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Graph-based self-supervised learning for repeat detection in metagenomic assembly Genome Res. (IF 6.2) Pub Date : 2024-07-19 Ali Azizpour, Advait Balaji, Todd J. Treangen, Santiago Segarra
Repetitive DNA (repeats) poses significant challenges for accurate and efficient genome assembly and sequence alignment. This is particularly true for metagenomic data, where genome dynamics such as horizontal gene transfer, gene duplication, and gene loss/gain complicate accurate genome assembly from metagenomic communities. Detecting repeats is a crucial first step in overcoming these challenges
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Haplotype-aware sequence alignment to pangenome graphs Genome Res. (IF 6.2) Pub Date : 2024-07-16 Ghanshyam Chandra, Daniel Gibney, Chirag Jain
Modern pangenome graphs are built using haplotype-resolved genome assemblies. When mapping reads to a pangenome graph, prioritizing alignments that are consistent with the known haplotypes improves genotyping accuracy. However, the existing rigorous formulations for co-linear chaining and alignment problems do not consider the haplotype paths in a pangenome graph. This often leads to spurious read
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High-fidelity, large-scale targeted profiling of microsatellites Genome Res. (IF 6.2) Pub Date : 2024-07-16 Caitlin A Loh, Danielle A Shields, Adam Schwing, Gilad D Evrony
Microsatellites are highly mutable sequences that can serve as markers for relationships among individuals or cells within a population. The accuracy and resolution of reconstructing these relationships depends on the fidelity of microsatellite profiling and the number of microsatellites profiled. However, current methods for targeted profiling of microsatellites incur significant "stutter" artifacts
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Single-cell discovery of m6A RNA modifications in the hippocampus Genome Res. (IF 6.2) Pub Date : 2024-07-15 Shuangshuang Feng, Maitena Tellaetxe-Abete, Yujie Zhang, Yan Peng, Han Zhou, Mingjie Dong, Erika Larrea, Liang Xue, Li Zhang, Magdalena J. Koziol
N6-Methyladenosine (m6A) is a prevalent and highly regulated RNA modification essential for RNA metabolism and normal brain function. It is particularly important in the hippocampus, where m6A is implicated in neurogenesis and learning. Although extensively studied, its presence in specific cell types remains poorly understood. We investigated m6A in the hippocampus at a single-cell resolution, revealing
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DEAD box RNA helicases are pervasive protein kinase interactors and activators Genome Res. (IF 6.2) Pub Date : 2024-07-10 Alexander Hirth, Edoardo Fatti, Eugen Netz, Sergio P. Acebron, Dimitris Papageorgiou, Andrea Švorinić, Cristina-Maria Cruciat, Emil Karaulanov, Alexandr Gopanenko, Tianheng Zhu, Irmgard Sinning, Jeroen Krijgsveld, Oliver Kohlbacher, Christof Niehrs
DEAD box (DDX) RNA helicases are a large family of ATPases, many of which have unknown functions. There is emerging evidence that besides their role in RNA biology, DDX proteins may stimulate protein kinases. To investigate if protein kinase–DDX interaction is a more widespread phenomenon, we conducted three orthogonal large-scale screens, including proteomics analysis with 32 RNA helicases, protein
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Accurate allocation of multimapped reads enables regulatory element analysis at repeats Genome Res. (IF 6.2) Pub Date : 2024-07-10 Alexis Morrissey, Jeffrey Shi, Daniela Q. James, Shaun Mahony
Transposable elements (TEs) and other repetitive regions have been shown to contain gene regulatory elements, including transcription factor binding sites. However, regulatory elements harbored by repeats have proven difficult to characterize using short-read sequencing assays such as ChIP-seq or ATAC-seq. Most regulatory genomics analysis pipelines discard “multimapped” reads that align equally well
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CoRAL accurately resolves extrachromosomal DNA genome structures with long-read sequencing Genome Res. (IF 6.2) Pub Date : 2024-07-09 Kaiyuan Zhu, Matthew Gregory Jones, Jens Luebeck, Xinxin Bu, Hyerim Yi, King L. Huang, Ivy Tsz-Lo Wong, Shu Zhang, Paul S. Mischel, Howard Chang, Vineet Bafna
Extrachromosomal DNA (ecDNA) is a central mechanism for focal oncogene amplification in cancer, occurring in approximately 15% of early-stage cancers and 30% of late-stage cancers. EcDNAs drive tumor formation, evolution, and drug resistance by dynamically modulating oncogene copy-number and rewiring gene-regulatory networks. Elucidating the genomic architecture of ecDNA amplifications is critical
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Accurate estimation of pathway activity in single cells for clustering and differential analysis Genome Res. (IF 6.2) Pub Date : 2024-07-09 Daniel Davis, Avishai Wizel, Yotam Drier
Inferring which and how biological pathways and gene sets change is a key question in many studies that utilize single-cell RNA sequencing. Typically, these questions are addressed by quantifying the enrichment of known gene sets in lists of genes derived from global analysis. Here we offer SiPSiC, a new method to infer pathway activity in every single cell. This allows more sensitive differential
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Single-cell analysis reveals transcriptional dynamics in healthy primary parathyroid tissue Genome Res. (IF 6.2) Pub Date : 2024-07-08 Aarthi Venkat, Maximillian J. Carlino, Betty R. Lawton, Manju L. Prasad, Matthew Amodio, Courtney E. Gibson, Caroline J. Zeiss, Scott E. Youlten, Smita Krishnaswamy, Diane S. Krause
Studies on human parathyroids are generally limited to hyperfunctioning glands owing to the difficulty in obtaining normal human tissue. We therefore obtained non-human primate (NHP) parathyroids to provide a suitable alternative for sequencing that would bear a close semblance to human organs. Single-cell RNA expression analysis of parathyroids from four healthy adult M. mulatta reveals a continuous
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Large-scale investigation of species-specific orphan genes in the human gut microbiome elucidates their evolutionary origins Genome Res. (IF 6.2) Pub Date : 2024-07-08 Nikolaos Vakirlis, Anne Kupczok
Species-specific genes, also known as orphans, are ubiquitous across life's domains. In prokaryotes, species-specific orphan genes (SSOGs) are mostly thought to originate in external elements such as viruses followed by horizontal gene transfer, whereas the scenario of native origination, through rapid divergence or de novo, is mostly dismissed. However, quantitative evidence supporting either scenario
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Comparative genomics of Cryptosporidium parvum reveals the emergence of an outbreak-associated population in Europe and its spread to the United States Genome Res. (IF 6.2) Pub Date : 2024-07-08 Greta Bellinzona, Tiago Nardi, Michele Castelli, Gherard Batisti Biffignandi, Karim Adjou, Martha Betson, Yannick Blanchard, Ioana Bujila, Rachel Chalmers, Rebecca Davidson, Nicoletta D'Avino, Tuulia Enbom, Jacinto Gomes, Gregory Karadjian, Christian Klotz, Emma Östlund, Judith Plutzer, Ruska Rimhanen-Finne, Guy Robinson, Anna Rosa Sannella, Jacek Sroka, Christen Rune Stensvold, Karin Troell, Paolo
The zoonotic parasite Cryptosporidium parvum is a global cause of gastrointestinal disease in humans and ruminants. Sequence analysis of the highly polymorphic gp60 gene enabled the classification of C. parvum isolates into multiple groups (e.g., IIa, IIc, Id) and a large number of subtypes. In Europe, subtype IIaA15G2R1 is largely predominant and has been associated with many water- and food-borne
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CodonBert large language model for mRNA vaccines Genome Res. (IF 6.2) Pub Date : 2024-07-01 Sizhen Li, Saeed Moayedpour, Ruijiang Li, Michael Bailey, Saleh Riahi, Lorenzo Kogler-Anele, Milad Miladi, Jacob Miner, Fabien Pertuy, Dinghai Zheng, Jun Wang, Akshay Balsubramani, Khang Tran, Minnie Zacharia, Monica Wu, Xiaobo Gu, Ryan Clinton, Carla Asquith, Joseph Skaleski, Lianne Boeglin, Sudha Chivukula, Anusha Dias, Tod Strugnell, Fernando Ulloa Montoya, Vikram Agarwal, Ziv Bar-Joseph, Sven Jager
mRNA-based vaccines and therapeutics are gaining popularity and usage across a wide range of conditions. One of the critical issues when designing such mRNAs is sequence optimization. Even small proteins or peptides can be encoded by an enormously large number of mRNAs. The actual mRNA sequence can have a large impact on several properties including expression, stability, immunogenicity, and more.
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Streamlined spatial and environmental expression signatures characterize the minimalist duckweed Wolffia australiana Genome Res. (IF 6.2) Pub Date : 2024-07-01 Tom Denyer, Pin-Jou Wu, Kelly Colt, Bradley Abramson, Zhili Pang, Pavel Solansky, Allen Mamerto, Tatsuya Nobori, Joseph Ecker, Eric Lam, Todd P. Michael, Marja CP Timmermans
Single-cell genomics permits a new resolution in the examination of molecular and cellular dynamics, allowing global, parallel assessments of cell types and cellular behaviors through development and in response to environmental circumstances, such as interaction with water and the light-dark cycle of the Earth. Here, we leverage the smallest, and possibly most structurally reduced plant, the semi-aquatic
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Interspecies regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes Genome Res. (IF 6.2) Pub Date : 2024-07-01 Guanjue Xiang, Xi He, Belinda M. Giardine, Kathryn J. Isaac, Dylan J. Taylor, Rajiv C. McCoy, Camden Jansen, Cheryl A. Keller, Alexander Q. Wixom, April Cockburn, Amber Miller, Qian Qi, Yanghua He, Yichao Li, Jens Lichtenberg, Elisabeth F. Heuston, Stacie M. Anderson, Jing Luan, Marit W. Vermunt, Feng Yue, Michael E.G. Sauria, Michael C. Schatz, James Taylor, Berthold Göttgens, Jim R. Hughes, Douglas
Knowledge of locations and activities of cis-regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using epigenetic features in one species, making comparisons difficult between species. In contrast, we conducted an interspecies study defining epigenetic
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Genome-wide relaxation of selection and the evolution of the island syndrome in Orkney voles Genome Res. (IF 6.2) Pub Date : 2024-07-02 Xuejing Wang, Gerald Heckel
Island populations often experience different ecological and demographic conditions than their counterparts on the continent, resulting in divergent evolutionary forces affecting their genomes. Random genetic drift and selection both may leave their imprints on island populations, although the relative impact depends strongly on the specific conditions. Here we address their contributions to the island
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Large-scale genomic analysis of the domestic dog informs biological discovery Genome Res. (IF 6.2) Pub Date : 2024-07-02 Reuben M. Buckley, Elaine A. Ostrander
Recent advances in genomics, coupled with a unique population structure and remarkable levels of variation, have propelled the domestic dog to new levels as a system for understanding fundamental principles in mammalian biology. Central to this advance are more than 350 recognized breeds, each a closed population that has undergone selection for unique features. Genetic variation in the domestic dog
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Delineating yeast cleavage and polyadenylation signals using deep learning Genome Res. (IF 6.2) Pub Date : 2024-06-24 Emily Stroup, Zhe Ji
3'-end cleavage and polyadenylation is an essential process for eukaryotic mRNA maturation. In yeast species, the polyadenylation signals that recruit the processing machinery are degenerate and remain poorly characterized compared to the well-defined regulatory elements in mammals. Here we address this question by developing deep learning models to deconvolute degenerate cis-regulatory elements and
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Long-read Ribo-STAMP simultaneously measures transcription and translation with isoform resolution Genome Res. (IF 6.2) Pub Date : 2024-06-21 Pratibha Jagannatha, Alexandra T Tankka, Daniel A Lorenz, Tao Yu, Brian A Yee, Kristopher W Brannan, Catherine Jiarui Zhou, Jason G Underwood, Gene W. Yeo
Transcription and translation are intertwined processes where mRNA isoforms are crucial intermediaries. However, methodological limitations in analyzing translation at the mRNA isoform level have left gaps in our understanding of critical biological processes. To address these gaps, we developed an integrated computational and experimental framework called long-read Ribo-STAMP (LR-Ribo-STAMP) that
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Size-based expectation maximization for characterizing nucleosome positions and subtypes Genome Res. (IF 6.2) Pub Date : 2024-06-17 Jianyu Yang, Kuangyu Yen, Shaun Mahony
Genome-wide nucleosome profiles are predominantly characterized using MNase-seq, which involves extensive MNase digestion and size selection to enrich for mono-nucleosome-sized fragments. Most available MNase-seq analysis packages assume that nucleosomes uniformly protect 147-bp DNA fragments. However, some nucleosomes with atypical histone or chemical compositions protect shorter lengths of DNA. The
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Fast and space-efficient taxonomic classification of long reads with hierarchical interleaved XOR filters Genome Res. (IF 6.2) Pub Date : 2024-06-17 Jens-Uwe Ulrich, Bernhard Y. Renard
Metagenomic long-read sequencing is gaining popularity for various applications, including pathogen detection and microbiome studies. To analyze the large data created in those studies, software tools need to taxonomically classify the sequenced molecules and estimate the relative abundances of organisms in the sequenced sample. Because of the exponential growth of reference genome databases, the current
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Simultaneous assessment of human genome and methylome data in a single experiment using limited deamination of methylated cytosine Genome Res. (IF 6.2) Pub Date : 2024-06-10 Bo Yan, Duan Wang, Laurence Ettwiller
Multiomics require concerted recording of independent information, ideally from a single experiment. In this study, we introduce RIMS-seq2, a high-throughput technique to simultaneously sequence genomes and overlay methylation information while requiring only a small modification of the experimental protocol for high-throughput DNA sequencing to include a controlled deamination step. Importantly, the
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DNA-m6A calling and integrated long-read epigenetic and genetic analysis with fibertools Genome Res. (IF 6.2) Pub Date : 2024-06-07 Anupama Jha, Stephanie C. Bohaczuk, Yizi Mao, Jane Ranchalis, Benjamin J. Mallory, Alan T. Min, Morgan O Hamm, Elliott Swanson, Danilo Dubocanin, Connor Finkbeiner, Tony Li, Dale Whittington, William Stafford Noble, Andrew Ben Stergachis, Mitchell R Vollger
Long-read DNA sequencing has recently emerged as a powerful tool for studying both genetic and epigenetic architectures at single-molecule and single-nucleotide resolution. Long-read epigenetic studies encompass both the direct identification of native cytosine methylation as well as the identification of exogenously placed DNA N6-methyladenine (DNA-m6A). However, detecting DNA-m6A modifications using
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Full resolution HLA and KIR gene annotations for human genome assemblies Genome Res. (IF 6.2) Pub Date : 2024-06-05 Ying Zhou, Li Song, Heng Li
The Human leukocyte antigens (HLA) genes and the Killer cell immunoglobulin like receptors (KIR) genes are critical to immune responses and are associated with many immune-related diseases. Located in highly polymorphic regions, they are hard to study with traditional short-read alignment-based methods. Although modern long-read assemblers can often assemble these genes, using existing tools to annotate
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Long read subcellular fractionation and sequencing reveals the translational fate of full-length mRNA isoforms during neuronal differentiation Genome Res. (IF 6.2) Pub Date : 2024-06-05 Alexander Ritter, Jolene M Draper, Christopher Vollmers, Jeremy Sanford
Alternative splicing (AS) alters the cis-regulatory landscape of mRNA isoforms leading to transcripts with distinct localization, stability and translational efficiency. To rigorously investigate mRNA isoform-specific ribosome association, we generated subcellular fractionation and sequencing (Frac-seq) libraries using both conventional short reads and long reads from human embryonic stem cells (ESC)
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Causes and consequences of a complex recombinational landscape in the ant Cardiocondyla obscurior Genome Res. (IF 6.2) Pub Date : 2024-06-05 Mohammed Errbii, Jürgen Gadau, Kerstin Becker, Lukas Schrader, Jan Oettler
Eusocial Hymenoptera have the highest recombination rates among all multicellular animals studied so far, but it is unclear why this is and how this affects the biology of individual species. A high-resolution linkage map for the ant Cardiocondyla obscurior corroborates genome-wide high recombination rates reported for ants (8.1 cM/Mb). However, recombination is locally suppressed in regions that are
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Erratum: Proving sequence aligners can guarantee accuracy in almost O(m log n) time through an average-case analysis of the seed-chain-extend heuristic Genome Res. (IF 6.2) Pub Date : 2024-05-01 Jim Shaw, Yun William Yu
Genome Research 33: 1175–1187 (2023)
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Genome-wide profiles of H3K9me3, H3K27me3 modifications, and DNA methylation during diapause of Asian corn borer (Ostrinia furnacalis) Genome Res. (IF 6.2) Pub Date : 2024-05-01 Pengfei Lv, Xingzhuo Yang, Xianguo Zhao, Zhangwu Zhao, Juan Du
Diapause represents a crucial adaptive strategy used by insects to cope with changing environmental conditions. In North China, the Asian corn borer (Ostrinia furnacalis) enters a winter larval diapause stage. Although there is growing evidence implicating epigenetic mechanisms in diapause regulation, it remains unclear whether dynamic genome-wide profiles of epigenetic modifications exist during this
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GeneMark-ETP significantly improves the accuracy of automatic annotation of large eukaryotic genomes Genome Res. (IF 6.2) Pub Date : 2024-05-01 Tomáš Brůna, Alexandre Lomsadze, Mark Borodovsky
Large-scale genomic initiatives, such as the Earth BioGenome Project, require efficient methods for eukaryotic genome annotation. Here we present an automatic gene finder, GeneMark-ETP, integrating genomic-, transcriptomic-, and protein-derived evidence that has been developed with a focus on large plant and animal genomes. GeneMark-ETP first identifies genomic loci where extrinsic data are sufficient
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BRAKER3: Fully automated genome annotation using RNA-seq and protein evidence with GeneMark-ETP, AUGUSTUS, and TSEBRA Genome Res. (IF 6.2) Pub Date : 2024-05-01 Lars Gabriel, Tomáš Brůna, Katharina J. Hoff, Matthis Ebel, Alexandre Lomsadze, Mark Borodovsky, Mario Stanke
Gene prediction has remained an active area of bioinformatics research for a long time. Still, gene prediction in large eukaryotic genomes presents a challenge that must be addressed by new algorithms. The amount and significance of the evidence available from transcriptomes and proteomes vary across genomes, between genes, and even along a single gene. User-friendly and accurate annotation pipelines
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Identifying genes within pathways in unannotated genomes with PaGeSearch Genome Res. (IF 6.2) Pub Date : 2024-05-01 Sohyoung Won, Jaewoong Yu, Heebal Kim
In biological research, the identification and comparison of genes within specific pathways across the genomes of various species are invaluable. However, annotating the entire genome is resource intensive, and sequence similarity searches often yield results that are not actually genes. To address these limitations, we introduce Pathway Gene Search (PaGeSearch), a tool designed to identify genes from
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Toward telomere-to-telomere cat genomes for precision medicine and conservation biology Genome Res. (IF 6.2) Pub Date : 2024-05-01 William J. Murphy, Andrew J. Harris
Genomic data from species of the cat family Felidae promise to stimulate veterinary and human medical advances, and clarify the coherence of genome organization. We describe how interspecies hybrids have been instrumental in the genetic analysis of cats, from the first genetic maps to propelling cat genomes toward the T2T standard set by the human genome project. Genotype-to-phenotype mapping in cat
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Single-cell spatial transcriptomics reveals a dystrophic trajectory following a developmental bifurcation of myoblast cell fates in facioscapulohumeral muscular dystrophy Genome Res. (IF 6.2) Pub Date : 2024-05-01 Lujia Chen, Xiangduo Kong, Kevin G. Johnston, Ali Mortazavi, Todd C. Holmes, Zhiqun Tan, Kyoko Yokomori, Xiangmin Xu
Facioscapulohumeral muscular dystrophy (FSHD) is linked to abnormal derepression of the transcription activator DUX4. This effect is localized to a low percentage of cells, requiring single-cell analysis. However, single-cell/nucleus RNA-seq cannot fully capture the transcriptome of multinucleated large myotubes. To circumvent these issues, we use multiplexed error-robust fluorescent in situ hybridization
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Machine learning identifies activation of RUNX/AP-1 as drivers of mesenchymal and fibrotic regulatory programs in gastric cancer Genome Res. (IF 6.2) Pub Date : 2024-05-01 Milad Razavi-Mohseni, Weitai Huang, Yu A. Guo, Dustin Shigaki, Shamaine Wei Ting Ho, Patrick Tan, Anders J. Skanderup, Michael A. Beer
Gastric cancer (GC) is the fifth most common cancer worldwide and is a heterogeneous disease. Among GC subtypes, the mesenchymal phenotype (Mes-like) is more invasive than the epithelial phenotype (Epi-like). Although gene expression of the epithelial-to-mesenchymal transition (EMT) has been studied, the regulatory landscape shaping this process is not fully understood. Here we use ATAC-seq and RNA-seq
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A harmonized public resource of deeply sequenced diverse human genomes Genome Res. (IF 6.2) Pub Date : 2024-05-01 Zan Koenig, Mary T. Yohannes, Lethukuthula L. Nkambule, Xuefang Zhao, Julia K. Goodrich, Heesu Ally Kim, Michael W. Wilson, Grace Tiao, Stephanie P. Hao, Nareh Sahakian, Katherine R. Chao, Mark A. Walker, Yunfei Lyu, gnomAD Project Consortium, Heidi L. Rehm, Benjamin M. Neale, Michael E. Talkowski, Mark J. Daly, Harrison Brand, Konrad J. Karczewski, Elizabeth G. Atkinson, Alicia R. Martin
Underrepresented populations are often excluded from genomic studies owing in part to a lack of resources supporting their analyses. The 1000 Genomes Project (1kGP) and Human Genome Diversity Project (HGDP), which have recently been sequenced to high coverage, are valuable genomic resources because of the global diversity they capture and their open data sharing policies. Here, we harmonized a high-quality
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Rapid evolution of piRNA clusters in the Drosophila melanogaster ovary Genome Res. (IF 6.2) Pub Date : 2024-05-01 Satyam P. Srivastav, Cédric Feschotte, Andrew G. Clark
The piRNA pathway is a highly conserved mechanism to repress transposable element (TE) activity in the animal germline via a specialized class of small RNAs called piwi-interacting RNAs (piRNAs). piRNAs are produced from discrete genomic regions called piRNA clusters (piCs). Although the molecular processes by which piCs function are relatively well understood in Drosophila melanogaster, much less
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Semiconservative transmission of DNA N6-adenine methylation in a unicellular eukaryote Genome Res. (IF 6.2) Pub Date : 2024-05-01 Yalan Sheng, Yuanyuan Wang, Wentao Yang, Xue Qing Wang, Jiuwei Lu, Bo Pan, Bei Nan, Yongqiang Liu, Fei Ye, Chun Li, Jikui Song, Yali Dou, Shan Gao, Yifan Liu
Although DNA N6-adenine methylation (6mA) is best known in prokaryotes, its presence in eukaryotes has recently generated great interest. Biochemical and genetic evidence supports that AMT1, an MT-A70 family methyltransferase (MTase), is crucial for 6mA deposition in unicellular eukaryotes. Nonetheless, the 6mA transmission mechanism remains to be elucidated. Taking advantage of single-molecule real-time
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Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice Genome Res. (IF 6.2) Pub Date : 2024-05-01 Leandros Boukas, Teresa Romeo Luperchio, Afrooz Razi, Kasper D. Hansen, Hans T. Bjornsson
Many Mendelian developmental disorders caused by coding variants in epigenetic regulators have now been discovered. Epigenetic regulators are broadly expressed, and each of these disorders typically shows phenotypic manifestations from many different organ systems. An open question is whether the chromatin disruption—the root of the pathogenesis—is similar in the different disease-relevant cell types
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Simulation of nanopore sequencing signal data with tunable parameters Genome Res. (IF 6.2) Pub Date : 2024-05-01 Hasindu Gamaarachchi, James M. Ferguson, Hiruna Samarakoon, Kisaru Liyanage, Ira W. Deveson
In silico simulation of high-throughput sequencing data is a technique used widely in the genomics field. However, there is currently a lack of effective tools for creating simulated data from nanopore sequencing devices, which measure DNA or RNA molecules in the form of time-series current signal data. Here, we introduce Squigulator, a fast and simple tool for simulation of realistic nanopore signal
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Estrogen receptor 1 chromatin profiling in human breast tumors reveals high inter-patient heterogeneity with enrichment of risk SNPs and enhancer activity at most-conserved regions Genome Res. (IF 6.2) Pub Date : 2024-04-01 Stacey E.P. Joosten, Sebastian Gregoricchio, Suzan Stelloo, Elif Yapıcı, Chia-Chi Flora Huang, Kerim Yavuz, Maria Donaldson Collier, Tunç Morova, Umut Berkay Altintaş, Yongsoo Kim, Sander Canisius, Cathy B. Moelans, Paul J. van Diest, Gozde Korkmaz, Nathan A. Lack, Michiel Vermeulen, Sabine C. Linn, Wilbert Zwart
Estrogen Receptor 1 (ESR1; also known as ERα, encoded by ESR1 gene) is the main driver and prime drug target in luminal breast cancer. ESR1 chromatin binding is extensively studied in cell lines and a limited number of human tumors, using consensi of peaks shared among samples. However, little is known about inter-tumor heterogeneity of ESR1 chromatin action, along with its biological implications
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Suv39h-catalyzed H3K9me3 is critical for euchromatic genome organization and the maintenance of gene transcription Genome Res. (IF 6.2) Pub Date : 2024-04-01 Christine R. Keenan, Hannah D. Coughlan, Nadia Iannarella, Andres Tapia del Fierro, Andrew Keniry, Timothy M. Johanson, Wing Fuk Chan, Alexandra L. Garnham, Lachlan W. Whitehead, Marnie E. Blewitt, Gordon K. Smyth, Rhys S. Allan
H3K9me3-dependent heterochromatin is critical for the silencing of repeat-rich pericentromeric regions and also has key roles in repressing lineage-inappropriate protein-coding genes in differentiation and development. Here, we investigate the molecular consequences of heterochromatin loss in cells deficient in both SUV39H1 and SUV39H2 (Suv39DKO), the major mammalian histone methyltransferase enzymes
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Combinatorial microRNA activity is essential for the transition of pluripotent cells from proliferation into dormancy Genome Res. (IF 6.2) Pub Date : 2024-04-01 Dhanur P. Iyer, Lambert Moyon, Lars Wittler, Chieh-Yu Cheng, Francisca R. Ringeling, Stefan Canzar, Annalisa Marsico, Aydan Bulut-Karslioğlu
Dormancy is a key feature of stem cell function in adult tissues as well as in embryonic cells in the context of diapause. The establishment of dormancy is an active process that involves extensive transcriptional, epigenetic, and metabolic rewiring. How these processes are coordinated to successfully transition cells to the resting dormant state remains unclear. Here we show that microRNA activity
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A new framework for exploratory network mediator analysis in omics data Genome Res. (IF 6.2) Pub Date : 2024-04-01 Qingpo Cai, Yinghao Fu, Cheng Lyu, Zihe Wang, Shun Rao, Jessica A. Alvarez, Yun Bai, Jian Kang, Tianwei Yu
Omics methods are widely used in basic biology and translational medicine research. More and more omics data are collected to explain the impact of certain risk factors on clinical outcomes. To explain the mechanism of the risk factors, a core question is how to find the genes/proteins/metabolites that mediate their effects on the clinical outcome. Mediation analysis is a modeling framework to study
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Ribosome decision graphs for the representation of eukaryotic RNA translation complexity Genome Res. (IF 6.2) Pub Date : 2024-04-01 Jack A.S. Tierney, Michał Świrski, Håkon Tjeldnes, Jonathan M. Mudge, Joanna Kufel, Nicola Whiffin, Eivind Valen, Pavel V. Baranov
The application of ribosome profiling has revealed an unexpected abundance of translation in addition to that responsible for the synthesis of previously annotated protein-coding regions. Multiple short sequences have been found to be translated within single RNA molecules, within both annotated protein-coding and noncoding regions. The biological significance of this translation is a matter of intensive
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Navigating the landscape of epitranscriptomics and host immunity Genome Res. (IF 6.2) Pub Date : 2024-04-01 Elaine Huang, Clara Frydman, Xinshu Xiao
RNA modifications, also termed epitranscriptomic marks, encompass chemical alterations to individual nucleotides, including processes such as methylation and editing. These marks contribute to a wide range of biological processes, many of which are related to host immune system defense. The functions of immune-related RNA modifications can be categorized into three main groups: regulation of immunogenic
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Probabilistic association of differentially expressed genes with cis-regulatory elements Genome Res. (IF 6.2) Pub Date : 2024-04-01 Brian S. Roberts, Ashlyn G. Anderson, E. Christopher Partridge, Gregory M. Cooper, Richard M. Myers
Differential gene expression in response to perturbations is mediated at least in part by changes in binding of transcription factors (TFs) and other proteins at specific genomic regions. Association of these cis-regulatory elements (CREs) with their target genes is a challenging task that is essential to address many biological and mechanistic questions. Many current approaches rely on chromatin conformation
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Transcriptional programs mediating neuronal toxicity and altered glial–neuronal signaling in a Drosophila knock-in tauopathy model Genome Res. (IF 6.2) Pub Date : 2024-04-01 Hassan Bukhari, Vanitha Nithianandam, Rachel A. Battaglia, Anthony Cicalo, Souvarish Sarkar, Aram Comjean, Yanhui Hu, Matthew J. Leventhal, Xianjun Dong, Mel B. Feany
Missense mutations in the gene encoding the microtubule-associated protein TAU (current and approved symbol is MAPT) cause autosomal dominant forms of frontotemporal dementia. Multiple models of frontotemporal dementia based on transgenic expression of human TAU in experimental model organisms, including Drosophila, have been described. These models replicate key features of the human disease but do
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Plant genome evolution in the genus Eucalyptus is driven by structural rearrangements that promote sequence divergence Genome Res. (IF 6.2) Pub Date : 2024-04-01 Scott Ferguson, Ashley Jones, Kevin Murray, Rose Andrew, Benjamin Schwessinger, Justin Borevitz
Genomes have a highly organized architecture (nonrandom organization of functional and nonfunctional genetic elements within chromosomes) that is essential for many biological functions, particularly gene expression and reproduction. Despite the need to conserve genome architecture, a high level of structural variation has been observed within species. As species separate and diverge, genome architecture
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Accelerated somatic mutation calling for whole-genome and whole-exome sequencing data from heterogenous tumor samples Genome Res. (IF 6.2) Pub Date : 2024-04-01 Shuangxi Ji, Tong Zhu, Ankit Sethia, Wenyi Wang
Accurate detection of somatic mutations in DNA sequencing data is a fundamental prerequisite for cancer research. Previous analytical challenges were overcome by consensus mutation calling from four to five popular callers. This, however, increases the already nontrivial computing time from individual callers. Here, we launch MuSE 2, powered by multistep parallelization and efficient memory allocation
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Corrigendum: A statistical learning method for simultaneous copy number estimation and subclone clustering with single-cell sequencing data Genome Res. (IF 6.2) Pub Date : 2024-03-01 Fei Qin, Guoshuai Cai, Christopher I. Amos, Feifei Xiao
Genome Research 34: 85–93 (2024)
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A systematic review on the biochemical threshold of mitochondrial genetic variants Genome Res. (IF 6.2) Pub Date : 2024-03-01 Karan K. Smith, Jesse D. Moreira, Callum R. Wilson, June O. Padera, Ashlee N. Lamason, Liying Xue, Deepa M. Gopal, David B. Flynn, Jessica L. Fetterman
Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a pathogenic variant, variant allele frequency (VAF), must reach a threshold before a biochemical defect occurs, termed the biochemical threshold. Whether the often-cited biochemical threshold of >60% VAF is similar across mtDNA variants and
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Phased nanopore assembly with Shasta and modular graph phasing with GFAse Genome Res. (IF 6.2) Pub Date : 2024-03-01 Ryan Lorig-Roach, Melissa Meredith, Jean Monlong, Miten Jain, Hugh E. Olsen, Brandy McNulty, David Porubsky, Tessa G. Montague, Julian K. Lucas, Chris Condon, Jordan M. Eizenga, Sissel Juul, Sean K. McKenzie, Sara E. Simmonds, Jimin Park, Mobin Asri, Sergey Koren, Evan E. Eichler, Richard Axel, Bruce Martin, Paolo Carnevali, Karen H. Miga, Benedict Paten
Reference-free genome phasing is vital for understanding allele inheritance and the impact of single-molecule DNA variation on phenotypes. To achieve thorough phasing across homozygous or repetitive regions of the genome, long-read sequencing technologies are often used to perform phased de novo assembly. As a step toward reducing the cost and complexity of this type of analysis, we describe new methods
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Extreme genome scrambling in marine planktonic Oikopleura dioica cryptic species Genome Res. (IF 6.2) Pub Date : 2024-03-01 Charles Plessy, Michael J. Mansfield, Aleksandra Bliznina, Aki Masunaga, Charlotte West, Yongkai Tan, Andrew W. Liu, Jan Grašič, María Sara del Río Pisula, Gaspar Sánchez-Serna, Marc Fabrega-Torrus, Alfonso Ferrández-Roldán, Vittoria Roncalli, Pavla Navratilova, Eric M. Thompson, Takeshi Onuma, Hiroki Nishida, Cristian Cañestro, Nicholas M. Luscombe
Genome structural variations within species are rare. How selective constraints preserve gene order and chromosome structure is a central question in evolutionary biology that remains unsolved. Our sequencing of several genomes of the appendicularian tunicate Oikopleura dioica around the globe reveals extreme genome scrambling caused by thousands of chromosomal rearrangements, although showing no obvious
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Systematic identification and characterization of exon–intron circRNAs Genome Res. (IF 6.2) Pub Date : 2024-03-01 Yinchun Zhong, Yan Yang, Xiaolin Wang, Bingbing Ren, Xueren Wang, Ge Shan, Liang Chen
Exon–intron circRNAs (EIciRNAs) are a circRNA subclass with retained introns. Global features of EIciRNAs remain largely unexplored, mainly owing to the lack of bioinformatic tools. The regulation of intron retention (IR) in EIciRNAs and the associated functionality also require further investigation. We developed a framework, FEICP, which efficiently detected EIciRNAs from high-throughput sequencing
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Ancestral aneuploidy and stable chromosomal duplication resulting in differential genome structure and gene expression control in trypanosomatid parasites Genome Res. (IF 6.2) Pub Date : 2024-03-01 João L. Reis-Cunha, Samuel A. Pimenta-Carvalho, Laila V. Almeida, Anderson Coqueiro-dos-Santos, Catarina A. Marques, Jennifer A. Black, Jeziel Damasceno, Richard McCulloch, Daniella C. Bartholomeu, Daniel C. Jeffares
Aneuploidy is widely observed in both unicellular and multicellular eukaryotes, usually associated with adaptation to stress conditions. Chromosomal duplication stability is a tradeoff between the fitness cost of having unbalanced gene copies and the potential fitness gained from increased dosage of specific advantageous genes. Trypanosomatids, a family of protozoans that include species that cause
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Systematic mapping of TF-mediated cell fate changes by a pooled induction coupled with scRNA-seq and multi-omics approaches Genome Res. (IF 6.2) Pub Date : 2024-03-01 Muyoung Lee, Qingqing Guo, Mijeong Kim, Joonhyuk Choi, Alia Segura, Alper Genceroglu, Lucy LeBlanc, Nereida Ramirez, Yu Jin Jang, Yeejin Jang, Bum-Kyu Lee, Edward M. Marcotte, Jonghwan Kim
Transcriptional regulation controls cellular functions through interactions between transcription factors (TFs) and their chromosomal targets. However, understanding the fate conversion potential of multiple TFs in an inducible manner remains limited. Here, we introduce iTF-seq as a method for identifying individual TFs that can alter cell fate toward specific lineages at a single-cell level. iTF-seq
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Robust chromatin state annotation Genome Res. (IF 6.2) Pub Date : 2024-03-01 Mehdi Foroozandeh Shahraki, Marjan Farahbod, Maxwell W. Libbrecht
With the goal of mapping genomic activity, international projects have recently measured epigenetic activity in hundreds of cell and tissue types. Chromatin state annotations produced by segmentation and genome annotation (SAGA) methods have emerged as the predominant way to summarize these epigenomic data sets in order to annotate the genome. These chromatin state annotations are essential for many
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Translation-dependent and -independent mRNA decay occur through mutually exclusive pathways defined by ribosome density during T cell activation Genome Res. (IF 6.2) Pub Date : 2024-03-01 Blandine C. Mercier, Emmanuel Labaronne, David Cluet, Laura Guiguettaz, Nicolas Fontrodona, Alicia Bicknell, Antoine Corbin, Mélanie Wencker, Fabien Aube, Laurent Modolo, Karina Jouravleva, Didier Auboeuf, Melissa J. Moore, Emiliano P. Ricci
mRNA translation and decay are tightly interconnected processes both in the context of mRNA quality-control pathways and for the degradation of functional mRNAs. Cotranslational mRNA degradation through codon usage, ribosome collisions, and the recruitment of specific proteins to ribosomes is an important determinant of mRNA turnover. However, the extent to which translation-dependent mRNA decay (TDD)
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The genome of the colonial hydroid Hydractinia reveals that their stem cells use a toolkit of evolutionarily shared genes with all animals Genome Res. (IF 6.2) Pub Date : 2024-03-01 Christine E. Schnitzler, E. Sally Chang, Justin Waletich, Gonzalo Quiroga-Artigas, Wai Yee Wong, Anh-Dao Nguyen, Sofia N. Barreira, Liam B. Doonan, Paul Gonzalez, Sergey Koren, James M. Gahan, Steven M. Sanders, Brian Bradshaw, Timothy Q. DuBuc, Febrimarsa, Danielle de Jong, Eric P. Nawrocki, Alexandra Larson, Samantha Klasfeld, Sebastian G. Gornik, R. Travis Moreland, Tyra G. Wolfsberg, Adam M. Phillippy
Hydractinia is a colonial marine hydroid that shows remarkable biological properties, including the capacity to regenerate its entire body throughout its lifetime, a process made possible by its adult migratory stem cells, known as i-cells. Here, we provide an in-depth characterization of the genomic structure and gene content of two Hydractinia species, Hydractinia symbiolongicarpus and Hydractinia
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Inference of selective forces on house mouse genomes during secondary contact in East Asia Genome Res. (IF 6.2) Pub Date : 2024-03-01 Kazumichi Fujiwara, Shunpei Kubo, Toshinori Endo, Toyoyuki Takada, Toshihiko Shiroishi, Hitoshi Suzuki, Naoki Osada
The house mouse (Mus musculus), which is commensal to humans, has spread globally via human activities, leading to secondary contact between genetically divergent subspecies. This pattern of genetic admixture can provide insights into the selective forces at play in this well-studied model organism. Our analysis of 163 house mouse genomes, with a particular focus on East Asia, revealed substantial
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Experimentally evolving Drosophila erecta populations may fail to establish an effective piRNA-based host defense against invading P-elements Genome Res. (IF 6.2) Pub Date : 2024-03-01 Divya Selvaraju, Filip Wierzbicki, Robert Kofler
To prevent the spread of transposable elements (TEs), hosts have developed sophisticated defense mechanisms. In mammals and invertebrates, a major defense mechanism operates through PIWI-interacting RNAs (piRNAs). To investigate the establishment of the host defense, we introduced the P-element, one of the most widely studied eukaryotic transposons, into naive lines of Drosophila erecta. We monitored