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A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in AFF3 associated with intellectual disability Nat. Genet. (IF 31.7) Pub Date : 2024-09-23 Bharati Jadhav, Paras Garg, Joke J. F. A. van Vugt, Kristina Ibanez, Delia Gagliardi, William Lee, Mariya Shadrina, Tom Mokveld, Egor Dolzhenko, Alejandro Martin-Trujillo, Scott J. Gies, Gabrielle Altman, Clarissa Rocca, Mafalda Barbosa, Miten Jain, Nayana Lahiri, Katherine Lachlan, Henry Houlden, Benedict Paten, Jan Veldink, Arianna Tucci, Andrew J. Sharp
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Self-sustaining long-term 3D epithelioid cultures reveal drivers of clonal expansion in esophageal epithelium Nat. Genet. (IF 31.7) Pub Date : 2024-09-23 Albert Herms, David Fernandez-Antoran, Maria P. Alcolea, Argyro Kalogeropoulou, Ujjwal Banerjee, Gabriel Piedrafita, Emilie Abby, Jose Antonio Valverde-Lopez, Inês S. Ferreira, Irene Caseda, Maria T. Bejar, Stefan C. Dentro, Sara Vidal-Notari, Swee Hoe Ong, Bartomeu Colom, Kasumi Murai, Charlotte King, Krishnaa Mahbubani, Kourosh Saeb-Parsy, Alan R. Lowe, Moritz Gerstung, Philip H. Jones
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Federated analysis of autosomal recessive coding variants in 29,745 developmental disorder patients from diverse populations Nat. Genet. (IF 31.7) Pub Date : 2024-09-23 V. Kartik Chundru, Zhancheng Zhang, Klaudia Walter, Sarah J. Lindsay, Petr Danecek, Ruth Y. Eberhardt, Eugene J. Gardner, Daniel S. Malawsky, Emilie M. Wigdor, Rebecca Torene, Kyle Retterer, Caroline F. Wright, Hildur Ólafsdóttir, Maria J. Guillen Sacoto, Akif Ayaz, Ismail Hakki Akbeyaz, Dilşad Türkdoğan, Aaisha Ibrahim Al Balushi, Aida Bertoli-Avella, Peter Bauer, Emmanuelle Szenker-Ravi, Bruno Reversade
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Long-read genome sequencing and variant reanalysis increase diagnostic yield in neurodevelopmental disorders Genome Res. (IF 6.2) Pub Date : 2024-09-19 Susan M Hiatt, James MJ Lawlor, Lori H Handley, Donald R Latner, Zachary T Bonnstetter, Candice R Finnila, Michelle L Thompson, Lori Beth Boston, Melissa Williams, Ivan Rodriguez-Nunez, Jerry Jenkins, Whitley V Kelley, E Martina Bebin, Michael A Lopez, Anna CE Hurst, Bruce R Korf, Jeremy Schmutz, Jane Grimwood, Gregory M. Cooper
Variant detection from long-read genome sequencing (lrGS) has proven to be more accurate and comprehensive than variant detection from short-read genome sequencing (srGS). However, the rate at which lrGS can increase molecular diagnostic yield for rare disease is not yet precisely characterized. We performed lrGS using Pacific Biosciences HiFi technology on 96 short-read-negative probands with rare
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Genome-scale models in human metabologenomics Nat. Rev. Genet. (IF 39.1) Pub Date : 2024-09-19 Adil Mardinoglu, Bernhard Ø. Palsson
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Recruitment of the m6A/m6Am demethylase FTO to target RNAs by the telomeric zinc finger protein ZBTB48 Genome Biol. (IF 10.1) Pub Date : 2024-09-19 Syed Nabeel-Shah, Shuye Pu, Giovanni L. Burke, Nujhat Ahmed, Ulrich Braunschweig, Shaghayegh Farhangmehr, Hyunmin Lee, Mingkun Wu, Zuyao Ni, Hua Tang, Guoqing Zhong, Edyta Marcon, Zhaolei Zhang, Benjamin J. Blencowe, Jack F. Greenblatt
N6-methyladenosine (m6A), the most abundant internal modification on eukaryotic mRNA, and N6, 2′-O-dimethyladenosine (m6Am), are epitranscriptomic marks that function in multiple aspects of posttranscriptional regulation. Fat mass and obesity-associated protein (FTO) can remove both m6A and m6Am; however, little is known about how FTO achieves its substrate selectivity. Here, we demonstrate that ZBTB48
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A dynamic regulome of shoot-apical-meristem-related homeobox transcription factors modulates plant architecture in maize Genome Biol. (IF 10.1) Pub Date : 2024-09-19 Zi Luo, Leiming Wu, Xinxin Miao, Shuang Zhang, Ningning Wei, Shiya Zhao, Xiaoyang Shang, Hongyan Hu, Jiquan Xue, Tifu Zhang, Fang Yang, Shutu Xu, Lin Li
The shoot apical meristem (SAM), from which all above-ground tissues of plants are derived, is critical to plant morphology and development. In maize (Zea mays), loss-of-function mutant studies have identified several SAM-related genes, most encoding homeobox transcription factors (TFs), located upstream of hierarchical networks of hundreds of genes. Here, we collect 46 transcriptome and 16 translatome
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A cellular identity crisis? Plasticity changes during aging and rejuvenation Genes Dev. (IF 7.5) Pub Date : 2024-09-18 Rebecca Gorelov, Konrad Hochedlinger
Cellular plasticity in adult multicellular organisms is a protective mechanism that allows certain tissues to regenerate in response to injury. Considering that aging involves exposure to repeated injuries over a lifetime, it is conceivable that cell identity itself is more malleable—and potentially erroneous—with age. In this review, we summarize and critically discuss the available evidence that
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Tumbling bacteria and non-genetic individuality Nat. Rev. Genet. (IF 39.1) Pub Date : 2024-09-18 Alejo E. Rodriguez-Fraticelli
In this Journal Club, Alejo Rodriguez-Fratelli discusses a paper by Spudich and Koshland Jr that characterized non-genetic cell individuality in bacteria, a concept with emerging relevance to cancer progression.
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Gene synthesis from a non-coding RNA Nat. Rev. Genet. (IF 39.1) Pub Date : 2024-09-18 Linda Koch
A study in Science investigating bacterial defence mechanisms against phages reports a novel mode of gene regulation through reverse transcription of a non-coding RNA template, leading to the formation of a toxic repetitive gene.
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Why geneticists should care about male infertility Nat. Rev. Genet. (IF 39.1) Pub Date : 2024-09-16 Joris A. Veltman, Frank Tüttelmann
The widespread use of medically assisted reproduction fosters the false impression that the underlying causes of male infertility are not important to know. However, to improve men’s reproductive and long-term health, as well as the health of their offspring, large-scale genetic studies are essential. Thus, reproductive genomics should be implemented in diagnostics as soon as possible. In this Comment
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Chemical restriction of PU.1 genomic binding sites activates alternate gene networks Nat. Genet. (IF 31.7) Pub Date : 2024-09-18
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Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study Nat. Genet. (IF 31.7) Pub Date : 2024-09-18 Eleni Friligkou, Solveig Løkhammer, Brenda Cabrera-Mendoza, Jie Shen, Jun He, Giovanni Deiana, Mihaela Diana Zanoaga, Zeynep Asgel, Abigail Pilcher, Luciana Di Lascio, Ana Makharashvili, Dora Koller, Daniel S. Tylee, Gita A. Pathak, Renato Polimanti
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Pharmacological restriction of genomic binding sites redirects PU.1 pioneer transcription factor activity Nat. Genet. (IF 31.7) Pub Date : 2024-09-18 Samuel J. Taylor, Jacob Stauber, Oliver Bohorquez, Goichi Tatsumi, Rajni Kumari, Joyeeta Chakraborty, Boris A. Bartholdy, Emily Schwenger, Sriram Sundaravel, Abdelbasset A. Farahat, Justin C. Wheat, Mendel Goldfinger, Amit Verma, Arvind Kumar, David W. Boykin, Kristy R. Stengel, Gregory M. K. Poon, Ulrich Steidl
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Spatial transcriptomic analysis of primary and metastatic pancreatic cancers highlights tumor microenvironmental heterogeneity Nat. Genet. (IF 31.7) Pub Date : 2024-09-18 Ateeq M. Khaliq, Meenakshi Rajamohan, Omer Saeed, Kimia Mansouri, Asif Adil, Chi Zhang, Anita Turk, Julienne L. Carstens, Michael House, Sikander Hayat, Ganji P. Nagaraju, Sam G. Pappas, Y. Alan. Wang, Nicholas J. Zyromski, Mateusz Opyrchal, Kelvin P. Lee, Heather O’Hagan, Bassel El Rayes, Ashiq Masood
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Chromosome-level subgenome-aware de novo assembly of Saccharomyces bayanus provides insight into genome divergence after hybridization Genome Res. (IF 6.2) Pub Date : 2024-09-17 Cory Gardner, Junhao Chen, Christina Hadfield, Zhaolian Lu, David Debruin, Yu Zhan, Maureen Donlin, Tae-Hyuk Ahn, Zhenguo Lin
Interspecies hybridization is prevalent in various eukaryotic lineages and plays important roles in phenotypic diversification, adaptation, and speciation. To better understand the changes that occurred in the different subgenomes of a hybrid species and how they facilitate adaptation, we completed chromosome-level de novo assemblies of all chromosomes for a recently formed hybrid yeast, Saccharomyces
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Full-length RNA transcript sequencing traces brain isoform diversity in house mouse natural populations Genome Res. (IF 6.2) Pub Date : 2024-09-17 Wenyu Zhang, Anja Guenther, Yuanxiao Gao, Kristian Ullrich, Bruno Huettel, Aftab Ahmad, Lei Duan, Kaizong Wei, Diethard Tautz
The ability to generate multiple RNA transcript isoforms from the same gene is a general phenomenon in eukaryotes. However, the complexity and diversity of alternative isoforms in natural populations remain largely unexplored. Using a newly developed full-length transcripts enrichment protocol with 5' CAP selection, we sequenced full-length RNA transcripts of 48 individuals from outbred populations
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High-throughput single telomere analysis using DNA microarray and fluorescent in situ hybridization Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-18 Yun-Ling Zheng, Xingjia Wu, Madeline Williams, Simon Verhulst, Jue Lin, Yusuke Takahashi, Jian-Xing Ma, Ying Wang
The human telomere system is highly dynamic. Both short and long leucocyte average telomere lengths (aTL) are associated with an increased risk of cancer and early death, illustrating the complex relationship between TL and human health and the importance of assessing TL distributions with single TL analysis. A DNA microarray and telomere fluorescent in situ hybridization (DNA-array-FISH) approach
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DciA secures bidirectional replication initiation in Vibrio cholerae Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-18 Amelie Besombes, Yazid Adam, Christophe Possoz, Ivan Junier, Francois-Xavier Barre, Jean-Luc Ferat
Replication is initiated bidirectionally in the three domains of life by the assembly of two replication forks at an origin of replication. This is made possible by the recruitment of two replicative helicases to a nucleoprotein platform built at the origin of replication with the initiator protein. The reason why replication is initiated bidirectionally has never been experimentally addressed due
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Polyubiquitinated PCNA triggers SLX4-mediated break-induced replication in alternative lengthening of telomeres (ALT) cancer cells Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-18 Sangin Kim, Su Hyung Park, Nalae Kang, Jae Sun Ra, Kyungjae Myung, Kyoo-young Lee
Replication stresses are the major source of break-induced replication (BIR). Here, we show that in alternative lengthening of telomeres (ALT) cells, replication stress-induced polyubiquitinated proliferating cell nuclear antigen (PCNA) (polyUb-PCNA) triggers BIR at telomeres and the common fragile site (CFS). Consistently, depleting RAD18, a PCNA ubiquitinating enzyme, reduces the occurrence of ALT-associated
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Correction to 'Advancing quantitative PCR with color cycle multiplex amplification'. Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-18
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Toward building a comprehensive human pan-genome: The SEN-GENOME project. Am. J. Hum. Genet. (IF 8.1) Pub Date : 2024-09-18 Amadou Gaye,Andrea Regina G Sene,Macoura Gadji,Alioune Deme,Aynina Cisse,Rokhaya Ndiaye
The human reference genome (GRCh38), primarily sourced from individuals of European descent, falls short in capturing the vast genetic diversity across global populations. Efforts to diversify the reference genome face challenges in accessibility and representation, exacerbating the scarcity of African genomic data crucial for studying diseases prevalent in these populations. Sherman et al. proposed
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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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Transcription start site scanning requires the fungi-specific hydrophobic loop of Tfb3 Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-17 Chun Yang, Pratik Basnet, Samah Sharmin, Hui Shen, Craig D Kaplan, Kenji Murakami
RNA polymerase II (pol II) initiates transcription from transcription start sites (TSSs) located ∼30–35 bp downstream of the TATA box in metazoans, whereas in the yeast Saccharomyces cerevisiae, pol II scans further downstream TSSs located ∼40–120 bp downstream of the TATA box. Previously, we found that removal of the kinase module TFIIK (Kin28–Ccl1–Tfb3) from TFIIH shifts the TSS in a yeast in vitro
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How to scan naked DNA using promiscuous recognition and no clamping: a model for pioneer transcription factors Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-17 Rama Reddy Goluguri, Catherine Ghosh, Joshua Quintong, Mourad Sadqi, Victor Muñoz
Most DNA scanning proteins uniquely recognize their cognate sequence motif and slide on DNA assisted by some sort of clamping interface. The pioneer transcription factors that control cell fate in eukaryotes must forgo both elements to gain access to DNA in naked and chromatin forms; thus, whether or how these factors scan naked DNA is unknown. Here, we use single-molecule techniques to investigate
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4CAC: 4-class classifier of metagenome contigs using machine learning and assembly graphs Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-17 Lianrong Pu, Ron Shamir
Microbial communities usually harbor a mix of bacteria, archaea, plasmids, viruses and microeukaryotes. Within these communities, viruses, plasmids, and microeukaryotes coexist in relatively low abundance, yet they engage in intricate interactions with bacteria. Moreover, viruses and plasmids, as mobile genetic elements, play important roles in horizontal gene transfer and the development of antibiotic
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Crystal structure and nucleic acid binding mode of CPV NSP9: implications for viroplasm in Reovirales Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-17 Yeda Wang, Hangtian Guo, Yuhao Lu, Wanbin Yang, Tinghan Li, Xiaoyun Ji
Cytoplasmic polyhedrosis viruses (CPVs), like other members of the order Reovirales, produce viroplasms, hubs of viral assembly that shield them from host immunity. Our study investigates the potential role of NSP9, a nucleic acid-binding non-structural protein encoded by CPVs, in viroplasm biogenesis. We determined the crystal structure of the NSP9 core (NSP9ΔC), which shows a dimeric organization
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G-quadruplexes in an SVA retrotransposon cause aberrant TAF1 gene expression in X-linked dystonia parkinsonism Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-17 Giulia Nicoletto, Marianna Terreri, Ilaria Maurizio, Emanuela Ruggiero, Filippo M Cernilogar, Christine A Vaine, Maria Vittoria Cottini, Irina Shcherbakova, Ellen B Penney, Irene Gallina, David Monchaud, D Cristopher Bragg, Gunnar Schotta, Sara N Richter
G-quadruplexes (G4s) are non-canonical nucleic acid structures that form in guanine (G)-rich genomic regions. X-linked dystonia parkinsonism (XDP) is an inherited neurodegenerative disease in which a SINE–VNTR–Alu (SVA) retrotransposon, characterised by amplification of a G-rich repeat, is inserted into the coding sequence of TAF1, a key partner of RNA polymerase II. XDP SVA alters TAF1 expression
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A deep learning-based method enables the automatic and accurate assembly of chromosome-level genomes Nucleic Acids Res. (IF 16.6) Pub Date : 2024-09-17 Zijie Jiang, Zhixiang Peng, Zhaoyuan Wei, Jiahe Sun, Yongjiang Luo, Lingzi Bie, Guoqing Zhang, Yi Wang
The application of high-throughput chromosome conformation capture (Hi-C) technology enables the construction of chromosome-level assemblies. However, the correction of errors and the anchoring of sequences to chromosomes in the assembly remain significant challenges. In this study, we developed a deep learning-based method, AutoHiC, to address the challenges in chromosome-level genome assembly by
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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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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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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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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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Congenital microcoria deletion in mouse links Sox21 dysregulation to disease and suggests a role for TGFB2 in glaucoma and myopia. Am. J. Hum. Genet. (IF 8.1) Pub Date : 2024-09-13 Elisa Erjavec,Clémentine Angée,Djihad Hadjadj,Bruno Passet,Pierre David,Corinne Kostic,Emmanuel Dodé,Xavier Zanlonghi,Nicolas Cagnard,Brigitte Nedelec,Sylvain V Crippa,Christine Bole-Feysot,Mohammed Zarhrate,Sophie Creuzet,Johan Castille,Jean-Luc Vilotte,Patrick Calvas,Julie Plaisancié,Nicolas Chassaing,Josseline Kaplan,Jean-Michel Rozet,Lucas Fares Taie
Congenital microcoria (MCOR) is a rare hereditary developmental defect of the iris dilator muscle frequently associated with high axial myopia and high intraocular pressure (IOP) glaucoma. The condition is caused by submicroscopic rearrangements of chromosome 13q32.1. However, the mechanisms underlying the failure of iris development and the origin of associated features remain elusive. Here, we present
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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