-
Competition shapes the landscape of X-chromosome-linked genetic diversity Nat. Genet. (IF 31.7) Pub Date : 2024-07-26 Teresa Buenaventura, Hakan Bagci, Ilinca Patrascan, Joshua J. Graham, Kelsey D. Hipwell, Roel Oldenkamp, James W. D. King, Jesus Urtasun, George Young, Daniel Mouzo, David Gomez-Cabrero, Benjamin D. Rowland, Daniel Panne, Amanda G. Fisher, Matthias Merkenschlager
-
Accurate assembly of circular RNAs with TERRACE Genome Res. (IF 6.2) Pub Date : 2024-07-26 Tasfia Zahin, Qian Shi, Xiaofei Carl Zang, Mingfu Shao
Circular RNA (circRNA) is a class of RNA molecules that forms a closed loop with its 5' and 3' ends covalently bonded. circRNAs are known to be more stable than linear RNAs, admit distinct properties and functions, and have been proven to be promising biomarkers. Existing methods for assembling circRNAs heavily rely on the annotated transcriptomes, hence exhibiting unsatisfactory accuracy without a
-
Parameter-efficient fine-tuning on large protein language models improves signal peptide prediction Genome Res. (IF 6.2) Pub Date : 2024-07-26 Shuai Zeng, Duolin Wang, Lei Jiang, Dong Xu
Signal peptides (SP) play a crucial role in protein translocation in cells. The development of large protein language models (PLMs) and prompt-based learning provides a new opportunity for SP prediction, especially for the categories with limited annotated data. We present a parameter-efficient fine-tuning (PEFT) framework for SP prediction, PEFT-SP, to effectively utilize pretrained PLMs. We integrated
-
Reference-informed prediction of alternative splicing and splicing-altering mutations from sequences Genome Res. (IF 6.2) Pub Date : 2024-07-26 Chencheng Xu, Suying Bao, Ye Wang, Wenxing Li, Hao Chen, Yufeng Shen, Tao Jiang, Chaolin Zhang
Alternative splicing plays a crucial role in protein diversity and gene expression regulation in higher eukaryotes and mutations causing dysregulated splicing underlie a range of genetic diseases. Computational prediction of alternative splicing from genomic sequences not only provides insight into gene-regulatory mechanisms but also helps identify disease-causing mutations and drug targets. However
-
Tolerance thresholds underlie responses to DNA damage during germline development Genes Dev. (IF 7.5) Pub Date : 2024-07-25 Gloria Jansen, Daniel Gebert, Tharini Ravindra Kumar, Emily Simmons, Sarah Murphy, Felipe Karam Teixeira
Selfish DNA modules like transposable elements (TEs) are particularly active in the germline, the lineage that passes genetic information across generations. New TE insertions can disrupt genes and impair the functionality and viability of germ cells. However, we found that in P–M hybrid dysgenesis in Drosophila, a sterility syndrome triggered by the P-element DNA transposon, germ cells harbor unexpectedly
-
SonicParanoid2: fast, accurate, and comprehensive orthology inference with machine learning and language models Genome Biol. (IF 10.1) Pub Date : 2024-07-25 Salvatore Cosentino, Sira Sriswasdi, Wataru Iwasaki
Accurate inference of orthologous genes constitutes a prerequisite for comparative and evolutionary genomics. SonicParanoid is one of the fastest tools for orthology inference; however, its scalability and accuracy have been hampered by time-consuming all-versus-all alignments and the existence of proteins with complex domain architectures. Here, we present a substantial update of SonicParanoid, where
-
Comparing the roles of sex chromosome-encoded protein homologs in gene regulation Genes Dev. (IF 7.5) Pub Date : 2024-07-24 Ellen Lavorando, Michael C. Owens, Kathy Fange Liu
The X and Y chromosomes play important roles outside of human reproduction; namely, their potential contribution to human sex biases in physiology and disease. While sex biases are often thought to be an effect of hormones and environmental exposures, genes encoded on the sex chromosomes also play a role. Seventeen homologous gene pairs exist on the X and Y chromosomes whose proteins have critical
-
HYENA detects oncogenes activated by distal enhancers in cancer Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-25 Anqi Yu, Ali E Yesilkanal, Ashish Thakur, Fan Wang, Yang Yang, William Phillips, Xiaoyang Wu, Alexander Muir, Xin He, Francois Spitz, Lixing Yang
Somatic structural variations (SVs) in cancer can shuffle DNA content in the genome, relocate regulatory elements, and alter genome organization. Enhancer hijacking occurs when SVs relocate distal enhancers to activate proto-oncogenes. However, most enhancer hijacking studies have only focused on protein-coding genes. Here, we develop a computational algorithm ‘HYENA’ to identify candidate oncogenes
-
Imaging and quantification of human and viral circular RNAs Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-25 Dabbu Kumar Jaijyan, Shaomin Yang, Santhamani Ramasamy, Alison Gu, Mulan Zeng, Selvakumar Subbian, Sanjay Tyagi, Hua Zhu
We present a robust approach for cellular detection, imaging, localization, and quantification of human and viral encoded circular RNAs (circRNA) using amplified fluorescence in situ hybridization (ampFISH). In this procedure, a pair of hairpin probes bind next to each other at contiguous stretches of sequence and then undergo a conformational reorganization which initiates a target-dependent hybridization
-
Mobile element insertions affect human pigmentation and skin cancer risk Nat. Genet. (IF 31.7) Pub Date : 2024-07-24 Jeffrey M. Kidd
-
-
A sequence of SVA retrotransposon insertions in ASIP shaped human pigmentation Nat. Genet. (IF 31.7) Pub Date : 2024-07-24 Nolan Kamitaki, Margaux L. A. Hujoel, Ronen E. Mukamel, Edward Gebara, Steven A. McCarroll, Po-Ru Loh
-
The correlation between CpG methylation and gene expression is driven by sequence variants Nat. Genet. (IF 31.7) Pub Date : 2024-07-24 Olafur Andri Stefansson, Brynja Dogg Sigurpalsdottir, Solvi Rognvaldsson, Gisli Hreinn Halldorsson, Kristinn Juliusson, Gardar Sveinbjornsson, Bjarni Gunnarsson, Doruk Beyter, Hakon Jonsson, Sigurjon Axel Gudjonsson, Thorunn Asta Olafsdottir, Saedis Saevarsdottir, Magnus Karl Magnusson, Sigrun Helga Lund, Vinicius Tragante, Asmundur Oddsson, Marteinn Thor Hardarson, Hannes Petur Eggertsson, Reynir
-
Unlocking plant genetics with telomere-to-telomere genome assemblies Nat. Genet. (IF 31.7) Pub Date : 2024-07-24 Vanika Garg, Abhishek Bohra, Martin Mascher, Manuel Spannagl, Xun Xu, Michael W. Bevan, Jeffrey L. Bennetzen, Rajeev K. Varshney
-
Single-cell multi-omic and spatial profiling of human kidneys implicates the fibrotic microenvironment in kidney disease progression Nat. Genet. (IF 31.7) Pub Date : 2024-07-24 Amin Abedini, Jonathan Levinsohn, Konstantin A. Klötzer, Bernhard Dumoulin, Ziyuan Ma, Julia Frederick, Poonam Dhillon, Michael S. Balzer, Rojesh Shrestha, Hongbo Liu, Steven Vitale, Andi M. Bergeson, Kishor Devalaraja-Narashimha, Paola Grandi, Tanmoy Bhattacharyya, Erding Hu, Steven S. Pullen, Carine M. Boustany-Kari, Paolo Guarnieri, Anil Karihaloo, Daniel Traum, Hanying Yan, Kyle Coleman, Matthew
-
Cohesin prevents cross-domain gene coactivation Nat. Genet. (IF 31.7) Pub Date : 2024-07-24 Peng Dong, Shu Zhang, Valentina Gandin, Liangqi Xie, Lihua Wang, Andrew L. Lemire, Wenhong Li, Hideo Otsuna, Takashi Kawase, Arthur D. Lander, Howard Y. Chang, Zhe J. Liu
-
The vast majority of somatic mutations in plants are layer-specific Genome Biol. (IF 10.1) Pub Date : 2024-07-24 Manish Goel, José A. Campoy, Kristin Krause, Lisa C. Baus, Anshupa Sahu, Hequan Sun, Birgit Walkemeier, Magdalena Marek, Randy Beaudry, David Ruiz, Bruno Huettel, Korbinian Schneeberger
Plant meristems are structured organs consisting of distinct layers of stem cells, which differentiate into new plant tissue. Mutations in meristematic layers can propagate into large sectors of the plant. However, the characteristics of meristematic mutations remain unclear, limiting our understanding of the genetic basis of somaclonal phenotypic variation. Here, we analyse the frequency and distribution
-
Structural analysis of the BisI family of modification dependent restriction endonucleases Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-23 Katarzyna Szafran, Dominik Rafalski, Krzysztof Skowronek, Marek Wojciechowski, Asgar Abbas Kazrani, Mirosław Gilski, Shuang-yong Xu, Matthias Bochtler
The BisI family of restriction endonucleases is unique in requiring multiple methylated or hydroxymethylated cytosine residues within a short recognition sequence (GCNGC), and in cleaving directly within this sequence, rather than at a distance. Here, we report that the number of modified cytosines that are required for cleavage can be tuned by the salt concentration. We present crystal structures
-
A single CAA interrupt in a DNA three-way junction containing a CAG repeat hairpin results in parity-dependent trapping Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-23 Gillian M Cadden, Svea J Wilken, Steven W Magennis
An increasing number of human disorders are attributed to genomic expansions of short tandem repeats (STRs). Secondary DNA structures formed by STRs are believed to play an important role in expansion, while the presence of nucleotide interruptions within the pure repeat sequence is known to delay the onset and progression of disease. We have used two single-molecule fluorescence techniques to analyse
-
Ribosomal protein RPL39L is an efficiency factor in the cotranslational folding of a subset of proteins with alpha helical domains Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-23 Arka Banerjee, Meric Ataman, Maciej Jerzy Smialek, Debdatto Mookherjee, Julius Rabl, Aleksei Mironov, Lea Mues, Ludovic Enkler, Mairene Coto-Llerena, Alexander Schmidt, Daniel Boehringer, Salvatore Piscuoglio, Anne Spang, Nitish Mittal, Mihaela Zavolan
Increasingly many studies reveal how ribosome composition can be tuned to optimally translate the transcriptome of individual cell types. In this study, we investigated the expression pattern, structure within the ribosome and effect on protein synthesis of the ribosomal protein paralog 39L (RPL39L). With a novel mass spectrometric approach we revealed the expression of RPL39L protein beyond mouse
-
Epigenetic editing works like a CHARM Nat. Rev. Genet. (IF 39.1) Pub Date : 2024-07-22 Kirsty Minton
Neumann, Bertozzi et al. describe a novel epigenetic editor termed CHARM and report its use to silence prion protein expression in the brain.
-
Large-scale genotype prediction from RNA sequence data necessitates a new ethical and policy framework Nat. Genet. (IF 31.7) Pub Date : 2024-07-22 Mary A. Majumder, Jeffrey T. Leek, Kasper D. Hansen, Afrooz Razi, Amy L. McGuire
Genotype prediction from RNA sequencing (RNA-seq) data has become widespread, but there is a lack of clarity in current policy and inconsistency in data handling. To address this we call for a framework consisting of registered access for RNA-seq data, controlled access for genotypes, a code of conduct and enhanced downstream protections.
-
Condensin I folds the Caenorhabditis elegans genome Nat. Genet. (IF 31.7) Pub Date : 2024-07-22 Moushumi Das, Jennifer I. Semple, Anja Haemmerli, Valeriia Volodkina, Janik Scotton, Todor Gitchev, Ahrmad Annan, Julie Campos, Cyril Statzer, Alexander Dakhovnik, Collin Y. Ewald, Julien Mozziconacci, Peter Meister
-
Mitochondrial DNA mosaicism in normal human somatic cells Nat. Genet. (IF 31.7) Pub Date : 2024-07-22 Jisong An, Chang Hyun Nam, Ryul Kim, Yunah Lee, Hyein Won, Seongyeol Park, Won Hee Lee, Hansol Park, Christopher J. Yoon, Yohan An, Jie-Hyun Kim, Jong Kwan Jun, Jeong Mo Bae, Eui-Cheol Shin, Bun Kim, Yong Jun Cha, Hyun Woo Kwon, Ji Won Oh, Jee Yoon Park, Min Jung Kim, Young Seok Ju
-
Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings Nat. Genet. (IF 31.7) Pub Date : 2024-07-22 Axel Schmidt, Magdalena Danyel, Kathrin Grundmann, Theresa Brunet, Hannah Klinkhammer, Tzung-Chien Hsieh, Hartmut Engels, Sophia Peters, Alexej Knaus, Shahida Moosa, Luisa Averdunk, Felix Boschann, Henrike Lisa Sczakiel, Sarina Schwartzmann, Martin Atta Mensah, Jean Tori Pantel, Manuel Holtgrewe, Annemarie Bösch, Claudia Weiß, Natalie Weinhold, Aude-Annick Suter, Corinna Stoltenburg, Julia Neugebauer
-
Genome-wide association meta-analysis identifies five loci associated with postpartum hemorrhage Nat. Genet. (IF 31.7) Pub Date : 2024-07-22 David Westergaard, Valgerdur Steinthorsdottir, Lilja Stefansdottir, Palle Duun Rohde, Xiaoping Wu, Frank Geller, Jaakko Tyrmi, Aki S. Havulinna, Pol Solé-Navais, Christopher Flatley, Sisse Rye Ostrowski, Ole Birger Pedersen, Christian Erikstrup, Erik Sørensen, Christina Mikkelsen, Mie Topholm Bruun, Bitten Aagaard Jensen, Thorsten Brodersen, Henrik Ullum, Per Magnus, Ole A. Andreassen, Pål R. Njolstad
-
Scalable summary statistics-based heritability estimation method with individual genotype level accuracy Genome Res. (IF 6.2) Pub Date : 2024-07-22 Moonseong Jeong, Ali Pazokitoroudi, Zhengtong Liu, Sriram Sankararaman
SNP heritability, the proportion of phenotypic variation explained by genotyped SNPs, is an important parameter in understanding the genetic architecture underlying various diseases and traits. Methods that aim to estimate SNP heritability from individual genotype and phenotype data are limited by their ability to scale to Biobank-scale datasets and by the restrictions in access to individual-level
-
SUMO promotes DNA repair protein collaboration to support alternative telomere lengthening in the absence of PML Genes Dev. (IF 7.5) Pub Date : 2024-07-22 Rongwei Zhao, Meng Xu, Xiaoyang Yu, Anne R. Wondisford, Rachel M. Lackner, Jayme Salsman, Graham Dellaire, David M. Chenoweth, Roderick J. O'Sullivan, Xiaolan Zhao, Huaiying Zhang
The alternative lengthening of telomeres (ALT) pathway maintains telomere length in a significant fraction of cancers that are associated with poor clinical outcomes. A better understanding of ALT mechanisms is therefore necessary for developing new treatment strategies for ALT cancers. SUMO modification of telomere proteins contributes to the formation of ALT telomere-associated PML bodies (APBs)
-
Monitoring nucleolar-nucleoplasmic protein shuttling in living cells by high-content microscopy and automated image analysis Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-22 Marina Engbrecht, David Grundei, Asisa M Dilger, Hannah Wiedemann, Ann-Kristin Aust, Sarah Baumgärtner, Stefan Helfrich, Felix Kergl-Räpple, Alexander Bürkle, Aswin Mangerich
The nucleolus has core functions in ribosome biosynthesis, but also acts as a regulatory hub in a plethora of non-canonical processes, including cellular stress. Upon DNA damage, several DNA repair factors shuttle between the nucleolus and the nucleoplasm. Yet, the molecular mechanisms underlying such spatio-temporal protein dynamics remain to be deciphered. Here, we present a novel imaging platform
-
Assembly of the bacterial ribosome with circularly permuted rRNA Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-22 Xiyu Dong, Kai Sheng, Luca F R Gebert, Sriram Aiyer, Ian J MacRae, Dmitry Lyumkis, James R Williamson
Co-transcriptional assembly is an integral feature of the formation of RNA–protein complexes that mediate translation. For ribosome synthesis, prior studies have indicated that the strict order of transcription of rRNA domains may not be obligatory during bacterial ribosome biogenesis, since a series of circularly permuted rRNAs are viable. In this work, we report the structural insights into assembly
-
The human mitochondrial translation factor TACO1 alleviates mitoribosome stalling at polyproline stretches Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-22 Michele Brischigliaro, Annika Krüger, J Conor Moran, Hana Antonicka, Ahram Ahn, Eric A Shoubridge, Joanna Rorbach, Antoni Barrientos
The prokaryotic translation elongation factor P (EF-P) and the eukaryotic/archaeal counterparts eIF5A/aIF5A are proteins that serve a crucial role in mitigating ribosomal stalling during the translation of specific sequences, notably those containing consecutive proline residues (1,2). Although mitochondrial DNA-encoded proteins synthesized by mitochondrial ribosomes also contain polyproline stretches
-
N6-methyladenosine writer METTL16-mediated alternative splicing and translation control are essential for murine spermatogenesis Genome Biol. (IF 10.1) Pub Date : 2024-07-19 Qian Ma, Yiqian Gui, Xixiang Ma, Bingqian Zhang, Wenjing Xiong, Shiyu Yang, Congcong Cao, Shaomei Mo, Ge Shu, Jing Ye, Kuan Liu, Xiaoli Wang, Yaoting Gui, Fengli Wang, Shuiqiao Yuan
The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive. We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional
-
A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data Genome Biol. (IF 10.1) Pub Date : 2024-07-19 Alessandro Vinceti, Raffaele M. Iannuzzi, Isabella Boyle, Lucia Trastulla, Catarina D. Campbell, Francisca Vazquez, Joshua M. Dempster, Francesco Iorio
CRISPR-Cas9 dropout screens are formidable tools for investigating biology with unprecedented precision and scale. However, biases in data lead to potential confounding effects on interpretation and compromise overall quality. The activity of Cas9 is influenced by structural features of the target site, including copy number amplifications (CN bias). More worryingly, proximal targeted loci tend to
-
Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers Genome Biol. (IF 10.1) Pub Date : 2024-07-18 Farhia Kabeer, Hoa Tran, Mirela Andronescu, Gurdeep Singh, Hakwoo Lee, Sohrab Salehi, Beixi Wang, Justina Biele, Jazmine Brimhall, David Gee, Viviana Cerda, Ciara O’Flanagan, Teresa Algara, Takako Kono, Sean Beatty, Elena Zaikova, Daniel Lai, Eric Lee, Richard Moore, Andrew J. Mungall, Marc J. Williams, Andrew Roth, Kieran R. Campbell, Sohrab P. Shah, Samuel Aparicio
The encoding of cell intrinsic drug resistance states in breast cancer reflects the contributions of genomic and non-genomic variations and requires accurate estimation of clonal fitness from co-measurement of transcriptomic and genomic data. Somatic copy number (CN) variation is the dominant mutational mechanism leading to transcriptional variation and notably contributes to platinum chemotherapy
-
Non-coding variants impact cis-regulatory coordination in a cell type-specific manner Genome Biol. (IF 10.1) Pub Date : 2024-07-18 Olga Pushkarev, Guido van Mierlo, Judith Franziska Kribelbauer, Wouter Saelens, Vincent Gardeux, Bart Deplancke
Interactions among cis-regulatory elements (CREs) play a crucial role in gene regulation. Various approaches have been developed to map these interactions genome-wide, including those relying on interindividual epigenomic variation to identify groups of covariable regulatory elements, referred to as chromatin modules (CMs). While CM mapping allows to investigate the relationship between chromatin modularity
-
Leveraging neighborhood representations of single-cell data to achieve sensitive DE testing with miloDE Genome Biol. (IF 10.1) Pub Date : 2024-07-18 Alsu Missarova, Emma Dann, Leah Rosen, Rahul Satija, John Marioni
Single-cell RNA-sequencing enables testing for differential expression (DE) between conditions at a cell type level. While powerful, one of the limitations of such approaches is that the sensitivity of DE testing is dictated by the sensitivity of clustering, which is often suboptimal. To overcome this, we present miloDE—a cluster-free framework for DE testing (available as an open-source R package)
-
Graph-based self-supervised learning for repeat detection in metagenomic assembly Genome Res. (IF 6.2) Pub Date : 2024-07-19 Ali Azizpour, Advait Balaji, Todd J. Treangen, Santiago Segarra
Repetitive DNA (repeats) poses significant challenges for accurate and efficient genome assembly and sequence alignment. This is particularly true for metagenomic data, where genome dynamics such as horizontal gene transfer, gene duplication, and gene loss/gain complicate accurate genome assembly from metagenomic communities. Detecting repeats is a crucial first step in overcoming these challenges
-
Sampling globally and locally correct RNA 3D structures using Ernwin, SPQR and experimental SAXS data Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-18 Bernhard C Thiel, Giovanni Bussi, Simón Poblete, Ivo L Hofacker
The determination of the three-dimensional structure of large RNA macromolecules in solution is a challenging task that often requires the use of several experimental and computational techniques. Small-angle X-ray scattering can provide insight into some geometrical properties of the probed molecule, but this data must be properly interpreted in order to generate a three-dimensional model. Here, we
-
DNA cytosine methyltransferases differentially regulate genome-wide hypermutation and interhomolog recombination in Trichoderma reesei meiosis Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-18 Lavernchy Jovanska, I-Chen Lin, Jhong-Syuan Yao, Chia-Ling Chen, Hou-Cheng Liu, Wan-Chen Li, Yu-Chien Chuang, Chi-Ning Chuang, Albert Chen-Hsin Yu, Hsin-Nan Lin, Wen-Li Pong, Chang-I Yu, Ching-Yuan Su, Yi-Ping Chen, Ruey-Shyang Chen, Yi-Ping Hsueh, Hanna S Yuan, Ljudmilla Timofejeva, Ting-Fang Wang
Trichoderma reesei is an economically important enzyme producer with several unique meiotic features. spo11, the initiator of meiotic double-strand breaks (DSBs) in most sexual eukaryotes, is dispensable for T. reesei meiosis. T. reesei lacks the meiosis-specific recombinase Dmc1. Rad51 and Sae2, the activator of the Mre11 endonuclease complex, promote DSB repair and chromosome synapsis in wild-type
-
Differential processing of RNA polymerase II at DNA damage correlates with transcription-coupled repair syndrome severity Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-18 Camila Gonzalo-Hansen, Barbara Steurer, Roel C Janssens, Di Zhou, Marjolein van Sluis, Hannes Lans, Jurgen A Marteijn
DNA damage severely impedes gene transcription by RNA polymerase II (Pol II), causing cellular dysfunction. Transcription-Coupled Nucleotide Excision Repair (TC-NER) specifically removes such transcription-blocking damage. TC-NER initiation relies on the CSB, CSA and UVSSA proteins; loss of any results in complete TC-NER deficiency. Strikingly, UVSSA deficiency results in UV-Sensitive Syndrome (UVSS)
-
Integrated analyses highlight interactions between the three-dimensional genome and DNA, RNA and epigenomic alterations in metastatic prostate cancer Nat. Genet. (IF 31.7) Pub Date : 2024-07-17 Shuang G. Zhao, Matthew Bootsma, Stanley Zhou, Raunak Shrestha, Thaidy Moreno-Rodriguez, Arian Lundberg, Chu Pan, Christopher Arlidge, James R. Hawley, Adam Foye, Alana S. Weinstein, Martin Sjöström, Meng Zhang, Haolong Li, Lisa N. Chesner, Nicholas R. Rydzewski, Kyle T. Helzer, Yue Shi, Molly Lynch, Scott M. Dehm, Joshua M. Lang, Joshi J. Alumkal, Hansen H. He, Alexander W. Wyatt, Rahul Aggarwal,
-
Haplotype-aware sequence alignment to pangenome graphs Genome Res. (IF 6.2) Pub Date : 2024-07-16 Ghanshyam Chandra, Daniel Gibney, Chirag Jain
Modern pangenome graphs are built using haplotype-resolved genome assemblies. When mapping reads to a pangenome graph, prioritizing alignments that are consistent with the known haplotypes improves genotyping accuracy. However, the existing rigorous formulations for co-linear chaining and alignment problems do not consider the haplotype paths in a pangenome graph. This often leads to spurious read
-
High-fidelity, large-scale targeted profiling of microsatellites Genome Res. (IF 6.2) Pub Date : 2024-07-16 Caitlin A Loh, Danielle A Shields, Adam Schwing, Gilad D Evrony
Microsatellites are highly mutable sequences that can serve as markers for relationships among individuals or cells within a population. The accuracy and resolution of reconstructing these relationships depends on the fidelity of microsatellite profiling and the number of microsatellites profiled. However, current methods for targeted profiling of microsatellites incur significant "stutter" artifacts
-
CLOCI: unveiling cryptic fungal gene clusters with generalized detection Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-17 Zachary Konkel, Laura Kubatko, Jason C Slot
Gene clusters are genomic loci that contain multiple genes that are functionally and genetically linked. Gene clusters collectively encode diverse functions, including small molecule biosynthesis, nutrient assimilation, metabolite degradation, and production of proteins essential for growth and development. Identifying gene clusters is a powerful tool for small molecule discovery and provides insight
-
Instability throughout the Saccharomyces cerevisiae genome resulting from Pms1 endonuclease deficiency Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-17 Scott A Lujan, Marta A Garbacz, Sascha E Liberti, Adam B Burkholder, Thomas A Kunkel
The endonuclease activity of Pms1 directs mismatch repair by generating a nick in the newly replicated DNA strand. Inactivating Pms2, the human homologue of yeast Pms1, increases the chances of colorectal and uterine cancers. Here we use whole genome sequencing to show that loss of this endonuclease activity, via the pms1-DE variant, results in strong mutator effects throughout the Saccharomyces cerevisiae
-
Understanding X chromosome loss Nat. Genet. (IF 31.7) Pub Date : 2024-07-15 Safia Danovi
Mosaic loss of one copy of the X chromosome (mLOX) occurs more frequently in female individuals than loss of autosomes. It preferentially affects the inactivated chromosome and is associated with an increased risk of leukemia. To discover its genetic drivers, Liu et al. performed an epidemiological and genetic meta-analysis of 883,574 female participants from 8 biobanks from Europe and East Asia. They
-
A one-stop shop for 3D spatial transcriptomics Nat. Genet. (IF 31.7) Pub Date : 2024-07-15 Tiago Faial
Spatial transcriptomic methods are developing rapidly and will undoubtedly facilitate the gain of new insights into both homeostatic and disease mechanisms. However, there are numerous challenges associated with them, including implementation, scaling, cost, and data resolution and interpretation. To address these issues, Schott et al. developed Open-ST, an open-source sequencing-based experimental
-
Measuring nascent transcription in single cells Nat. Genet. (IF 31.7) Pub Date : 2024-07-15 Chiara Anania
Single-cell transcriptomic technologies enable the profiling of gene expression in individual cells but lack the ability to measure nascent transcription. This caveat hinders a precise understanding of the timing and mechanistic underpinnings of transcriptional dynamics. To address this limitation, Mahat et al. developed a global run-on sequencing (GRO-seq) method that uses click chemistry to barcode
-
Finding cancer mutagens using signature analysis Nat. Genet. (IF 31.7) Pub Date : 2024-07-15 Michael Fletcher
Tumor somatic mutational signatures offer insights into disease etiology, and such analyses may identify exposures underlying differential cancer incidence between countries. Past work on esophageal cancer did not find major mutational differences, in contrast with a new study by Senkin et al. on clear cell renal carcinoma. Whole-genome sequencing was carried out on 962 clear cell renal carcinomas
-
GSearch: ultra-fast and scalable genome search by combining K-mer hashing with hierarchical navigable small world graphs Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Jianshu Zhao, Jean Pierre Both, Luis M Rodriguez-R, Konstantinos T Konstantinidis
Genome search and/or classification typically involves finding the best-match database (reference) genomes and has become increasingly challenging due to the growing number of available database genomes and the fact that traditional methods do not scale well with large databases. By combining k-mer hashing-based probabilistic data structures (i.e. ProbMinHash, SuperMinHash, Densified MinHash and SetSketch)
-
Adenovirus small E1A directs activation of Alu transcription at YAP/TEAD- and AP-1-bound enhancers through interactions with the EP400 chromatin remodeler Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Simona Cantarella, Marco Vezzoli, Davide Carnevali, Marco Morselli, Nathan R Zemke, Barbara Montanini, Coralie F Daussy, Harald Wodrich, Martin Teichmann, Matteo Pellegrini, Arnold J Berk, Giorgio Dieci, Roberto Ferrari
Alu retrotransposons, which form the largest family of mobile DNA elements in the human genome, have recently come to attention as a potential source of regulatory novelties, most notably by participating in enhancer function. Even though Alu transcription by RNA polymerase III is subjected to tight epigenetic silencing, their expression has long been known to increase in response to various types
-
Analysis of bacterial transcriptome and epitranscriptome using nanopore direct RNA sequencing Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Lu Tan, Zhihao Guo, Yanwen Shao, Lianwei Ye, Miaomiao Wang, Xin Deng, Sheng Chen, Runsheng Li
Bacterial gene expression is a complex process involving extensive regulatory mechanisms. Along with growing interests in this field, Nanopore Direct RNA Sequencing (DRS) provides a promising platform for rapid and comprehensive characterization of bacterial RNA biology. However, the DRS of bacterial RNA is currently deficient in the yield of mRNA-mapping reads and has yet to be exploited for transcriptome-wide
-
The critical role of the iron–sulfur cluster and CTC components in DOG-1/BRIP1 function in Caenorhabditis elegans Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Xiao Li, Ivette Maria Menendez Perdomo, Victoria Rodrigues Alves Barbosa, Catherine Diao, Maja Tarailo-Graovac
FANCJ/BRIP1, initially identified as DOG-1 (Deletions Of G-rich DNA) in Caenorhabditis elegans, plays a critical role in genome integrity by facilitating DNA interstrand cross-link repair and resolving G-quadruplex structures. Its function is tightly linked to a conserved [4Fe–4S] cluster-binding motif, mutations of which contribute to Fanconi anemia and various cancers. This study investigates the
-
Rapid functional activation of horizontally transferred eukaryotic intron-containing genes in the bacterial recipient Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Wen Yuan, Jing Yu, Zhichao Li
Horizontal gene transfer has occurred across all domains of life and contributed substantially to the evolution of both prokaryotes and eukaryotes. Previous studies suggest that many horizontally transferred eukaryotic genes conferred selective advantages to bacterial recipients, but how these eukaryotic genes evolved into functional bacterial genes remained unclear, particularly how bacteria overcome
-
Trypanosome mRNA recapping is triggered by hypermethylation originating from cap 4 Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Anna V Ignatochkina, Jesavel A Iguchi, Anilkumar R Kore, C Kiong Ho
RNA methylation adjacent to the 5′ cap plays a critical role in controlling mRNA stability and protein synthesis. In trypanosomes the 5′-terminus of mRNA is protected by hypermethylated cap 4. Trypanosomes encode a cytoplasmic recapping enzyme TbCe1 which possesses an RNA kinase and guanylyltransferase activities that can convert decapped 5′-monophosphate-terminated pRNA into GpppRNA. Here, we demonstrated
-
Re-engineered guide RNA enables DNA loops and contacts modulating repression in E. coli Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Yunshi Yang, Iris Rocamonde-Lago, Boxuan Shen, Ieva Berzina, Johanna Zipf, Björn Högberg
RNA serves as information media as well as molecular scaffold in nature and synthetic systems. The single guide RNA (sgRNA) widely applied in CRISPR techniques exemplifies both functions, with a guide region bearing DNA base-pairing information, and a structural motif for Cas9 protein scaffolding. The scaffold region has been modified by fusing RNA aptamers to the tetra-stem loop. The guide region
-
SigAlign: an alignment algorithm guided by explicit similarity criteria Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Kunhyung Bahk, Joohon Sung
In biological sequence alignment, prevailing heuristic aligners achieve high-throughput by several approximation techniques, but at the cost of sacrificing the clarity of output criteria and creating complex parameter spaces. To surmount these challenges, we introduce ‘SigAlign’, a novel alignment algorithm that employs two explicit cutoffs for the results: minimum length and maximum penalty per length
-
mRNA-specific readthrough of nonsense codons by antisense oligonucleotides (R-ASOs) Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Denis Susorov, Dimas Echeverria, Anastasia Khvorova, Andrei A Korostelev
Nonsense mutations account for >10% of human genetic disorders, including cystic fibrosis, Alagille syndrome, and Duchenne muscular dystrophy. A nonsense mutation results in the expression of a truncated protein, and therapeutic strategies aim to restore full-length protein expression. Most strategies under development, including small-molecule aminoglycosides, suppressor tRNAs, or the targeted degradation
-
Single-mode termination of phage transcriptions, disclosing bacterial adaptation for facilitated reinitiations Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Eunho Song, Sun Han, Heesoo Uhm, Changwon Kang, Sungchul Hohng
Bacterial and bacteriophage RNA polymerases (RNAPs) have divergently evolved and share the RNA hairpin-dependent intrinsic termination of transcription. Here, we examined phage T7, T3 and SP6 RNAP terminations utilizing the single-molecule fluorescence assays we had developed for bacterial terminations. We discovered the phage termination mode or outcome is virtually single with decomposing termination
-
The RNA helicase DDX39 contributes to the nuclear export of spliceosomal U snRNA by loading of PHAX onto RNA Nucleic Acids Res. (IF 16.6) Pub Date : 2024-07-16 Ichiro Taniguchi, Tetsuro Hirose, Mutsuhito Ohno
RNA helicases are involved in RNA metabolism in an ATP-dependent manner. Although many RNA helicases unwind the RNA structure and/or remove proteins from the RNA, some can load their interacting proteins onto RNAs. Here, we developed an in vitro strategy to identify the ATP-dependent factors involved in spliceosomal uridine-rich small nuclear RNA (U snRNA) export. We identified the RNA helicase UAP56/DDX39B