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Variation in the fitness impact of translationally optimal codons among animals Genome Res. (IF 6.2) Pub Date : 2025-02-10 Florian Bénitière, Tristan Lefébure, Laurent Duret
Early studies in invertebrate model organisms (fruit flies, nematodes) showed that their synonymous codon usage is under selective pressure to optimize translation efficiency in highly expressed genes (a process called translational selection). In contrast, mammals show little evidence of selection for translationally optimal codons. To understand this difference, we examined the use of synonymous
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Nucleosome-binding by TP53, TP63, and TP73 is determined by the composition, accessibility, and helical orientation of their binding sites Genome Res. (IF 6.2) Pub Date : 2025-02-10 Patrick Wilson, Xinyang Yu, Christopher R Handelmann, Michael J Buck
The TP53 family of transcription factors plays key roles in driving development and combating cancer by regulating gene expression. TP53, TP63, and TP73 - the three members of the TP53 family - regulate gene expression by binding to their DNA binding sites, many of which are situated within nucleosomes. To thoroughly examine the nucleosome-binding abilities of the TP53 family, we used Pioneer-seq,
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Kernel-bounded clustering for spatial transcriptomics enables scalable discovery of complex spatial domains Genome Res. (IF 6.2) Pub Date : 2025-02-05 Hang Zhang, Yi Zhang, Kai Ming Ting, Jie Zhang, Qiuran Zhao
Spatial transcriptomics are a collection of technologies that have enabled characterization of gene expression profiles and spatial information in tissue samples. Existing methods for clustering spatial transcriptomics data have primarily focused on data transformation techniques to represent the data suitably for subsequent clustering analysis, often using an existing clustering algorithm. These methods
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The additional diagnostic yield of long-read sequencing in undiagnosed rare diseases Genome Res. (IF 6.2) Pub Date : 2025-02-03 Giulia F. Del Gobbo, Kym M. Boycott
Long-read sequencing (LRS) is a promising technology positioned to study the significant proportion of rare diseases (RDs) that remain undiagnosed as it addresses many of the limitations of short-read sequencing, detecting and clarifying additional disease-associated variants that may be missed by the current standard diagnostic workflow for RDs. Some key areas where additional diagnostic yields may
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k-mer approaches for biodiversity genomics Genome Res. (IF 6.2) Pub Date : 2025-01-31 Katharine M. Jenike, Lucía Campos-Domínguez, Marilou Boddé, José Cerca, Christina N. Hodson, Michael C. Schatz, Kamil S. Jaron
The wide array of currently available genomes displays a wonderful diversity in size, composition, and structure and is quickly expanding thanks to several global biodiversity genomics initiatives. However, sequencing of genomes, even with the latest technologies, can still be challenging for both technical (e.g., small physical size, contaminated samples, or access to appropriate sequencing platforms)
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Rapid and accurate demultiplexing of direct RNA nanopore sequencing datasets with SeqTagger Genome Res. (IF 6.2) Pub Date : 2025-01-29 Leszek P Pryszcz, Gregor Diensthuber, Laia Llovera, Rebeca Medina, Anna Delgado-Tejedor, Luca Cozzuto, Julia Ponomarenko, Eva Maria Novoa
Nanopore direct RNA sequencing (DRS) enables direct measurement of RNA molecules, including their native RNA modifications, without prior conversion to cDNA. However, commercial methods for molecular barcoding of multiple DRS samples are lacking, and community-driven efforts, such as DeePlexiCon, are not compatible with newer RNA chemistry flowcells and the latest-generation GPU cards. To overcome
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Enhancing nanopore adaptive sampling for PromethION using readfish at scale Genome Res. (IF 6.2) Pub Date : 2025-01-30 Rory Munro, Alex Payne, Nadine Holmes, Chris Moore, Inswasti Cahyani, Matt Loose
A unique feature of Oxford Nanopore Technologies sequencers, adaptive sampling, allows precise DNA molecule selection from sequencing libraries. Here we present enhancements to our tool, readfish, enabling all features for the industrial scale PromethION sequencer, including standard and "barcode-aware" adaptive sampling. We demonstrate effective coverage enrichment and assessment of multiple human
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Nanopore-based consensus sequencing enables accurate multimodal tumor cell-free DNA profiling Genome Res. (IF 6.2) Pub Date : 2025-01-13 Li-Ting Chen, Myrthe Jager, Dàmi Rebergen, Geertruid J. Brink, Tom van den Ende, Willem Vanderlinden, Pauline Kolbeck, Marc Pagès-Gallego, Ymke van der Pol, Nicolle Besselink, Norbert Moldovan, Nizar Hami, Wigard P. Kloosterman, Hanneke van Laarhoven, Florent Mouliere, Ronald Zweemer, Jan Lipfert, Sarah Derks, Alessio Marcozzi, Jeroen de Ridder
Shallow genome-wide cell-free DNA (cfDNA) sequencing holds great promise for non-invasive cancer monitoring by providing reliable copy number alteration (CNA) and fragmentomic profiles. Single nucleotide variations (SNVs) are, however, much harder to identify with low sequencing depth due to sequencing errors. Here we present Nanopore Rolling Circle Amplification (RCA)-enhanced Consensus Sequencing
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Interactive visualization and interpretation of pangenome graphs by linear reference–based coordinate projection and annotation integration Genome Res. (IF 6.2) Pub Date : 2025-01-13 Zepu Miao, Jia-Xing Yue
With the increasing availability of high-quality genome assemblies, pangenome graphs emerged as a new paradigm in the genomic field for identifying, encoding, and presenting genomic variation at both the population and species level. However, it remains challenging to truly dissect and interpret pangenome graphs via biologically informative visualization. To facilitate better exploration and understanding
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Characterization of the role of spatial proximity of DNA double-strand breaks in the formation of CRISPR-Cas9-induced large structural variations Genome Res. (IF 6.2) Pub Date : 2025-01-13 Mikkel Dahl-Jessen, Thorkild Terkelsen, Rasmus O. Bak, Uffe Birk Jensen
Structural variations (SVs) play important roles in genetic diversity, evolution, and carcinogenesis and are, as such, important for human health. However, it remains unclear how spatial proximity of double-strand breaks (DSBs) affects the formation of SVs. To investigate if spatial proximity between two DSBs affects DNA repair, we used data from 3C experiments (Hi-C, ChIA-PET, and ChIP-seq) to identify
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Single-cell Rapid Capture Hybridization sequencing to reliably detect isoform usage and coding mutations in targeted genes Genome Res. (IF 6.2) Pub Date : 2025-01-10 Hongke Peng, Jafar S. Jabbari, Luyi Tian, Changqing Wang, Yupei You, Chong Chyn Chua, Natasha S. Anstee, Noorul Amin, Andrew H. Wei, Nadia Davidson, Andrew W. Roberts, David Huang, Matthew E Ritchie, Rachel Thijssen
Single-cell long-read sequencing has transformed our understanding of isoform usage and the mutation heterogeneity between cells. Despite unbiased in-depth analysis, the low sequencing throughput often results in insufficient read coverage thereby limiting our ability to perform mutation calling for specific genes. Here, we developed a single-cell Rapid Capture Hybridization sequencing (scRaCH-seq)
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Proxy panels enable privacy-aware outsourcing of genotype imputation Genome Res. (IF 6.2) Pub Date : 2025-01-10 Degui Zhi, Xiaoqian Jiang, Arif Harmanci
One of the major challenges in genomic data sharing is protecting participants’ privacy in collaborative studies and in cases when genomic data are outsourced to perform analysis tasks, for example, genotype imputation services and federated collaborations genomic analysis. Although numerous cryptographic methods have been developed, these methods may not yet be practical for population-scale tasks
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Timescale and genetic linkage explain the variable impact of defense systems on horizontal gene transfer Genome Res. (IF 6.2) Pub Date : 2025-01-10 Yang Liu, João Botelho, Jaime Iranzo
Prokaryotes have evolved a wide repertoire of defense systems to prevent invasion by mobile genetic elements (MGEs). However, because MGEs are vehicles for the exchange of beneficial accessory genes, defense systems could consequently impede rapid adaptation in microbial populations. Here, we study how defense systems impact horizontal gene transfer (HGT) in the short term and long term. By combining
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Ultraviolet damage and repair maps in Drosophila reveal the impact of domain-specific changes in nucleosome repeat length on repair efficiency Genome Res. (IF 6.2) Pub Date : 2025-01-06 Benjamin Morledge-Hampton, Kathiresan Selvam, Manish Chauhan, Alan G. Goodman, John J. Wyrick
Cyclobutane pyrimidine dimers (CPDs) are formed in DNA following exposure to ultraviolet (UV) light and are mutagenic unless repaired by nucleotide excision repair (NER). It is known that CPD repair rates vary in different genome regions owing to transcription-coupled NER and differences in chromatin accessibility; however, the impact of regional chromatin organization on CPD formation remains unclear
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Identification of the shortest species-specific oligonucleotide sequences Genome Res. (IF 6.2) Pub Date : 2025-01-02 Ioannis Mouratidis, Maxwell A. Konnaris, Nikol Chantzi, Candace S.Y. Chan, Michail Patsakis, Kimonas Provatas, Austin Montgomery, Fotis A. Baltoumas, Congzhou M. Sha, Manvita Mareboina, Georgios A. Pavlopoulos, Dionysios V. Chartoumpekis, Ilias Georgakopoulos-Soares
Despite the exponential increase in sequencing information driven by massively parallel DNA sequencing technologies, universal and succinct genomic fingerprints for each organism are still missing. Identifying the shortest species-specific nucleotide sequences offers insights into species evolution and holds potential practical applications in agriculture, wildlife conservation, and healthcare. We
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Artificial intelligence and machine learning in cell-free-DNA-based diagnostics Genome Res. (IF 6.2) Pub Date : 2025-01-01 W.H. Adrian Tsui, Spencer C. Ding, Peiyong Jiang, Y.M. Dennis Lo
The discovery of circulating fetal and tumor cell-free DNA (cfDNA) molecules in plasma has opened up tremendous opportunities in noninvasive diagnostics such as the detection of fetal chromosomal aneuploidies and cancers and in posttransplantation monitoring. The advent of high-throughput sequencing technologies makes it possible to scrutinize the characteristics of cfDNA molecules, opening up the
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Common and specific gene regulatory programs in zebrafish caudal fin regeneration at single-cell resolution Genome Res. (IF 6.2) Pub Date : 2025-01-01 Yujie Chen, Yiran Hou, Qinglin Zeng, Irene Wang, Meiru Shang, Kwangdeok Shin, Christopher Hemauer, Xiaoyun Xing, Junsu Kang, Guoyan Zhao, Ting Wang
Following amputation, zebrafish regenerate their injured caudal fin through lineage-restricted reprogramming. Although previous studies have charted various genetic and epigenetic dimensions of this process, the intricate gene regulatory programs shared by, or unique to, different regenerating cell types remain underinvestigated. Here, we mapped the regulatory landscape of fin regeneration by applying
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Post-transcriptional cross- and auto-regulation buffer expression of the human RNA helicases DDX3X and DDX3Y Genome Res. (IF 6.2) Pub Date : 2025-01-01 Shruthi Rengarajan, Jason Derks, Daniel W. Bellott, Nikolai Slavov, David C. Page
The Y-linked gene DDX3Y and its X-linked homolog DDX3X survived the evolution of the human sex chromosomes from ordinary autosomes. DDX3X encodes a multifunctional RNA helicase, with mutations causing developmental disorders and cancers. We find that, among X-linked genes with surviving Y homologs, DDX3X is extraordinarily dosage sensitive. Studying cells of individuals with sex chromosome aneuploidy
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Fusion, fission, and scrambling of the bilaterian genome in Bryozoa Genome Res. (IF 6.2) Pub Date : 2025-01-01 Thomas D. Lewin, Isabel Jiah-Yih Liao, Mu-En Chen, John D.D. Bishop, Peter W.H. Holland, Yi-Jyun Luo
Groups of orthologous genes are commonly found together on the same chromosome over vast evolutionary distances. This extensive physical gene linkage, known as macrosynteny, is seen between bilaterian phyla as divergent as Chordata, Echinodermata, Mollusca, and Nemertea. Here, we report a unique pattern of genome evolution in Bryozoa, an understudied phylum of colonial invertebrates. Using comparative
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Hierarchical architecture of neo-sex chromosomes and accelerated adaptive evolution in tortricid moths Genome Res. (IF 6.2) Pub Date : 2025-01-01 Fangyuan Yang, Li-Jun Cao, Petr Nguyen, Zhong-Zheng Ma, Jin-Cui Chen, Wei Song, Shu-Jun Wei
Sex chromosomes can expand through fusion with autosomes, thereby acquiring unique evolutionary patterns. In butterflies and moths (Lepidoptera), these sex chromosome–autosome (SA) fusions occur relatively frequently, suggesting possible evolutionary advantages. Here, we investigated how SA fusion affects chromosome features and molecular evolution in leafroller moths (Lepidoptera: Tortricidae). Phylogenomic
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Inferring disease progression stages in single-cell transcriptomics using a weakly supervised deep learning approach Genome Res. (IF 6.2) Pub Date : 2025-01-01 Fabien Wehbe, Levi Adams, Jordan Babadoudou, Samantha Yuen, Yoon-Seong Kim, Yoshiaki Tanaka
Application of single-cell/nucleus genomic sequencing to patient-derived tissues offers potential solutions to delineate disease mechanisms in humans. However, individual cells in patient-derived tissues are in different pathological stages, and hence, such cellular variability impedes subsequent differential gene expression analyses. To overcome such a heterogeneity issue, we present a novel deep
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The rate and spectrum of new mutations in mice inferred by long-read sequencing Genome Res. (IF 6.2) Pub Date : 2025-01-01 Eugenio López-Cortegano, Jobran Chebib, Anika Jonas, Anastasia Vock, Sven Künzel, Peter D. Keightley, Diethard Tautz
All forms of genetic variation originate from new mutations, making it crucial to understand their rates and mechanisms. Here, we use long-read sequencing from Pacific Biosciences (PacBio) to investigate de novo mutations that accumulated in 12 inbred mouse lines derived from three commonly used inbred strains (C3H, C57BL/6, and FVB) maintained for 8 to 15 generations in a mutation accumulation (MA)
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Single-nucleus CUT&RUN elucidates the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression Genome Res. (IF 6.2) Pub Date : 2025-01-01 Howard J. Womersley, Daniel Muliaditan, Ramanuj DasGupta, Lih Feng Cheow
Interrogating regulatory epigenetic alterations during tumor progression at the resolution of single cells has remained an understudied area of research. Here we developed a highly sensitive single-nucleus CUT&RUN (snCUT&RUN) assay to profile histone modifications in isogenic primary, metastatic, and cisplatin-resistant head and neck squamous cell carcinoma (HNSCC) patient–derived tumor cell lines
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Analysis of a cell-free DNA–based cancer screening cohort links fragmentomic profiles, nuclease levels, and plasma DNA concentrations Genome Res. (IF 6.2) Pub Date : 2025-01-01 Yasine Malki, Guannan Kang, W.K. Jacky Lam, Qing Zhou, Suk Hang Cheng, Peter P.H. Cheung, Jinyue Bai, Ming Lok Chan, Chui Ting Lee, Wenlei Peng, Yiqiong Zhang, Wanxia Gai, Winsome W.S. Wong, Mary-Jane L. Ma, Wenshuo Li, Xinzhou Xu, Zhuoran Gao, Irene O.L. Tse, Huimin Shang, L.Y. Lois Choy, Peiyong Jiang, K.C. Allen Chan, Y.M. Dennis Lo
The concentration of circulating cell-free DNA (cfDNA) in plasma is an important determinant of the robustness of liquid biopsies. However, biological mechanisms that lead to inter-individual differences in cfDNA concentrations remain unexplored. The concentration of plasma cfDNA is governed by an interplay between its release and clearance. We hypothesized that cfDNA clearance by nucleases might be
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Chimeric mitochondrial RNA transcripts predict mitochondrial genome deletion mutations in mitochondrial genetic diseases and aging Genome Res. (IF 6.2) Pub Date : 2025-01-01 Amy R. Vandiver, Allen Herbst, Paul Stothard, Jonathan Wanagat
Although it is well understood that mitochondrial DNA (mtDNA) deletion mutations cause incurable diseases and contribute to aging, little is known about the transcriptional products that arise from these DNA structural variants. We hypothesized that mitochondrial genomes containing deletion mutations express chimeric mitochondrial RNAs. To test this, we analyzed human and rat RNA sequencing data to
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A deconvolution framework that uses single-cell sequencing plus a small benchmark data set for accurate analysis of cell type ratios in complex tissue samples Genome Res. (IF 6.2) Pub Date : 2025-01-01 Shuai Guo, Xiaoqian Liu, Xuesen Cheng, Yujie Jiang, Shuangxi Ji, Qingnan Liang, Andrew Koval, Yumei Li, Leah A. Owen, Ivana K. Kim, Ana Aparicio, Sanghoon Lee, Anil K. Sood, Scott Kopetz, John Paul Shen, John N. Weinstein, Margaret M. DeAngelis, Rui Chen, Wenyi Wang
Bulk deconvolution with single-cell/nucleus RNA-seq data is critical for understanding heterogeneity in complex biological samples, yet the technological discrepancy across sequencing platforms limits deconvolution accuracy. To address this, we utilize an experimental design to match inter-platform biological signals, hence revealing the technological discrepancy, and then develop a deconvolution framework
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The chromatin landscape of the histone-possessing Bacteriovorax bacteria Genome Res. (IF 6.2) Pub Date : 2025-01-01 Georgi K. Marinov, Benjamin Doughty, Anshul Kundaje, William J. Greenleaf
Histone proteins have traditionally been thought to be restricted to eukaryotes and most archaea, with eukaryotic nucleosomal histones deriving from their archaeal ancestors. In contrast, bacteria lack histones as a rule. However, histone proteins have recently been identified in a few bacterial clades, most notably the phylum Bdellovibrionota, and these histones have been proposed to exhibit a range
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KAS-ATAC reveals the genome-wide single-stranded accessible chromatin landscape of the human genome Genome Res. (IF 6.2) Pub Date : 2025-01-01 Samuel H. Kim, Georgi K. Marinov, William J. Greenleaf
Gene regulation in most eukaryotes involves two fundamental processes: alterations in genome packaging by nucleosomes, with active cis-regulatory elements (CREs) generally characterized by open-chromatin configuration, and transcriptional activation. Mapping these physical properties and biochemical activities, through profiling chromatin accessibility and active transcription, is a key tool for understanding
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Modeling gene interactions in polygenic prediction via geometric deep learning Genome Res. (IF 6.2) Pub Date : 2025-01-01 Han Li, Jianyang Zeng, Michael P. Snyder, Sai Zhang
Polygenic risk score (PRS) is a widely used approach for predicting individuals’ genetic risk of complex diseases, playing a pivotal role in advancing precision medicine. Traditional PRS methods, predominantly following a linear structure, often fall short in capturing the intricate relationships between genotype and phenotype. In this study, we present PRS-Net, an interpretable geometric deep learning–based
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High-quality sika deer omics data and integrative analysis reveal genic and cellular regulation of antler regeneration Genome Res. (IF 6.2) Pub Date : 2025-01-01 Zihe Li, Ziyu Xu, Lei Zhu, Tao Qin, Jinrui Ma, Zhanying Feng, Huishan Yue, Qing Guan, Botong Zhou, Ge Han, Guokun Zhang, Chunyi Li, Shuaijun Jia, Qiang Qiu, Dingjun Hao, Yong Wang, Wen Wang
The antler is the only organ that can fully regenerate annually in mammals. However, the regulatory pattern and mechanism of gene expression and cell differentiation during this process remain largely unknown. Here, we obtain comprehensive assembly and gene annotation of the sika deer (Cervus nippon) genome. We construct, together with large-scale chromatin accessibility and gene expression data, gene
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ISWI1 complex proteins facilitate developmental genome editing in Paramecium Genome Res. (IF 6.2) Pub Date : 2025-01-01 Aditi Singh, Lilia Häußermann, Christiane Emmerich, Emily Nischwitz, Brandon K.B. Seah, Falk Butter, Mariusz Nowacki, Estienne C. Swart
One of the most extensive forms of natural genome editing occurs in ciliates, a group of microbial eukaryotes. Ciliate germline and somatic genomes are contained in distinct nuclei within the same cell. During the massive reorganization process of somatic genome development, ciliates eliminate tens of thousands of DNA sequences from a germline genome copy. Recently, we showed that the chromatin remodeler
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Combining DNA and protein alignments to improve genome annotation with LiftOn Genome Res. (IF 6.2) Pub Date : 2024-12-27 Kuan-Hao Chao, Jakob M. Heinz, Celine Hoh, Alan Mao, Alaina Shumate, Mihaela Pertea, Steven L. Salzberg
As the number and variety of assembled genomes continue to grow, the number of annotated genomes is falling behind, particularly for eukaryotes. DNA-based mapping tools help to address this challenge, but they are only able to transfer annotation between closely related species. Here we introduce LiftOn, a homology-based software tool that integrates DNA and protein alignments to enhance the accuracy
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Probing the eukaryotic microbes of ruminants with a deep-learning classifier and comprehensive protein databases Genome Res. (IF 6.2) Pub Date : 2024-12-27 Ming Yan, Thea O. Andersen, Phillip B. Pope, Zhongtang Yu
Metagenomics, particularly genome-resolved metagenomics, have significantly deepened our understanding of microbes, illuminating their taxonomic and functional diversity and roles in ecology, physiology, and evolution. However, eukaryotic populations within various microbiomes, including those in the mammalian gastrointestinal (GI) tract, remain relatively underexplored in metagenomic studies owing
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Evaluation of strategies for evidence-driven genome annotation using long-read RNA-seq Genome Res. (IF 6.2) Pub Date : 2024-12-23 Alejandro Paniagua, Cristina Agustin-García, Francisco J Pardo-Palacios, Thomas Brown, Maite De Maria, Nancy D Denslow, Camila Mazzoni, Ana Conesa
While the production of a draft genome has become more accessible due to long-read sequencing, the annotation of these new genomes has not been developed at the same pace. Long-read RNA sequencing (lrRNA-seq) offers a promising solution for enhancing gene annotation. In this study, we explore how sequencing platforms, Oxford Nanopore R9.4.1 chemistry or PacBio Sequel II CCS, and data processing methods
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Aberrant homeodomain–DNA cooperative dimerization underlies distinct developmental defects in two dominant CRX retinopathy models Genome Res. (IF 6.2) Pub Date : 2024-12-23 Yiqiao Zheng, Gary D. Stormo, Shiming Chen
Paired-class homeodomain (HD) transcription factors (TFs) play essential roles in vertebrate development, and their mutations are linked to human diseases. One unique feature of a paired-class HD is cooperative dimerization on specific palindrome DNA sequences. Yet, the functional significance of HD cooperative dimerization in animal development and its dysregulation in diseases remains elusive. Using
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Taurine pangenome uncovers a segmental duplication upstream of KIT associated with depigmentation in white-headed cattle Genome Res. (IF 6.2) Pub Date : 2024-12-18 Sotiria Milia, Alexander Leonard, Xena Marie Mapel, Sandra Milena Bernal Ulloa, Cord Drögemüller, Hubert Pausch
Cattle have been selectively bred for coat color, spotting, and depigmentation patterns. The assumed autosomal dominant inherited genetic variants underlying the characteristic white head of Fleckvieh, Simmental, and Hereford cattle have not been identified yet, although the contribution of structural variation upstream the KIT gene has been proposed. Here, we construct a graph pangenome from 24 haplotype
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Diffusion-based generation of gene regulatory networks from scRNA-seq data with DigNet Genome Res. (IF 6.2) Pub Date : 2024-12-18 Chuanyuan Wang, Zhi-Ping Liu
A gene regulatory network (GRN) intricately encodes the interconnectedness of identities and functionalities of genes within cells, ultimately shaping cellular specificity. Despite decades of endeavors, reverse engineering of GRNs from gene expression profiling data remains a profound challenge, particularly when it comes to reconstructing cell-specific GRNs that are tailored to precise cellular and
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Rearrangements of viral and human genomes at human papillomavirus integration events and their allele-specific impacts on cancer genome regulation Genome Res. (IF 6.2) Pub Date : 2024-12-05 Vanessa L. Porter, Michelle Ng, Kieran O'Neill, Signe MacLennan, Richard D. Corbett, Luka Culibrk, Zeid Hamadeh, Marissa Iden, Rachel Schmidt, Shirng-Wern Tsaih, Carolyn Nakisige, Martin Origa, Jackson Orem, Glenn Chang, Jeremy Fan, Ka Ming Nip, Vahid Akbari, Simon K. Chan, James Hopkins, Richard A. Moore, Eric Chuah, Karen L. Mungall, Andrew J. Mungall, Inanc Birol, Steven J.M. Jones, Janet S. Rader
Human papillomavirus (HPV) integration has been implicated in transforming HPV infection into cancer. To resolve genome dysregulation associated with HPV integration, we performed Oxford Nanopore long-read sequencing on 72 cervical cancer genomes from an Ugandan dataset that was previously characterized using short-read sequencing. We found recurrent structural rearrangement patterns at HPV integration
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MCHelper automatically curates transposable element libraries across eukaryotic species Genome Res. (IF 6.2) Pub Date : 2024-12-01 Simon Orozco-Arias, Pío Sierra, Richard Durbin, Josefa González
The number of species with high-quality genome sequences continues to increase, in part due to the scaling up of multiple large-scale biodiversity sequencing projects. While the need to annotate genic sequences in these genomes is widely acknowledged, the parallel need to annotate transposable element (TE) sequences that have been shown to alter genome architecture, rewire gene regulatory networks
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Resolving the chromatin impact of mosaic variants with targeted Fiber-seq Genome Res. (IF 6.2) Pub Date : 2024-12-01 Stephanie C. Bohaczuk, Zachary J. Amador, Chang Li, Benjamin J. Mallory, Elliott G. Swanson, Jane Ranchalis, Mitchell R. Vollger, Katherine M. Munson, Tom Walsh, Morgan O. Hamm, Yizi Mao, Andre Lieber, Andrew B. Stergachis
Accurately quantifying the functional consequences of noncoding mosaic variants requires the pairing of DNA sequences with both accessible and closed chromatin architectures along individual DNA molecules—a pairing that cannot be achieved using traditional fragmentation-based chromatin assays. We demonstrate that targeted single-molecule chromatin fiber sequencing (Fiber-seq) achieves this, permitting
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An integrative TAD catalog in lymphoblastoid cell lines discloses the functional impact of deletions and insertions in human genomes Genome Res. (IF 6.2) Pub Date : 2024-12-01 Chong Li, Marc Jan Bonder, Sabriya Syed, Matthew Jensen, Human Genome Structural Variation Consortium (HGSVC), HGSVC Functional Analysis Working Group, Mark B. Gerstein, Michael C. Zody, Mark J.P. Chaisson, Michael E. Talkowski, Tobias Marschall, Jan O. Korbel, Evan E. Eichler, Charles Lee, Xinghua Shi
The human genome is packaged within a three-dimensional (3D) nucleus and organized into structural units known as compartments, topologically associating domains (TADs), and loops. TAD boundaries, separating adjacent TADs, have been found to be well conserved across mammalian species and more evolutionarily constrained than TADs themselves. Recent studies show that structural variants (SVs) can modify
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Hydra has mammal-like mutation rates facilitating fast adaptation despite its nonaging phenotype Genome Res. (IF 6.2) Pub Date : 2024-12-01 Arne Sahm, Konstantin Riege, Marco Groth, Martin Bens, Johann Kraus, Martin Fischer, Hans Kestler, Christoph Englert, Ralf Schaible, Matthias Platzer, Steve Hoffmann
Growing evidence suggests that somatic mutations may be a major cause of the aging process. However, it remains to be tested whether the predictions of the theory also apply to species with longer life spans than humans. Hydra is a genus of freshwater polyps with remarkable regeneration abilities and a potentially unlimited life span under laboratory conditions. By genome sequencing of single cells
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Characterization of DNA methylation reader proteins in Arabidopsis thaliana Genome Res. (IF 6.2) Pub Date : 2024-12-01 Jonathan Cahn, James P.B. Lloyd, Ino D. Karemaker, Pascal W.T.C. Jansen, Jahnvi Pflueger, Owen Duncan, Jakob Petereit, Ozren Bogdanovic, A. Harvey Millar, Michiel Vermeulen, Ryan Lister
In plants, cytosine DNA methylation (mC) is largely associated with transcriptional repression of transposable elements, but it can also be found in the body of expressed genes, referred to as gene body methylation (gbM). gbM is correlated with ubiquitously expressed genes; however, its function, or absence thereof, is highly debated. The different outputs that mC can have raise questions as to how
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Structure-optimized sgRNA selection with PlatinumCRISPr for efficient Cas9 generation of knockouts Genome Res. (IF 6.2) Pub Date : 2024-12-01 Irmgard U. Haussmann, Thomas C. Dix, David W.J. McQuarrie, Veronica Dezi, Abdullah I. Hans, Roland Arnold, Matthias Soller
A single guide RNA (sgRNA) directs Cas9 nuclease for gene-specific scission of double-stranded DNA. High Cas9 activity is essential for efficient gene editing to generate gene deletions and gene replacements by homologous recombination. However, cleavage efficiency is below 50% for more than half of randomly selected sgRNA sequences in human cell culture screens or model organisms. We used in vitro
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A low-abundance class of Dicer-dependent siRNAs produced from a variety of features in C. elegans Genome Res. (IF 6.2) Pub Date : 2024-12-01 Thiago L. Knittel, Brooke E. Montgomery, Alex J. Tate, Ennis W. Deihl, Anastasia S. Nawrocki, Frederic J. Hoerndli, Taiowa A. Montgomery
Canonical small interfering RNAs (siRNAs) are processed from double-stranded RNA (dsRNA) by Dicer and associate with Argonautes to direct RNA silencing. In Caenorhabditis elegans, 22G-RNAs and 26G-RNAs are often referred to as siRNAs but display distinct characteristics. For example, 22G-RNAs do not originate from dsRNA and do not depend on Dicer, whereas 26G-RNAs require Dicer but derive from an atypical
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Global identification of mammalian host and nested gene pairs reveal tissue-specific transcriptional interplay Genome Res. (IF 6.2) Pub Date : 2024-12-01 Bertille Montibus, James A. Cain, Rocio T. Martinez-Nunez, Rebecca J. Oakey
Nucleotide sequences along a gene provide instructions to transcriptional and cotranscriptional machinery allowing genome expansion into the transcriptome. Nucleotide sequence can often be shared between two genes and in some occurrences, a gene is located completely within a different gene; these are known as host/nested gene pairs. In these instances, if both genes are transcribed, overlap can result
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Convergent relaxation of molecular constraint in herbivores reveals the changing role of liver and kidney functions across mammalian diets Genome Res. (IF 6.2) Pub Date : 2024-12-01 Matthew D. Pollard, Wynn K. Meyer, Emily E. Puckett
Mammalia comprises a great diversity of diet types and associated adaptations. An understanding of the genomic mechanisms underlying these adaptations may offer insights for improving human health. Comparative genomic studies of diet that employ taxonomically restricted analyses or simplified diet classifications may suffer reduced power to detect molecular convergence associated with diet evolution
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Advancements in prospective single-cell lineage barcoding and their applications in research Genome Res. (IF 6.2) Pub Date : 2024-12-01 Xiaoli Zhang, Yirui Huang, Yajing Yang, Qi-En Wang, Lang Li
Single-cell lineage tracing (scLT) has emerged as a powerful tool, providing unparalleled resolution to investigate cellular dynamics, fate determination, and the underlying molecular mechanisms. This review thoroughly examines the latest prospective lineage DNA barcode tracing technologies. It further highlights pivotal studies that leverage single-cell lentiviral integration barcoding technology
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Binding profiles for 961 Drosophila and C. elegans transcription factors reveal tissue-specific regulatory relationships Genome Res. (IF 6.2) Pub Date : 2024-12-01 Michelle Kudron, Louis Gevirtzman, Alec Victorsen, Bridget C. Lear, Jiahao Gao, Jinrui Xu, Swapna Samanta, Emily Frink, Adri Tran-Pearson, Chau Huynh, Dionne Vafeados, Ann Hammonds, William Fisher, Martha Wall, Greg Wesseling, Vanessa Hernandez, Zhichun Lin, Mary Kasparian, Kevin White, Ravi Allada, Mark Gerstein, LaDeana Hillier, Susan E. Celniker, Valerie Reinke, Robert H. Waterston
A catalog of transcription factor (TF) binding sites in the genome is critical for deciphering regulatory relationships. Here, we present the culmination of the efforts of the modENCODE (model organism Encyclopedia of DNA Elements) and modERN (model organism Encyclopedia of Regulatory Networks) consortia to systematically assay TF binding events in vivo in two major model organisms, Drosophila melanogaster
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Inferring ancestry with the hierarchical soft clustering approach tangleGen Genome Res. (IF 6.2) Pub Date : 2024-12-01 Klara Elisabeth Burger, Solveig Klepper, Ulrike von Luxburg, Franz Baumdicker
Understanding the genetic ancestry of populations is central to numerous scientific and societal fields. It contributes to a better understanding of human evolutionary history, advances personalized medicine, aids in forensic identification, and allows individuals to connect to their genealogical roots. Existing methods, such as ADMIXTURE, have significantly improved our ability to infer ancestries
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Analyzing super-enhancer temporal dynamics reveals potential critical enhancers and their gene regulatory networks underlying skeletal muscle development Genome Res. (IF 6.2) Pub Date : 2024-12-01 Song Zhang, Chao Wang, Shenghua Qin, Choulin Chen, Yongzhou Bao, Yuanyuan Zhang, Lingna Xu, Qingyou Liu, Yunxiang Zhao, Kui Li, Zhonglin Tang, Yuwen Liu
Super-enhancers (SEs) govern the expression of genes defining cell identity. However, the dynamic landscape of SEs and their critical constituent enhancers involved in skeletal muscle development remains unclear. In this study, using pig as a model, we employed cleavage under targets and tagmentation (CUT&Tag) to profile the enhancer-associated histone modification marker H3K27ac in skeletal muscle
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Ultrasensitive allele inference from immune repertoire sequencing data with MiXCR Genome Res. (IF 6.2) Pub Date : 2024-12-01 Artem Mikelov, George Nefediev, Alexander Tashkeev, Oscar L. Rodriguez, Diego Aguilar Ortmans, Valeriia Skatova, Mark Izraelson, Alexey N. Davydov, Stanislav Poslavsky, Souad Rahmouni, Corey T. Watson, Dmitriy Chudakov, Scott D. Boyd, Dmitry Bolotin
Allelic variability in the adaptive immune receptor loci, which harbor the gene segments that encode B cell and T cell receptors (BCR/TCR), is of critical importance for immune responses to pathogens and vaccines. Adaptive immune receptor repertoire sequencing (AIRR-seq) has become widespread in immunology research making it the most readily available source of information about allelic diversity in
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Multisample motif discovery and visualization for tandem repeats Genome Res. (IF 6.2) Pub Date : 2024-11-13 Yaran Zhang, Marc Hulsman, Alex Salazar, Niccoló Tesi, Lydian Knoop, Sven van der Lee, Sanduni Wijesekera, Jana Krizova, Erik-Jan Kamsteeg, Henne Holstege
Tandem Repeats (TR) occupy a significant portion of the human genome and are the source of polymorphism due to variations in sizes and motif compositions. Some of these variations have been associated with various neuropathological disorders, highlighting the clinical importance of assessing the motif structure of TRs. Moreover, assessing the TR motif variation can offer valuable insights into evolutionary
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Multiple paralogues and recombination mechanisms contribute to the high incidence of 22q11.2 Deletion Syndrome Genome Res. (IF 6.2) Pub Date : 2024-11-13 Lisanne Vervoort, Nicolas Dierckxsens, Marta Sousa Santos, Senne Meynants, Erika Souche, Ruben Cools, Tracy Heung, Koen Devriendt, Hilde Peeters, Donna McDonald-McGinn, Ann Swillen, Jeroen Breckpot, Beverly S. Emanuel, Hilde Van Esch, Anne S. Bassett, Joris R. Vermeesch
The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion disorder. Why the incidence of 22q11.2DS is much greater than that of other genomic disorders remains unknown. Short read sequencing cannot resolve the complex segmental duplicon structure to provide direct confirmation of the hypothesis that the rearrangements are caused by nonallelic homologous recombination between the low
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Understanding isoform expression by pairing long-read sequencing with single-cell and spatial transcriptomics Genome Res. (IF 6.2) Pub Date : 2024-11-01 Natan Belchikov, Justine Hsu, Xiang Jennie Li, Julien Jarroux, Wen Hu, Anoushka Joglekar, Hagen U. Tilgner
RNA isoform diversity, produced via alternative splicing, and alternative usage of transcription start and poly(A) sites, results in varied transcripts being derived from the same gene. Distinct isoforms can play important biological roles, including by changing the sequences or expression levels of protein products. The first single-cell approaches to RNA sequencing—and later, spatial approaches—which
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Challenges in identifying mRNA transcript starts and ends from long-read sequencing data Genome Res. (IF 6.2) Pub Date : 2024-11-01 Ezequiel Calvo-Roitberg, Rachel F. Daniels, Athma A. Pai
Long-read sequencing (LRS) technologies have the potential to revolutionize scientific discoveries in RNA biology through the comprehensive identification and quantification of full-length mRNA isoforms. Despite great promise, challenges remain in the widespread implementation of LRS technologies for RNA-based applications, including concerns about low coverage, high sequencing error, and robust computational
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Leveraging the power of long reads for targeted sequencing Genome Res. (IF 6.2) Pub Date : 2024-11-01 Shruti V. Iyer, Sara Goodwin, William Richard McCombie
Long-read sequencing technologies have improved the contiguity and, as a result, the quality of genome assemblies by generating reads long enough to span and resolve complex or repetitive regions of the genome. Several groups have shown the power of long reads in detecting thousands of genomic and epigenomic features that were previously missed by short-read sequencing approaches. While these studies
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Revolutionizing genomics and medicine—one long molecule at a time Genome Res. (IF 6.2) Pub Date : 2024-11-01 Ana Conesa, Alexander Hoischen, Fritz J. Sedlazeck
Long-read sequencing (LRS) has matured, and the dramatically increased accuracy, ever-increasing throughput, and access now allow new and advanced studies even at scale. This Special Issue of Genome Research on “Long-read DNA and RNA Sequencing Applications in Biology and Medicine” garnered a record number of submissions, reflecting both the intense and broad interest in the technologies and the next
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Haplotype-resolved genome and population genomics of the threatened garden dormouse in Europe Genome Res. (IF 6.2) Pub Date : 2024-11-01 Paige A. Byerly, Alina von Thaden, Evgeny Leushkin, Leon Hilgers, Shenglin Liu, Sven Winter, Tilman Schell, Charlotte Gerheim, Alexander Ben Hamadou, Carola Greve, Christian Betz, Hanno J. Bolz, Sven Büchner, Johannes Lang, Holger Meinig, Evax Marie Famira-Parcsetich, Sarah P. Stubbe, Alice Mouton, Sandro Bertolino, Goedele Verbeylen, Thomas Briner, Lídia Freixas, Lorenzo Vinciguerra, Sarah A. Mueller
Genomic resources are important for evaluating genetic diversity and supporting conservation efforts. The garden dormouse (Eliomys quercinus) is a small rodent that has experienced one of the most severe modern population declines in Europe. We present a high-quality haplotype-resolved reference genome for the garden dormouse, and combine comprehensive short and long-read transcriptomics data sets