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Identifying off-target effects of genome editing with Tracking-seq Nat. Rev. Genet. (IF 39.1) Pub Date : 2024-09-17 Ming Zhu
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Reshaping Waddington’s developmental landscape Nat. Rev. Genet. (IF 39.1) Pub Date : 2024-09-17 Yimiao Qu, Kyle M. Loh
Yimiao Qu and Kyle Loh discuss a 2004 paper by Xie et al., who demonstrated that B cells can be reprogrammed into macrophages through the enforced expression of a single transcription factor, providing insights into cellular plasticity and lineage conversion.
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A model for a dual function of N6-methyladenosine in R-loop regulation Nat. Genet. (IF 31.7) Pub Date : 2024-09-17 Abdulkadir Abakir, Alexey Ruzov
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Long-read RNA sequencing of archival tissues reveals novel genes and transcripts associated with clear cell renal cell carcinoma recurrence and immune evasion Genome Res. (IF 6.2) Pub Date : 2024-09-16 Joshua Lee, Elizabeth A Snell, Joanne Brown, Charlotte Elizabeth Booth, Rosamonde E Banks, Daniel J Turner, Naveen Vasudev, Dimitris Lagos
The use of long-read direct RNA sequencing (DRS) and PCR cDNA sequencing (PCS) in clinical oncology remains limited, with no direct comparison between the two methods. We used DRS and PCS to study clear cell renal cell carcinoma (ccRCC), focussing on new transcript and gene discovery. Twelve primary ccRCC archival tumors, six from patients who went on to relapse, were analysed. Results were validated
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Measuring X inactivation skew for X-linked diseases with adaptive nanopore sequencing Genome Res. (IF 6.2) Pub Date : 2024-09-16 Sena A Gocuk, James Lancaster, Shian Su, Jasleen K Jolly, Thomas L Edwards, Doron G Hickey, Matthew E Ritchie, Marnie E Blewitt, Lauren N Ayton, Quentin Gouil
X-linked genetic disorders typically affect females less severely than males due to the presence of a second X Chromosome not carrying the deleterious variant. However, the phenotypic expression in females is highly variable, which may be explained by an allelic skew in X-Chromosome inactivation. Accurate measurement of X inactivation skew is crucial to understand and predict disease phenotype in carrier
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Systematic prioritization of functional variants and effector genes underlying colorectal cancer risk Nat. Genet. (IF 31.7) Pub Date : 2024-09-16 Philip J. Law, James Studd, James Smith, Jayaram Vijayakrishnan, Bradley T. Harris, Maria Mandelia, Charlie Mills, Malcolm G. Dunlop, Richard S. Houlston
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Interpreting cis-regulatory interactions from large-scale deep neural networks Nat. Genet. (IF 31.7) Pub Date : 2024-09-16 Shushan Toneyan, Peter K. Koo
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Antagonism between H3K27me3 and genome–lamina association drives atypical spatial genome organization in the totipotent embryo Nat. Genet. (IF 31.7) Pub Date : 2024-09-16 Isabel Guerreiro, Franka J. Rang, Yumiko K. Kawamura, Carla Kroon-Veenboer, Jeroen Korving, Femke C. Groenveld, Ramada E. van Beek, Silke J. A. Lochs, Ellen Boele, Antoine H. M. F. Peters, Jop Kind
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Atlas of telomeric repeat diversity in Arabidopsis thaliana Genome Biol. (IF 10.1) Pub Date : 2024-09-16 Yueqi Tao, Wenfei Xian, Zhigui Bao, Fernando A. Rabanal, Andrea Movilli, Christa Lanz, Gautam Shirsekar, Detlef Weigel
Telomeric repeat arrays at the ends of chromosomes are highly dynamic in composition, but their repetitive nature and technological limitations have made it difficult to assess their true variation in genome diversity surveys. We have comprehensively characterized the sequence variation immediately adjacent to the canonical telomeric repeat arrays at the very ends of chromosomes in 74 genetically diverse
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Splam: a deep-learning-based splice site predictor that improves spliced alignments Genome Biol. (IF 10.1) Pub Date : 2024-09-16 Kuan-Hao Chao, Alan Mao, Steven L. Salzberg, Mihaela Pertea
The process of splicing messenger RNA to remove introns plays a central role in creating genes and gene variants. We describe Splam, a novel method for predicting splice junctions in DNA using deep residual convolutional neural networks. Unlike previous models, Splam looks at a 400-base-pair window flanking each splice site, reflecting the biological splicing process that relies primarily on signals
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ESCHR: a hyperparameter-randomized ensemble approach for robust clustering across diverse datasets Genome Biol. (IF 10.1) Pub Date : 2024-09-16 Sarah M. Goggin, Eli R. Zunder
Clustering is widely used for single-cell analysis, but current methods are limited in accuracy, robustness, ease of use, and interpretability. To address these limitations, we developed an ensemble clustering method that outperforms other methods at hard clustering without the need for hyperparameter tuning. It also performs soft clustering to characterize continuum-like regions and quantify clustering
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A novel approach for in vivo DNA footprinting using short double-stranded cell-free DNA from plasma Genome Res. (IF 6.2) Pub Date : 2024-09-13 Jan Müller, Christina Hartwig, Mirko Sonntag, Lisa Bitzer, Christopher Adelmann, Yevhen Vainshtein, Karolina Glanz, Sebastian O. Decker, Thorsten Brenner, Georg F. Weber, Arndt von Haeseler, Kai Sohn
Here, we present a method for enrichment of double-stranded cfDNA with an average length of ∼40 bp from cfDNA for high-throughput DNA sequencing. This class of cfDNA is enriched at gene promoters and binding sites of transcription factors or structural DNA-binding proteins, so that a genome-wide DNA footprint is directly captured from liquid biopsies. In short double-stranded cfDNA from healthy individuals
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Enhanced detection of RNA modifications and read mapping with high-accuracy nanopore RNA basecalling models Genome Res. (IF 6.2) Pub Date : 2024-09-13 Gregor Diensthuber, Leszek P Pryszcz, Laia Llovera, Morghan C Lucas, Anna Delgado-Tejedor, Sonia Cruciani, Jean-Yves Roignant, Oguzhan Begik, Eva Maria Novoa
In recent years, nanopore direct RNA sequencing (DRS) became a valuable tool for studying the epitranscriptome, due to its ability to detect multiple modifications within the same full-length native RNA molecules. While RNA modifications can be identified in the form of systematic basecalling 'errors' in DRS datasets, N6-methyladenosine (m6A) modifications produce relatively low 'errors' compared to
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Long-read transcriptome sequencing of CLL and MDS patients uncovers molecular effects of SF3B1 mutations Genome Res. (IF 6.2) Pub Date : 2024-09-13 Alicja Pacholewska, Matthias Lienhard, Mirko Brueggemann, Heike Haenel, Lorina Bilalli, Anja Koenigs, Felix Hess, Kerstin Becker, Karl Koehrer, Jesko Fabian Kaiser, Holger Gohlke, Norbert Gattermann, Michael Hallek, Carmen Diana Herling, Julian Koenig, Christina Grimm, Ralf Herwig, Kathi Zarnack, Michal R. Schweiger
Mutations in splicing factor 3B subunit 1 (SF3B1) frequently occur in patients with chronic lymphocytic leukemia (CLL) and myelodysplastic syndromes (MDS). These mutations have different effects on the disease prognosis with beneficial effect in MDS and worse prognosis in CLL patients. A full-length transcriptome approach can expand our knowledge on SF3B1 mutation effects on RNA splicing and its contribution
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Long-read DNA and cDNA sequencing identify cancer-predisposing deep intronic variation in tumor-suppressor genes Genome Res. (IF 6.2) Pub Date : 2024-09-13 Suleyman Gulsuner, Amal AbuRayyan, Jessica B. Mandell, Ming K. Lee, Greta V. Bernier, Barbara M. Norquist, Sarah B. Pierce, Mary-Claire King, Tom Walsh
The vast majority of deeply intronic genomic variants are benign, but some extremely rare or private deep intronic variants lead to exonification of intronic sequence with abnormal transcriptional consequences. Damaging variants of this class are likely underreported as causes of disease for several reasons: Most clinical DNA and RNA testing does not include full intronic sequences; many of these variants
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Comprehensive identification of genomic and environmental determinants of phenotypic plasticity in maize Genome Res. (IF 6.2) Pub Date : 2024-09-13 Laura E. Tibbs-Cortes, Tingting Guo, Carson M. Andorf, Xianran Li, Jianming Yu
Maize phenotypes are plastic, determined by the complex interplay of genetics and environmental variables. Uncovering the genes responsible and understanding how their effects change across a large geographic region are challenging. In this study, we conducted systematic analysis to identify environmental indices that strongly influence 19 traits (including flowering time, plant architecture, and yield
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Reconstruction of a robust bacterial replication module Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-14 Tao Wang, Fan He, Ting He, Chen Lin, Xin Guan, Zhongjun Qin, Xiaoli Xue
Chromosomal DNA replication is a fundamental process of life, involving the assembly of complex machinery and dynamic regulation. In this study, we reconstructed a bacterial replication module (pRC) by artificially clustering 23 genes involved in DNA replication and sequentially deleting these genes from their naturally scattered loci on the chromosome of Escherichia coli. The integration of pRC into
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Mei5–Sae3 stabilizes Dmc1 nucleating clusters for efficient Dmc1 assembly on RPA-coated single-stranded DNA Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-14 Chin-Dian Wei, Hao-Yen Chang, Chia-Hua Lu, Chih-Chun Chang, Asako Furukohri, Stephen Mwaniki, Akira Shinohara, Peter Chi, Hung-Wen Li
Interhomolog recombination in meiosis requires a meiosis-specific recombinase, Dmc1. In Saccharomyces cerevisiae, the Mei5–Sae3 complex facilitates the loading of Dmc1 onto the replication protein A (RPA)-coated single-stranded DNA (ssDNA) to form nucleoprotein filaments. In vivo, Dmc1 and Mei5–Sae3 are interdependent in their colocalization on the chromosomes. However, the mechanistic role of Mei5–Sae3
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IRescue: uncertainty-aware quantification of transposable elements expression at single cell level Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-14 Benedetto Polimeni, Federica Marasca, Valeria Ranzani, Beatrice Bodega
Transposable elements (TEs) are mobile DNA repeats known to shape the evolution of eukaryotic genomes. In complex organisms, they exhibit tissue-specific transcription. However, understanding their role in cellular diversity across most tissues remains a challenge, when employing single-cell RNA sequencing (scRNA-seq), due to their widespread presence and genetic similarity. To address this, we present
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Using nucleolytic toxins as restriction enzymes enables new RNA applications Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-14 Ulli Rothweiler, Sigurd Eidem Gundesø, Emma Wu Mikalsen, Steingrim Svenning, Mahavir Singh, Francis Combes, Frida J Pettersson, Antonia Mangold, Yvonne Piotrowski, Felix Schwab, Olav Lanes, Bernd Ketelsen Striberny
Over the past five decades, DNA restriction enzymes have revolutionized biotechnology. While these enzymes are widely used in DNA research and DNA engineering, the emerging field of RNA and mRNA therapeutics requires sequence-specific RNA endoribonucleases. Here, we describe EcoToxN1, a member of the type III toxin-antitoxin family of sequence-specific RNA endoribonucleases, and its use in RNA and
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Advancing microRNA target site prediction with transformer and base-pairing patterns Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-14 Yue Bi, Fuyi Li, Cong Wang, Tong Pan, Chen Davidovich, Geoffrey I Webb, Jiangning Song
MicroRNAs (miRNAs) are short non-coding RNAs involved in various cellular processes, playing a crucial role in gene regulation. Identifying miRNA targets remains a central challenge and is pivotal for elucidating the complex gene regulatory networks. Traditional computational approaches have predominantly focused on identifying miRNA targets through perfect Watson–Crick base pairings within the seed
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DNA breathing integration with deep learning foundational model advances genome-wide binding prediction of human transcription factors Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-14 Anowarul Kabir, Manish Bhattarai, Selma Peterson, Yonatan Najman-Licht, Kim Ø Rasmussen, Amarda Shehu, Alan R Bishop, Boian Alexandrov, Anny Usheva
It was previously shown that DNA breathing, thermodynamic stability, as well as transcriptional activity and transcription factor (TF) bindings are functionally correlated. To ascertain the precise relationship between TF binding and DNA breathing, we developed the multi-modal deep learning model EPBDxDNABERT-2, which is based on the Extended Peyrard-Bishop-Dauxois (EPBD) nonlinear DNA dynamics model
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Accelerated discovery and miniaturization of novel single-stranded cytidine deaminases Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-14 Jiacheng Deng, Xueyuan Li, Hao Yu, Lin Yang, Ziru Wang, Wenfeng Yi, Ying Liu, Wenyu Xiao, Hongyong Xiang, Zicong Xie, Dongmei Lv, Hongsheng Ouyang, Daxin Pang, Hongming Yuan
Cytidine base editors (CBEs) hold significant potential in genetic disease treatment and in breeding superior traits into animals. However, their large protein sizes limit their delivery by adeno-associated virus (AAV), given its packing capacity of <4.7 kb. To overcome this, we employed a web-based fast generic discovery (WFG) strategy, identifying several small ssDNA deaminases (Sdds) and constructing
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DrugMAP 2.0: molecular atlas and pharma-information of all drugs Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-14 Fengcheng Li, Minjie Mou, Xiaoyi Li, Weize Xu, Jiayi Yin, Yang Zhang, Feng Zhu
The escalating costs and high failure rates have decelerated the pace of drug development, which amplifies the research interests in developing combinatorial/repurposed drugs and understanding off-target adverse drug reaction (ADR). In other words, it is demanded to delineate the molecular atlas and pharma-information for the combinatorial/repurposed drugs and off-target interactions. However, such
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Striving for clarity in language about gene expression Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-14 Ana S G Cunningham, Myriam Gorospe
What do we mean when we say ‘gene expression’? In the decades following Crick's 1958 central dogma of molecular biology, whereby genetic information flows from DNA (genes) to RNA (transcripts) to protein (products), we have learned a great deal about DNA, RNA, proteins, and the ensuing phenotypic changes. With the advent of high-throughput technologies (1990s), molecular biologists and computer scientists
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Developmental regulation of dermal adipose tissue by BCL11b Genes Dev. (IF 7.5) Pub Date : 2024-09-12 Sarah Traynor, Shashwati Bhattacharya, Kirill Batmanov, Lan Cheng, Angela Weller, Natalie Moore, Carmen Flesher, David Merrick
The distinct anatomic environment in which adipose tissues arise during organogenesis is a principle determinant of their adult expansion capacity. Metabolic disease results from a deficiency in hyperplastic adipose expansion within the dermal/subcutaneous depot; thus, understanding the embryonic origins of dermal adipose is imperative. Using single-cell transcriptomics throughout murine embryogenesis
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CRISETR: an efficient technology for multiplexed refactoring of biosynthetic gene clusters. Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-13 Fuqiang He,Xinpeng Liu,Min Tang,Haiyi Wang,Yun Wu,Shufang Liang
The efficient refactoring of natural product biosynthetic gene clusters (BGCs) for activating silent BGCs is a central challenge for the discovery of new bioactive natural products. Herein, we have developed a simple and robust CRISETR (CRISPR/Cas9 and RecET-mediated Refactoring) technique, combining clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas9 and RecET, for the multiplexed
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RTP801 interacts with the tRNA ligase complex and dysregulates its RNA ligase activity in Alzheimer’s disease Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-13 Genís Campoy-Campos, Julia Solana-Balaguer, Anna Guisado-Corcoll, Almudena Chicote-González, Pol Garcia-Segura, Leticia Pérez-Sisqués, Adrian Gabriel Torres, Mercè Canal, Laura Molina-Porcel, Joaquín Fernández-Irigoyen, Enrique Santamaria, Lluís Ribas de Pouplana, Jordi Alberch, Eulàlia Martí, Albert Giralt, Esther Pérez-Navarro, Cristina Malagelada
RTP801/REDD1 is a stress-responsive protein overexpressed in neurodegenerative diseases such as Alzheimer’s disease (AD) that contributes to cognitive deficits and neuroinflammation. Here, we found that RTP801 interacts with HSPC117, DDX1 and CGI-99, three members of the tRNA ligase complex (tRNA-LC), which ligates the excised exons of intron-containing tRNAs and the mRNA exons of the transcription
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PerturbDB for unraveling gene functions and regulatory networks Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-13 Bing Yang, Man Zhang, Yanmei Shi, Bing-Qi Zheng, Chuanping Shi, Daning Lu, Zhi-Zhi Yang, Yi-Ming Dong, Liwen Zhu, Xingyu Ma, Jingyuan Zhang, Jiehua He, Yin Zhang, Kaishun Hu, Haoming Lin, Jian-You Liao, Dong Yin
Perturb-Seq combines CRISPR (clustered regularly interspaced short palindromic repeats)-based genetic screens with single-cell RNA sequencing readouts for high-content phenotypic screens. Despite the rapid accumulation of Perturb-Seq datasets, there remains a lack of a user-friendly platform for their efficient reuse. Here, we developed PerturbDB (http://research.gzsys.org.cn/perturbdb), a platform
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Five latent factors underlie response to immunotherapy Nat. Genet. (IF 31.7) Pub Date : 2024-09-12 Joseph Usset, Axel Rosendahl Huber, Maria A. Andrianova, Eduard Batlle, Joan Carles, Edwin Cuppen, Elena Elez, Enriqueta Felip, Marina Gómez-Rey, Deborah Lo Giacco, Francisco Martinez-Jimenez, Eva Muñoz-Couselo, Lillian L. Siu, Josep Tabernero, Ana Vivancos, Ferran Muiños, Abel Gonzalez-Perez, Nuria Lopez-Bigas
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Widespread position-dependent transcriptional regulatory sequences in plants Nat. Genet. (IF 31.7) Pub Date : 2024-09-12 Yoav Voichek, Gabriela Hristova, Almudena Mollá-Morales, Detlef Weigel, Magnus Nordborg
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X chromosome dosage shapes renal cell carcinoma risk Nat. Genet. (IF 31.7) Pub Date : 2024-09-11 Tiago Faial
Xp11 translocation renal cell carcinoma (tRCC) is a cancer subtype that occurs mainly in female individuals and is caused by a fusion between the TFE3 gene located on chromosome Xp11.2 and another gene on an autosome or on the X chromosome. However, mechanistic details are incomplete regarding the origin of the TFE3 fusion segment — from the active (chrXa) or inactive (chrXi) X chromosome — the types
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Human intestinal immuno-organoids Nat. Genet. (IF 31.7) Pub Date : 2024-09-11 Chiara Anania
The intestinal mucosa contains immune cells that regulate tissue homeostasis. Their functions are disrupted in various diseases, such as infectious and autoimmune disorders or cancer. Existing in vitro organoid models have attempted to mimic the interaction between the intestinal epithelium and immune cells, but none of them include autologous adult lymphocytes. Recaldin et al. developed intestinal
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The genomics of childhood T-lineage acute lymphoblastic leukemia Nat. Genet. (IF 31.7) Pub Date : 2024-09-11 Safia Danovi
The outlook for children with relapsed or refractory T-lineage acute lymphoblastic leukemia (T-ALL) is poor. Underpinning this is a lack of understanding of the drivers of relapsed disease, which means that it is not currently possible to identify children at high risk, and there are few treatment options when relapse occurs. To address this issue, Pölönen et al. combined whole-genome, epigenomic and
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Polygenic basis for seedless grapes Nat. Genet. (IF 31.7) Pub Date : 2024-09-11 Kyle Vogan
Fruit seedlessness is a desirable trait for many crops, including grapevine. To gain further insights into the genetic architecture of this trait, Wang et al. generated haplotype-resolved genome assemblies for two seedless grape varieties, Thompson Seedless and Black Monukka, and mapped structural variation in these genomes relative to other available assemblies, including inversions found uniquely
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Disease prediction with multi-omics and biomarkers empowers case–control genetic discoveries in the UK Biobank Nat. Genet. (IF 31.7) Pub Date : 2024-09-11 Manik Garg, Marcin Karpinski, Dorota Matelska, Lawrence Middleton, Oliver S. Burren, Fengyuan Hu, Eleanor Wheeler, Katherine R. Smith, Margarete A. Fabre, Jonathan Mitchell, Amanda O’Neill, Euan A. Ashley, Andrew R. Harper, Quanli Wang, Ryan S. Dhindsa, Slavé Petrovski, Dimitrios Vitsios
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Synergistic effect of split DNA activators of Cas12a with exon-unwinding and induced targeting effect. Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-11 Shen Huang,Yongliang Lou,Laibao Zheng
CRISPR-Cas12a, an RNA-guided nuclease, has been repurposed for genome editing and molecular diagnostics due to its capability of cis-cleavage on target DNA and trans-cleavage on non-target single-strand DNA (ssDNA). However, the mechanisms underlying the activation of trans-cleavage activity of Cas12a, particularly in the context of split DNA activators, remain poorly understood. We elucidate the synergistic
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HIV-1 usurps mixed-charge domain-dependent CPSF6 phase separation for higher-order capsid binding, nuclear entry and viral DNA integration. Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-11 Sooin Jang,Gregory J Bedwell,Satya P Singh,Hyun Jae Yu,Bjarki Arnarson,Parmit K Singh,Rajalingam Radhakrishnan,AidanDarian W Douglas,Zachary M Ingram,Christian Freniere,Onno Akkermans,Stefan G Sarafianos,Zandrea Ambrose,Yong Xiong,Praju V Anekal,Paula Montero Llopis,Vineet N KewalRamani,Ashwanth C Francis,Alan N Engelman
HIV-1 integration favors nuclear speckle (NS)-proximal chromatin and viral infection induces the formation of capsid-dependent CPSF6 condensates that colocalize with nuclear speckles (NSs). Although CPSF6 displays liquid-liquid phase separation (LLPS) activity in vitro, the contributions of its different intrinsically disordered regions, which includes a central prion-like domain (PrLD) with capsid
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DORQ-seq: high-throughput quantification of femtomol tRNA pools by combination of cDNA hybridization and Deep sequencing. Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-11 Kristen Marco,Lander Marc,Kilz Lea-Marie,Gleue Lukas,Jörg Marko,Bregeon Damien,Hamdane Djemel,Marchand Virginie,Motorin Yuri,Friedland Kristina,Helm Mark
Due to its high modification content tRNAs are notoriously hard to quantify by reverse transcription and RNAseq. Bypassing numerous biases resulting from concatenation of enzymatic treatments, we here report a hybrid approach that harnesses the advantages of hybridization-based and deep sequencing-based approaches. The method renders obsolete any RNAseq related workarounds and correction factors that
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CRISPR screening uncovers nucleolar RPL22 as a heterochromatin destabilizer and senescence driver. Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-11 Hong-Yu Li,Min Wang,Xiaoyu Jiang,Yaobin Jing,Zeming Wu,Yifang He,Kaowen Yan,Shuhui Sun,Shuai Ma,Zhejun Ji,Si Wang,Juan Carlos Izpisua Belmonte,Jing Qu,Weiqi Zhang,Taotao Wei,Guang-Hui Liu
Dysfunction of the ribosome manifests during cellular senescence and contributes to tissue aging, functional decline, and development of aging-related disorders in ways that have remained enigmatic. Here, we conducted a comprehensive CRISPR-based loss-of-function (LOF) screen of ribosome-associated genes (RAGs) in human mesenchymal progenitor cells (hMPCs). Through this approach, we identified ribosomal
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A single rare σ70 variant establishes a unique gene expression pattern in the E. coli pathobiont LF82. Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-11 Melissa Arroyo-Mendoza,Alexandra Proctor,Abraham Correa-Medina,Sarah DeWolf,Meghan Wymore Brand,Virginia Rosas,Hernan Lorenzi,Michael J Wannemuehler,Gregory J Phillips,Deborah M Hinton
LF82, an adherent-invasive Escherichia coli (AIEC) pathobiont, is associated with Crohn's disease, an inflammatory bowel disease of unknown etiology. Although AIEC phenotypes differ from those of 'commensal' or pathogenic E. coli, work has failed to identify genetic features accounting for these differences. We have investigated a natural, but rare, single nucleotide polymorphism (SNP) in LF82 present
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MBNL splicing factors regulate the microtranscriptome of skeletal muscles. Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-11 Agnieszka Piasecka,Michał W Szcześniak,Michał Sekrecki,Arkadiusz Kajdasz,Łukasz J Sznajder,Anna Baud,Krzysztof Sobczak
Muscleblind like splicing regulators (MBNLs) govern various RNA-processing steps, including alternative splicing, polyadenylation, RNA stability and mRNA intracellular localization. In myotonic dystrophy type 1 (DM1), the most common muscular dystrophy in adults, MBNLs are sequestered on toxic RNA containing expanded CUG repeats, which leads to disruption of MBNL-regulated processes and disease features
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Custom microfluidic chip design enables cost-effective three-dimensional spatiotemporal transcriptomics with a wide field of view Nat. Genet. (IF 31.7) Pub Date : 2024-09-10 Junjie Zhu, Kun Pang, Beiyu Hu, Ruiqiao He, Ning Wang, Zewen Jiang, Peifeng Ji, Fangqing Zhao
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Stepwise de novo establishment of inactive X chromosome architecture in early development Nat. Genet. (IF 31.7) Pub Date : 2024-09-10 Zhenhai Du, Liangjun Hu, Zhuoning Zou, Meishuo Liu, Zihan Li, Xukun Lu, Clair Harris, Yunlong Xiang, Fengling Chen, Guang Yu, Kai Xu, Feng Kong, Qianhua Xu, Bo Huang, Ling Liu, Qiang Fan, Haifeng Wang, Sundeep Kalantry, Wei Xie
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Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function Nat. Genet. (IF 31.7) Pub Date : 2024-09-10 Gabriel B. Loeb, Pooja Kathail, Richard W. Shuai, Ryan Chung, Reinier J. Grona, Sailaja Peddada, Volkan Sevim, Scot Federman, Karl Mader, Audrey Y. Chu, Jonathan Davitte, Juan Du, Alexander R. Gupta, Chun Jimmie Ye, Shawn Shafer, Laralynne Przybyla, Radu Rapiteanu, Nilah M. Ioannidis, Jeremy F. Reiter
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Differences in activity and stability drive transposable element variation in tropical and temperate maize Genome Res. (IF 6.2) Pub Date : 2024-09-09 Shujun Ou, Armin Scheben, Tyler Collins, Yinjie Qiu, Arun S. Seetharam, Claire C. Menard, Nancy Manchanda, Jonathan I. Gent, Michael C. Schatz, Sarah N. Anderson, Matthew B. Hufford, Candice N. Hirsch
Much of the profound interspecific variation in genome content has been attributed to transposable elements (TEs). To explore the extent of TE variation within species, we developed an optimized open-source algorithm, panEDTA, to de novo annotate TEs in a pangenome context. We then generated a unified TE annotation for a maize pangenome derived from 26 reference-quality genomes, which reveals an excess
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Genetic complexity of killer-cell immunoglobulin-like receptor genes in human pangenome assemblies Genome Res. (IF 6.2) Pub Date : 2024-09-09 Tsung-Kai Hung, Wan-Chi Liu, Sheng-Kai Lai, Hui-Wen Chuang, Yi-Che Lee, Hong-Ye Lin, Chia-Lang Hsu, Chien-Yu Chen, Ya-Chien Yang, Jacob Shujui Hsu, Pei-Lung Chen
The killer-cell immunoglobulin-like receptor (KIR) gene complex, a highly polymorphic region of the human genome that encodes proteins involved in immune responses, poses strong challenges in genotyping owing to its remarkable genetic diversity and structural intricacy. Accurate analysis of KIR alleles, including their structural variations, is crucial for understanding their roles in various immune
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Evidence for compensatory evolution within pleiotropic regulatory elements Genome Res. (IF 6.2) Pub Date : 2024-09-10 Zane Kliesmete, Peter Orchard, Victor Yan Kin Lee, Johanna Geuder, Simon M. Krauß, Mari Ohnuki, Jessica Jocher, Beate Vieth, Wolfgang Enard, Ines Hellmann
Pleiotropy, measured as expression breadth across tissues, is one of the best predictors for protein sequence and expression conservation. In this study, we investigated its effect on the evolution of cis-regulatory elements (CREs). To this end, we carefully reanalyzed the Epigenomics Roadmap data for nine fetal tissues, assigning a measure of pleiotropic degree to nearly half a million CREs. To assess
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Defining and pursuing diversity in human genetic studies Nat. Genet. (IF 31.7) Pub Date : 2024-09-09 Maili C. Raven-Adams, Tina Hernandez-Boussard, Yann Joly, Bartha Maria Knoppers, Subhashini Chandrasekharan, Adrian Thorogood, Judit Kumuthini, Calvin Wai Loon Ho, Ariana Gonzlez, Sarah C. Nelson, Yvonne Bombard, Donrich Thaldar, Hanshi Liu, Alessia Costa, Vijaytha Muralidharan, Sasha Henriques, Jamal Nasir, Aimé Lumaka, Beatrice Kaiser, Saumya Shekhar Jamuar, Anna C. F. Lewis
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NSD2 is a requisite subunit of the AR/FOXA1 neo-enhanceosome in promoting prostate tumorigenesis Nat. Genet. (IF 31.7) Pub Date : 2024-09-09 Abhijit Parolia, Sanjana Eyunni, Brijesh Kumar Verma, Eleanor Young, Yihan Liu, Lianchao Liu, James George, Shweta Aras, Chandan Kanta Das, Rahul Mannan, Reyaz ur Rasool, Erick Mitchell-Velasquez, Somnath Mahapatra, Jie Luo, Sandra E. Carson, Lanbo Xiao, Prathibha R. Gajjala, Sharan Venkatesh, Mustapha Jaber, Xiaoju Wang, Tongchen He, Yuanyuan Qiao, Matthew Pang, Yuping Zhang, Jean Ching-Yi Tien, Micheala
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High-quality genome of a modern soybean cultivar and resequencing of 547 accessions provide insights into the role of structural variation Nat. Genet. (IF 31.7) Pub Date : 2024-09-09 Caiying Zhang, Zhenqi Shao, Youbin Kong, Hui Du, Wenlong Li, Zhanwu Yang, Xiangkong Li, Huifeng Ke, Zhengwen Sun, Jiabiao Shao, Shiliang Chen, Hua Zhang, Jiahao Chu, Xinzhu Xing, Rui Tian, Ning Qin, Junru Li, Meihong Huang, Yaqian Sun, Xiaobo Huo, Chengsheng Meng, Guoning Wang, Yuan Liu, Zhiying Ma, Shilin Tian, Xihuan Li
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Dimension reduction, cell clustering, and cell–cell communication inference for single-cell transcriptomics with DcjComm Genome Biol. (IF 10.1) Pub Date : 2024-09-09 Qian Ding, Wenyi Yang, Guangfu Xue, Hongxin Liu, Yideng Cai, Jinhao Que, Xiyun Jin, Meng Luo, Fenglan Pang, Yuexin Yang, Yi Lin, Yusong Liu, Haoxiu Sun, Renjie Tan, Pingping Wang, Zhaochun Xu, Qinghua Jiang
Advances in single-cell transcriptomics provide an unprecedented opportunity to explore complex biological processes. However, computational methods for analyzing single-cell transcriptomics still have room for improvement especially in dimension reduction, cell clustering, and cell–cell communication inference. Herein, we propose a versatile method, named DcjComm, for comprehensive analysis of single-cell
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Making target sites in large structured RNAs accessible to RNA-cleaving DNAzymes through hybridization with synthetic DNA oligonucleotides Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-09 Connor Nurmi, Jimmy Gu, Amal Mathai, John D Brennan, Yingfu Li
The 10–23 DNAzyme is one of the most active DNA-based enzymes, and in theory, can be designed to target any purine-pyrimidine junction within an RNA sequence for cleavage. However, purine-pyrimidine junctions within a large, structured RNA (lsRNA) molecule of biological origin are not always accessible to 10–23, negating its general utility as an RNA-cutting molecular scissor. Herein, we report a generalizable
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DFF-ChIP: a method to detect and quantify complex interactions between RNA polymerase II, transcription factors, and chromatin Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-09 Benjamin M Spector, Juan F Santana, Miles A Pufall, David H Price
Recently, we introduced a chromatin immunoprecipitation (ChIP) technique utilizing the human DNA Fragmentation Factor (DFF) to digest the DNA prior to immunoprecipitation (DFF-ChIP) that provides the precise location of transcription complexes and their interactions with neighboring nucleosomes. Here we expand the technique to new targets and provide useful information concerning purification of DFF
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Trinucleotide cap analogs with triphosphate chain modifications: synthesis, properties, and evaluation as mRNA capping reagents Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-09 Marcin Warminski, Anais Depaix, Kamil Ziemkiewicz, Tomasz Spiewla, Joanna Zuberek, Karolina Drazkowska, Hanna Kedzierska, Agnieszka Popielec, Marek R Baranowski, Marta Sklucka, Marcelina Bednarczyk, Miroslaw Smietanski, Karol Wolosewicz, Bartosz Majewski, Remigiusz A Serwa, Dominika Nowis, Jakub Golab, Joanna Kowalska, Jacek Jemielity
The recent COVID-19 pandemics have demonstrated the great therapeutic potential of in vitro transcribed (IVT) mRNAs, but improvements in their biochemical properties, such as cellular stability, reactogenicity and translational activity, are critical for further practical applications in gene replacement therapy and anticancer immunotherapy. One of the strategies to overcome these limitations is the
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Mapping the structural landscape of the yeast Ty3 retrotransposon RNA genome. Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-09 Angelika Andrzejewska-Romanowska,Julita Gumna,Ewa Tykwińska,Katarzyna Pachulska-Wieczorek
Long terminal repeat (LTR)-retrotransposons are significant contributors to the evolution and diversity of eukaryotic genomes. Their RNA genomes (gRNA) serve as a template for protein synthesis and reverse transcription to a DNA copy, which can integrate into the host genome. Here, we used the SHAPE-MaP strategy to explore Ty3 retrotransposon gRNA structure in yeast and under cell-free conditions.
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A comprehensive map of the aging blood methylome in humans Genome Biol. (IF 10.1) Pub Date : 2024-09-06 Kirsten Seale, Andrew Teschendorff, Alexander P. Reiner, Sarah Voisin, Nir Eynon
During aging, the human methylome undergoes both differential and variable shifts, accompanied by increased entropy. The distinction between variably methylated positions (VMPs) and differentially methylated positions (DMPs), their contribution to epigenetic age, and the role of cell type heterogeneity remain unclear. We conduct a comprehensive analysis of > 32,000 human blood methylomes from 56 datasets
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DeepKINET: a deep generative model for estimating single-cell RNA splicing and degradation rates Genome Biol. (IF 10.1) Pub Date : 2024-09-06 Chikara Mizukoshi, Yasuhiro Kojima, Satoshi Nomura, Shuto Hayashi, Ko Abe, Teppei Shimamura
Messenger RNA splicing and degradation are critical for gene expression regulation, the abnormality of which leads to diseases. Previous methods for estimating kinetic rates have limitations, assuming uniform rates across cells. DeepKINET is a deep generative model that estimates splicing and degradation rates at single-cell resolution from scRNA-seq data. DeepKINET outperforms existing methods on
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Protein domain embeddings for fast and accurate similarity search Genome Res. (IF 6.2) Pub Date : 2024-09-05 Benjamin Giovanni Iovino, Haixu Tang, Yuzhen Ye
Recently developed protein language models have enabled a variety of applications with the protein contextual embeddings they produce. Per-protein representations (each protein is represented as a vector of fixed dimension) can be derived via averaging the embeddings of individual residues, or applying matrix transformation techniques such as the discrete cosine transformation to matrices of residue
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A Bayesian framework for inferring dynamic intercellular interactions from time-series single-cell data Genome Res. (IF 6.2) Pub Date : 2024-09-05 Cameron Y Park, Shouvik Mani, Nicolas Beltran-Velez, Katie Maurer, Teddy Huang, Shuqiang Li, Satyen Gohil, Kenneth J Livak, David A Knowles, Catherine J Wu, Elham Azizi
Characterizing cell-cell communication and tracking its variability over time are crucial for understanding the coordination of biological processes mediating normal development, disease progression, and responses to perturbations such as therapies. Existing tools fail to capture time-dependent intercellular interactions, and primarily rely on existing databases compiled from limited contexts. We introduce