Nucleic Acids Research最新文献

{"title":"Ensembl 2025","authors":"Sarah C Dyer, Olanrewaju Austine-Orimoloye, Andrey G Azov, Matthieu Barba, If Barnes, Vianey Paola Barrera-Enriquez, Arne Becker, Ruth Bennett, Martin Beracochea, Andrew Berry, Jyothish Bhai, Simarpreet Kaur Bhurji, Sanjay Boddu, Paulo R Branco Lins, Lucy Brooks, Shashank Budhanuru Ramaraju, Lahcen I Campbell, Manuel Carbajo Martinez, Mehrnaz Charkhchi, Lucas A Cortes, Claire Davidson, Sukanya Denni, Kamalkumar Dodiya, Sarah Donaldson, Bilal El Houdaigui, Tamara El Naboulsi, Oluwadamilare Falola, Reham Fatima, Thiago Genez, Jose Gonzalez Martinez, Tatiana Gurbich, Matthew Hardy, Zoe Hollis, Toby Hunt, Mike Kay, Vinay Kaykala, Diana Lemos, Disha Lodha, Nourhen Mathlouthi, Gabriela Alejandra Merino, Ryan Merritt, Louisse Paola Mirabueno, Aleena Mushtaq, Syed Nakib Hossain, José G Pérez-Silva, Malcolm Perry, Ivana Piližota, Daniel Poppleton, Irina Prosovetskaia, Shriya Raj, Ahamed Imran Abdul Salam, Shradha Saraf, Nuno Saraiva-Agostinho, Swati Sinha, Botond Sipos, Vasily Sitnik, Emily Steed, Marie-Marthe Suner, Likhitha Surapaneni, Kyösti Sutinen, Francesca Floriana Tricomi, Ian Tsang, David Urbina-Gómez, Andres Veidenberg, Thomas A Walsh, Natalie L Willhoft, Jamie Allen, Jorge Alvarez-Jarreta, Marc Chakiachvili, Jitender Cheema, Jorge Batista da Rocha, Nishadi H De Silva, Stefano Giorgetti, Leanne Haggerty, Garth R Ilsley, Jon Keatley, Jane E Loveland, Benjamin Moore, Jonathan M Mudge, Guy Naamati, John Tate, Stephen J Trevanion, Andrea Winterbottom, Bethany Flint, Adam Frankish, Sarah E Hunt, Robert D Finn, Mallory A Freeberg, Peter W Harrison, Fergal J Martin, Andrew D Yates","doi":"10.1093/nar/gkae1071","DOIUrl":"https://doi.org/10.1093/nar/gkae1071","url":null,"abstract":"Ensembl (www.ensembl.org) is an open platform integrating publicly available genomics data across the tree of life with a focus on eukaryotic species related to human health, agriculture and biodiversity. This year has seen a continued expansion in the number of species represented, with >4800 eukaryotic and >31 300 prokaryotic genomes available. The new Ensembl site, currently in beta, has continued to develop, currently holding >2700 eukaryotic genome assemblies. The new site provides genome, gene, transcript, homology and variation views, and will replace the current Rapid Release site; this represents a key step towards provision of a single integrated Ensembl site. Additional activities have included developing improved regulatory annotation for human, mouse and agricultural species, and expanding the Ensembl Variant Effect Predictor tool. To learn more about Ensembl, help and documentation are available along with an extensive training program that can be accessed via our training pages.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"19 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accurate quantification of nascent and mature RNAs from single-cell and single-nucleus RNA-seq","authors":"Delaney K Sullivan, Kristján Eldjárn Hjörleifsson, Nikhila P Swarna, Conrad Oakes, Guillaume Holley, Páll Melsted, Lior Pachter","doi":"10.1093/nar/gkae1137","DOIUrl":"https://doi.org/10.1093/nar/gkae1137","url":null,"abstract":"In single-cell and single-nucleus RNA sequencing (RNA-seq), the coexistence of nascent (unprocessed) and mature (processed) messenger RNA (mRNA) poses challenges in accurate read mapping and the interpretation of count matrices. The traditional transcriptome reference, defining the “region of interest” in bulk RNA-seq, restricts its focus to mature mRNA transcripts. This restriction leads to two problems: reads originating outside of the “region of interest” are prone to mismapping within this region, and additionally, such external reads cannot be matched to specific transcript targets. Expanding the “region of interest” to encompass both nascent and mature mRNA transcript targets provides a more comprehensive framework for RNA-seq analysis. Here, we introduce the concept of distinguishing flanking k-mers (DFKs) to improve mapping of sequencing reads. We have developed an algorithm to identify DFKs, which serve as a sophisticated “background filter”, enhancing the accuracy of mRNA quantification. This dual strategy of an expanded region of interest coupled with the use of DFKs enhances the precision in quantifying both mature and nascent mRNA molecules, as well as in delineating reads of ambiguous status.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"10 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An sRNA overexpression library reveals AbnZ as a negative regulator of an essential translocation module in Caulobacter crescentus","authors":"Manuel Velasco-Gomariz, Johannes Sulzer, Franziska Faber, Kathrin S Fröhlich","doi":"10.1093/nar/gkae1139","DOIUrl":"https://doi.org/10.1093/nar/gkae1139","url":null,"abstract":"Small RNAs (sRNAs) play a crucial role in modulating target gene expression through short base-pairing interactions and serve as integral components of many stress response pathways and regulatory circuits in bacteria. Transcriptome analyses have facilitated the annotation of dozens of sRNA candidates in the ubiquitous environmental model bacterium Caulobacter crescentus, but their physiological functions have not been systematically investigated so far. To address this gap, we have established CauloSOEP, a multi-copy plasmid library of C. crescentus sRNAs, which can be studied in a chosen genetic background and under select conditions. Demonstrating the power of CauloSOEP, we identified sRNA AbnZ to impair cell viability and morphology. AbnZ is processed from the 3′ end of the polycistronic abn mRNA encoding the tripartite envelope-spanning efflux pump AcrAB-NodT. A combinatorial approach revealed the essential membrane translocation module TamAB as a target of AbnZ, implying that growth inhibition by AbnZ is linked to repression of this system.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"24 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The C-terminal PHDVC5HCH tandem domain of NSD2 is a combinatorial reader of unmodified H3K4 and tri-methylated H3K27 that regulates transcription of cell adhesion genes in multiple myeloma","authors":"Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan D Licht, Giovanna Musco","doi":"10.1093/nar/gkae1121","DOIUrl":"https://doi.org/10.1093/nar/gkae1121","url":null,"abstract":"Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 (H3K27me3). This is the first PHD tandem cassette known to decode the methylation status of H3K27. Importantly, in a NSD2-dependent MM cellular model, we show that expression of NSD2 mutants, engineered to disrupt the interaction between H3K27me3 and PHDVC5HCH, display in comparison to wild-type NSD2: incomplete loss of H3K27 methylation throughout the genome, decreased activation of adhesive properties and cell adhesion genes, and a decrease of the corresponding H3K27ac signal at promoters. Collectively, these data suggest that the PHDVC5HCH domain of NSD2 plays an important role in modulating gene expression and chromatin modification, providing new opportunities for pharmacological intervention.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"28 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QClus: a droplet filtering algorithm for enhanced snRNA-seq data quality in challenging samples","authors":"Eloi Schmauch, Johannes Ojanen, Kyriakitsa Galani, Juho Jalkanen, Kristiina Harju, Maija Hollmén, Hannu Kokki, Jarmo Gunn, Jari Halonen, Juha Hartikainen, Tuomas Kiviniemi, Pasi Tavi, Minna U Kaikkonen, Manolis Kellis, Suvi Linna-Kuosmanen","doi":"10.1093/nar/gkae1145","DOIUrl":"https://doi.org/10.1093/nar/gkae1145","url":null,"abstract":"Single-nuclei RNA sequencing remains a challenge for many human tissues, as incomplete removal of background signal masks cell-type-specific signals and interferes with downstream analyses. Here, we present Quality Clustering (QClus), a droplet filtering algorithm targeted toward challenging samples. QClus uses additional metrics, such as cell-type-specific marker gene expression, to cluster nuclei and filter empty and highly contaminated droplets, providing reliable filtering of samples with varying number of nuclei and contamination levels. In a benchmarking analysis against seven alternative methods across six datasets, consisting of 252 samples and over 1.9 million nuclei, QClus achieved the highest quality in the greatest number of samples over all evaluated quality metrics and recorded no processing failures, while robustly retaining numbers of nuclei within the expected range. QClus combines high quality, automation and robustness with flexibility and user-adjustability, catering to diverse experimental needs and datasets.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"21 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Domainator, a flexible software suite for domain-based annotation and neighborhood analysis, identifies proteins involved in antiviral systems","authors":"Sean R Johnson, Peter R Weigele, Alexey Fomenkov, Andrew Ge, Anna Vincze, James B Eaglesham, Richard J Roberts, Zhiyi Sun","doi":"10.1093/nar/gkae1175","DOIUrl":"https://doi.org/10.1093/nar/gkae1175","url":null,"abstract":"The availability of large databases of biological sequences presents an opportunity for in-depth exploration of gene diversity and function. Bacterial defense systems are a rich source of diverse but difficult to annotate genes with biotechnological applications. In this work, we present Domainator, a flexible and modular software suite for domain-based gene neighborhood and protein search, extraction and clustering. We demonstrate the utility of Domainator through three examples related to bacterial defense systems. First, we cluster CRISPR-associated Rossman fold (CARF) containing proteins with difficult to annotate effector domains, classifying most of them as likely transcriptional regulators and a subset as likely RNases. Second, we extract and cluster P4-like phage satellite defense hotspots, identify an abundant variant of Lamassu defense systems and demonstrate its in vivo activity against several T-even phages. Third, we integrate a protein language model into Domainator and use it to identify restriction endonucleases with low similarity to known reference sequences, validating the activity of one example in vitro. Domainator is made available as an open-source package with detailed documentation and usage examples.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"81 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bgee in 2024: focus on curated single-cell RNA-seq datasets, and query tools","authors":"Frederic B Bastian, Alessandro Brandulas Cammarata, Sara Carsanaro, Harald Detering, Wan-Ting Huang, Sagane Joye, Anne Niknejad, Marion Nyamari, Tarcisio Mendes de Farias, Sébastien Moretti, Marianna Tzivanopoulou, Julien Wollbrett, Marc Robinson-Rechavi","doi":"10.1093/nar/gkae1118","DOIUrl":"https://doi.org/10.1093/nar/gkae1118","url":null,"abstract":"Bgee (https://www.bgee.org/) is a database to retrieve and compare gene expression patterns in multiple animal species. Expression data are integrated and made comparable between species thanks to consistent data annotation and processing. In the past years, we have integrated single-cell RNA-sequencing expression data into Bgee through careful curation of public datasets in multiple species. We have fully integrated this new technology along with the wealth of other data existing in Bgee. As a result, Bgee can now provide one definitive answer all the way to the cell resolution about a gene’s expression pattern, comparable between species. We have updated our programmatic access tools to adapt to these changes accordingly. We have introduced a new web interface, providing detailed access to our annotations and expression data. It enables users to retrieve data, e.g. for specific organs, cell types or developmental stages, and leverages ontology reasoning to build powerful queries. Finally, we have expanded our species count from 29 to 52, emphasizing fish species critical for vertebrate genome studies, species of agronomic and veterinary importance and nonhuman primates.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"230 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive whole-genome sequencing reveals origins of mutational signatures associated with aging, mismatch repair deficiency and temozolomide chemotherapy","authors":"Taejoo Hwang, Lukasz Karol Sitko, Ratih Khoirunnisa, Fernanda Navarro-Aguad, David M Samuel, Hajoong Park, Banyoon Cheon, Luthfiyyah Mutsnaini, Jaewoong Lee, Burçak Otlu, Shunichi Takeda, Semin Lee, Dmitri Ivanov, Anton Gartner","doi":"10.1093/nar/gkae1122","DOIUrl":"https://doi.org/10.1093/nar/gkae1122","url":null,"abstract":"In a comprehensive study to decipher the multi-layered response to the chemotherapeutic agent temozolomide (TMZ), we analyzed 427 genomes and determined mutational patterns in a collection of ∼40 isogenic DNA repair-deficient human TK6 lymphoblast cell lines. We first demonstrate that the spontaneous mutational background is very similar to the aging-associated mutational signature SBS40 and mainly caused by polymerase zeta-mediated translesion synthesis (TLS). MSH2-/- mismatch repair (MMR) knockout in conjunction with additional repair deficiencies uncovers cryptic mutational patterns. We next report how distinct mutational signatures are induced by TMZ upon sequential inactivation of DNA repair pathways, mirroring the acquisition of chemotherapy resistance by glioblastomas. The most toxic adduct induced by TMZ, O6-meG, is directly repaired by the O6-methylguanine-DNA methyltransferase (MGMT). In MGMT-/- cells, MMR leads to cell death and limits mutagenesis. MMR deficiency results in TMZ resistance, allowing the accumulation of ∼105 C > T substitutions corresponding to signature SBS11. Under these conditions, N3-methyladenine (3-meA), processed by base excision repair (BER), limits cell survival. Without BER, 3-meA is read through via error-prone TLS, causing T > A substitutions but not affecting survival. Blocking BER after abasic site formation results in large deletions and TMZ hypersensitization. Our findings reveal potential vulnerabilities of TMZ-resistant tumors.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"113 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to 'Enhancing disease risk gene discovery by integrating transcription factor-linked trans-variants into transcriptome-wide association analyses'.","authors":"","doi":"10.1093/nar/gkae1239","DOIUrl":"https://doi.org/10.1093/nar/gkae1239","url":null,"abstract":"","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The RodentGPOmics Atlas: a comprehensive database of rodent biology for genomes and pathogens","authors":"Zhiwen Jiang, Ziqing Yan, Yali Hou, Jia Tang, Mengdi Zheng, Meng Lu, Xiang Ji, Karthik Gangavarapu, Xinxin Li, Shuo Su","doi":"10.1093/nar/gkae1074","DOIUrl":"https://doi.org/10.1093/nar/gkae1074","url":null,"abstract":"Rodents represent the most abundant order of mammals, exhibiting remarkable diversity in morphology, habitats, behaviors, and hosted pathogens. Significant attention is currently focused on rodents as experimental animals for biomedical research. However, numerous aspects of rodents remain unexplored, such as their potential in unconventional biomedical models, molecular underpinnings of intriguing complex phenotypes, adaptations to environment or climate change, and host-pathogen interactions and arms race evolution. These challenges require a systematic framework to integrate the genomic variations among rodents with information on rodent-borne pathogens. To address this gap, we have established a comprehensive, freely accessible, and user-friendly atlas named Rodent Genome and Pathogen multi-Omics (RodentGPOmics), which provides comparative analysis of rodent genomes and information on zoonotic pathogen sequences in rodents. The RodentGPOmics Atlas provides: (i) basic information on 2706 rodent species; (ii) chromosome-level visualization of genomes, functional annotations, and genomic comparisons across 121 rodent species; (iii) epidemiological profiles based on 21 852 pathogen sequences reported in rodents and (iv) a few genomic tools for in-depth exploration of rodent multi-omics. This resource aims to advance the development of biomedical models for humans for promoting public health, as well as innovate the genetics, genomics, and molecular evolution in rodents, and offer valuable knowledge on rodent-borne emerging/re-emerging zoonotic infectious diseases. The resources are freely available and easy-to-use at http://RodentGPOmics.njau.edu.cn:8888/Rodent/index/homePage.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"21 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}