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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
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RExPRT: a machine learning tool to predict pathogenicity of tandem repeat loci Genome Biol. (IF 12.3) Pub Date : 2024-01-31 Sarah Fazal, Matt C. Danzi, Isaac Xu, Shilpa Nadimpalli Kobren, Shamil Sunyaev, Chloe Reuter, Shruti Marwaha, Matthew Wheeler, Egor Dolzhenko, Francesca Lucas, Stefan Wuchty, Mustafa Tekin, Stephan Züchner, Vanessa Aguiar-Pulido
Expansions of tandem repeats (TRs) cause approximately 60 monogenic diseases. We expect that the discovery of additional pathogenic repeat expansions will narrow the diagnostic gap in many diseases. A growing number of TR expansions are being identified, and interpreting them is a challenge. We present RExPRT (Repeat EXpansion Pathogenicity pRediction Tool), a machine learning tool for distinguishing
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Computational validation of clonal and subclonal copy number alterations from bulk tumor sequencing using CNAqc Genome Biol. (IF 12.3) Pub Date : 2024-01-31 Alice Antonello, Riccardo Bergamin, Nicola Calonaci, Jacob Househam, Salvatore Milite, Marc J. Williams, Fabio Anselmi, Alberto d’Onofrio, Vasavi Sundaram, Alona Sosinsky, William C. H. Cross, Giulio Caravagna
Copy number alterations (CNAs) are among the most important genetic events in cancer, but their detection from sequencing data is challenging because of unknown sample purity, tumor ploidy, and general intra-tumor heterogeneity. Here, we present CNAqc, an evolution-inspired method to perform the computational validation of clonal and subclonal CNAs detected from bulk DNA sequencing. CNAqc is validated
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deMULTIplex2: robust sample demultiplexing for scRNA-seq Genome Biol. (IF 12.3) Pub Date : 2024-01-30 Qin Zhu, Daniel N. Conrad, Zev J. Gartner
Sample multiplexing enables pooled analysis during single-cell RNA sequencing workflows, thereby increasing throughput and reducing batch effects. A challenge for all multiplexing techniques is to link sample-specific barcodes with cell-specific barcodes, then demultiplex sample identity post-sequencing. However, existing demultiplexing tools fail under many real-world conditions where barcode cross-contamination
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Mosaic loss of Y chromosome is associated with aging and epithelial injury in chronic kidney disease Genome Biol. (IF 12.3) Pub Date : 2024-01-29 Parker C. Wilson, Amit Verma, Yasuhiro Yoshimura, Yoshiharu Muto, Haikuo Li, Nicole P. Malvin, Eryn E. Dixon, Benjamin D. Humphreys
Mosaic loss of Y chromosome (LOY) is the most common chromosomal alteration in aging men. Here, we use single-cell RNA and ATAC sequencing to show that LOY is present in the kidney and increases with age and chronic kidney disease. The likelihood of a cell having LOY varies depending on its location in the nephron. Cortical epithelial cell types have a greater proportion of LOY than medullary or glomerular
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Gene panel selection for targeted spatial transcriptomics Genome Biol. (IF 12.3) Pub Date : 2024-01-25 Yida Zhang, Viktor Petukhov, Evan Biederstedt, Richard Que, Kun Zhang, Peter V. Kharchenko
Targeted spatial transcriptomics hold particular promise in analyzing complex tissues. Most such methods, however, measure only a limited panel of transcripts, which need to be selected in advance to inform on the cell types or processes being studied. A limitation of existing gene selection methods is their reliance on scRNA-seq data, ignoring platform effects between technologies. Here we describe
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Quartet metabolite reference materials for inter-laboratory proficiency test and data integration of metabolomics profiling Genome Biol. (IF 12.3) Pub Date : 2024-01-24 Naixin Zhang, Qiaochu Chen, Peipei Zhang, Kejun Zhou, Yaqing Liu, Haiyan Wang, Shumeng Duan, Yongming Xie, Wenxiang Yu, Ziqing Kong, Luyao Ren, Wanwan Hou, Jingcheng Yang, Xiaoyun Gong, Lianhua Dong, Xiang Fang, Leming Shi, Ying Yu, Yuanting Zheng
Various laboratory-developed metabolomic methods lead to big challenges in inter-laboratory comparability and effective integration of diverse datasets. As part of the Quartet Project, we establish a publicly available suite of four metabolite reference materials derived from B lymphoblastoid cell lines from a family of parents and monozygotic twin daughters. We generate comprehensive LC–MS-based metabolomic
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The unusual gene architecture of polyubiquitin is created by dual-specific splice sites Genome Biol. (IF 12.3) Pub Date : 2024-01-24 Chaorui Duan, Truman Mooney, Luke Buerer, Cory Bowers, Stephen Rong, Seong Won Kim, Alger M. Fredericks, Sean F. Monaghan, William G. Fairbrother
The removal of introns occurs through the splicing of a 5′ splice site (5′ss) with a 3′ splice site (3′ss). These two elements are recognized by distinct components of the spliceosome. However, introns in higher eukaryotes contain many matches to the 5′ and 3′ splice-site motifs that are presumed not to be used. Here, we find that many of these sites can be used. We also find occurrences of the AGGT
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Unraveling the phylogenomic diversity of Methanomassiliicoccales and implications for mitigating ruminant methane emissions Genome Biol. (IF 12.3) Pub Date : 2024-01-23 Fei Xie, Shengwei Zhao, Xiaoxiu Zhan, Yang Zhou, Yin Li, Weiyun Zhu, Phillip B. Pope, Graeme T. Attwood, Wei Jin, Shengyong Mao
Methanomassiliicoccales are a recently identified order of methanogens that are diverse across global environments particularly the gastrointestinal tracts of animals; however, their metabolic capacities are defined via a limited number of cultured strains. Here, we profile and analyze 243 Methanomassiliicoccales genomes assembled from cultured representatives and uncultured metagenomes recovered from
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FMRP-mediated spatial regulation of physiologic NMD targets in neuronal cells Genome Biol. (IF 12.3) Pub Date : 2024-01-23 Tatsuaki Kurosaki, Xavier Rambout, Lynne E. Maquat
In non-polarized cells, nonsense-mediated mRNA decay (NMD) generally begins during the translation of newly synthesized mRNAs after the mRNAs are exported to the cytoplasm. Binding of the FMRP translational repressor to UPF1 on NMD targets mainly inhibits NMD. However, in polarized cells like neurons, FMRP additionally localizes mRNAs to cellular projections. Here, we review the literature and evaluate
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Structural variation and DNA methylation shape the centromere-proximal meiotic crossover landscape in Arabidopsis Genome Biol. (IF 12.3) Pub Date : 2024-01-22 Joiselle B. Fernandes, Matthew Naish, Qichao Lian, Robin Burns, Andrew J. Tock, Fernando A. Rabanal, Piotr Wlodzimierz, Anette Habring, Robert E. Nicholas, Detlef Weigel, Raphael Mercier, Ian R. Henderson
Centromeres load kinetochore complexes onto chromosomes, which mediate spindle attachment and allow segregation during cell division. Although centromeres perform a conserved cellular function, their underlying DNA sequences are highly divergent within and between species. Despite variability in DNA sequence, centromeres are also universally suppressed for meiotic crossover recombination, across eukaryotes
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PICALO: principal interaction component analysis for the identification of discrete technical, cell-type, and environmental factors that mediate eQTLs Genome Biol. (IF 12.3) Pub Date : 2024-01-22 Martijn Vochteloo, Patrick Deelen, Britt Vink, Ellen A. Tsai, Heiko Runz, Sergio Andreu-Sánchez, Jingyuan Fu, Alexandra Zhernakova, Harm-Jan Westra, Lude Franke
Expression quantitative trait loci (eQTL) offer insights into the regulatory mechanisms of trait-associated variants, but their effects often rely on contexts that are unknown or unmeasured. We introduce PICALO, a method for hidden variable inference of eQTL contexts. PICALO identifies and disentangles technical from biological context in heterogeneous blood and brain bulk eQTL datasets. These contexts
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SURGE: uncovering context-specific genetic-regulation of gene expression from single-cell RNA sequencing using latent-factor models Genome Biol. (IF 12.3) Pub Date : 2024-01-22 Benjamin J. Strober, Karl Tayeb, Joshua Popp, Guanghao Qi, M. Grace Gordon, Richard Perez, Chun Jimmie Ye, Alexis Battle
Genetic regulation of gene expression is a complex process, with genetic effects known to vary across cellular contexts such as cell types and environmental conditions. We developed SURGE, a method for unsupervised discovery of context-specific expression quantitative trait loci (eQTLs) from single-cell transcriptomic data. This allows discovery of the contexts or cell types modulating genetic regulation
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DeepVelo: deep learning extends RNA velocity to multi-lineage systems with cell-specific kinetics Genome Biol. (IF 12.3) Pub Date : 2024-01-19 Haotian Cui, Hassaan Maan, Maria C. Vladoiu, Jiao Zhang, Michael D. Taylor, Bo Wang
Existing RNA velocity estimation methods strongly rely on predefined dynamics and cell-agnostic constant transcriptional kinetic rates, assumptions often violated in complex and heterogeneous single-cell RNA sequencing (scRNA-seq) data. Using a graph convolution network, DeepVelo overcomes these limitations by generalizing RNA velocity to cell populations containing time-dependent kinetics and multiple
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Haplotype-resolved assembly of a tetraploid potato genome using long reads and low-depth offspring data Genome Biol. (IF 12.3) Pub Date : 2024-01-19 Rebecca Serra Mari, Sven Schrinner, Richard Finkers, Freya Maria Rosemarie Ziegler, Paul Arens, Maximilian H.-W. Schmidt, Björn Usadel, Gunnar W. Klau, Tobias Marschall
Potato is one of the world’s major staple crops, and like many important crop plants, it has a polyploid genome. Polyploid haplotype assembly poses a major computational challenge. We introduce a novel strategy for the assembly of polyploid genomes and present an assembly of the autotetraploid potato cultivar Altus. Our method uses low-depth sequencing data from an offspring population to achieve chromosomal
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Compact CRISPR genetic screens enabled by improved guide RNA library cloning Genome Biol. (IF 12.3) Pub Date : 2024-01-19 Seok-Jin Heo, Lauren D. Enriquez, Scot Federman, Amy Y. Chang, Rachel Mace, Kaivalya Shevade, Phuong Nguyen, Adam J. Litterman, Shawn Shafer, Laralynne Przybyla, Eric D. Chow
CRISPR genome editing approaches theoretically enable researchers to define the function of each human gene in specific cell types, but challenges remain to efficiently perform genetic perturbations in relevant models. In this work, we develop a library cloning protocol that increases sgRNA uniformity and greatly reduces bias in existing genome-wide libraries. We demonstrate that our libraries can
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Structure-primed embedding on the transcription factor manifold enables transparent model architectures for gene regulatory network and latent activity inference Genome Biol. (IF 12.3) Pub Date : 2024-01-18 Andreas Tjärnberg, Maggie Beheler-Amass, Christopher A. Jackson, Lionel A. Christiaen, David Gresham, Richard Bonneau
Modeling of gene regulatory networks (GRNs) is limited due to a lack of direct measurements of genome-wide transcription factor activity (TFA) making it difficult to separate covariance and regulatory interactions. Inference of regulatory interactions and TFA requires aggregation of complementary evidence. Estimating TFA explicitly is problematic as it disconnects GRN inference and TFA estimation and
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Improved modeling of RNA-binding protein motifs in an interpretable neural model of RNA splicing Genome Biol. (IF 12.3) Pub Date : 2024-01-16 Kavi Gupta, Chenxi Yang, Kayla McCue, Osbert Bastani, Phillip A. Sharp, Christopher B. Burge, Armando Solar-Lezama
Sequence-specific RNA-binding proteins (RBPs) play central roles in splicing decisions. Here, we describe a modular splicing architecture that leverages in vitro-derived RNA affinity models for 79 human RBPs and the annotated human genome to produce improved models of RBP binding and activity. Binding and activity are modeled by separate Motif and Aggregator components that can be mixed and matched
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Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes Genome Biol. (IF 12.3) Pub Date : 2024-01-16 Jonathan P. Bradfield, Rachel L. Kember, Anna Ulrich, Zhanna Balkiyarova, Akram Alyass, Izzuddin M. Aris, Joshua A. Bell, K. Alaine Broadaway, Zhanghua Chen, Jin-Fang Chai, Neil M. Davies, Dietmar Fernandez-Orth, Mariona Bustamante, Ruby Fore, Amitavo Ganguli, Anni Heiskala, Jouke-Jan Hottenga, Carmen Íñiguez, Sayuko Kobes, Jaakko Leinonen, Estelle Lowry, Leo-Pekka Lyytikainen, Anubha Mahajan, Niina
Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis
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Chromatin activity identifies differential gene regulation across human ancestries Genome Biol. (IF 12.3) Pub Date : 2024-01-15 Kade P. Pettie, Maxwell Mumbach, Amanda J. Lea, Julien Ayroles, Howard Y. Chang, Maya Kasowski, Hunter B. Fraser
Current evidence suggests that cis-regulatory elements controlling gene expression may be the predominant target of natural selection in humans and other species. Detecting selection acting on these elements is critical to understanding evolution but remains challenging because we do not know which mutations will affect gene regulation. To address this, we devise an approach to search for lineage-specific
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scSNV-seq: high-throughput phenotyping of single nucleotide variants by coupled single-cell genotyping and transcriptomics Genome Biol. (IF 12.3) Pub Date : 2024-01-15 Sarah E. Cooper, Matthew A. Coelho, Magdalena E. Strauss, Aleksander M. Gontarczyk, Qianxin Wu, Mathew J. Garnett, John C. Marioni, Andrew R. Bassett
CRISPR screens with single-cell transcriptomic readouts are a valuable tool to understand the effect of genetic perturbations including single nucleotide variants (SNVs) associated with diseases. Interpretation of these data is currently limited as genotypes cannot be accurately inferred from guide RNA identity alone. scSNV-seq overcomes this limitation by coupling single-cell genotyping and transcriptomics
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ARMC5 controls the degradation of most Pol II subunits, and ARMC5 mutation increases neural tube defect risks in mice and humans Genome Biol. (IF 12.3) Pub Date : 2024-01-15 Hongyu Luo, Linjiang Lao, Kit Sing Au, Hope Northrup, Xiao He, Diane Forget, Marie-Soleil Gauthier, Benoit Coulombe, Isabelle Bourdeau, Wei Shi, Lucia Gagliardi, Maria Candida Barisson Villares Fragoso, Junzheng Peng, Jiangping Wu
Neural tube defects (NTDs) are caused by genetic and environmental factors. ARMC5 is part of a novel ubiquitin ligase specific for POLR2A, the largest subunit of RNA polymerase II (Pol II). We find that ARMC5 knockout mice have increased incidence of NTDs, such as spina bifida and exencephaly. Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11
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Evaluating spatially variable gene detection methods for spatial transcriptomics data Genome Biol. (IF 12.3) Pub Date : 2024-01-15 Carissa Chen, Hani Jieun Kim, Pengyi Yang
The identification of genes that vary across spatial domains in tissues and cells is an essential step for spatial transcriptomics data analysis. Given the critical role it serves for downstream data interpretations, various methods for detecting spatially variable genes (SVGs) have been proposed. However, the lack of benchmarking complicates the selection of a suitable method. Here we systematically
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Phase separation as a possible mechanism for dosage sensitivity Genome Biol. (IF 12.3) Pub Date : 2024-01-15 Liang Yang, Jiali Lyu, Xi Li, Gaigai Guo, Xueya Zhou, Taoyu Chen, Yi Lin, Tingting Li
Deletion of haploinsufficient genes or duplication of triplosensitive ones results in phenotypic effects in a concentration-dependent manner, and the mechanisms underlying these dosage-sensitive effects remain elusive. Phase separation drives functional compartmentalization of biomolecules in a concentration-dependent manner as well, which suggests a potential link between these two processes, and
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RNA-binding protein RBM5 plays an essential role in acute myeloid leukemia by activating the oncogenic protein HOXA9 Genome Biol. (IF 12.3) Pub Date : 2024-01-12 Mengli Zhang, Judith Hyle, Xiaowen Chen, Ye Xin, Yingcai Jin, Jianxiang Zhang, Xue Yang, Xinfeng Chen, Shaela Wright, Zhenling Liu, Wojciech Rosikiewicz, Beisi Xu, Liusheng He, Hong Liu, Nana Ping, Depei Wu, Feiqiu Wen, Chunliang Li, Peng Xu
The oncogenic protein HOXA9 plays a critical role in leukemia transformation and maintenance, and its aberrant expression is a hallmark of most aggressive acute leukemia. Although inhibiting the upstream regulators of HOXA9 has been proven as a significant therapeutic intervention, the comprehensive regulation network controlling HOXA9 expression in leukemia has not been systematically investigated
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ChIPr: accurate prediction of cohesin-mediated 3D genome organization from 2D chromatin features Genome Biol. (IF 12.3) Pub Date : 2024-01-12 Ahmed Abbas, Khyati Chandratre, Yunpeng Gao, Jiapei Yuan, Michael Q. Zhang, Ram S. Mani
The three-dimensional genome organization influences diverse nuclear processes. Here we present Chromatin Interaction Predictor (ChIPr), a suite of regression models based on deep neural networks, random forest, and gradient boosting to predict cohesin-mediated chromatin interaction strength between any two loci in the genome. The predictions of ChIPr correlate well with ChIA-PET data in four cell
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Niche-DE: niche-differential gene expression analysis in spatial transcriptomics data identifies context-dependent cell-cell interactions Genome Biol. (IF 12.3) Pub Date : 2024-01-12 Kaishu Mason, Anuja Sathe, Paul R. Hess, Jiazhen Rong, Chi-Yun Wu, Emma Furth, Katalin Susztak, Jonathan Levinsohn, Hanlee P. Ji, Nancy Zhang
Existing methods for analysis of spatial transcriptomic data focus on delineating the global gene expression variations of cell types across the tissue, rather than local gene expression changes driven by cell-cell interactions. We propose a new statistical procedure called niche-differential expression (niche-DE) analysis that identifies cell-type-specific niche-associated genes, which are differentially
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Improved prediction of bacterial CRISPRi guide efficiency from depletion screens through mixed-effect machine learning and data integration Genome Biol. (IF 12.3) Pub Date : 2024-01-11 Yanying Yu, Sandra Gawlitt, Lisa Barros de Andrade e Sousa, Erinc Merdivan, Marie Piraud, Chase L. Beisel, Lars Barquist
CRISPR interference (CRISPRi) is the leading technique to silence gene expression in bacteria; however, design rules remain poorly defined. We develop a best-in-class prediction algorithm for guide silencing efficiency by systematically investigating factors influencing guide depletion in genome-wide essentiality screens, with the surprising discovery that gene-specific features substantially impact
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GTax: improving de novo transcriptome assembly by removing foreign RNA contamination Genome Biol. (IF 12.3) Pub Date : 2024-01-08 Roberto Vera Alvarez, David Landsman
The cost and complexity of generating a complete reference genome means that many organisms lack an annotated reference. An alternative is to use a de novo reference transcriptome. This technology is cost-effective but is susceptible to off-target RNA contamination. In this manuscript, we present GTax, a taxonomy-structured database of genomic sequences that can be used with BLAST to detect and remove