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A systematic review on the biochemical threshold of mitochondrial genetic variants Genome Res. (IF 7.0) Pub Date : 2024-04-16 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 7.0) Pub Date : 2024-04-16 Ryan Lorig-Roach, Melissa Meredith, Jean Monlong, Miten Jain, Hugh Olsen, Brandy McNulty, David Porubsky, Tessa Montague, Julian Lucas, Chris Condon, Jordan M. Eizenga, Sissel Juul, Sean McKenzie, Sara E. Simmonds, Jimin Park, Mobin Asri, Sergey Koren, Evan Eichler, Richard Axel, Bruce Martin, Paolo Carnevali, Karen 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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Probabilistic association of differentially expressed genes with cis-regulatory elements Genome Res. (IF 7.0) Pub Date : 2024-04-17 Brian S Roberts, Ashlyn G Anderson, Chris 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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Extreme genome scrambling in marine planktonic Oikopleura dioica cryptic species Genome Res. (IF 7.0) Pub Date : 2024-04-15 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 7.0) Pub Date : 2024-04-12 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 7.0) Pub Date : 2024-04-11 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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Transcriptional programs mediating neuronal toxicity and altered glial-neuronal signaling in a Drosophila knock-in tauopathy model Genome Res. (IF 7.0) Pub Date : 2024-04-10 Hassan Bukhari, Vanitha Nithianadam, 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 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 not faithfully recreate the genetic
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Plant genome evolution in the genus Eucalyptus driven by structural rearrangements that promote sequence divergence Genome Res. (IF 7.0) Pub Date : 2024-04-08 Scott Ferguson, Ashley Jones, Kevin Murray, Rose Andrew, Benjamin Schwessinger, Justin O 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 7.0) Pub Date : 2024-04-08 Shuangxi Ji, Wenyi Wang, Tong Zhu, Ankit Sethia
Accurate detection of somatic mutations in DNA sequencing data is a fundamental prerequisite for cancer research. Previous analytical challenge was 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 multi-step parallelization and efficient memory allocation
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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 7.0) Pub Date : 2024-04-05 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 7.0) Pub Date : 2024-03-21 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 7.0) Pub Date : 2024-03-20 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 7.0) Pub Date : 2024-03-20 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 7.0) Pub Date : 2024-03-20 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 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 defense, 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 : 2024-02-01 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 : 2024-02-01 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 : 2024-02-01 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 : 2024-02-01 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 : 2024-02-01 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 : 2024-02-01 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 : 2024-02-01 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 : 2024-02-01 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 : 2024-02-01 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 : 2024-02-01 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 : 2024-02-01 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 : 2024-02-01 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 : 2024-02-01 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