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Library size confounds biology in spatial transcriptomics data Genome Biol. (IF 12.3) Pub Date : 2024-04-18 Dharmesh D. Bhuva, Chin Wee Tan, Agus Salim, Claire Marceaux, Marie A. Pickering, Jinjin Chen, Malvika Kharbanda, Xinyi Jin, Ning Liu, Kristen Feher, Givanna Putri, Wayne D. Tilley, Theresa E. Hickey, Marie-Liesse Asselin-Labat, Belinda Phipson, Melissa J. Davis
Spatial molecular data has transformed the study of disease microenvironments, though, larger datasets pose an analytics challenge prompting the direct adoption of single-cell RNA-sequencing tools including normalization methods. Here, we demonstrate that library size is associated with tissue structure and that normalizing these effects out using commonly applied scRNA-seq normalization methods will
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Characterizing glucokinase variant mechanisms using a multiplexed abundance assay Genome Biol. (IF 12.3) Pub Date : 2024-04-16 Sarah Gersing, Thea K. Schulze, Matteo Cagiada, Amelie Stein, Frederick P. Roth, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Amino acid substitutions can perturb protein activity in multiple ways. Understanding their mechanistic basis may pinpoint how residues contribute to protein function. Here, we characterize the mechanisms underlying variant effects in human glucokinase (GCK) variants, building on our previous comprehensive study on GCK variant activity. Using a yeast growth-based assay, we score the abundance of 95%
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Benchmarking bioinformatic virus identification tools using real-world metagenomic data across biomes Genome Biol. (IF 12.3) Pub Date : 2024-04-15 Ling-Yi Wu, Yasas Wijesekara, Gonçalo J. Piedade, Nikolaos Pappas, Corina P. D. Brussaard, Bas E. Dutilh
As most viruses remain uncultivated, metagenomics is currently the main method for virus discovery. Detecting viruses in metagenomic data is not trivial. In the past few years, many bioinformatic virus identification tools have been developed for this task, making it challenging to choose the right tools, parameters, and cutoffs. As all these tools measure different biological signals, and use different
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Powerful and accurate detection of temporal gene expression patterns from multi-sample multi-stage single-cell transcriptomics data with TDEseq Genome Biol. (IF 12.3) Pub Date : 2024-04-15 Yue Fan, Lei Li, Shiquan Sun
We present a non-parametric statistical method called TDEseq that takes full advantage of smoothing splines basis functions to account for the dependence of multiple time points in scRNA-seq studies, and uses hierarchical structure linear additive mixed models to model the correlated cells within an individual. As a result, TDEseq demonstrates powerful performance in identifying four potential temporal
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Machine-learning analysis reveals an important role for negative selection in shaping cancer aneuploidy landscapes Genome Biol. (IF 12.3) Pub Date : 2024-04-15 Juman Jubran, Rachel Slutsky, Nir Rozenblum, Lior Rokach, Uri Ben-David, Esti Yeger-Lotem
Aneuploidy, an abnormal number of chromosomes within a cell, is a hallmark of cancer. Patterns of aneuploidy differ across cancers, yet are similar in cancers affecting closely related tissues. The selection pressures underlying aneuploidy patterns are not fully understood, hindering our understanding of cancer development and progression. Here, we apply interpretable machine learning methods to study
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Demuxafy: improvement in droplet assignment by integrating multiple single-cell demultiplexing and doublet detection methods Genome Biol. (IF 12.3) Pub Date : 2024-04-15 Drew Neavin, Anne Senabouth, Himanshi Arora, Jimmy Tsz Hang Lee, Aida Ripoll-Cladellas, Lude Franke, Shyam Prabhakar, Chun Jimmie Ye, Davis J. McCarthy, Marta Melé, Martin Hemberg, Joseph E. Powell
Recent innovations in single-cell RNA-sequencing (scRNA-seq) provide the technology to investigate biological questions at cellular resolution. Pooling cells from multiple individuals has become a common strategy, and droplets can subsequently be assigned to a specific individual by leveraging their inherent genetic differences. An implicit challenge with scRNA-seq is the occurrence of doublets—droplets
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Scoary2: rapid association of phenotypic multi-omics data with microbial pan-genomes Genome Biol. (IF 12.3) Pub Date : 2024-04-11 Thomas Roder, Grégory Pimentel, Pascal Fuchsmann, Mireille Tena Stern, Ueli von Ah, Guy Vergères, Stephan Peischl, Ola Brynildsrud, Rémy Bruggmann, Cornelia Bär
Unraveling bacterial gene function drives progress in various areas, such as food production, pharmacology, and ecology. While omics technologies capture high-dimensional phenotypic data, linking them to genomic data is challenging, leaving 40–60% of bacterial genes undescribed. To address this bottleneck, we introduce Scoary2, an ultra-fast microbial genome-wide association studies (mGWAS) software
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Evaluating and improving the representation of bacterial contents in long-read metagenome assemblies Genome Biol. (IF 12.3) Pub Date : 2024-04-11 Xiaowen Feng, Heng Li
In the metagenomic assembly of a microbial community, abundant species are often thought to assemble well given their deeper sequencing coverage. This conjuncture is rarely tested or evaluated in practice. We often do not know how many abundant species are missing and do not have an approach to recover them. Here, we propose k-mer based and 16S RNA based methods to measure the completeness of metagenome
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A comprehensive benchmark of graph-based genetic variant genotyping algorithms on plant genomes for creating an accurate ensemble pipeline Genome Biol. (IF 12.3) Pub Date : 2024-04-08 Ze-Zhen Du, Jia-Bao He, Wen-Biao Jiao
Although sequencing technologies have boosted the measurement of the genomic diversity of plant crops, it remains challenging to accurately genotype millions of genetic variants, especially structural variations, with only short reads. In recent years, many graph-based variation genotyping methods have been developed to address this issue and tested for human genomes. However, their performance in
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scifi-ATAC-seq: massive-scale single-cell chromatin accessibility sequencing using combinatorial fluidic indexing Genome Biol. (IF 12.3) Pub Date : 2024-04-08 Xuan Zhang, Alexandre P. Marand, Haidong Yan, Robert J. Schmitz
Single-cell ATAC-seq has emerged as a powerful approach for revealing candidate cis-regulatory elements genome-wide at cell-type resolution. However, current single-cell methods suffer from limited throughput and high costs. Here, we present a novel technique called scifi-ATAC-seq, single-cell combinatorial fluidic indexing ATAC-sequencing, which combines a barcoded Tn5 pre-indexing step with droplet-based
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SuperCellCyto: enabling efficient analysis of large scale cytometry datasets Genome Biol. (IF 12.3) Pub Date : 2024-04-08 Givanna H. Putri, George Howitt, Felix Marsh-Wakefield, Thomas M. Ashhurst, Belinda Phipson
Advancements in cytometry technologies have enabled quantification of up to 50 proteins across millions of cells at single cell resolution. Analysis of cytometry data routinely involves tasks such as data integration, clustering, and dimensionality reduction. While numerous tools exist, many require extensive run times when processing large cytometry data containing millions of cells. Existing solutions
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PMF-GRN: a variational inference approach to single-cell gene regulatory network inference using probabilistic matrix factorization Genome Biol. (IF 12.3) Pub Date : 2024-04-08 Claudia Skok Gibbs, Omar Mahmood, Richard Bonneau, Kyunghyun Cho
Inferring gene regulatory networks (GRNs) from single-cell data is challenging due to heuristic limitations. Existing methods also lack estimates of uncertainty. Here we present Probabilistic Matrix Factorization for Gene Regulatory Network Inference (PMF-GRN). Using single-cell expression data, PMF-GRN infers latent factors capturing transcription factor activity and regulatory relationships. Using
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Increased DNA methylation contributes to the early ripening of pear fruits during domestication and improvement Genome Biol. (IF 12.3) Pub Date : 2024-04-05 Bobo Song, Jinshan Yu, Xiaolong Li, Jiaming Li, Jing Fan, Hainan Liu, Weilin Wei, Lingchao Zhang, Kaidi Gu, Dongliang Liu, Kejiao Zhao, Jun Wu
DNA methylation is an essential epigenetic modification. However, its contribution to trait changes and diversity in the domestication of perennial fruit trees remains unknown. Here, we investigate the variation in DNA methylation during pear domestication and improvement using whole-genome bisulfite sequencing in 41 pear accessions. Contrary to the significant decrease during rice domestication, we
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Response to: “Merit of integrating in situ transcriptomics and anatomical information for cell annotation and lineage construction in single-cell analyses of Populus” Genome Biol. (IF 12.3) Pub Date : 2024-04-03 Shaoming Liang, Yiling Li, Yang Chen, Heng Huang, Sijia Li, Yuanzhong Jiang, Tao Ma
We appreciate the correspondence from Chen et al. [1] regarding four recent studies on single-cell RNA-seq in poplar xylem [2,3,4,5]. Over the past 2 years, six research groups have investigated the cell types and differentiation trajectories in poplar woody tissues using single-cell and/or spatial transcriptome techniques [2,3,4,5,6,7], which provided valuable insights for future research on cambium
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Merit of integrating in situ transcriptomics and anatomical information for cell annotation and lineage construction in single-cell analyses of Populus Genome Biol. (IF 12.3) Pub Date : 2024-04-03 Ying-Lan Chen, Jo-Wei Allison Hsieh, Shang-Che Kuo, Chung-Ting Kao, Chia-Chun Tung, Jhong-He Yu, Tien-Hsien Chang, Chuan Ku, Jianbo Xie, Deqiang Zhang, Quanzi Li, Ying-Chung Jimmy Lin
Cell type annotation and lineage construction are two of the most critical tasks conducted in the analyses of single-cell RNA sequencing (scRNA-seq). Four recent scRNA-seq studies of differentiating xylem propose four models on differentiating xylem development in Populus. The differences are mostly caused by the use of different strategies for cell type annotation and subsequent lineage interpretation
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DNA methylation remodeling and the functional implication during male gametogenesis in rice Genome Biol. (IF 12.3) Pub Date : 2024-04-02 Xue Li, Bo Zhu, Yue Lu, Feng Zhao, Qian Liu, Jiahao Wang, Miaomiao Ye, Siyuan Chen, Junwei Nie, Lizhong Xiong, Yu Zhao, Changyin Wu, Dao-Xiu Zhou
Epigenetic marks are reprogrammed during sexual reproduction. In flowering plants, DNA methylation is only partially remodeled in the gametes and the zygote. However, the timing and functional significance of the remodeling during plant gametogenesis remain obscure. Here we show that DNA methylation remodeling starts after male meiosis in rice, with non-CG methylation, particularly at CHG sites, being
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Species-aware DNA language models capture regulatory elements and their evolution Genome Biol. (IF 12.3) Pub Date : 2024-04-02 Alexander Karollus, Johannes Hingerl, Dennis Gankin, Martin Grosshauser, Kristian Klemon, Julien Gagneur
The rise of large-scale multi-species genome sequencing projects promises to shed new light on how genomes encode gene regulatory instructions. To this end, new algorithms are needed that can leverage conservation to capture regulatory elements while accounting for their evolution. Here, we introduce species-aware DNA language models, which we trained on more than 800 species spanning over 500 million
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Bento: a toolkit for subcellular analysis of spatial transcriptomics data Genome Biol. (IF 12.3) Pub Date : 2024-04-02 Clarence K. Mah, Noorsher Ahmed, Nicole A. Lopez, Dylan C. Lam, Avery Pong, Alexander Monell, Colin Kern, Yuanyuan Han, Gino Prasad, Anthony J. Cesnik, Emma Lundberg, Quan Zhu, Hannah Carter, Gene W. Yeo
The spatial organization of molecules in a cell is essential for their functions. While current methods focus on discerning tissue architecture, cell–cell interactions, and spatial expression patterns, they are limited to the multicellular scale. We present Bento, a Python toolkit that takes advantage of single-molecule information to enable spatial analysis at the subcellular scale. Bento ingests
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FixNCut: single-cell genomics through reversible tissue fixation and dissociation Genome Biol. (IF 12.3) Pub Date : 2024-03-29 Laura Jiménez-Gracia, Domenica Marchese, Juan C. Nieto, Ginevra Caratù, Elisa Melón-Ardanaz, Victoria Gudiño, Sara Roth, Kellie Wise, Natalie K. Ryan, Kirk B. Jensen, Xavier Hernando-Momblona, Joana P. Bernardes, Florian Tran, Laura Katharina Sievers, Stefan Schreiber, Maarten van den Berge, Tessa Kole, Petra L. van der Velde, Martijn C. Nawijn, Philip Rosenstiel, Eduard Batlle, Lisa M. Butler, Ian
The use of single-cell technologies for clinical applications requires disconnecting sampling from downstream processing steps. Early sample preservation can further increase robustness and reproducibility by avoiding artifacts introduced during specimen handling. We present FixNCut, a methodology for the reversible fixation of tissue followed by dissociation that overcomes current limitations. We
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Divergent composition and transposon-silencing activity of small RNAs in mammalian oocytes Genome Biol. (IF 12.3) Pub Date : 2024-03-26 Li Hou, Wei Liu, Hongdao Zhang, Ronghong Li, Miao Liu, Huijuan Shi, Ligang Wu
Small RNAs are essential for germ cell development and fertilization. However, fundamental questions remain, such as the level of conservation in small RNA composition between species and whether small RNAs control transposable elements in mammalian oocytes. Here, we use high-throughput sequencing to profile small RNAs and poly(A)-bearing long RNAs in oocytes of 12 representative vertebrate species
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Eukaryotic-driven directed evolution of Cas9 nucleases Genome Biol. (IF 12.3) Pub Date : 2024-03-25 Giulia Vittoria Ruta, Matteo Ciciani, Eyemen Kheir, Michele Domenico Gentile, Simone Amistadi, Antonio Casini, Anna Cereseto
Further advancement of genome editing highly depends on the development of tools with higher compatibility with eukaryotes. A multitude of described Cas9s have great potential but require optimization for genome editing purposes. Among these, the Cas9 from Campylobacter jejuni, CjCas9, has a favorable small size, facilitating delivery in mammalian cells. Nonetheless, its full exploitation is limited
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Next-Gen GWAS: full 2D epistatic interaction maps retrieve part of missing heritability and improve phenotypic prediction Genome Biol. (IF 12.3) Pub Date : 2024-03-25 Clément Carré, Jean Baptiste Carluer, Christian Chaux, Chad Estoup-Streiff, Nicolas Roche, Eric Hosy, André Mas, Gabriel Krouk
The problem of missing heritability requires the consideration of genetic interactions among different loci, called epistasis. Current GWAS statistical models require years to assess the entire combinatorial epistatic space for a single phenotype. We propose Next-Gen GWAS (NGG) that evaluates over 60 billion single nucleotide polymorphism combinatorial first-order interactions within hours. We apply
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txci-ATAC-seq: a massive-scale single-cell technique to profile chromatin accessibility Genome Biol. (IF 12.3) Pub Date : 2024-03-22 Hao Zhang, Ryan M. Mulqueen, Natalie Iannuzo, Dominique O. Farrera, Francesca Polverino, James J. Galligan, Julie G. Ledford, Andrew C. Adey, Darren A. Cusanovich
We develop a large-scale single-cell ATAC-seq method by combining Tn5-based pre-indexing with 10× Genomics barcoding, enabling the indexing of up to 200,000 nuclei across multiple samples in a single reaction. We profile 449,953 nuclei across diverse tissues, including the human cortex, mouse brain, human lung, mouse lung, mouse liver, and lung tissue from a club cell secretory protein knockout (CC16−/−)
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Depletion of lamins B1 and B2 promotes chromatin mobility and induces differential gene expression by a mesoscale-motion-dependent mechanism Genome Biol. (IF 12.3) Pub Date : 2024-03-22 Emily M. Pujadas Liwag, Xiaolong Wei, Nicolas Acosta, Lucas M. Carter, Jiekun Yang, Luay M. Almassalha, Surbhi Jain, Ali Daneshkhah, Suhas S. P. Rao, Fidan Seker-Polat, Kyle L. MacQuarrie, Joe Ibarra, Vasundhara Agrawal, Erez Lieberman Aiden, Masato T. Kanemaki, Vadim Backman, Mazhar Adli
B-type lamins are critical nuclear envelope proteins that interact with the three-dimensional genomic architecture. However, identifying the direct roles of B-lamins on dynamic genome organization has been challenging as their joint depletion severely impacts cell viability. To overcome this, we engineered mammalian cells to rapidly and completely degrade endogenous B-type lamins using Auxin-inducible
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Cataloging the phylogenetic diversity of human bladder bacterial isolates Genome Biol. (IF 12.3) Pub Date : 2024-03-21 Jingjie Du, Mark Khemmani, Thomas Halverson, Adriana Ene, Roberto Limeira, Lana Tinawi, Baylie R. Hochstedler-Kramer, Melline Fontes Noronha, Catherine Putonti, Alan J. Wolfe
Although the human bladder is reported to harbor unique microbiota, our understanding of how these microbial communities interact with their human hosts is limited, mostly owing to the lack of isolates to test mechanistic hypotheses. Niche-specific bacterial collections and associated reference genome databases have been instrumental in expanding knowledge of the microbiota of other anatomical sites
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miR-430 regulates zygotic mRNA during zebrafish embryogenesis Genome Biol. (IF 12.3) Pub Date : 2024-03-19 Danielson Baia Amaral, Rhonda Egidy, Anoja Perera, Ariel A Bazzini
Early embryonic developmental programs are guided by the coordinated interplay between maternally inherited and zygotically manufactured RNAs and proteins. Although these processes happen concomitantly and affecting gene function during this period is bound to affect both pools of mRNAs, it has been challenging to study their expression dynamics separately. By employing SLAM-seq, a nascent mRNA labeling
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Multi-slice spatial transcriptome domain analysis with SpaDo Genome Biol. (IF 12.3) Pub Date : 2024-03-19 Bin Duan, Shaoqi Chen, Xiaojie Cheng, Qi Liu
With the rapid advancements in spatial transcriptome sequencing, multiple tissue slices are now available, enabling the integration and interpretation of spatial cellular landscapes. Herein, we introduce SpaDo, a tool for multi-slice spatial domain analysis, including modules for multi-slice spatial domain detection, reference-based annotation, and multiple slice clustering at both single-cell and
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DANCE: a deep learning library and benchmark platform for single-cell analysis Genome Biol. (IF 12.3) Pub Date : 2024-03-19 Jiayuan Ding, Renming Liu, Hongzhi Wen, Wenzhuo Tang, Zhaoheng Li, Julian Venegas, Runze Su, Dylan Molho, Wei Jin, Yixin Wang, Qiaolin Lu, Lingxiao Li, Wangyang Zuo, Yi Chang, Yuying Xie, Jiliang Tang
DANCE is the first standard, generic, and extensible benchmark platform for accessing and evaluating computational methods across the spectrum of benchmark datasets for numerous single-cell analysis tasks. Currently, DANCE supports 3 modules and 8 popular tasks with 32 state-of-art methods on 21 benchmark datasets. People can easily reproduce the results of supported algorithms across major benchmark
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Multiplex DNA fluorescence in situ hybridization to analyze maternal vs. paternal C. elegans chromosomes Genome Biol. (IF 12.3) Pub Date : 2024-03-14 Silvia Gutnik, Jia Emil You, Ahilya N. Sawh, Aude Andriollo, Susan E. Mango
Recent advances in microscopy have enabled studying chromosome organization at the single-molecule level, yet little is known about inherited chromosome organization. Here we adapt single-molecule chromosome tracing to distinguish two C. elegans strains (N2 and HI) and find that while their organization is similar, the N2 chromosome influences the folding parameters of the HI chromosome, in particular
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Multi-omics provide insights into the regulation of DNA methylation in pear fruit metabolism Genome Biol. (IF 12.3) Pub Date : 2024-03-14 Chao Gu, Mao-Song Pei, Zhi-Hua Guo, Lei Wu, Kai-Jie Qi, Xue-Ping Wang, Hong Liu, Zhongchi Liu, Zhaobo Lang, Shaoling Zhang
Extensive research has been conducted on fruit development in crops, but the metabolic regulatory networks underlying perennial fruit trees remain poorly understood. To address this knowledge gap, we conduct a comprehensive analysis of the metabolome, proteome, transcriptome, DNA methylome, and small RNAome profiles of pear fruit flesh at 11 developing stages, spanning from fruitlet to ripening. Here
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A comparison of methods for detecting DNA methylation from long-read sequencing of human genomes Genome Biol. (IF 12.3) Pub Date : 2024-03-11 Brynja D. Sigurpalsdottir, Olafur A. Stefansson, Guillaume Holley, Doruk Beyter, Florian Zink, Marteinn Þ. Hardarson, Sverrir Þ. Sverrisson, Nina Kristinsdottir, Droplaug N. Magnusdottir, Olafur Þ. Magnusson, Daniel F. Gudbjartsson, Bjarni V. Halldorsson, Kari Stefansson
Long-read sequencing can enable the detection of base modifications, such as CpG methylation, in single molecules of DNA. The most commonly used methods for long-read sequencing are nanopore developed by Oxford Nanopore Technologies (ONT) and single molecule real-time (SMRT) sequencing developed by Pacific Bioscience (PacBio). In this study, we systematically compare the performance of CpG methylation
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Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes Genome Biol. (IF 12.3) Pub Date : 2024-03-11 Adrià Aterido, María López-Lasanta, Francisco Blanco, Antonio Juan-Mas, María Luz García-Vivar, Alba Erra, Carolina Pérez-García, Simón Ángel Sánchez-Fernández, Raimon Sanmartí, Antonio Fernández-Nebro, Mercedes Alperi-López, Jesús Tornero, Ana María Ortiz, Carlos Marras Fernández-Cid, Núria Palau, Wenjing Pan, Miranda Byrne-Steele, Dmytro Starenki, Daniel Weber, Ivan Rodriguez-Nunez, Jian Han, Richard
In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire
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Liquid–liquid phase separation of H3K27me3 reader BP1 regulates transcriptional repression Genome Biol. (IF 12.3) Pub Date : 2024-03-11 Guangfei Tang, Haoxue Xia, Yufei Huang, Yuanwen Guo, Yun Chen, Zhonghua Ma, Wende Liu
Bromo-adjacent homology-plant homeodomain domain containing protein 1 (BP1) is a reader of histone post-translational modifications in fungi. BP1 recognizes trimethylation of lysine 27 in histone H3 (H3K27me3), an epigenetic hallmark of gene silencing. However, whether and how BP1 participates in transcriptional repression remains poorly understood. We report that BP1 forms phase-separated liquid condensates
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Prediction of metabolites associated with somatic mutations in cancers by using genome-scale metabolic models and mutation data Genome Biol. (IF 12.3) Pub Date : 2024-03-11 GaRyoung Lee, Sang Mi Lee, Sungyoung Lee, Chang Wook Jeong, Hyojin Song, Sang Yup Lee, Hongseok Yun, Youngil Koh, Hyun Uk Kim
Oncometabolites, often generated as a result of a gene mutation, show pro-oncogenic function when abnormally accumulated in cancer cells. Identification of such mutation-associated metabolites will facilitate developing treatment strategies for cancers, but is challenging due to the large number of metabolites in a cell and the presence of multiple genes associated with cancer development. Here we
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Joint analysis of mutational and transcriptional landscapes in human cancer reveals key perturbations during cancer evolution Genome Biol. (IF 12.3) Pub Date : 2024-03-08 Jae-Won Cho, Jingyi Cao, Martin Hemberg
Tumors are able to acquire new capabilities, including traits such as drug resistance and metastasis that are associated with unfavorable clinical outcomes. Single-cell technologies have made it possible to study both mutational and transcriptomic profiles, but as most studies have been conducted on model systems, little is known about cancer evolution in human patients. Hence, a better understanding
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Early-life ruminal microbiome-derived indole-3-carboxaldehyde and prostaglandin D2 are effective promoters of rumen development Genome Biol. (IF 12.3) Pub Date : 2024-03-04 Daming Sun, Gaorui Bian, Kai Zhang, Ning Liu, Yuyang Yin, Yuanlong Hou, Fei Xie, Weiyun Zhu, Shengyong Mao, Junhua Liu
The function of diverse ruminal microbes is tightly linked to rumen development and host physiology. The system of ruminal microbes is an excellent model to clarify the fundamental ecological relationships among complex nutrient–microbiome–host interactions. Here, neonatal lambs are introduced to different dietary regimes to investigate the influences of early-life crosstalk between nutrients and microbiome
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Three near-complete genome assemblies reveal substantial centromere dynamics from diploid to tetraploid in Brachypodium genus Genome Biol. (IF 12.3) Pub Date : 2024-03-04 Chuanye Chen, Siying Wu, Yishuang Sun, Jingwei Zhou, Yiqian Chen, Jing Zhang, James A. Birchler, Fangpu Han, Ning Yang, Handong Su
Centromeres are critical for maintaining genomic stability in eukaryotes, and their turnover shapes genome architectures and drives karyotype evolution. However, the co-evolution of centromeres from different species in allopolyploids over millions of years remains largely unknown. Here, we generate three near-complete genome assemblies, a tetraploid Brachypodium hybridum and its two diploid ancestors
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scAbsolute: measuring single-cell ploidy and replication status Genome Biol. (IF 12.3) Pub Date : 2024-03-04 Michael P. Schneider, Amy E. Cullen, Justina Pangonyte, Jason Skelton, Harvey Major, Elke Van Oudenhove, Maria J. Garcia, Blas Chaves Urbano, Anna M. Piskorz, James D. Brenton, Geoff Macintyre, Florian Markowetz
Cancer cells often exhibit DNA copy number aberrations and can vary widely in their ploidy. Correct estimation of the ploidy of single-cell genomes is paramount for downstream analysis. Based only on single-cell DNA sequencing information, scAbsolute achieves accurate and unbiased measurement of single-cell ploidy and replication status, including whole-genome duplications. We demonstrate scAbsolute’s
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Genomic insight into the origin, domestication, dispersal, diversification and human selection of Tartary buckwheat Genome Biol. (IF 12.3) Pub Date : 2024-02-27 Yuqi He, Kaixuan Zhang, Yaliang Shi, Hao Lin, Xu Huang, Xiang Lu, Zhirong Wang, Wei Li, Xibo Feng, Taoxiong Shi, Qingfu Chen, Junzhen Wang, Yu Tang, Mark A. Chapman, Mateja Germ, Zlata Luthar, Ivan Kreft, Dagmar Janovská, Vladimir Meglič, Sun-Hee Woo, Muriel Quinet, Alisdair R. Fernie, Xu Liu, Meiliang Zhou
Tartary buckwheat, Fagopyrum tataricum, is a pseudocereal crop with worldwide distribution and high nutritional value. However, the origin and domestication history of this crop remain to be elucidated. Here, by analyzing the population genomics of 567 accessions collected worldwide and reviewing historical documents, we find that Tartary buckwheat originated in the Himalayan region and then spread
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Rapid and sensitive detection of genome contamination at scale with FCS-GX Genome Biol. (IF 12.3) Pub Date : 2024-02-26 Alexander Astashyn, Eric S. Tvedte, Deacon Sweeney, Victor Sapojnikov, Nathan Bouk, Victor Joukov, Eyal Mozes, Pooja K. Strope, Pape M. Sylla, Lukas Wagner, Shelby L. Bidwell, Larissa C. Brown, Karen Clark, Emily W. Davis, Brian Smith-White, Wratko Hlavina, Kim D. Pruitt, Valerie A. Schneider, Terence D. Murphy
Assembled genome sequences are being generated at an exponential rate. Here we present FCS-GX, part of NCBI’s Foreign Contamination Screen (FCS) tool suite, optimized to identify and remove contaminant sequences in new genomes. FCS-GX screens most genomes in 0.1–10 min. Testing FCS-GX on artificially fragmented genomes demonstrates high sensitivity and specificity for diverse contaminant species. We
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Precise fine-turning of GhTFL1 by base editing tools defines ideal cotton plant architecture Genome Biol. (IF 12.3) Pub Date : 2024-02-26 Guanying Wang, Fuqiu Wang, Zhongping Xu, Ying Wang, Can Zhang, Yi Zhou, Fengjiao Hui, Xiyan Yang, Xinhui Nie, Xianlong Zhang, Shuangxia Jin
CRISPR/Cas-derived base editor enables precise editing of target sites and has been widely used for basic research and crop genetic improvement. However, the editing efficiency of base editors at different targets varies greatly. Here, we develop a set of highly efficient base editors in cotton plants. GhABE8e, which is fused to conventional nCas9, exhibits 99.9% editing efficiency, compared to GhABE7
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HiHo-AID2: boosting homozygous knock-in efficiency enables robust generation of human auxin-inducible degron cells Genome Biol. (IF 12.3) Pub Date : 2024-02-26 Shiqian Li, Yafei Wang, Miesje van der Stoel, Xin Zhou, Shrinidhi Madhusudan, Kristiina Kanerva, Van Dien Nguyen, Nazli Eskici, Vesa M. Olkkonen, You Zhou, Taneli Raivio, Elina Ikonen
Recent developments in auxin-inducible degron (AID) technology have increased its popularity for chemogenetic control of proteolysis. However, generation of human AID cell lines is challenging, especially in human embryonic stem cells (hESCs). Here, we develop HiHo-AID2, a streamlined procedure for rapid, one-step generation of human cancer and hESC lines with high homozygous degron-tagging efficiency
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scGIST: gene panel design for spatial transcriptomics with prioritized gene sets Genome Biol. (IF 12.3) Pub Date : 2024-02-26 Mashrur Ahmed Yafi, Md. Hasibul Husain Hisham, Francisco Grisanti, James F. Martin, Atif Rahman, Md. Abul Hassan Samee
A critical challenge of single-cell spatial transcriptomics (sc-ST) technologies is their panel size. Being based on fluorescence in situ hybridization, they are typically limited to panels of about a thousand genes. This constrains researchers to build panels from only the marker genes of different cell types and forgo other genes of interest, e.g., genes encoding ligand-receptor complexes or those
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A comparison of marker gene selection methods for single-cell RNA sequencing data Genome Biol. (IF 12.3) Pub Date : 2024-02-26 Jeffrey M. Pullin, Davis J. McCarthy
The development of single-cell RNA sequencing (scRNA-seq) has enabled scientists to catalog and probe the transcriptional heterogeneity of individual cells in unprecedented detail. A common step in the analysis of scRNA-seq data is the selection of so-called marker genes, most commonly to enable annotation of the biological cell types present in the sample. In this paper, we benchmark 59 computational
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SHARE-Topic: Bayesian interpretable modeling of single-cell multi-omic data Genome Biol. (IF 12.3) Pub Date : 2024-02-23 Nour El Kazwini, Guido Sanguinetti
Multi-omic single-cell technologies, which simultaneously measure the transcriptional and epigenomic state of the same cell, enable understanding epigenetic mechanisms of gene regulation. However, noisy and sparse data pose fundamental statistical challenges to extract biological knowledge from complex datasets. SHARE-Topic, a Bayesian generative model of multi-omic single cell data using topic models
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Structured 3′ UTRs destabilize mRNAs in plants Genome Biol. (IF 12.3) Pub Date : 2024-02-22 Tianru Zhang, Changhao Li, Jiaying Zhu, Yanjun Li, Zhiye Wang, Chun-Yip Tong, Yu Xi, Yi Han, Hisashi Koiwa, Xu Peng, Xiuren Zhang
RNA secondary structure (RSS) can influence the regulation of transcription, RNA processing, and protein synthesis, among other processes. 3′ untranslated regions (3′ UTRs) of mRNA also hold the key for many aspects of gene regulation. However, there are often contradictory results regarding the roles of RSS in 3′ UTRs in gene expression in different organisms and/or contexts. Here, we incidentally
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CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods Genome Biol. (IF 12.3) Pub Date : 2024-02-22
The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors
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DNA satellite and chromatin organization at mouse centromeres and pericentromeres Genome Biol. (IF 12.3) Pub Date : 2024-02-20 Jenika Packiaraj, Jitendra Thakur
Centromeres are essential for faithful chromosome segregation during mitosis and meiosis. However, the organization of satellite DNA and chromatin at mouse centromeres and pericentromeres is poorly understood due to the challenges of assembling repetitive genomic regions. Using recently available PacBio long-read sequencing data from the C57BL/6 strain, we find that contrary to the previous reports
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Undetectable off-target effects induced by FokI catalytic domain in mouse embryos Genome Biol. (IF 12.3) Pub Date : 2024-02-20 Long Xie, Hu Feng, Zhifang Li, Di Li, Xiali Yang, Tanglong Yuan, Nana Yan, Chenfei He, Jitan Zheng, Zhenrui Zuo, Yaxuan Zheng, Yaqi Cao, Yangqing Lu, Xing Yao Xiong, Erwei Zuo
The FokI catalytic domain can be fused to various DNA binding architectures to improve the precision of genome editing tools. However, evaluation of off-target effects is essential for developing these tools. We use Genome-wide Off-target analysis by Two-cell embryo Injection (GOTI) to detect low-frequency off-target editing events in mouse embryos injected with FokI-based architectures. Specifically
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Author Correction: Cross-phyla protein annotation by structural prediction and alignment Genome Biol. (IF 12.3) Pub Date : 2024-02-19 Fabian Ruperti, Nikolaos Papadopoulos, Jacob M. Musser, Milot Mirdita, Martin Steinegger, Detlev Arendt
Author Correction: Genome Biol 24, 113 (2023) https://doi.org/10.1186/s13059-023-02942-9 Following publication of the original article [1], the authors identified two errors in the citations. First, in citation 109, the predicted S. lacustris protein structures are not deposited under https://doi.org/10.5452/ma-yoep2 but rather https://doi.org/10.5452/ma-coffe-slac. Second, the Biological Structure
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RUBICON: a framework for designing efficient deep learning-based genomic basecallers Genome Biol. (IF 12.3) Pub Date : 2024-02-16 Gagandeep Singh, Mohammed Alser, Kristof Denolf, Can Firtina, Alireza Khodamoradi, Meryem Banu Cavlak, Henk Corporaal, Onur Mutlu
Nanopore sequencing generates noisy electrical signals that need to be converted into a standard string of DNA nucleotide bases using a computational step called basecalling. The performance of basecalling has critical implications for all later steps in genome analysis. Therefore, there is a need to reduce the computation and memory cost of basecalling while maintaining accuracy. We present RUBICON
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Dissecting the sequence and structural determinants guiding m6A deposition and evolution via inter- and intra-species hybrids Genome Biol. (IF 12.3) Pub Date : 2024-02-15 Ran Shachar, David Dierks, Miguel Angel Garcia-Campos, Anna Uzonyi, Ursula Toth, Walter Rossmanith, Schraga Schwartz
N6-methyladenosine (m6A) is the most abundant mRNA modification, and controls mRNA stability. m6A distribution varies considerably between and within species. Yet, it is unclear to what extent this variability is driven by changes in genetic sequences (‘cis’) or cellular environments (‘trans’) and via which mechanisms. Here we dissect the determinants governing RNA methylation via interspecies and
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pyHiM: a new open-source, multi-platform software package for spatial genomics based on multiplexed DNA-FISH imaging Genome Biol. (IF 12.3) Pub Date : 2024-02-13 Xavier Devos, Jean-Bernard Fiche, Marion Bardou, Olivier Messina, Christophe Houbron, Julian Gurgo, Marie Schaeffer, Markus Götz, Thomas Walter, Florian Mueller, Marcelo Nollmann
Genome-wide ensemble sequencing methods improved our understanding of chromatin organization in eukaryotes but lack the ability to capture single-cell heterogeneity and spatial organization. To overcome these limitations, new imaging-based methods have emerged, giving rise to the field of spatial genomics. Here, we present pyHiM, a user-friendly python toolbox specifically designed for the analysis
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SSBlazer: a genome-wide nucleotide-resolution model for predicting single-strand break sites Genome Biol. (IF 12.3) Pub Date : 2024-02-12 Sheng Xu, Junkang Wei, Siqi Sun, Jizhou Zhang, Ting-Fung Chan, Yu Li
Single-strand breaks are the major DNA damage in the genome and serve a crucial role in various biological processes. To reveal the significance of single-strand breaks, multiple sequencing-based single-strand break detection methods have been developed, which are costly and unfeasible for large-scale analysis. Hence, we propose SSBlazer, an explainable and scalable deep learning framework for single-strand
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IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy Genome Biol. (IF 12.3) Pub Date : 2024-02-07 Georgette Tanner, Rhiannon Barrow, Shoaib Ajaib, Muna Al-Jabri, Nazia Ahmed, Steven Pollock, Martina Finetti, Nora Rippaus, Alexander F. Bruns, Khaja Syed, James A. Poulter, Laura Matthews, Thomas Hughes, Erica Wilson, Colin Johnson, Frederick S. Varn, Anke Brüning-Richardson, Catherine Hogg, Alastair Droop, Arief Gusnanto, Matthew A. Care, Luisa Cutillo, David R. Westhead, Susan C. Short, Michael
Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumors almost always fatally recur. Using RNA sequencing data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumors, we identify two responder subtypes based on longitudinal changes in gene expression. In two
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The androgen receptor interacts with GATA3 to transcriptionally regulate a luminal epithelial cell phenotype in breast cancer Genome Biol. (IF 12.3) Pub Date : 2024-02-05 Leila Hosseinzadeh, Zoya Kikhtyak, Geraldine Laven-Law, Stephen M. Pederson, Caroline G. Puiu, Clive S. D’Santos, Elgene Lim, Jason S. Carroll, Wayne D. Tilley, Amy R. Dwyer, Theresa E. Hickey
The androgen receptor (AR) is a tumor suppressor in estrogen receptor (ER) positive breast cancer, a role sustained in some ER negative breast cancers. Key factors dictating AR genomic activity in a breast context are largely unknown. Herein, we employ an unbiased chromatin immunoprecipitation-based proteomic technique to identify endogenous AR interacting co-regulatory proteins in ER positive and
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Simple but powerful interactive data analysis in R with R/LinekdCharts Genome Biol. (IF 12.3) Pub Date : 2024-02-05 Svetlana Ovchinnikova, Simon Anders
In research involving data-rich assays, exploratory data analysis is a crucial step. Typically, this involves jumping back and forth between visualizations that provide overview of the whole data and others that dive into details. For example, it might be helpful to have one chart showing a summary statistic for all samples, while a second chart provides details for points selected in the first chart
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Mapping the functional impact of non-coding regulatory elements in primary T cells through single-cell CRISPR screens Genome Biol. (IF 12.3) Pub Date : 2024-02-02 Celia Alda-Catalinas, Ximena Ibarra-Soria, Christina Flouri, Jorge Esparza Gordillo, Diana Cousminer, Anna Hutchinson, Bin Sun, William Pembroke, Sebastian Ullrich, Adam Krejci, Adrian Cortes, Alison Acevedo, Sunir Malla, Carl Fishwick, Gerard Drewes, Radu Rapiteanu
Drug targets with genetic evidence are expected to increase clinical success by at least twofold. Yet, translating disease-associated genetic variants into functional knowledge remains a fundamental challenge of drug discovery. A key issue is that the vast majority of complex disease associations cannot be cleanly mapped to a gene. Immune disease-associated variants are enriched within regulatory elements
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AnnoPRO: a strategy for protein function annotation based on multi-scale protein representation and a hybrid deep learning of dual-path encoding Genome Biol. (IF 12.3) Pub Date : 2024-02-01 Lingyan Zheng, Shuiyang Shi, Mingkun Lu, Pan Fang, Ziqi Pan, Hongning Zhang, Zhimeng Zhou, Hanyu Zhang, Minjie Mou, Shijie Huang, Lin Tao, Weiqi Xia, Honglin Li, Zhenyu Zeng, Shun Zhang, Yuzong Chen, Zhaorong Li, Feng Zhu
Protein function annotation has been one of the longstanding issues in biological sciences, and various computational methods have been developed. However, the existing methods suffer from a serious long-tail problem, with a large number of GO families containing few annotated proteins. Herein, an innovative strategy named AnnoPRO was therefore constructed by enabling sequence-based multi-scale protein
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BORIS/CTCFL epigenetically reprograms clustered CTCF binding sites into alternative transcriptional start sites Genome Biol. (IF 12.3) Pub Date : 2024-01-31 Elena M. Pugacheva, Dharmendra Nath Bhatt, Samuel Rivero-Hinojosa, Md Tajmul, Liron Fedida, Emma Price, Yon Ji, Dmitri Loukinov, Alexander V. Strunnikov, Bing Ren, Victor V. Lobanenkov
Pervasive usage of alternative promoters leads to the deregulation of gene expression in carcinogenesis and may drive the emergence of new genes in spermatogenesis. However, little is known regarding the mechanisms underpinning the activation of alternative promoters. Here we describe how alternative cancer-testis-specific transcription is activated. We show that intergenic and intronic CTCF binding