Yves Moreau
Genomic prediction encompasses the techniques used in agricultural technology to predict the genetic merit of individuals towards valuable phenotypic traits. It is related to Genome Interpretation in humans, which models the individual risk of developing disease traits. Genomic prediction is dominated by linear mixed models, such as the Genomic Best Linear Unbiased Prediction (GBLUP), which computes
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Integrative omics analysis reveals the genetic basis of fatty acid composition in Brassica napus seeds Genome Biol. (IF 10.1) Pub Date : 2025-04-02 Yuting Zhang, Yunhao Liu, Zhanxiang Zong, Liang Guo, Wenhao Shen, Hu Zhao
The fatty acid content represents a crucial quality trait in Brassica napus or rapeseed. Improvements in fatty acid composition markedly enhance the quality of rapeseed oil. Here, we perform a genome-wide association study (GWAS) to identify quantitative trait locus (QTLs) associated with fatty acid content. We identify a total of seven stable QTLs and find two loci, qFA.A08 and qFA.A09.1, subjected
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Chromosome-level genome assembly and single-cell analysis unveil molecular mechanisms of arm regeneration in the ophiuroid Ophiura sarsii vadicola Genome Biol. (IF 10.1) Pub Date : 2025-03-31 Qin-Zeng Xu, Yi-Xuan Li, Wen-Ge Shi, Yue Dong, Zhong Li, Jack Chi-Ho Ip, Matthew P. Galaska, Chen Han, Qian Zhang, Yu-Yao Sun, Lin-Lin Zhao, Kai-Ming Sun, Zong-Ling Wang, Jian-Wen Qiu, Xue-Lei Zhang
Ophiuroids, belonging to Ophiuroidea in Echinodermata, possess remarkable regenerative capacities in their arms, relying on cellular recruitment and de-differentiation. However, limited high-quality genomic resources have hindered the investigation of the underlying molecular mechanisms of ophiuroid regeneration. Here, we report a chromosome-level genome of Ophiura sarsii vadicola, 259.28 Mbp in length
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Genotype inference from aggregated chromatin accessibility data reveals genetic regulatory mechanisms Genome Biol. (IF 10.1) Pub Date : 2025-03-30 Brandon M. Wenz, Yuan He, Nae-Chyun Chen, Joseph K. Pickrell, Jeremiah H. Li, Max F. Dudek, Taibo Li, Rebecca Keener, Benjamin F. Voight, Christopher D. Brown, Alexis Battle
Understanding the genetic causes underlying variability in chromatin accessibility can shed light on the molecular mechanisms through which genetic variants may affect complex traits. Thousands of ATAC-seq samples have been collected that hold information about chromatin accessibility across diverse cell types and contexts, but most of these are not paired with genetic information and come from distinct
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SOAPy: a Python package to dissect spatial architecture, dynamics, and communication Genome Biol. (IF 10.1) Pub Date : 2025-03-29 Heqi Wang, Jiarong Li, Siyu Jing, Ping Lin, Yiling Qiu, Xi Yan, Jiao Yuan, ZhiXuan Tang, Yu Li, Haibing Zhang, Yujie Chen, Zhen Wang, Hong Li
Advances in spatial omics enable deeper insights into tissue microenvironments while posing computational challenges. Therefore, we developed SOAPy, a comprehensive tool for analyzing spatial omics data, which offers methods for spatial domain identification, spatial expression tendency, spatiotemporal expression pattern, cellular co-localization, multi-cellular niches, cell–cell communication, and
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MACAW: a method for semi-automatic detection of errors in genome-scale metabolic models Genome Biol. (IF 10.1) Pub Date : 2025-03-28 Devlin C. Moyer, Justin Reimertz, Daniel Segrè, Juan I. Fuxman Bass
Genome-scale metabolic models (GSMMs) are used to predict metabolic fluxes, with applications ranging from identifying novel drug targets to engineering microbial metabolism. Erroneous or missing reactions, scattered throughout densely interconnected networks, are a limiting factor in these applications. We present Metabolic Accuracy Check and Analysis Workflow (MACAW), a suite of algorithms that helps
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Publisher Correction: The haplotype-resolved genome assembly of an ancient citrus variety provides insights into the domestication history and fruit trait formation of loose-skin mandarins Genome Biol. (IF 10.1) Pub Date : 2025-03-28 Minqiang Yin, Xiaochan Song, Chao He, Xiyuan Li, Mengyuan Li, Jiangbo Li, Hao Wu, Chuanwu Chen, Li Zhang, Zhenmei Cai, Liqing Lu, Yanhui Xu, Xin Wang, Hualin Yi, Juxun Wu
Correction: Genome Biol 26, 61 (2025) https://doi.org/10.1186/s13059-025–03535-4 Following publication of the original article [1], the authors identified a typesetting error in the PDF version of the article. Figure 2b was erroneously missing content. The incorrect Fig. 2 is as follows: The correct Fig. 2 is as follows: The original article [1] has been corrected. Yin M, Song X, He C, et al. The haplotype-resolved
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Benchmarking spatial transcriptomics technologies with the multi-sample SpatialBenchVisium dataset Genome Biol. (IF 10.1) Pub Date : 2025-03-28 Mei R. M. Du, Changqing Wang, Charity W. Law, Daniela Amann-Zalcenstein, Casey J. A. Anttila, Ling Ling, Peter F. Hickey, Callum J. Sargeant, Yunshun Chen, Lisa J. Ioannidis, Pradeep Rajasekhar, Raymond K. H. Yip, Kelly L. Rogers, Diana S. Hansen, Rory Bowden, Matthew E. Ritchie
Spatial transcriptomics allows gene expression to be measured within complex tissue contexts. Among the array of spatial capture technologies available is 10x Genomics’ Visium platform, a popular method which enables transcriptome-wide profiling of tissue sections. Visium offers a range of sample handling and library construction methods which introduces a need for benchmarking to compare data quality
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DEMINERS enables clinical metagenomics and comparative transcriptomic analysis by increasing throughput and accuracy of nanopore direct RNA sequencing Genome Biol. (IF 10.1) Pub Date : 2025-03-28 Junwei Song, Li-an Lin, Chao Tang, Chuan Chen, Qingxin Yang, Dan Zhang, Yuancun Zhao, Han-cheng Wei, Kepan Linghu, Zijie Xu, Tingfeng Chen, Zhifeng He, Defu Liu, Yu Zhong, Weizhen Zhu, Wanqin Zeng, Li Chen, Guiqin Song, Mutian Chen, Juan Jiang, Juan Zhou, Jing Wang, Bojiang Chen, Binwu Ying, Yuan Wang, Jia Geng, Jing-wen Lin, Lu Chen
Nanopore direct RNA sequencing (DRS) is a powerful tool for RNA biology but suffers from low basecalling accuracy, low throughput, and high input requirements. We present DEMINERS, a novel DRS toolkit combining an RNA multiplexing workflow, a Random Forest-based barcode classifier, and an optimized convolutional neural network basecaller with species-specific training. DEMINERS enables accurate demultiplexing
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Pamoic acid and carbenoxolone specifically inhibit CRISPR/Cas9 in bacteria, mammalian cells, and mice in a DNA topology-specific manner Genome Biol. (IF 10.1) Pub Date : 2025-03-28 Yuxuan Zhang, Wentao Zou, Yueyang Zhou, Jiaqi Chen, Youtian Hu, Fang Wu
Regulation of the target DNA cleavage activity of CRISPR/Cas has naturally evolved in a few bacteria or bacteriophages but is lacking in higher species. Thus, identification of bioactive agents and mechanisms that can suppress the activity of Cas9 is urgently needed to rebalance this new genetic pressure. Here, we identify four specific inhibitors of Cas9 by screening 4607 compounds that could inhibit
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Survey of gene, lncRNA and transposon transcription patterns in four mouse organs highlights shared and organ-specific sex-biased regulation Genome Biol. (IF 10.1) Pub Date : 2025-03-26 Qinwei Kim-Wee Zhuang, Klara Bauermeister, Jose Hector Galvez, Najla Alogayil, Enkhjin Batdorj, Fernando Pardo Manuel de Villena, Teruko Taketo, Guillaume Bourque, Anna K. Naumova
Sex-biased gene regulation is the basis of sexual dimorphism in phenotypes and has been studied across different cell types and different developmental stages. However, sex-biased expression of transposable elements (TEs), which represent nearly half of the mammalian genome and have the potential of influencing genome integrity and regulation, remains underexplored. We report a survey of gene, lncRNA
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Regulatory and disruptive variants in the CLCN2 gene are associated with modified skin color pattern phenotypes in the corn snake Genome Biol. (IF 10.1) Pub Date : 2025-03-26 Sophie A. Montandon, Pierre Beaudier, Asier Ullate-Agote, Pierre-Yves Helleboid, Maya Kummrow, Sergi Roig-Puiggros, Denis Jabaudon, Leif Andersson, Michel C. Milinkovitch, Athanasia C. Tzika
Snakes exhibit a broad variety of adaptive colors and color patterns, generated by the spatial arrangement of chromatophores, but little is known of the mechanisms responsible for these spectacular traits. Here, we investigate a mono-locus trait with two recessive alleles, motley and stripe, that both cause pattern aberrations in the corn snake. We use mapping-by-sequencing to identify the genomic
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LocusMasterTE: integrating long-read RNA sequencing improves locus-specific quantification of transposable element expression Genome Biol. (IF 10.1) Pub Date : 2025-03-26 Sojung Lee, Jayne A. Barbour, Yee Man Tam, Haocheng Yang, Yuanhua Huang, Jason W. H. Wong
Transposable elements (TEs) can influence human diseases by disrupting genome integrity, yet their quantification has been challenging due to the repetitive nature of these sequences across the genome. We develop LocusMasterTE, a method that integrates long-read with short-read RNA-seq to increase the accuracy of TE expression quantification. By incorporating fractional transcript per million values
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Author Correction: Combining different CRISPR nucleases for simultaneous knock-in and base editing prevents translocations in multiplex-edited CAR T cells Genome Biol. (IF 10.1) Pub Date : 2025-03-26 Viktor Glaser, Christian Flugel, Jonas Kath, Weijie Du, Vanessa Drosdek, Clemens Franke, Maik Stein, Axel Pruß, Michael Schmueck-Henneresse, Hans-Dieter Volk, Petra Reinke, Dimitrios L. Wagner
Correction: Genome Biol 24, 89 (2023) https://doi.org/10.1186/s13059-023–02928-7 Following publication of the original article [1], the authors identified an error in one of the guide RNA spacer sequences disclosed in Supplementary Table S3. The correct sequence for base editing mediated silencing of the CIITA is 5’−3’: CACTCACCTTAGCCTGAGCA, as originally described in Gaudelli et al. 2020 [2]. This
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Clonal expansion dictates the efficacy of mitochondrial lineage tracing in single cells Genome Biol. (IF 10.1) Pub Date : 2025-03-26 Xin Wang, Kun Wang, Weixing Zhang, Zhongjie Tang, Hao Zhang, Yuying Cheng, Da Zhou, Chao Zhang, Wen-Zhao Zhong, Qing Ma, Jin Xu, Zheng Hu
Mitochondrial DNA (mtDNA) variants hold promise as endogenous barcodes for tracking human cell lineages, but their efficacy as reliable lineage markers are hindered by the complex dynamics of mtDNA in somatic tissues. Here, we use computational modeling and single-cell genomics to thoroughly interrogate the origin and clonal dynamics of mtDNA variants across various biological settings. Our findings
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Functional genomic profiling of O-GlcNAc reveals its context-specific interplay with RNA polymerase II Genome Biol. (IF 10.1) Pub Date : 2025-03-24 Sofia Rucli, Nicolas Descostes, Yulia Ermakova, Urvashi Chitnavis, Jeanne Couturier, Ana Boskovic, Matthieu Boulard
How reversible glycosylation of DNA-bound proteins acts on transcription remains scarcely understood. O-linked β-N-acetylglucosamine (O-GlcNAc) is the only known form of glycosylation modifying nuclear proteins, including RNA polymerase II (RNA Pol II) and many transcription factors. Yet, the regulatory function of the O-GlcNAc modification in mammalian chromatin remains unclear. Here, we combine genome-wide
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ASPM mediates nuclear entrapment of FOXM1 via liquid-liquid phase separation to promote progression of hepatocarcinoma Genome Biol. (IF 10.1) Pub Date : 2025-03-23 Xunliang Jiang, Jun Liu, Ke Wang, Jianyong Sun, Huilong Yin, Yu Jiang, Yongkang Liu, Ningbo Wang, Xiaochen Ding, Pu Gao, Lin Li, Xiang Zhang, Jipeng Li, Rui Zhang
Fork-head box protein M1 (FOXM1) plays critical roles in development and progression of multiple cancers, including hepatocellular carcinoma (HCC). However, the exact regulatory hierarchy of FOXM1 remains unclear. Here, a genome-wide screen is performed to identify intranuclear proteins that promote FOXM1 transcription activity via liquid–liquid phase separation (LLPS). Abnormal spindle-like microcephaly
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Dissecting the genetic architecture of key agronomic traits in lettuce using a MAGIC population Genome Biol. (IF 10.1) Pub Date : 2025-03-23 Hongyun Chen, Jiongjiong Chen, Ruifang Zhai, Dean Lavelle, Yue Jia, Qiwei Tang, Ting Zhu, Menglu Wang, Zedong Geng, Jianzhong Zhu, Hui Feng, Junru An, Jiansheng Liu, Weibo Li, Shenzhao Deng, Wandi Wang, Weiyi Zhang, Xiaoyan Zhang, Guangbao Luo, Xin Wang, Sunil Kumar Sahu, Huan Liu, Richard Michelmore, Wanneng Yang, Tong Wei, Hanhui Kuang
Lettuce is a globally important leafy vegetable that exhibits diverse horticultural types and strong population structure, which complicates genetic analyses. To address this challenge, we develop the first multi-parent, advanced generation inter-cross (MAGIC) population for lettuce using 16 diverse founder lines. Whole-genome sequencing of the 16 founder lines and 381 inbred progeny reveal minimal
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aurora: a machine learning gwas tool for analyzing microbial habitat adaptation Genome Biol. (IF 10.1) Pub Date : 2025-03-23 Dalimil Bujdoš, Jens Walter, Paul W. O’Toole
A primary goal of microbial genome-wide association studies is identifying genomic variants associated with a particular habitat. Existing tools fail to identify known causal variants if the analyzed trait shaped the phylogeny. Furthermore, due to inclusion of allochthonous strains or metadata errors, the stated sources of strains in public databases are often incorrect, and strains may not be adapted
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Global profiling of CPL3-mediated alternative splicing reveals regulatory mechanisms of DGK5 in plant immunity and phosphatidic acid homeostasis Genome Biol. (IF 10.1) Pub Date : 2025-03-21 Sung-Il Kim, Xiyu Ma, Liang Kong, Wenbin Guo, Lahong Xu, Libo Shan, Runxuan Zhang, Ping He
Alternative splicing of precursor mRNAs serves as a crucial mechanism to enhance gene expression plasticity for organismal adaptation. However, the precise regulation and function of alternative splicing in plant immune gene regulation remain elusive. Here, by deploying in-depth transcriptome profiling with deep genome coverage coupled with differential expression, differential alternative splicing
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scVAEDer: integrating deep diffusion models and variational autoencoders for single-cell transcriptomics analysis Genome Biol. (IF 10.1) Pub Date : 2025-03-21 Mehrshad Sadria, Anita Layton
Discovering a lower-dimensional embedding of single-cell data can improve downstream analysis. The embedding should encapsulate both the high-level features and low-level variations. While existing generative models attempt to learn such low-dimensional representations, they have limitations. Here, we introduce scVAEDer, a scalable deep-learning model that combines the power of variational autoencoders
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Analysis of 30 chromosome-level Drosophila genome assemblies reveals dynamic evolution of centromeric satellite repeats Genome Biol. (IF 10.1) Pub Date : 2025-03-18 Daniel Gebert, Amir D. Hay, Jennifer P. Hoang, Adam E. Gibbon, Ian R. Henderson, Felipe Karam Teixeira
The Drosophila genus is ideal for studying genome evolution due to its relatively simple chromosome structure and small genome size, with rearrangements mainly restricted to within chromosome arms, such as Muller elements. However, work on the rapidly evolving repetitive genomic regions, composed of transposons and tandem repeats, have been hampered by the lack of genus-wide chromosome-level assemblies
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A special short-wing petal faba genome and genetic dissection of floral and yield-related traits accelerate breeding and improvement of faba bean Genome Biol. (IF 10.1) Pub Date : 2025-03-17 Rong Liu, Chaoqin Hu, Dan Gao, Mengwei Li, Xingxing Yuan, Liyang Chen, Qin Shu, Zonghe Wang, Xin Yang, Zhengming Dai, Haitian Yu, Feng Yang, Aiqing Zheng, Meiyuan Lv, Vanika Garg, Chengzhi Jiao, Hongyan Zhang, Wanwei Hou, Changcai Teng, Xianli Zhou, Chengzhang Du, Chao Xiang, Dongxu Xu, Yongsheng Tang, Annapurna Chitikineni, Yinmei Duan, Fouad Maalouf, Shiv Kumar Agrawal, Libin Wei, Na Zhao, Rutwik
A comprehensive study of the genome and genetics of superior germplasms is fundamental for crop improvement. As a widely adapted protein crop with high yield potential, the improvement in breeding and development of the seeds industry of faba bean have been greatly hindered by its giant genome size and high outcrossing rate. To fully explore the genomic diversity and genetic basis of important agronomic
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The haplotype-resolved genome assembly of an ancient citrus variety provides insights into the domestication history and fruit trait formation of loose-skin mandarins Genome Biol. (IF 10.1) Pub Date : 2025-03-17 Minqiang Yin, Xiaochan Song, Chao He, Xiyuan Li, Mengyuan Li, Jiangbo Li, Hao Wu, Chuanwu Chen, Li Zhang, Zhenmei Cai, Liqing Lu, Yanhui Xu, Xin Wang, Hualin Yi, Juxun Wu
Loose-skin mandarins (LSMs) are among the oldest domesticated horticultural crops, yet their domestication history and the genetic basis underlying the formation of key selected traits remain unclear. We provide a chromosome-scale and haplotype-resolved assembly for the ancient Chinese citrus variety Nanfengmiju tangerine. Through the integration of 77 resequenced and 114 published citrus germplasm
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Widespread impact of transposable elements on the evolution of post-transcriptional regulation in the cotton genus Gossypium Genome Biol. (IF 10.1) Pub Date : 2025-03-17 Xuehan Tian, Ruipeng Wang, Zhenping Liu, Sifan Lu, Xinyuan Chen, Zeyu Zhang, Fang Liu, Hongbin Li, Xianlong Zhang, Maojun Wang
Transposable element (TE) expansion has long been known to mediate genome evolution and phenotypic diversity in organisms, but its impact on the evolution of post-transcriptional regulation following species divergence remains unclear. To address this issue, we perform long-read direct RNA sequencing, polysome profiling sequencing, and small RNA sequencing in the cotton genus Gossypium, the species
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Systematic interrogation of functional genes underlying cholesterol and lipid homeostasis Genome Biol. (IF 10.1) Pub Date : 2025-03-17 Haihuan Shan, Shuangshuang Fan, Quanrun Li, Ruipu Liang, Zhisong Chen, Shengnan Wang, Xiaofeng Wang, Yurong Li, Shuai Chen, Kun Yu, Teng Fei
Dyslipidemia or hypercholesterolemia are among the main risk factors for cardiovascular diseases. Unraveling the molecular basis of lipid or cholesterol homeostasis would help to identify novel drug targets and develop effective therapeutics. Here, we adopt a systematic approach to catalog the genes underlying lipid and cholesterol homeostasis by combinatorial use of high-throughput CRISPR screening
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Exploring and mitigating shortcomings in single-cell differential expression analysis with a new statistical paradigm Genome Biol. (IF 10.1) Pub Date : 2025-03-17 Chih-Hsuan Wu, Xiang Zhou, Mengjie Chen
Differential expression analysis is pivotal in single-cell transcriptomics for unraveling cell-type–specific responses to stimuli. While numerous methods are available to identify differentially expressed genes in single-cell data, recent evaluations of both single-cell–specific methods and methods adapted from bulk studies have revealed significant shortcomings in performance. In this paper, we dissect
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Multi-task benchmarking of spatially resolved gene expression simulation models Genome Biol. (IF 10.1) Pub Date : 2025-03-17 Xiaoqi Liang, Marni Torkel, Yue Cao, Jean Yee Hwa Yang
Computational methods for spatially resolved transcriptomics (SRT) are often developed and assessed using simulated data. The effectiveness of these evaluations relies on the ability of simulation methods to accurately reflect experimental data. However, a systematic evaluation framework for spatial simulators is currently lacking. Here, we present SpatialSimBench, a comprehensive evaluation framework
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A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients Genome Biol. (IF 10.1) Pub Date : 2025-03-14 Yered Pita-Juarez, Dimitra Karagkouni, Nikolaos Kalavros, Johannes C. Melms, Sebastian Niezen, Toni M. Delorey, Adam L. Essene, Olga R. Brook, Deepti Pant, Disha Skelton-Badlani, Pourya Naderi, Pinzhu Huang, Liuliu Pan, Tyler Hether, Tallulah S. Andrews, Carly G. K. Ziegler, Jason Reeves, Andriy Myloserdnyy, Rachel Chen, Andy Nam, Stefan Phelan, Yan Liang, Mark Gregory, Shanshan He, Michael Patrick
The molecular underpinnings of organ dysfunction in severe COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we perform single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identify hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected
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Integrative phenomics, metabolomics and genomics analysis provides new insights for deciphering the genetic basis of metabolism in polished rice Genome Biol. (IF 10.1) Pub Date : 2025-03-12 Hui Feng, Yufei Li, Guoxin Dai, Zhuang Yang, Jingyan Song, Bingjie Lu, Yuan Gao, Yongqi Chen, Jiawei Shi, Luis A. J. Mur, Lejun Yu, Jie Luo, Wanneng Yang
Metabolomics is one of the most widely used omics tools for deciphering the functional networks of the metabolites for crop improvement. However, it is technically demanding and costly. We propose a relatively inexpensive approach for metabolomics analysis in which metabolomics is combined with hyperspectral imaging via machine learning. This approach can be used to target important steps in flavonoid
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mRNA m6A regulates gene expression via H3K4me3 shift in 5’ UTR Genome Biol. (IF 10.1) Pub Date : 2025-03-12 Yuna Yang, Yuqing Huang, Tian Wang, Song Li, Jiafu Jiang, Sumei Chen, Fadi Chen, Likai Wang
N6-methyladenosine (m6A) is a prevalent and conserved RNA modification in eukaryotes. While its roles in the 3’ untranslated regions (3’ UTR) are well-studied, its role in the 5' UTR and its relationship with histone modifications remain underexplored. We demonstrate that m6A methylation in the 5’ UTR of mRNA triggers a downstream shift in H3K4me3 modification. This regulatory mechanism is conserved
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Recruitment and rejoining of remote double-strand DNA breaks for enhanced and precise chromosome editing Genome Biol. (IF 10.1) Pub Date : 2025-03-11 Mingyao Wang, Pengchong Fu, Ziheng Chen, Xiangnan Wang, Hanhui Ma, Xuedi Zhang, Guanjun Gao
Chromosomal rearrangements, such as translocations, deletions, and inversions, underlie numerous genetic diseases and cancers, yet precise engineering of these rearrangements remains challenging. Here, we present a CRISPR-based homologous recombination-mediated rearrangement (HRMR) strategy that leverages homologous donor templates to align and repair broken chromosome ends. HRMR improves efficiency
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Single-cell RNA-seq data have prevalent blood contamination but can be rescued by Originator, a computational tool separating single-cell RNA-seq by genetic and contextual information Genome Biol. (IF 10.1) Pub Date : 2025-03-11 Thatchayut Unjitwattana, Qianhui Huang, Yiwen Yang, Leyang Tao, Youqi Yang, Mengtian Zhou, Yuheng Du, Lana X. Garmire
Single-cell RNA sequencing (scRNA-seq) data from complex human tissues have prevalent blood cell contamination during the sample preparation process. They may also comprise cells of different genetic makeups. We propose a new computational framework, Originator, which deciphers single cells by genetic origin and separates immune cells of blood contamination from those of expected tissue-resident cells
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Precise engineering of gene expression by editing plasticity Genome Biol. (IF 10.1) Pub Date : 2025-03-10 Yang Qiu, Lifen Liu, Jiali Yan, Xianglei Xiang, Shouzhe Wang, Yun Luo, Kaixuan Deng, Jieting Xu, Minliang Jin, Xiaoyu Wu, Liwei Cheng, Ying Zhou, Weibo Xie, Hai-Jun Liu, Alisdair R. Fernie, Xuehai Hu, Jianbing Yan
Identifying transcriptional cis-regulatory elements (CREs) and understanding their role in gene expression are essential for the precise manipulation of gene expression and associated phenotypes. This knowledge is fundamental for advancing genetic engineering and improving crop traits. We here demonstrate that CREs can be accurately predicted and utilized to precisely regulate gene expression beyond
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Trans-ancestral rare variant association study with machine learning-based phenotyping for metabolic dysfunction-associated steatotic liver disease Genome Biol. (IF 10.1) Pub Date : 2025-03-10 Robert Chen, Ben Omega Petrazzini, Áine Duffy, Ghislain Rocheleau, Daniel Jordan, Meena Bansal, Ron Do
Genome-wide association studies (GWAS) have identified common variants associated with metabolic dysfunction-associated steatotic liver disease (MASLD). However, rare coding variant studies have been limited by phenotyping challenges and small sample sizes. We test associations of rare and ultra-rare coding variants with proton density fat fraction (PDFF) and MASLD case–control status in 736,010 participants
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DAGIP: alleviating cell-free DNA sequencing biases with optimal transport Genome Biol. (IF 10.1) Pub Date : 2025-03-07 Antoine Passemiers, Stefania Tuveri, Tatjana Jatsenko, Adriaan Vanderstichele, Pieter Busschaert, An Coosemans, Dirk Timmerman, Sabine Tejpar, Peter Vandenberghe, Diether Lambrechts, Daniele Raimondi, Joris Robert Vermeesch, Yves Moreau
Cell-free DNA (cfDNA) is a rich source of biomarkers for various pathophysiological conditions. Preanalytical variables, such as the library preparation protocol or sequencing platform, are major confounders of cfDNA analysis. We present DAGIP, a novel data correction method that builds on optimal transport theory and deep learning, which explicitly corrects for the effect of such preanalytical variables
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Ultra-sensitive detection of transposon insertions across multiple families by transposable element display sequencing Genome Biol. (IF 10.1) Pub Date : 2025-03-06 Pol Vendrell-Mir, Basile Leduque, Leandro Quadrana
Mobilization of transposable elements (TEs) can generate large effect mutations. However, due to the difficulty of detecting new TE insertions in genomes and the typically rare occurrence of transposition, the actual rate, distribution, and population dynamics of new insertions remain largely unexplored. We present a TE display sequencing approach that leverages target amplification of TE extremities
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Genome assembly of the maize B chromosome provides insight into its epigenetic characteristics and effects on the host genome Genome Biol. (IF 10.1) Pub Date : 2025-03-06 Qian Liu, Yang Liu, Congyang Yi, Zhi Gao, Zeyan Zhang, Congle Zhu, James A. Birchler, Fangpu Han
B chromosomes contribute to the genetic variation in numerous eukaryotes. Yet their genetic and epigenetic characteristics, as well as their effects on the host genome remain poorly understood. Here, we present a comprehensive genome assembly of diploid maize B73 with two copies of B chromosomes using long-read sequencing. We annotate a total of 1124 high-confidence protein-coding genes and 119,579
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Benchmarking single-cell cross-omics imputation methods for surface protein expression Genome Biol. (IF 10.1) Pub Date : 2025-03-04 Chen-Yang Li, Yong-Jia Hong, Bo Li, Xiao-Fei Zhang
Recent advances in single-cell multimodal omics sequencing have facilitated the simultaneous profiling of transcriptomes and surface proteomes within individual cells, offering insights into cellular functions and heterogeneity. However, the high costs and technical complexity of protocols like CITE-seq and REAP-seq constrain large-scale dataset generation. To overcome this limitation, surface protein
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Decoding subcellular RNA localization one molecule at a time Genome Biol. (IF 10.1) Pub Date : 2025-03-03 Josep Biayna, Gabrijela Dumbović
Eukaryotic cells are highly structured and composed of multiple membrane-bound and membraneless organelles. Subcellular RNA localization is a critical regulator of RNA function, influencing various biological processes. At any given moment, RNAs must accurately navigate the three-dimensional subcellular environment to ensure proper localization and function, governed by numerous factors, including
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CTCF is selectively required for maintaining chromatin accessibility and gene expression in human erythropoiesis Genome Biol. (IF 10.1) Pub Date : 2025-02-28 Xue Yang, Li Cheng, Ye Xin, Jianxiang Zhang, Xinfeng Chen, Jinchao Xu, Mengli Zhang, Ruopeng Feng, Judith Hyle, Wenjie Qi, Wojciech Rosikiewicz, Beisi Xu, Chunliang Li, Peng Xu
CTCF is considered as the most essential transcription factor regulating chromatin architecture and gene expression. However, genome-wide impact of CTCF on erythropoiesis has not been extensively investigated. Using a state-of-the-art human erythroid progenitor cell model (HUDEP-2 and HEL cell lines), we systematically investigate the effects of acute CTCF loss by an auxin-inducible degron system on
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Admixture as a source for HLA variation in Neolithic European farming communities Genome Biol. (IF 10.1) Pub Date : 2025-02-28 Nicolas Antonio da Silva, Onur Özer, Magdalena Haller-Caskie, Yan-Rong Chen, Daniel Kolbe, Sabine Schade-Lindig, Joachim Wahl, Carola Berszin, Michael Francken, Irina Görner, Kerstin Schierhold, Joachim Pechtl, Gisela Grupe, Christoph Rinne, Johannes Müller, Tobias L. Lenz, Almut Nebel, Ben Krause-Kyora
The northern European Neolithic is characterized by two major demographic events: immigration of early farmers from Anatolia at 7500 years before present, and their admixture with local western hunter-gatherers forming late farmers, from around 6200 years before present. The influence of this admixture event on variation in the immune-relevant human leukocyte antigen (HLA) region is understudied. We
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PRODE recovers essential and context-essential genes through neighborhood-informed scores Genome Biol. (IF 10.1) Pub Date : 2025-02-28 Thomas Cantore, Paola Gasperini, Riccardo Bevilacqua, Yari Ciani, Sanju Sinha, Eytan Ruppin, Francesca Demichelis
Gene context-essentiality assessment supports precision oncology opportunities. The variability of gene effects inference from loss-of-function screenings across models and technologies limits identifying robust hits. We propose a computational framework named PRODE that integrates gene effects with protein–protein interactions to generate neighborhood-informed essential (NIE) and neighborhood-informed
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Genome-wide CRISPR guide RNA design and specificity analysis with GuideScan2 Genome Biol. (IF 10.1) Pub Date : 2025-02-26 Henri Schmidt, Minsi Zhang, Dimitar Chakarov, Vineet Bansal, Haralambos Mourelatos, Francisco J. Sánchez-Rivera, Scott W. Lowe, Andrea Ventura, Christina S. Leslie, Yuri Pritykin
We present GuideScan2 for memory-efficient, parallelizable construction of high-specificity CRISPR guide RNA (gRNA) databases and user-friendly design and analysis of individual gRNAs and gRNA libraries for targeting coding and non-coding regions in custom genomes. GuideScan2 analysis identifies widespread confounding effects of low-specificity gRNAs in published CRISPR screens and enables construction