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N6-methyladenosine writer METTL16-mediated alternative splicing and translation control are essential for murine spermatogenesis Genome Biol. (IF 10.1) Pub Date : 2024-07-19 Qian Ma, Yiqian Gui, Xixiang Ma, Bingqian Zhang, Wenjing Xiong, Shiyu Yang, Congcong Cao, Shaomei Mo, Ge Shu, Jing Ye, Kuan Liu, Xiaoli Wang, Yaoting Gui, Fengli Wang, Shuiqiao Yuan
The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive. We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional
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A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data Genome Biol. (IF 10.1) Pub Date : 2024-07-19 Alessandro Vinceti, Raffaele M. Iannuzzi, Isabella Boyle, Lucia Trastulla, Catarina D. Campbell, Francisca Vazquez, Joshua M. Dempster, Francesco Iorio
CRISPR-Cas9 dropout screens are formidable tools for investigating biology with unprecedented precision and scale. However, biases in data lead to potential confounding effects on interpretation and compromise overall quality. The activity of Cas9 is influenced by structural features of the target site, including copy number amplifications (CN bias). More worryingly, proximal targeted loci tend to
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Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers Genome Biol. (IF 10.1) Pub Date : 2024-07-18 Farhia Kabeer, Hoa Tran, Mirela Andronescu, Gurdeep Singh, Hakwoo Lee, Sohrab Salehi, Beixi Wang, Justina Biele, Jazmine Brimhall, David Gee, Viviana Cerda, Ciara O’Flanagan, Teresa Algara, Takako Kono, Sean Beatty, Elena Zaikova, Daniel Lai, Eric Lee, Richard Moore, Andrew J. Mungall, Marc J. Williams, Andrew Roth, Kieran R. Campbell, Sohrab P. Shah, Samuel Aparicio
The encoding of cell intrinsic drug resistance states in breast cancer reflects the contributions of genomic and non-genomic variations and requires accurate estimation of clonal fitness from co-measurement of transcriptomic and genomic data. Somatic copy number (CN) variation is the dominant mutational mechanism leading to transcriptional variation and notably contributes to platinum chemotherapy
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Non-coding variants impact cis-regulatory coordination in a cell type-specific manner Genome Biol. (IF 10.1) Pub Date : 2024-07-18 Olga Pushkarev, Guido van Mierlo, Judith Franziska Kribelbauer, Wouter Saelens, Vincent Gardeux, Bart Deplancke
Interactions among cis-regulatory elements (CREs) play a crucial role in gene regulation. Various approaches have been developed to map these interactions genome-wide, including those relying on interindividual epigenomic variation to identify groups of covariable regulatory elements, referred to as chromatin modules (CMs). While CM mapping allows to investigate the relationship between chromatin modularity
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Leveraging neighborhood representations of single-cell data to achieve sensitive DE testing with miloDE Genome Biol. (IF 10.1) Pub Date : 2024-07-18 Alsu Missarova, Emma Dann, Leah Rosen, Rahul Satija, John Marioni
Single-cell RNA-sequencing enables testing for differential expression (DE) between conditions at a cell type level. While powerful, one of the limitations of such approaches is that the sensitivity of DE testing is dictated by the sensitivity of clustering, which is often suboptimal. To overcome this, we present miloDE—a cluster-free framework for DE testing (available as an open-source R package)
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Comprehensive and deep evaluation of structural variation detection pipelines with third-generation sequencing data Genome Biol. (IF 10.1) Pub Date : 2024-07-15 Zhi Liu, Zhi Xie, Miaoxin Li
Structural variation (SV) detection methods using third-generation sequencing data are widely employed, yet accurately detecting SVs remains challenging. Different methods often yield inconsistent results for certain SV types, complicating tool selection and revealing biases in detection. This study comprehensively evaluates 53 SV detection pipelines using simulated and real data from PacBio (CLR:
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Systemic interindividual DNA methylation variants in cattle share major hallmarks with those in humans Genome Biol. (IF 10.1) Pub Date : 2024-07-15 Wen-Jou Chang, Maria S. Baker, Eleonora Laritsky, Chathura J. Gunasekara, Uditha Maduranga, Justine C. Galliou, Joseph W. McFadden, Jessica R. Waltemyer, Bruce Berggren-Thomas, Brianna N. Tate, Hanxue Zhang, Benjamin D. Rosen, Curtis P. Van Tassell, George E. Liu, Cristian Coarfa, Yi Athena Ren, Robert A. Waterland
We recently identified ~ 10,000 correlated regions of systemic interindividual epigenetic variation (CoRSIVs) in the human genome. These methylation variants are amenable to population studies, as DNA methylation measurements in blood provide information on epigenetic regulation throughout the body. Moreover, establishment of DNA methylation at human CoRSIVs is labile to periconceptional influences
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TFscope: systematic analysis of the sequence features involved in the binding preferences of transcription factors Genome Biol. (IF 10.1) Pub Date : 2024-07-10 Raphaël Romero, Christophe Menichelli, Christophe Vroland, Jean-Michel Marin, Sophie Lèbre, Charles-Henri Lecellier, Laurent Bréhélin
Characterizing the binding preferences of transcription factors (TFs) in different cell types and conditions is key to understand how they orchestrate gene expression. Here, we develop TFscope, a machine learning approach that identifies sequence features explaining the binding differences observed between two ChIP-seq experiments targeting either the same TF in two conditions or two TFs with similar
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sciMET-cap: high-throughput single-cell methylation analysis with a reduced sequencing burden Genome Biol. (IF 10.1) Pub Date : 2024-07-10 Sonia N. Acharya, Ruth V. Nichols, Lauren E. Rylaarsdam, Brendan L. O’Connell, Theodore P. Braun, Andrew C. Adey
DNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature of DNA methylation results in a high sequencing burden per cell. Here, we leverage target enrichment with sciMET to capture sufficient information per
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The contribution of silencer variants to human diseases Genome Biol. (IF 10.1) Pub Date : 2024-07-08 Di Huang, Ivan Ovcharenko
Although disease-causal genetic variants have been found within silencer sequences, we still lack a comprehensive analysis of the association of silencers with diseases. Here, we profiled GWAS variants in 2.8 million candidate silencers across 97 human samples derived from a diverse panel of tissues and developmental time points, using deep learning models. We show that candidate silencers exhibit
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Massively integrated coexpression analysis reveals transcriptional regulation, evolution and cellular implications of the yeast noncanonical translatome Genome Biol. (IF 10.1) Pub Date : 2024-07-08 April Rich, Omer Acar, Anne-Ruxandra Carvunis
Recent studies uncovered pervasive transcription and translation of thousands of noncanonical open reading frames (nORFs) outside of annotated genes. The contribution of nORFs to cellular phenotypes is difficult to infer using conventional approaches because nORFs tend to be short, of recent de novo origins, and lowly expressed. Here we develop a dedicated coexpression analysis framework that accounts
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Author Correction: CelFiE-ISH: a probabilistic model for multi-cell type deconvolution from single-molecule DNA methylation haplotypes Genome Biol. (IF 10.1) Pub Date : 2024-07-08 Irene Unterman, Dana Avrahami, Efrat Katsman, Timothy J. Triche, Benjamin Glaser, Benjamin P. Berman
Correction: Genome Biol 25, 151 (2024) https://doi.org/10.1186/s13059-024-03275-x Following publication of the original article [1], the authors identified an error in the author name of Timothy J. Triche Jr. The given name and family name were erroneously transposed. The incorrect author name is: Triche Tim Jr. The correct author name is: Timothy J. Triche Jr. The author group has been updated above
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Panpipes: a pipeline for multiomic single-cell and spatial transcriptomic data analysis Genome Biol. (IF 10.1) Pub Date : 2024-07-08 Fabiola Curion, Charlotte Rich-Griffin, Devika Agarwal, Sarah Ouologuem, Kevin Rue-Albrecht, Lilly May, Giulia E. L. Garcia, Lukas Heumos, Tom Thomas, Wojciech Lason, David Sims, Fabian J. Theis, Calliope A. Dendrou
Single-cell multiomic analysis of the epigenome, transcriptome, and proteome allows for comprehensive characterization of the molecular circuitry that underpins cell identity and state. However, the holistic interpretation of such datasets presents a challenge given a paucity of approaches for systematic, joint evaluation of different modalities. Here, we present Panpipes, a set of computational workflows
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Detection of allele-specific expression in spatial transcriptomics with spASE Genome Biol. (IF 10.1) Pub Date : 2024-07-08 Luli S. Zou, Dylan M. Cable, Irving A. Barrera-Lopez, Tongtong Zhao, Evan Murray, Martin J. Aryee, Fei Chen, Rafael A. Irizarry
Spatial transcriptomics technologies permit the study of the spatial distribution of RNA at near-single-cell resolution genome-wide. However, the feasibility of studying spatial allele-specific expression (ASE) from these data remains uncharacterized. Here, we introduce spASE, a computational framework for detecting and estimating spatial ASE. To tackle the challenges presented by cell type mixtures
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TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA Genome Biol. (IF 10.1) Pub Date : 2024-07-07 Chong Xu, Jiyanuo Cao, Huanran Qiang, Yu Liu, Jialin Wu, Qiudan Luo, Meng Wan, Yujie Wang, Peiliang Wang, Qian Cheng, Guohua Zhou, Jian Sima, Yongjian Guo, Shu Xu
Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer’s disease model, we demonstrate
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Author Correction: The shaky foundations of simulating single-cell RNA sequencing data Genome Biol. (IF 10.1) Pub Date : 2024-07-05 Helena L. Crowell, Sarah X. Morillo Leonardo, Charlotte Soneson, Mark D. Robinson
Correction: Genome Biol 24, 62 (2023) https://doi.org/10.1186/s13059-023-02904-1 Following publication of the original article [1], it was pointed out that the legend to Table 1 did not match the content of the table. The incorrect Table 1 is as follows: Table 1 Overview of scRNA-seq simulators compared in this study. Methods are ordered alphabetically and annotated according to their (in)ability to
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VirRep: a hybrid language representation learning framework for identifying viruses from human gut metagenomes Genome Biol. (IF 10.1) Pub Date : 2024-07-04 Yanqi Dong, Wei-Hua Chen, Xing-Ming Zhao
Identifying viruses from metagenomes is a common step to explore the virus composition in the human gut. Here, we introduce VirRep, a hybrid language representation learning framework, for identifying viruses from human gut metagenomes. VirRep combines a context-aware encoder and an evolution-aware encoder to improve sequence representation by incorporating k-mer patterns and sequence homologies. Benchmarking
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LongTR: genome-wide profiling of genetic variation at tandem repeats from long reads Genome Biol. (IF 10.1) Pub Date : 2024-07-04 Helyaneh Ziaei Jam, Justin M. Zook, Sara Javadzadeh, Jonghun Park, Aarushi Sehgal, Melissa Gymrek
Tandem repeats are frequent across the human genome, and variation in repeat length has been linked to a variety of traits. Recent improvements in long read sequencing technologies have the potential to greatly improve tandem repeat analysis, especially for long or complex repeats. Here, we introduce LongTR, which accurately genotypes tandem repeats from high-fidelity long reads available from both
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SETDB1 regulates short interspersed nuclear elements and chromatin loop organization in mouse neural precursor cells Genome Biol. (IF 10.1) Pub Date : 2024-07-03 Daijing Sun, Yueyan Zhu, Wenzhu Peng, Shenghui Zheng, Jie Weng, Shulong Dong, Jiaqi Li, Qi Chen, Chuanhui Ge, Liyong Liao, Yuhao Dong, Yun Liu, Weida Meng, Yan Jiang
Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain
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Gut microbiota DPP4-like enzymes are increased in type-2 diabetes and contribute to incretin inactivation Genome Biol. (IF 10.1) Pub Date : 2024-07-03 Marta Olivares, Paula Hernández-Calderón, Sonia Cárdenas-Brito, Rebeca Liébana-García, Yolanda Sanz, Alfonso Benítez-Páez
The gut microbiota controls broad aspects of human metabolism and feeding behavior, but the basis for this control remains largely unclear. Given the key role of human dipeptidyl peptidase 4 (DPP4) in host metabolism, we investigate whether microbiota DPP4-like counterparts perform the same function. We identify novel functional homologs of human DPP4 in several bacterial species inhabiting the human
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Detecting haplotype-specific transcript variation in long reads with FLAIR2 Genome Biol. (IF 10.1) Pub Date : 2024-07-02 Alison D. Tang, Colette Felton, Eva Hrabeta-Robinson, Roger Volden, Christopher Vollmers, Angela N. Brooks
RNA-seq has brought forth significant discoveries regarding aberrations in RNA processing, implicating these RNA variants in a variety of diseases. Aberrant splicing and single nucleotide variants (SNVs) in RNA have been demonstrated to alter transcript stability, localization, and function. In particular, the upregulation of ADAR, an enzyme that mediates adenosine-to-inosine editing, has been previously
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Benchmarking computational variant effect predictors by their ability to infer human traits Genome Biol. (IF 10.1) Pub Date : 2024-07-01 Daniel R. Tabet, Da Kuang, Megan C. Lancaster, Roujia Li, Karen Liu, Jochen Weile, Atina G. Coté, Yingzhou Wu, Robert A. Hegele, Dan M. Roden, Frederick P. Roth
Computational variant effect predictors offer a scalable and increasingly reliable means of interpreting human genetic variation, but concerns of circularity and bias have limited previous methods for evaluating and comparing predictors. Population-level cohorts of genotyped and phenotyped participants that have not been used in predictor training can facilitate an unbiased benchmarking of available
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Tagging large CNV blocks in wheat boosts digitalization of germplasm resources by ultra-low-coverage sequencing Genome Biol. (IF 10.1) Pub Date : 2024-07-01 Jianxia Niu, Wenxi Wang, Zihao Wang, Zhe Chen, Xiaoyu Zhang, Zhen Qin, Lingfeng Miao, Zhengzhao Yang, Chaojie Xie, Mingming Xin, Huiru Peng, Yingyin Yao, Jie Liu, Zhongfu Ni, Qixin Sun, Weilong Guo
The massive structural variations and frequent introgression highly contribute to the genetic diversity of wheat, while the huge and complex genome of polyploid wheat hinders efficient genotyping of abundant varieties towards accurate identification, management, and exploitation of germplasm resources. We develop a novel workflow that identifies 1240 high-quality large copy number variation blocks
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RIBAP: a comprehensive bacterial core genome annotation pipeline for pangenome calculation beyond the species level Genome Biol. (IF 10.1) Pub Date : 2024-07-01 Kevin Lamkiewicz, Lisa-Marie Barf, Konrad Sachse, Martin Hölzer
Microbial pangenome analysis identifies present or absent genes in prokaryotic genomes. However, current tools are limited when analyzing species with higher sequence diversity or higher taxonomic orders such as genera or families. The Roary ILP Bacterial core Annotation Pipeline (RIBAP) uses an integer linear programming approach to refine gene clusters predicted by Roary for identifying core genes
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Heterogeneous pseudobulk simulation enables realistic benchmarking of cell-type deconvolution methods Genome Biol. (IF 10.1) Pub Date : 2024-07-01 Mengying Hu, Maria Chikina
Computational cell type deconvolution enables the estimation of cell type abundance from bulk tissues and is important for understanding tissue microenviroment, especially in tumor tissues. With rapid development of deconvolution methods, many benchmarking studies have been published aiming for a comprehensive evaluation for these methods. Benchmarking studies rely on cell-type resolved single-cell
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Immune evasion impacts the landscape of driver genes during cancer evolution Genome Biol. (IF 10.1) Pub Date : 2024-06-26 Lucie Gourmet, Andrea Sottoriva, Simon Walker-Samuel, Maria Secrier, Luis Zapata
Carcinogenesis is driven by interactions between genetic mutations and the local tumor microenvironment. Recent research has identified hundreds of cancer driver genes; however, these studies often include a mixture of different molecular subtypes and ecological niches and ignore the impact of the immune system. In this study, we compare the landscape of driver genes in tumors that escaped the immune
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Resolving intra-repeat variation in medically relevant VNTRs from short-read sequencing data using the cardiovascular risk gene LPA as a model Genome Biol. (IF 10.1) Pub Date : 2024-06-26 Silvia Di Maio, Peter Zöscher, Hansi Weissensteiner, Lukas Forer, Johanna F. Schachtl-Riess, Stephan Amstler, Gertraud Streiter, Cathrin Pfurtscheller, Bernhard Paulweber, Florian Kronenberg, Stefan Coassin, Sebastian Schönherr
Variable number tandem repeats (VNTRs) are highly polymorphic DNA regions harboring many potentially disease-causing variants. However, VNTRs often appear unresolved (“dark”) in variation databases due to their repetitive nature. One particularly complex and medically relevant VNTR is the KIV-2 VNTR located in the cardiovascular disease gene LPA which encompasses up to 70% of the coding sequence. Using
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Splice_sim: a nucleotide conversion-enabled RNA-seq simulation and evaluation framework Genome Biol. (IF 10.1) Pub Date : 2024-06-25 Niko Popitsch, Tobias Neumann, Arndt von Haeseler, Stefan L. Ameres
Nucleotide conversion RNA sequencing techniques interrogate chemical RNA modifications in cellular transcripts, resulting in mismatch-containing reads. Biases in mapping the resulting reads to reference genomes remain poorly understood. We present splice_sim, a splice-aware RNA-seq simulation and evaluation pipeline that introduces user-defined nucleotide conversions at set frequencies, creates mixture
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A feedback loop driven by H3K9 lactylation and HDAC2 in endothelial cells regulates VEGF-induced angiogenesis Genome Biol. (IF 10.1) Pub Date : 2024-06-25 Wei Fan, Shuhao Zeng, Xiaotang Wang, Guoqing Wang, Dan Liao, Ruonan Li, Siyuan He, Wanqian Li, Jiaxing Huang, Xingran Li, Jiangyi Liu, Na Li, Shengping Hou
Vascular endothelial growth factor (VEGF) is one of the most powerful proangiogenic factors and plays an important role in multiple diseases. Increased glycolytic rates and lactate accumulation are associated with pathological angiogenesis. Here, we show that a feedback loop between H3K9 lactylation (H3K9la) and histone deacetylase 2 (HDAC2) in endothelial cells drives VEGF-induced angiogenesis. We
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scHolography: a computational method for single-cell spatial neighborhood reconstruction and analysis Genome Biol. (IF 10.1) Pub Date : 2024-06-24 Yuheng C. Fu, Arpan Das, Dongmei Wang, Rosemary Braun, Rui Yi
Spatial transcriptomics has transformed our ability to study tissue complexity. However, it remains challenging to accurately dissect tissue organization at single-cell resolution. Here we introduce scHolography, a machine learning-based method designed to reconstruct single-cell spatial neighborhoods and facilitate 3D tissue visualization using spatial and single-cell RNA sequencing data. scHolography
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Evaluation of somatic copy number variation detection by NGS technologies and bioinformatics tools on a hyper-diploid cancer genome Genome Biol. (IF 10.1) Pub Date : 2024-06-20 Daniall Masood, Luyao Ren, Cu Nguyen, Francesco G. Brundu, Lily Zheng, Yongmei Zhao, Erich Jaeger, Yong Li, Seong Won Cha, Aaron Halpern, Sean Truong, Michael Virata, Chunhua Yan, Qingrong Chen, Andy Pang, Reyes Alberto, Chunlin Xiao, Zhaowei Yang, Wanqiu Chen, Charles Wang, Frank Cross, Severine Catreux, Leming Shi, Julia A. Beaver, Wenming Xiao, Daoud M. Meerzaman
Copy number variation (CNV) is a key genetic characteristic for cancer diagnostics and can be used as a biomarker for the selection of therapeutic treatments. Using data sets established in our previous study, we benchmark the performance of cancer CNV calling by six most recent and commonly used software tools on their detection accuracy, sensitivity, and reproducibility. In comparison to other orthogonal
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Alternative splicing coupled to nonsense-mediated decay coordinates downregulation of non-neuronal genes in developing mouse neurons Genome Biol. (IF 10.1) Pub Date : 2024-06-20 Anna Zhuravskaya, Karen Yap, Fursham Hamid, Eugene V. Makeyev
The functional coupling between alternative pre-mRNA splicing (AS) and the mRNA quality control mechanism called nonsense-mediated decay (NMD) can modulate transcript abundance. Previous studies have identified several examples of such a regulation in developing neurons. However, the systems-level effects of AS-NMD in this context are poorly understood. We developed an R package, factR2, which offers
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An integrated single-cell RNA-seq map of human neuroblastoma tumors and preclinical models uncovers divergent mesenchymal-like gene expression programs Genome Biol. (IF 10.1) Pub Date : 2024-06-19 Richard H. Chapple, Xueying Liu, Sivaraman Natarajan, Margaret I. M. Alexander, Yuna Kim, Anand G. Patel, Christy W. LaFlamme, Min Pan, William C. Wright, Hyeong-Min Lee, Yinwen Zhang, Meifen Lu, Selene C. Koo, Courtney Long, John Harper, Chandra Savage, Melissa D. Johnson, Thomas Confer, Walter J. Akers, Michael A. Dyer, Heather Sheppard, John Easton, Paul Geeleher
Neuroblastoma is a common pediatric cancer, where preclinical studies suggest that a mesenchymal-like gene expression program contributes to chemotherapy resistance. However, clinical outcomes remain poor, implying we need a better understanding of the relationship between patient tumor heterogeneity and preclinical models. Here, we generate single-cell RNA-seq maps of neuroblastoma cell lines, patient-derived
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Author Correction: Legal aspects of privacy-enhancing technologies in genome-wide association studies and their impact on performance and feasibility Genome Biol. (IF 10.1) Pub Date : 2024-06-18 Alissa Brauneck, Louisa Schmalhorst, Stefan Weiss, Linda Baumbach, Uwe Völker, David Ellinghaus, Jan Baumbach, Gabriele Buchholtz
Correction: Genome Biol 25, 154 (2024) https://doi.org/10.1186/s13059-024-03296-6 Following publication of the original article [1], the authors reported an error in the second equal contribution statement of their article. David Ellinghaus, Jan Baumbach and Gabriele Buchholtz are shared last authors. David Ellinghaus was erroneously omitted from this statement. The original article [1] has been corrected
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Beyond benchmarking and towards predictive models of dataset-specific single-cell RNA-seq pipeline performance Genome Biol. (IF 10.1) Pub Date : 2024-06-17 Cindy Fang, Alina Selega, Kieran R. Campbell
The advent of single-cell RNA-sequencing (scRNA-seq) has driven significant computational methods development for all steps in the scRNA-seq data analysis pipeline, including filtering, normalization, and clustering. The large number of methods and their resulting parameter combinations has created a combinatorial set of possible pipelines to analyze scRNA-seq data, which leads to the obvious question:
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DNA methylation variations underlie lettuce domestication and divergence Genome Biol. (IF 10.1) Pub Date : 2024-06-17 Shuai Cao, Nunchanoke Sawettalake, Ping Li, Sheng Fan, Lisha Shen
Lettuce (Lactuca sativa L.) is an economically important vegetable crop worldwide. Lettuce is believed to be domesticated from a single wild ancestor Lactuca serriola and subsequently diverged into two major morphologically distinct vegetable types: leafy lettuce and stem lettuce. However, the role of epigenetic variation in lettuce domestication and divergence remains largely unknown. To understand
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LABS: linear amplification-based bisulfite sequencing for ultrasensitive cancer detection from cell-free DNA Genome Biol. (IF 10.1) Pub Date : 2024-06-14 Xiao-Long Cui, Ji Nie, Houxiang Zhu, Krissana Kowitwanich, Alana V. Beadell, Diana C. West-Szymanski, Zhou Zhang, Urszula Dougherty, Akushika Kwesi, Zifeng Deng, Yan Li, Danqing Meng, Kevin Roggin, Teresa Barry, Ryan Owyang, Ben Fefferman, Chang Zeng, Lu Gao, Carolyn W. T. Zhao, Yuri Malina, Jiangbo Wei, Melanie Weigert, Wenjun Kang, Ajay Goel, Brian C.-H. Chiu, Marc Bissonnette, Wei Zhang, Mengjie
Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here, we report linear amplification-based
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CpG island turnover events predict evolutionary changes in enhancer activity Genome Biol. (IF 10.1) Pub Date : 2024-06-13 Acadia A. Kocher, Emily V. Dutrow, Severin Uebbing, Kristina M. Yim, María F. Rosales Larios, Marybeth Baumgartner, Timothy Nottoli, James P. Noonan
Genetic changes that modify the function of transcriptional enhancers have been linked to the evolution of biological diversity across species. Multiple studies have focused on the role of nucleotide substitutions, transposition, and insertions and deletions in altering enhancer function. CpG islands (CGIs) have recently been shown to influence enhancer activity, and here we test how their turnover
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Leaf: an ultrafast filter for population-scale long-read SV detection Genome Biol. (IF 10.1) Pub Date : 2024-06-13 Chenxu Pan, Knut Reinert
Advances in sequencing technology have facilitated population-scale long-read structural variant (SV) detection. Arguably, one of the main challenges in population-scale analysis is developing effective computational pipelines. Here, we present a new filter-based pipeline for population-scale long-read SV detection. It better captures SV signals at an early stage than conventional assembly-based or
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Legal aspects of privacy-enhancing technologies in genome-wide association studies and their impact on performance and feasibility Genome Biol. (IF 10.1) Pub Date : 2024-06-13 Alissa Brauneck, Louisa Schmalhorst, Stefan Weiss, Linda Baumbach, Uwe Völker, David Ellinghaus, Jan Baumbach, Gabriele Buchholtz
Genomic data holds huge potential for medical progress but requires strict safety measures due to its sensitive nature to comply with data protection laws. This conflict is especially pronounced in genome-wide association studies (GWAS) which rely on vast amounts of genomic data to improve medical diagnoses. To ensure both their benefits and sufficient data security, we propose a federated approach
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Gene count normalization in single-cell imaging-based spatially resolved transcriptomics Genome Biol. (IF 10.1) Pub Date : 2024-06-12 Lyla Atta, Kalen Clifton, Manjari Anant, Gohta Aihara, Jean Fan
Recent advances in imaging-based spatially resolved transcriptomics (im-SRT) technologies now enable high-throughput profiling of targeted genes and their locations in fixed tissues. Normalization of gene expression data is often needed to account for technical factors that may confound underlying biological signals. Here, we investigate the potential impact of different gene count normalization methods
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FoldPAthreader: predicting protein folding pathway using a novel folding force field model derived from known protein universe Genome Biol. (IF 10.1) Pub Date : 2024-06-11 Kailong Zhao, Pengxin Zhao, Suhui Wang, Yuhao Xia, Guijun Zhang
Protein folding has become a tractable problem with the significant advances in deep learning-driven protein structure prediction. Here we propose FoldPAthreader, a protein folding pathway prediction method that uses a novel folding force field model by exploring the intrinsic relationship between protein evolution and folding from the known protein universe. Further, the folding force field is used
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CelFiE-ISH: a probabilistic model for multi-cell type deconvolution from single-molecule DNA methylation haplotypes Genome Biol. (IF 10.1) Pub Date : 2024-06-10 Irene Unterman, Dana Avrahami, Efrat Katsman, Triche Tim Jr., Benjamin Glaser, Benjamin P. Berman
Deconvolution methods infer quantitative cell type estimates from bulk measurement of mixed samples including blood and tissue. DNA methylation sequencing measures multiple CpGs per read, but few existing deconvolution methods leverage this within-read information. We develop CelFiE-ISH, which extends an existing method (CelFiE) to use within-read haplotype information. CelFiE-ISH outperforms CelFiE
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Author Correction: The senescent methylome and its relationship with cancer, ageing and germline genetic variation in humans Genome Biol. (IF 10.1) Pub Date : 2024-06-10 Robert Lowe, Marita G. Overhoff, Sreeram V. Ramagopalan, James C. Garbe, James Koh, Martha R. Stampfer, David H. Beach, Vardhman K. Rakyan, Cleo L. Bishop
Author Correction: Genome Biol 16, 194 (2015) https://doi.org/10.1186/s13059-015-0748-4 Following publication of the original article [1], the authors reported two errors in Fig. 1B and Fig. 2B. 1. The two EP + siGLO and DS + siGLO brightfield/β-gal images from Fig. 2A were accidentally duplicated in Fig. 1B. The images in Fig. 2A are correct. The images in Fig. 1B are replaced with representative
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TMO-Net: an explainable pretrained multi-omics model for multi-task learning in oncology Genome Biol. (IF 10.1) Pub Date : 2024-06-06 Feng-ao Wang, Zhenfeng Zhuang, Feng Gao, Ruikun He, Shaoting Zhang, Liansheng Wang, Junwei Liu, Yixue Li
Cancer is a complex disease composing systemic alterations in multiple scales. In this study, we develop the Tumor Multi-Omics pre-trained Network (TMO-Net) that integrates multi-omics pan-cancer datasets for model pre-training, facilitating cross-omics interactions and enabling joint representation learning and incomplete omics inference. This model enhances multi-omics sample representation and empowers
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Structural variant landscapes reveal convergent signatures of evolution in sheep and goats Genome Biol. (IF 10.1) Pub Date : 2024-06-06 Ji Yang, Dong-Feng Wang, Jia-Hui Huang, Qiang-Hui Zhu, Ling-Yun Luo, Ran Lu, Xing-Long Xie, Hosein Salehian-Dehkordi, Ali Esmailizadeh, George E. Liu, Meng-Hua Li
Sheep and goats have undergone domestication and improvement to produce similar phenotypes, which have been greatly impacted by structural variants (SVs). Here, we report a high-quality chromosome-level reference genome of Asiatic mouflon, and implement a comprehensive analysis of SVs in 897 genomes of worldwide wild and domestic populations of sheep and goats to reveal genetic signatures underlying
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iIMPACT: integrating image and molecular profiles for spatial transcriptomics analysis Genome Biol. (IF 10.1) Pub Date : 2024-06-06 Xi Jiang, Shidan Wang, Lei Guo, Bencong Zhu, Zhuoyu Wen, Liwei Jia, Lin Xu, Guanghua Xiao, Qiwei Li
Current clustering analysis of spatial transcriptomics data primarily relies on molecular information and fails to fully exploit the morphological features present in histology images, leading to compromised accuracy and interpretability. To overcome these limitations, we have developed a multi-stage statistical method called iIMPACT. It identifies and defines histology-based spatial domains based
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DNA methylation patterns of transcription factor binding regions characterize their functional and evolutionary contexts Genome Biol. (IF 10.1) Pub Date : 2024-06-06 Martina Rimoldi, Ning Wang, Jilin Zhang, Diego Villar, Duncan T. Odom, Jussi Taipale, Paul Flicek, Maša Roller
DNA methylation is an important epigenetic modification which has numerous roles in modulating genome function. Its levels are spatially correlated across the genome, typically high in repressed regions but low in transcription factor (TF) binding sites and active regulatory regions. However, the mechanisms establishing genome-wide and TF binding site methylation patterns are still unclear. Here we
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Systematic evaluation with practical guidelines for single-cell and spatially resolved transcriptomics data simulation under multiple scenarios Genome Biol. (IF 10.1) Pub Date : 2024-06-03 Hongrui Duo, Yinghong Li, Yang Lan, Jingxin Tao, Qingxia Yang, Yingxue Xiao, Jing Sun, Lei Li, Xiner Nie, Xiaoxi Zhang, Guizhao Liang, Mingwei Liu, Youjin Hao, Bo Li
Single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (SRT) have led to groundbreaking advancements in life sciences. To develop bioinformatics tools for scRNA-seq and SRT data and perform unbiased benchmarks, data simulation has been widely adopted by providing explicit ground truth and generating customized datasets. However, the performance of simulation methods under multiple
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Predicting gene expression state and prioritizing putative enhancers using 5hmC signal Genome Biol. (IF 10.1) Pub Date : 2024-06-03 Edahi Gonzalez-Avalos, Atsushi Onodera, Daniela Samaniego-Castruita, Anjana Rao, Ferhat Ay
Like its parent base 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) is a direct epigenetic modification of cytosines in the context of CpG dinucleotides. 5hmC is the most abundant oxidized form of 5mC, generated through the action of TET dioxygenases at gene bodies of actively-transcribed genes and at active or lineage-specific enhancers. Although such enrichments are reported for 5hmC, to
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X-chromosome inactivation in human iPSCs provides insight into X-regulated gene expression in autosomes Genome Biol. (IF 10.1) Pub Date : 2024-05-31 Hande Topa, Clara Benoit-Pilven, Taru Tukiainen, Olli Pietiläinen
Variation in X chromosome inactivation (XCI) in human-induced pluripotent stem cells (hiPSCs) can impact their ability to model biological sex biases. The gene-wise landscape of X chromosome gene dosage remains unresolved in female hiPSCs. To characterize patterns of de-repression and escape from inactivation, we performed a systematic survey of allele specific expression in 165 female hiPSC lines
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Sequential drug treatment targeting cell cycle and cell fate regulatory programs blocks non-genetic cancer evolution in acute lymphoblastic leukemia Genome Biol. (IF 10.1) Pub Date : 2024-05-31 Alena Malyukova, Mari Lahnalampi, Ton Falqués-Costa, Petri Pölönen, Mikko Sipola, Juha Mehtonen, Susanna Teppo, Karen Akopyan, Johanna Viiliainen, Olli Lohi, Anna K. Hagström-Andersson, Merja Heinäniemi, Olle Sangfelt
Targeted therapies exploiting vulnerabilities of cancer cells hold promise for improving patient outcome and reducing side-effects of chemotherapy. However, efficacy of precision therapies is limited in part because of tumor cell heterogeneity. A better mechanistic understanding of how drug effect is linked to cancer cell state diversity is crucial for identifying effective combination therapies that
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Reproductive isolation arises during laboratory adaptation to a novel hot environment Genome Biol. (IF 10.1) Pub Date : 2024-05-28 Sheng-Kai Hsu, Wei-Yun Lai, Johannes Novak, Felix Lehner, Ana Marija Jakšić, Elisabetta Versace, Christian Schlötterer
Reproductive isolation can result from adaptive processes (e.g., ecological speciation and mutation-order speciation) or stochastic processes such as “system drift” model. Ecological speciation predicts barriers to gene flow between populations from different environments, but not among replicate populations from the same environment. In contrast, reproductive isolation among populations independently
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ePRINT: exonuclease assisted mapping of protein-RNA interactions Genome Biol. (IF 10.1) Pub Date : 2024-05-28 Sophie Hawkins, Alexandre Mondaini, Seema C. Namboori, Grady G. Nguyen, Gene W. Yeo, Asif Javed, Akshay Bhinge
RNA-binding proteins (RBPs) regulate key aspects of RNA processing including alternative splicing, mRNA degradation and localization by physically binding RNA molecules. Current methods to map these interactions, such as CLIP, rely on purifying single proteins at a time. Our new method, ePRINT, maps RBP-RNA interaction networks on a global scale without purifying individual RBPs. ePRINT uses exoribonuclease
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Current status of community resources and priorities for weed genomics research Genome Biol. (IF 10.1) Pub Date : 2024-05-27 Jacob Montgomery, Sarah Morran, Dana R. MacGregor, J. Scott McElroy, Paul Neve, Célia Neto, Martin M. Vila-Aiub, Maria Victoria Sandoval, Analia I. Menéndez, Julia M. Kreiner, Longjiang Fan, Ana L. Caicedo, Peter J. Maughan, Bianca Assis Barbosa Martins, Jagoda Mika, Alberto Collavo, Aldo Merotto, Nithya K. Subramanian, Muthukumar V. Bagavathiannan, Luan Cutti, Md. Mazharul Islam, Bikram S. Gill, Robert
Weeds are attractive models for basic and applied research due to their impacts on agricultural systems and capacity to swiftly adapt in response to anthropogenic selection pressures. Currently, a lack of genomic information precludes research to elucidate the genetic basis of rapid adaptation for important traits like herbicide resistance and stress tolerance and the effect of evolutionary mechanisms
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Rosace: a robust deep mutational scanning analysis framework employing position and mean-variance shrinkage Genome Biol. (IF 10.1) Pub Date : 2024-05-24 Jingyou Rao, Ruiqi Xin, Christian Macdonald, Matthew K. Howard, Gabriella O. Estevam, Sook Wah Yee, Mingsen Wang, James S. Fraser, Willow Coyote-Maestas, Harold Pimentel
Deep mutational scanning (DMS) measures the effects of thousands of genetic variants in a protein simultaneously. The small sample size renders classical statistical methods ineffective. For example, p-values cannot be correctly calibrated when treating variants independently. We propose Rosace, a Bayesian framework for analyzing growth-based DMS data. Rosace leverages amino acid position information
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Effect of genomic and cellular environments on gene expression noise Genome Biol. (IF 10.1) Pub Date : 2024-05-24 Clarice K. Y. Hong, Avinash Ramu, Siqi Zhao, Barak A. Cohen
Individual cells from isogenic populations often display large cell-to-cell differences in gene expression. This “noise” in expression derives from several sources, including the genomic and cellular environment in which a gene resides. Large-scale maps of genomic environments have revealed the effects of epigenetic modifications and transcription factor occupancy on mean expression levels, but leveraging
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scCDC: a computational method for gene-specific contamination detection and correction in single-cell and single-nucleus RNA-seq data Genome Biol. (IF 10.1) Pub Date : 2024-05-23 Weijian Wang, Yihui Cen, Zezhen Lu, Yueqing Xu, Tianyi Sun, Ying Xiao, Wanlu Liu, Jingyi Jessica Li, Chaochen Wang
In droplet-based single-cell and single-nucleus RNA-seq assays, systematic contamination of ambient RNA molecules biases the quantification of gene expression levels. Existing methods correct the contamination for all genes globally. However, there lacks specific evaluation of correction efficacy for varying contamination levels. Here, we show that DecontX and CellBender under-correct highly contaminating
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In vivo rescue of genetic dilated cardiomyopathy by systemic delivery of nexilin Genome Biol. (IF 10.1) Pub Date : 2024-05-23 Yanjiao Shao, Canzhao Liu, Hsin-Kai Liao, Ran Zhang, Baolei Yuan, Hanyan Yang, Ronghui Li, Siting Zhu, Xi Fang, Concepcion Rodriguez Esteban, Ju Chen, Juan Carlos Izpisua Belmonte
Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. Multiple identified mutations in nexilin (NEXN) have been suggested to be linked with severe DCM. However, the exact association between multiple mutations of Nexn and DCM remains unclear. Moreover, it is critical for the development of precise and effective therapeutics in treatments of DCM. In our study, Nexn global knockout
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Identification of the RSX interactome in a marsupial shows functional coherence with the Xist interactome during X inactivation Genome Biol. (IF 10.1) Pub Date : 2024-05-23 Kim L. McIntyre, Shafagh A. Waters, Ling Zhong, Gene Hart-Smith, Mark Raftery, Zahra A. Chew, Hardip R. Patel, Jennifer A. Marshall Graves, Paul D. Waters
The marsupial specific RSX lncRNA is the functional analogue of the eutherian specific XIST, which coordinates X chromosome inactivation. We characterized the RSX interactome in a marsupial representative (the opossum Monodelphis domestica), identifying 135 proteins, of which 54 had orthologues in the XIST interactome. Both interactomes were enriched for biological pathways related to RNA processing