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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 7.0) Pub Date : 2024-03-15 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 defence we introduced the P-element, one of the most widely studied eukaryotic transposons, into naive lines of Drosophila erecta. We monitored
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Haplotype-resolved 3D chromatin architecture of the hybrid pig Genome Res. (IF 7.0) Pub Date : 2024-03-13 Yu Lin, Jing Li, Yiren Gu, Long Jin, Jingyi Bai, Jiaman Zhang, Yujie Wang, Pengliang Liu, Keren Long, Mengnan He, Diyan Li, Can Liu, Ziyin Han, Yu Zhang, Xiaokai Li, Bo Zeng, Lu Lu, Fanli Kong, Ying Sun, Yongliang Fan, Xun Wang, Tao Wang, An'an Jiang, Jideng Ma, Linyuan Shen, Li Zhu, Yanzhi Jiang, Guoqing Tang, Xiaolan Fan, Qingyou Liu, Hua Li, Jinyong Wang, Li Chen, Liangpeng Ge, Xuewei Li, Qianzi
In diploid mammals, allele-specific three-dimensional (3D) genome architecture may lead to imbalanced gene expression. Through ultradeep in situ Hi-C sequencing of three representative somatic tissues (liver, skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization
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Modeling alternative translation initiation sites in plants reveals evolutionarily conserved cis-regulatory codes in eukaryotes Genome Res. (IF 7.0) Pub Date : 2024-03-13 Ting-Ying Wu, Ya-Ru Li, Kai-Jyun Chang, Jhen-Cheng Fang, Daisuke Urano, Ming-Jung Liu
mRNA translation relies on identifying translation initiation sites (TISs) in mRNAs. Alternative TISs are prevalent across plant transcriptomes, but the mechanisms for their recognition are unclear. Using ribosome profiling and machine learning, we developed models for predicting alternative TISs in the tomato (Solanum lycopersicum). Distinct feature sets were predictive of AUG and nonAUG TISs in 5′
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Major impacts of widespread structural variation on sorghum Genome Res. (IF 7.0) Pub Date : 2024-03-13 Zhihai Zhang, Joao Paulo Gomes Viana, Bosen Zhang, Kimberly K.O. Walden, Hans Müller Paul, Stephen P. Moose, Geoffrey P. Morris, Chris Daum, Kerrie W. Barry, Nadia Shakoor, Matthew E. Hudson
Genetic diversity is critical to crop breeding and improvement, and dissection of the genomic variation underlying agronomic traits can both assist breeding and give insight into basic biological mechanisms. Although recent genome analyses in plants reveal many structural variants (SVs), most current studies of crop genetic variation are dominated by single-nucleotide polymorphisms (SNPs). The extent
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The structure, function, and evolution of plant centromeres Genome Res. (IF 7.0) Pub Date : 2024-03-14 Matthew Naish, Ian R. Henderson
Centromeres are essential regions of eukaryotic chromosomes responsible for the formation of kinetochore complexes, which connect to spindle microtubules during cell division. Notably, although centromeres maintain a conserved function in chromosome segregation, the underlying DNA sequences are diverse both within and between species and are predominantly repetitive in nature. The repeat content of
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Dynamic DNA N6-adenine methylation (6mA) governs the encystment process, showcased in the unicellular eukaryote Pseudocohnilembus persalinus Genome Res. (IF 7.0) Pub Date : 2024-03-12 Yongqiang Liu, Junhua Niu, Fei Ye, Therese Solberg, Borong Lu, Chundi Wang, Mariusz Nowacki, Shan Gao
The formation of resting cysts commonly found in unicellular eukaryotes is a complex and highly regulated survival strategy against environmental stress that involves drastic physiological and biochemical changes. Although most studies have focused on the morphology and structure of cysts, little is known about the molecular mechanisms that control this process. Recent studies indicate that DNA N6-adenine
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RNA Pol II–dependent transcription efficiency fine-tunes A-to-I editing levels Genome Res. (IF 7.0) Pub Date : 2024-03-12 Brigitta Szabo, Therese C. Mandl, Bernhard Woldrich, Gregor Diensthuber, David Martin, Michael F. Jantsch, Konstantin Licht
A-to-I RNA editing is a widespread epitranscriptomic phenomenon leading to the conversion of adenosines to inosines, which are primarily interpreted as guanosines by cellular machines. Consequently, A-to-I editing can alter splicing or lead to recoding of transcripts. As misregulation of editing can cause a variety of human diseases, A-to-I editing requires tight regulation of the extent of deamination
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Tyrosine 1–phosphorylated RNA polymerase II transcribes PROMPTs to facilitate proximal promoter pausing and induce global transcriptional repression in response to DNA damage Genome Res. (IF 7.0) Pub Date : 2024-03-11 Kamal Ajit, Adele Alagia, Kaspar Burger, Monika Gullerova
DNA damage triggers a complex transcriptional response that involves both activation and repression of gene expression. In this study, we investigated global changes in transcription in response to ionizing irradiation (IR), which induces double-strand breaks in DNA. We used mNET-seq to profile nascent transcripts bound to different phosphorylated forms of the RNA polymerase II (RNA Pol II) C-terminal
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Comprehensive assessment of 11 de novo HiFi assemblers on complex eukaryotic genomes and metagenomes Genome Res. (IF 7.0) Pub Date : 2024-03-01 Wenjuan Yu, Haohui Luo, Jinbao Yang, Shengchen Zhang, Heling Jiang, Xianjia Zhao, Xingqi Hui, Da Sun, Liang Li, Xiu-qing Wei, Stefano Lonardi, Weihua Pan
Pacific Biosciences (PacBio) HiFi sequencing technology generates long reads (>10 kbp) with very high accuracy (<0.01% sequencing error). Although several de novo assembly tools are available for HiFi reads, there are no comprehensive studies on the evaluation of these assemblers. We evaluated the performance of 11 de novo HiFi assemblers on (1) real data for three eukaryotic genomes; (2) 34 synthetic
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Genomic origin, fragmentomics, and transcriptional properties of long cell-free DNA molecules in human plasma Genome Res. (IF 7.0) Pub Date : 2024-02-26 Huiwen Che, Peiyong Jiang, L.Y. Lois Choy, Suk Hang Cheng, Wenlei Peng, Rebecca W.Y. Chan, Jing Liu, Qing Zhou, W.K. Jacky Lam, Stephanie C.Y. Yu, So Ling Lau, Tak Y. Leung, John Wong, Vincent Wai-Sun Wong, Grace L.H. Wong, Stephen L. Chan, K.C. Allen Chan, Y.M. Dennis Lo
Recent studies have revealed an unexplored population of long cell-free DNA (cfDNA) molecules in human plasma using long-read sequencing technologies. However, the biological properties of long cfDNA molecules (>500 bp) remain largely unknown. To this end, we have investigated the origins of long cfDNA molecules from different genomic elements. Analysis of plasma cfDNA using long-read sequencing reveals
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Differences in molecular sampling and data processing explain variation among single-cell and single-nucleus RNA-seq experiments Genome Res. (IF 7.0) Pub Date : 2024-02-14 John T. Chamberlin, Younghee Lee, Gabor T. Marth, Aaron R. Quinlan
A mechanistic understanding of the biological and technical factors that impact transcript measurements is essential to designing and analyzing single-cell and single-nucleus RNA sequencing experiments. Nuclei contain the same pre-mRNA population as cells, but they contain a small subset of the mRNAs. Nonetheless, early studies argued that single-nucleus analysis yielded results comparable to cellular
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Pangenome-genotyped structural variation improves molecular phenotype mapping in cattle Genome Res. (IF 7.0) Pub Date : 2024-02-14 Alexander S. Leonard, Xena M. Mapel, Hubert Pausch
Expression and splicing quantitative trait loci (e/sQTL) are large contributors to phenotypic variability. Achieving sufficient statistical power for e/sQTL mapping requires large cohorts with both genotypes and molecular phenotypes, and so, the genomic variation is often called from short-read alignments, which are unable to comprehensively resolve structural variation. Here we build a pangenome from
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Pathogenic variants in CRX have distinct cis-regulatory effects on enhancers and silencers in photoreceptors Genome Res. (IF 7.0) Pub Date : 2024-02-14 James L. Shepherdson, Ryan Z. Friedman, Yiqiao Zheng, Chi Sun, Inez Y. Oh, David M. Granas, Barak A. Cohen, Shiming Chen, Michael A. White
Dozens of variants in the gene for the homeodomain transcription factor (TF) cone-rod homeobox (CRX) are linked with human blinding diseases that vary in their severity and age of onset. How different variants in this single TF alter its function in ways that lead to a range of phenotypes is unclear. We characterized the effects of human disease-causing variants on CRX cis-regulatory function by deploying
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Preferential formation of Z-RNA over intercalated motifs in long noncoding RNA Genome Res. (IF 7.0) Pub Date : 2024-02-14 Uditi Bhatt, Anne Cucchiarini, Yu Luo, Cameron W. Evans, Jean-Louis Mergny, K. Swaminathan Iyer, Nicole M. Smith
Secondary structure is a principal determinant of lncRNA function, predominantly regarding scaffold formation and interfaces with target molecules. Noncanonical secondary structures that form in nucleic acids have known roles in regulating gene expression and include G-quadruplexes (G4s), intercalated motifs (iMs), and R-loops (RLs). In this paper, we used the computational tools G4-iM Grinder and
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Corrigendum: A mosquito small RNA genomics resource reveals dynamic evolution and host responses to viruses and transposons Genome Res. (IF 7.0) Pub Date : 2024-01-01 Qicheng Ma, Satyam P. Srivastav, Stephanie Gamez, Gargi Dayama, Fabiana Feitosa-Suntheimer, Edward I. Patterson, Rebecca M. Johnson, Erik M. Matson, Alexander S. Gold, Douglas E. Brackney, John H. Connor, Tonya M. Colpitts, Grant L. Hughes, Jason L. Rasgon, Tony Nolan, Omar S. Akbari, Nelson C. Lau
Genome Research 31: 512–528 (2021)
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Oxidative stress accelerates intestinal tumorigenesis by enhancing 8-oxoguanine-mediated mutagenesis in MUTYH-deficient mice Genome Res. (IF 7.0) Pub Date : 2024-01-01 Mizuki Ohno, Noriko Takano, Kyoko Hidaka, Fumiko Sasaki, Kazumi Yamauchi, Yasunobu Aoki, Takehiko Nohmi, Yusaku Nakabeppu, Yoshimichi Nakatsu, Teruhisa Tsuzuki
Oxidative stress–induced DNA damage and its repair systems are related to cancer etiology; however, the molecular basis triggering tumorigenesis is not well understood. Here, we aimed to explore the causal relationship between oxidative stress, somatic mutations in pre-tumor-initiated normal tissues, and tumor incidence in the small intestines of MUTYH-proficient and MUTYH-deficient mice. MUTYH is
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A statistical learning method for simultaneous copy number estimation and subclone clustering with single-cell sequencing data Genome Res. (IF 7.0) Pub Date : 2024-01-01 Fei Qin, Guoshuai Cai, Christopher I. Amos, Feifei Xiao
The availability of single-cell sequencing (SCS) enables us to assess intra-tumor heterogeneity and identify cellular subclones without the confounding effect of mixed cells. Copy number aberrations (CNAs) have been commonly used to identify subclones in SCS data using various clustering methods, as cells comprising a subpopulation are found to share a genetic profile. However, currently available
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GenomeMUSter mouse genetic variation service enables multitrait, multipopulation data integration and analysis Genome Res. (IF 7.0) Pub Date : 2024-01-01 Robyn L. Ball, Molly A. Bogue, Hongping Liang, Anuj Srivastava, David G. Ashbrook, Anna Lamoureux, Matthew W. Gerring, Alexander S. Hatoum, Matthew J. Kim, Hao He, Jake Emerson, Alexander K. Berger, David O. Walton, Keith Sheppard, Baha El Kassaby, Francisco Castellanos, Govindarajan Kunde-Ramamoorthy, Lu Lu, John Bluis, Sejal Desai, Beth A. Sundberg, Gary Peltz, Zhuoqing Fang, Gary A. Churchill, Robert
Hundreds of inbred mouse strains and intercross populations have been used to characterize the function of genetic variants that contribute to disease. Thousands of disease-relevant traits have been characterized in mice and made publicly available. New strains and populations including consomics, the collaborative cross, expanded BXD, and inbred wild-derived strains add to existing complex disease
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Histone deacetylases maintain expression of the pluripotent gene network via recruitment of RNA polymerase II to coding and noncoding loci Genome Res. (IF 7.0) Pub Date : 2024-01-01 Richard D.W. Kelly, Kristy R. Stengel, Aditya Chandru, Lyndsey C. Johnson, Scott W. Hiebert, Shaun M. Cowley
Histone acetylation is a dynamic modification regulated by the opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Deacetylation of histone tails results in chromatin tightening, and therefore, HDACs are generally regarded as transcriptional repressors. Counterintuitively, simultaneous deletion of Hdac1 and Hdac2 in embryonic stem cells (ESCs) reduces expression
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A Bayesian framework to study tumor subclone–specific expression by combining bulk DNA and single-cell RNA sequencing data Genome Res. (IF 7.0) Pub Date : 2024-01-01 Yi Qiao, Xiaomeng Huang, Philip J. Moos, Jonathan M. Ahmann, Anthony D. Pomicter, Michael W. Deininger, John C. Byrd, Jennifer A. Woyach, Deborah M. Stephens, Gabor T. Marth
Genetic and gene expression heterogeneity is an essential hallmark of many tumors, allowing the cancer to evolve and to develop resistance to treatment. Currently, the most commonly used data types for studying such heterogeneity are bulk tumor/normal whole-genome or whole-exome sequencing (WGS, WES); and single-cell RNA sequencing (scRNA-seq), respectively. However, tools are currently lacking to
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High-throughput and genome-scale targeted mutagenesis using CRISPR in a nonmodel multicellular organism, Bombyx mori Genome Res. (IF 7.0) Pub Date : 2024-01-01 Sanyuan Ma, Tong Zhang, Ruolin Wang, Pan Wang, Yue Liu, Jiasong Chang, Aoming Wang, Xinhui Lan, Le Sun, Hao Sun, Run Shi, Wei Lu, Dan Liu, Na Zhang, Wenbo Hu, Xiaogang Wang, Weiqing Xing, Ling Jia, Qingyou Xia
Large-scale genetic mutant libraries are powerful approaches to interrogating genotype–phenotype correlations and identifying genes responsible for certain environmental stimuli, both of which are the central goal of life science study. We produced the first large-scale CRISPR-Cas9-induced library in a nonmodel multicellular organism, Bombyx mori. We developed a piggyBac-delivered binary genome editing
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Small polymorphisms are a source of ancestral bias in structural variant breakpoint placement Genome Res. (IF 7.0) Pub Date : 2024-01-01 Peter A. Audano, Christine R. Beck
High-quality genome assemblies and sophisticated algorithms have increased sensitivity for a wide range of variant types, and breakpoint accuracy for structural variants (SVs, ≥50 bp) has improved to near base pair precision. Despite these advances, many SV breakpoint locations are subject to systematic bias affecting variant representation. To understand why SV breakpoints are inconsistent across
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Power-law behavior of transcriptional bursting regulated by enhancer–promoter communication Genome Res. (IF 7.0) Pub Date : 2024-01-01 Zihao Wang, Zhenquan Zhang, Songhao Luo, Tianshou Zhou, Jiajun Zhang
Revealing how transcriptional bursting kinetics are genomically encoded is challenging because genome structures are stochastic at the organization level and are suggestively linked to gene transcription. To address this challenge, we develop a generic theoretical framework that integrates chromatin dynamics, enhancer–promoter (E-P) communication, and gene-state switching to study transcriptional bursting
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Characterization of the distribution and dynamics of chromatin states in the C. elegans germline reveals substantial H3K4me3 remodeling during oogenesis Genome Res. (IF 7.0) Pub Date : 2024-01-01 Mariateresa Mazzetto, Lauren E. Gonzalez, Nancy Sanchez, Valerie Reinke
Chromatin organization in the C. elegans germline is tightly regulated and critical for germ cell differentiation. Although certain germline epigenetic regulatory mechanisms have been identified, how they influence chromatin structure and ultimately gene expression remains unclear, in part because most genomic studies have focused on data collected from intact worms comprising both somatic and germline
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Data integration and inference of gene regulation using single-cell temporal multimodal data with scTIE Genome Res. (IF 7.0) Pub Date : 2024-01-01 Yingxin Lin, Tung-Yu Wu, Xi Chen, Sheng Wan, Brian Chao, Jingxue Xin, Jean Y.H. Yang, Wing H. Wong, Y.X. Rachel Wang
Single-cell technologies offer unprecedented opportunities to dissect gene regulatory mechanisms in context-specific ways. Although there are computational methods for extracting gene regulatory relationships from scRNA-seq and scATAC-seq data, the data integration problem, essential for accurate cell type identification, has been mostly treated as a standalone challenge. Here we present scTIE, a unified
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Identification and validation of supervariants reveal novel loci associated with human white matter microstructure Genome Res. (IF 7.0) Pub Date : 2024-01-01 Shiying Wang, Ting Li, Bingxin Zhao, Wei Dai, Yisha Yao, Cai Li, Tengfei Li, Hongtu Zhu, Heping Zhang
As an essential part of the central nervous system, white matter coordinates communications between different brain regions and is related to a wide range of neurodegenerative and neuropsychiatric disorders. Previous genome-wide association studies (GWASs) have uncovered loci associated with white matter microstructure. However, GWASs suffer from limited reproducibility and difficulties in detecting
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Aberrant landscapes of maternal meiotic crossovers contribute to aneuploidies in human embryos Genome Res. (IF 7.0) Pub Date : 2024-01-01 Daniel Ariad, Svetlana Madjunkova, Mitko Madjunkov, Siwei Chen, Rina Abramov, Clifford Librach, Rajiv C. McCoy
Meiotic recombination is crucial for human genetic diversity and chromosome segregation accuracy. Understanding its variation across individuals and the processes by which it goes awry are long-standing goals in human genetics. Current approaches for inferring recombination landscapes rely either on population genetic patterns of linkage disequilibrium (LD)—capturing a time-averaged view—or on direct
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De novo transcriptome assembly of mouse male germ cells reveals novel genes, stage-specific bidirectional promoter activity, and noncoding RNA expression Genome Res. (IF 7.0) Pub Date : 2023-12-01 Mark E. Gill, Alexia Rohmer, Serap Erkek-Ozhan, Ching-Yeu Liang, Sunwoo Chun, Evgeniy A. Ozonov, Antoine H.F.M. Peters
In mammals, the adult testis is the tissue with the highest diversity in gene expression. Much of that diversity is attributed to germ cells, primarily meiotic spermatocytes and postmeiotic haploid spermatids. Exploiting a newly developed cell purification method, we profiled the transcriptomes of such postmitotic germ cells of mice. We used a de novo transcriptome assembly approach and identified
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Revisiting chromatin packaging in mouse sperm Genome Res. (IF 7.0) Pub Date : 2023-12-01 Qiangzong Yin, Chih-Hsiang Yang, Olga S. Strelkova, Jingyi Wu, Yu Sun, Sneha Gopalan, Liyan Yang, Job Dekker, Thomas G. Fazzio, Xin Zhiguo Li, Johan Gibcus, Oliver J. Rando
Mammalian sperm show an unusual and heavily compacted genomic packaging state. In addition to its role in organizing the compact and hydrodynamic sperm head, it has been proposed that sperm chromatin architecture helps to program gene expression in the early embryo. Scores of genome-wide surveys in sperm have reported patterns of chromatin accessibility, nucleosome localization, histone modification
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Cohesin and CTCF do not assemble TADs in Xenopus sperm and male pronuclei Genome Res. (IF 7.0) Pub Date : 2023-12-01 Gregor Jessberger, Csilla Várnai, Roman R. Stocsits, Wen Tang, Georg Stary, Jan-Michael Peters
Paternal genomes are compacted during spermiogenesis and decompacted following fertilization. These processes are fundamental for inheritance but incompletely understood. We analyzed these processes in the frog Xenopus laevis, whose sperm can be assembled into functional pronuclei in egg extracts in vitro. In such extracts, cohesin extrudes DNA into loops, but in vivo cohesin only assembles topologically
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Assessing and mitigating privacy risks of sparse, noisy genotypes by local alignment to haplotype databases Genome Res. (IF 7.0) Pub Date : 2023-12-01 Prashant S. Emani, Maya N. Geradi, Gamze Gürsoy, Monica R. Grasty, Andrew Miranker, Mark B. Gerstein
Single nucleotide polymorphisms (SNPs) from omics data create a reidentification risk for individuals and their relatives. Although the ability of thousands of SNPs (especially rare ones) to identify individuals has been repeatedly shown, the availability of small sets of noisy genotypes, from environmental DNA samples or functional genomics data, motivated us to quantify their informativeness. We
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Spatiotemporal kinetics of CAF-1-dependent chromatin maturation ensures transcription fidelity during S-phase Genome Res. (IF 7.0) Pub Date : 2023-12-01 Boning Chen, Heather K. MacAlpine, Alexander J. Hartemink, David M. MacAlpine
Proper maintenance of epigenetic information after replication is dependent on the rapid assembly and maturation of chromatin. Chromatin Assembly Complex 1 (CAF-1) is a conserved histone chaperone that deposits (H3-H4)2 tetramers as part of the replication-dependent chromatin assembly process. Loss of CAF-1 leads to a delay in chromatin maturation, albeit with minimal impact on steady-state chromatin
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Using long-read CAGE sequencing to profile cryptic-promoter-derived transcripts and their contribution to the immunopeptidome Genome Res. (IF 7.0) Pub Date : 2023-12-01 Ju Heon Maeng, H. Josh Jang, Alan Y. Du, Shin-Cheng Tzeng, Ting Wang
Recent studies have shown that the noncoding genome can produce unannotated proteins as antigens that induce immune response. One major source of this activity is the aberrant epigenetic reactivation of transposable elements (TEs). In tumors, TEs often provide cryptic or alternate promoters, which can generate transcripts that encode tumor-specific unannotated proteins. Thus, TE-derived transcripts
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Evidence for selfing in a vertebrate from whole-genome sequencing Genome Res. (IF 7.0) Pub Date : 2023-12-01 Astrid Böhne, Zeynep Oğuzhan, Ioannis Chrysostomakis, Simon Vitt, Denis Meuthen, Sebastian Martin, Sandra Kukowka, Timo Thünken
A growing number of recent genomic studies report asexual parthenogenetic reproduction in a wide range of taxa, including vertebrate species from the reptile, bird, and fish lineages. Yet, self-fertilization (selfing) has been recorded only in a single vertebrate, the mangrove killifish Kryptolebias marmoratus. In cichlid fishes, sex determination is notably diverse and can be influenced by the environment
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Whole-genome long-read sequencing downsampling and its effect on variant-calling precision and recall Genome Res. (IF 7.0) Pub Date : 2023-12-01 William T. Harvey, Peter Ebert, Jana Ebler, Peter A. Audano, Katherine M. Munson, Kendra Hoekzema, David Porubsky, Christine R. Beck, Tobias Marschall, Kiran Garimella, Evan E. Eichler
Advances in long-read sequencing (LRS) technologies continue to make whole-genome sequencing more complete, affordable, and accurate. LRS provides significant advantages over short-read sequencing approaches, including phased de novo genome assembly, access to previously excluded genomic regions, and discovery of more complex structural variants (SVs) associated with disease. Limitations remain with
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A naturally occurring variant of MBD4 causes maternal germline hypermutation in primates Genome Res. (IF 7.0) Pub Date : 2023-12-01 Alexandra M. Stendahl, Rashesh Sanghvi, Samuel Peterson, Karina Ray, Ana C. Lima, Raheleh Rahbari, Donald F. Conrad
As part of an ongoing genome sequencing project at the Oregon National Primate Research Center, we identified a rhesus macaque with a rare homozygous frameshift mutation in the gene methyl-CpG binding domain 4, DNA glycosylase (MBD4). MBD4 is responsible for the repair of C > T deamination mutations at CpG dinucleotides and has been linked to somatic hypermutation and cancer predisposition in humans
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tRNA-derived small RNAs are embedded in the gene regulatory network instructing Drosophila metamorphosis Genome Res. (IF 7.0) Pub Date : 2023-12-01 Junling Shi, Jiaqi Xu, Jun Ma, Feng He
A class of noncoding RNAs, referred to as tsRNAs, is emerging with a potential to exert a new layer in gene regulation. These RNAs are breakdown products of tRNAs, either through active processing or passive cleavage or both. Since tRNAs are part of the general machinery for translation, their expression levels and activities are tightly controlled, raising the possibility that their breakdown products
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A DNA methylation haplotype block landscape in human tissues and preimplantation embryos reveals regulatory elements defined by comethylation patterns Genome Res. (IF 7.0) Pub Date : 2023-12-01 Yan Feng, Zhiqiang Zhang, Yuyang Hong, Yi Ding, Leiqin Liu, Siqi Gao, Hai Fang, Jiantao Shi
DNA methylation and associated regulatory elements play a crucial role in gene expression regulation. Previous studies have focused primarily on the distribution of mean methylation levels. Advances in whole-genome bisulfite sequencing (WGBS) have enabled the characterization of DNA methylation haplotypes (MHAPs), representing CpG sites from the same read fragment on a single chromosome, and the subsequent
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Transposon wave remodeled the epigenomic landscape in the rapid evolution of X-Chromosome dosage compensation Genome Res. (IF 7.0) Pub Date : 2023-11-01 David C.H. Metzger, Imogen Porter, Brendan Mobley, Benjamin A. Sandkam, Lydia J.M. Fong, Andrew P. Anderson, Judith E. Mank
Sex chromosome dosage compensation is a model to understand the coordinated evolution of transcription; however, the advanced age of the sex chromosomes in model systems makes it difficult to study how the complex regulatory mechanisms underlying chromosome-wide dosage compensation can evolve. The sex chromosomes of Poecilia picta have undergone recent and rapid divergence, resulting in widespread
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Integrating SNVs and CNAs on a phylogenetic tree from single-cell DNA sequencing data Genome Res. (IF 7.0) Pub Date : 2023-11-01 Liting Zhang, Hank W. Bass, Jerome Irianto, Xian Mallory
Single-cell DNA sequencing enables the construction of evolutionary trees that can reveal how tumors gain mutations and grow. Different whole-genome amplification procedures render genomic materials of different characteristics, often suitable for the detection of either single-nucleotide variation or copy number aberration, but not ideally for both. Consequently, this hinders the inference of a comprehensive
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Proteome-wide structural analysis quantifies structural conservation across distant species Genome Res. (IF 7.0) Pub Date : 2023-11-01 Shijie Zhang, Teng Zhang, Yuan Fu
Traditional evolutionary biology research mainly relies on sequence information to infer evolutionary relationships between genes or proteins. In contrast, protein structural information has long been overlooked, although structures are more conserved and closely linked to the functions than the sequences. To address this gap, we conducted a proteome-wide structural analysis using experimental and
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Characterization of meiotic recombination intermediates through gene knockouts in founder hybrid mice Genome Res. (IF 7.0) Pub Date : 2023-11-01 Benjamin Davies, Gang Zhang, Daniela Moralli, Samy Alghadban, Daniel Biggs, Chris Preece, Peter Donnelly, Anjali Gupta Hinch
Mammalian meiotic recombination proceeds via repair of hundreds of programmed DNA double-strand breaks, which requires choreographed binding of RPA, DMC1, and RAD51 to single-stranded DNA substrates. High-resolution in vivo binding maps of these proteins provide insights into the underlying molecular mechanisms. When assayed in F1-hybrid mice, these maps can distinguish the broken chromosome from the
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Cellular age explains variation in age-related cell-to-cell transcriptome variability Genome Res. (IF 7.0) Pub Date : 2023-11-01 Ming Yang, Benjamin R. Harrison, Daniel E.L. Promislow
Organs and tissues age at different rates within a single individual. Such asynchrony in aging has been widely observed at multiple levels, from functional hallmarks, such as anatomical structures and physiological processes, to molecular endophenotypes, such as the transcriptome and metabolome. However, we lack a conceptual framework to understand why some components age faster than others. Just as
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The human genome contains over a million autonomous exons Genome Res. (IF 7.0) Pub Date : 2023-11-01 Nicholas Stepankiw, Ally W.H. Yang, Timothy R. Hughes
Mammalian mRNA and lncRNA exons are often small compared to introns. The exon definition model predicts that exons splice autonomously, dependent on proximal exon sequence features, explaining their delineation within large introns. This model has not been examined on a genome-wide scale, however, leaving open the question of how often mRNA and lncRNA exons are autonomous. It is also unknown how frequently
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De novo reconstruction of satellite repeat units from sequence data Genome Res. (IF 7.0) Pub Date : 2023-11-01 Yujie Zhang, Justin Chu, Haoyu Cheng, Heng Li
Satellite DNA are long tandemly repeating sequences in a genome and may be organized as high-order repeats (HORs). They are enriched in centromeres and are challenging to assemble. Existing algorithms for identifying satellite repeats either require the complete assembly of satellites or only work for simple repeat structures without HORs. Here we describe Satellite Repeat Finder (SRF), a new algorithm
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E4F1 and ZNF148 are transcriptional activators of the −57A > C and wild-type TERT promoter Genome Res. (IF 7.0) Pub Date : 2023-11-01 Boon Haow Chua, Nurkaiyisah Zaal Anuar, Laure Ferry, Cecilia Domrane, Anna Wittek, Vineeth T. Mukundan, Sudhakar Jha, Falk Butter, Daniel G. Tenen, Pierre-Antoine Defossez, Dennis Kappei
Point mutations within the TERT promoter are the most recurrent somatic noncoding mutations identified across different cancer types, including glioblastoma, melanoma, hepatocellular carcinoma, and bladder cancer. They are most abundant at −146C > T and −124C > T, and rarer at −57A > C, with the latter originally described as a familial case, but subsequently shown also to occur somatically. All three
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Telomeric repeat evolution in the phylum Nematoda revealed by high-quality genome assemblies and subtelomere structures Genome Res. (IF 7.0) Pub Date : 2023-11-01 Jiseon Lim, Wonjoo Kim, Jun Kim, Junho Lee
Telomeres are composed of tandem arrays of telomeric-repeat motifs (TRMs) and telomere-binding proteins (TBPs), which are responsible for ensuring end-protection and end-replication of chromosomes. TRMs are highly conserved owing to the sequence specificity of TBPs, although significant alterations in TRM have been observed in several taxa, except Nematoda. We used public whole-genome sequencing data
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miRNA-like secondary structures in maize (Zea mays) genes and transposable elements correlate with small RNAs, methylation, and expression Genome Res. (IF 7.0) Pub Date : 2023-11-01 Galen T. Martin, Edwin Solares, Jeanelle Guadardo-Mendez, Aline Muyle, Alexandros Bousios, Brandon S. Gaut
RNA molecules carry information in their primary sequence and also their secondary structure. Secondary structure can confer important functional information, but it is also a signal for an RNAi-like host epigenetic response mediated by small RNAs (smRNAs). In this study, we used two bioinformatic methods to predict local secondary structures across features of the maize genome, focusing on small regions
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Genome-wide chromatin interaction profiling reveals a vital role of super-enhancers and rearrangements in host enhancer contacts during BmNPV infection Genome Res. (IF 7.0) Pub Date : 2023-11-01 Shudi Zhao, Yuedong Li, Guanping Chen, Xingyang Wang, Nan Chen, Xiaofeng Wu
As influential regulatory elements in the genome, enhancers control gene expression under specific cellular conditions, and such connections are dynamic under different conditions. However, because of the lack of a genome-wide enhancer–gene connection map, the roles and regulatory pattern of enhancers were poorly investigated in insects, and the dynamic changes of enhancer contacts and functions under
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Characterization of human transcription factor function and patterns of gene regulation in HepG2 cells Genome Res. (IF 7.0) Pub Date : 2023-11-01 Belle A. Moyers, E. Christopher Partridge, Mark Mackiewicz, Michael J. Betti, Roshan Darji, Sarah K. Meadows, Kimberly M. Newberry, Laurel A. Brandsmeier, Barbara J. Wold, Eric M. Mendenhall, Richard M. Myers
Transcription factors (TFs) are trans-acting proteins that bind cis-regulatory elements (CREs) in DNA to control gene expression. Here, we analyzed the genomic localization profiles of 529 sequence-specific TFs and 151 cofactors and chromatin regulators in the human cancer cell line HepG2, for a total of 680 broadly termed DNA-associated proteins (DAPs). We used this deep collection to model each TF's
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Multiscale network modeling reveals the gene regulatory landscape driving cancer prognosis in 32 cancer types Genome Res. (IF 7.0) Pub Date : 2023-10-01 Peng Xu, Bin Zhang
Cancer is a complex disease with diverse molecular mechanisms that affect patient prognosis. Network-based approaches are effective in revealing a holistic picture of cancer prognosis and gene interactions. However, a comprehensive landscape of coexpression networks and prognostic gene modules across multiple cancer types remains elusive. In this study, we performed a systematic analysis of coexpression
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Infernape uncovers cell type–specific and spatially resolved alternative polyadenylation in the brain Genome Res. (IF 7.0) Pub Date : 2023-10-01 Bowei Kang, Yalan Yang, Kaining Hu, Xiangbin Ruan, Yi-Lin Liu, Pinky Lee, Jasper Lee, Jingshu Wang, Xiaochang Zhang
Differential polyadenylation sites (PAs) critically regulate gene expression, but their cell type–specific usage and spatial distribution in the brain have not been systematically characterized. Here, we present Infernape, which infers and quantifies PA usage from single-cell and spatial transcriptomic data and show its application in the mouse brain. Infernape uncovers alternative intronic PAs and
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The pig pangenome provides insights into the roles of coding structural variations in genetic diversity and adaptation Genome Res. (IF 7.0) Pub Date : 2023-10-01 Zhengcao Li, Xiaohong Liu, Chen Wang, Zhenyang Li, Bo Jiang, Ruifeng Zhang, Lu Tong, Youping Qu, Sheng He, Haifan Chen, Yafei Mao, Qingnan Li, Torsten Pook, Yu Wu, Yanjun Zan, Hui Zhang, Lu Li, Keying Wen, Yaosheng Chen
Structural variations have emerged as an important driving force for genome evolution and phenotypic variation in various organisms, yet their contributions to genetic diversity and adaptation in domesticated animals remain largely unknown. Here we constructed a pangenome based on 250 sequenced individuals from 32 pig breeds in Eurasia and systematically characterized coding sequence presence/absence
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Latent feature extraction with a prior-based self-attention framework for spatial transcriptomics Genome Res. (IF 7.0) Pub Date : 2023-10-01 Zhen Li, Xiaoyang Chen, Xuegong Zhang, Rui Jiang, Shengquan Chen
Rapid advances in spatial transcriptomics (ST) have revolutionized the interrogation of spatial heterogeneity and increase the demand for comprehensive methods to effectively characterize spatial domains. As a prerequisite for ST data analysis, spatial domain characterization is a crucial step for downstream analyses and biological implications. Here we propose a prior-based self-attention framework
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GC-biased gene conversion drives accelerated evolution of ultraconserved elements in mammalian and avian genomes Genome Res. (IF 7.0) Pub Date : 2023-10-01 Anguo Liu, Nini Wang, Guoxiang Xie, Yang Li, Xixi Yan, Xinmei Li, Zhenliang Zhu, Zhuohui Li, Jing Yang, Fanxin Meng, Mingle Dou, Weihuang Chen, Nange Ma, Yu Jiang, Yuanpeng Gao, Yu Wang
Ultraconserved elements (UCEs) are the most conserved regions among the genomes of evolutionarily distant species and are thought to play critical biological functions. However, some UCEs rapidly evolved in specific lineages, and whether they contributed to adaptive evolution is still controversial. Here, using an increased number of sequenced genomes with high taxonomic coverage, we identified 2191
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Single-cell transcriptome and metagenome profiling reveals the genetic basis of rumen functions and convergent developmental patterns in ruminants Genome Res. (IF 7.0) Pub Date : 2023-10-01 Juan Deng, Ya-Jing Liu, Wen-Tian Wei, Qi-Xuan Huang, Li-Ping Zhao, Ling-Yun Luo, Qi Zhu, Lin Zhang, Yuan Chen, Yan-Ling Ren, Shan-Gang Jia, Yu-Luan Lin, Ji Yang, Feng-Hua Lv, Hong-Ping Zhang, Feng-E Li, Li Li, Meng-Hua Li
The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features
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Clustered and diverse transcription factor binding underlies cell type specificity of enhancers for housekeeping genes Genome Res. (IF 7.0) Pub Date : 2023-10-01 Iris Zhu, David Landsman
Housekeeping genes are considered to be regulated by common enhancers across different tissues. Here we report that most of the commonly expressed mouse or human genes across different cell types, including more than half of the previously identified housekeeping genes, are associated with cell type–specific enhancers. Furthermore, the binding of most transcription factors (TFs) is cell type–specific
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Identifying crossovers and shared genetic material in whole genome sequencing data from families Genome Res. (IF 7.0) Pub Date : 2023-10-01 Kelley Paskov, Brianna Chrisman, Nathaniel Stockham, Peter Yigitcan Washington, Kaitlyn Dunlap, Jae-Yoon Jung, Dennis P. Wall
Large, whole-genome sequencing (WGS) data sets containing families provide an important opportunity to identify crossovers and shared genetic material in siblings. However, the high variant calling error rates of WGS in some areas of the genome can result in spurious crossover calls, and the special inheritance status of the X Chromosome presents challenges. We have developed a hidden Markov model
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Localizing unmapped sequences with families to validate the Telomere-to-Telomere assembly and identify new hotspots for genetic diversity Genome Res. (IF 7.0) Pub Date : 2023-10-01 Brianna Chrisman, Chloe He, Jae-Yoon Jung, Nate Stockham, Kelley Paskov, Peter Washington, Juli Petereit, Dennis P. Wall
Although it is ubiquitous in genomics, the current human reference genome (GRCh38) is incomplete: It is missing large sections of heterochromatic sequence, and as a singular, linear reference genome, it does not represent the full spectrum of human genetic diversity. To characterize gaps in GRCh38 and human genetic diversity, we developed an algorithm for sequence location approximation using nuclear