Nucleic Acids Research最新文献_第8页

SHARK: web server for alignment-free homology assessment for intrinsically disordered and unalignable protein regions. SHARK：用于对内在无序和不可对齐的蛋白质区域进行无比对同源性评估的web服务器。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-21 DOI: 10.1093/nar/gkaf408

Chi Fung Willis Chow,Maxim Scheremetjew,HongKee Moon,Soumyadeep Ghosh,Anna Hadarovich,Lena Hersemann,Agnes Toth-Petroczy

{"title":"SHARK: web server for alignment-free homology assessment for intrinsically disordered and unalignable protein regions.","authors":"Chi Fung Willis Chow,Maxim Scheremetjew,HongKee Moon,Soumyadeep Ghosh,Anna Hadarovich,Lena Hersemann,Agnes Toth-Petroczy","doi":"10.1093/nar/gkaf408","DOIUrl":"https://doi.org/10.1093/nar/gkaf408","url":null,"abstract":"Whereas alignment has been fundamental to sequence-based assessments of protein homology, it is ineffective for intrinsically disordered regions (IDRs) due to their lowered sequence conservation and unique sequence properties. Here, we present a web server implementation of SHARK (bio-shark.org), an alignment-free algorithm for homology classification that compares the overall amino acid composition and short regions (k-mers) shared between sequences (SHARK-scores). The output of such k-mer-based comparisons is used by SHARK-dive, a machine learning classifier to detect homology between unalignable, disordered sequences. SHARK-web provides sequence-versus-database assessment of protein sequence homology akin to conventional tools such as BLAST and HMMER. Additionally, we provide precomputed sets of IDR sequences from 16 model organism proteomes facilitating searches against species-specific IDR-omes. SHARK-dive offers superior overall homology detection performance to BLAST and HMMER, driven by a large increase in sensitivity to low sequence identity homologs, and can be used to facilitate the study of sequence-function relationships in disordered, difficult-to-align regions.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"18 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103598","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}

引用次数: 0

RegRNA 3.0: expanding regulatory RNA analysis with new features for motif, interaction, and annotation. RegRNA 3.0：扩展调控RNA分析与motif，相互作用和注释的新功能。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-21 DOI: 10.1093/nar/gkaf405

Yixian Huang,Zhiyong Zhang,Zhengkai Zou,Lingquan Zhang,Yigang Chen,Jingting Wan,Zihao Zhu,Sicong Yu,Huali Zuo,Yang-Chi-Dung Lin,Hsi-Yuan Huang,Hsien-Da Huang

{"title":"RegRNA 3.0: expanding regulatory RNA analysis with new features for motif, interaction, and annotation.","authors":"Yixian Huang,Zhiyong Zhang,Zhengkai Zou,Lingquan Zhang,Yigang Chen,Jingting Wan,Zihao Zhu,Sicong Yu,Huali Zuo,Yang-Chi-Dung Lin,Hsi-Yuan Huang,Hsien-Da Huang","doi":"10.1093/nar/gkaf405","DOIUrl":"https://doi.org/10.1093/nar/gkaf405","url":null,"abstract":"Functional RNA molecules are crucial for biological processes from gene regulation to protein synthesis, and analyzing functional motifs and elements is essential for understanding RNA regulation. Building on RegRNA 1.0 and 2.0, we present RegRNA 3.0, a sophisticated meta-workflow that integrates 26 computational tools and 28 databases for annotation, enabling one-step and customizable RNA motif predictions. RegRNA streamlines multi-step analysis and enhances result interpretation with interactive visualizations and comprehensive reporting tools. When provided with an RNA sequence, RegRNA 3.0 generates predictions for RNA functional motifs, RNA interaction motifs, and comprehensive RNA annotations. Specifically, RNA functional motifs include core promoter elements, RNA decay, G-quadruplex, and 14 previous types. RNA interaction motifs include newly added RNA-ligand interactions and RNA-binding protein predictions, along with three previous types. RNA annotation includes RNA family classification, blood exosomes RNA, subcellular localizations, A-to-I editing events, modifications, and 3D structures, along with four previously supported features. RegRNA 3.0 accelerates gene regulation and RNA biology discoveries by offering a user-friendly platform for identifying and analyzing RNA motifs and interactions. The web interface has been improved for intuitive visualizations of predicted motifs and structures, with flexible download options in multiple formats. It is available at http://awi.cuhk.edu.cn/∼RegRNA/.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"131 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103541","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}

引用次数: 0

hAb-Convergent: an antibody rearrangement analysis system for therapeutic antibody engineering based on convergent evolution. hAb-Convergent：基于收敛进化的治疗性抗体工程抗体重排分析系统。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-21 DOI: 10.1093/nar/gkaf407

Jinfeng Wang,Xiaomeng Ge,Qinglan Sun,Minlong Chen,Shijie Qin,Dongmei Liu,Tao Deng,Juncai Ma,Songnian Hu,Ronghua Jin,Zhou Tong,Linhuan Wu

{"title":"hAb-Convergent: an antibody rearrangement analysis system for therapeutic antibody engineering based on convergent evolution.","authors":"Jinfeng Wang,Xiaomeng Ge,Qinglan Sun,Minlong Chen,Shijie Qin,Dongmei Liu,Tao Deng,Juncai Ma,Songnian Hu,Ronghua Jin,Zhou Tong,Linhuan Wu","doi":"10.1093/nar/gkaf407","DOIUrl":"https://doi.org/10.1093/nar/gkaf407","url":null,"abstract":"In therapeutic antibody engineering, utilizing naturally occurring mutations in the human body as a reference for modification is an emerging trend. The theory of convergent evolution presents a viable solution. Nevertheless, the nonuniformity of the antibody rearrangement analysis system and the difficulty in identifying the heavy-chain D-region are significant challenges to research and application. To address these limitations, we developed hAb (human antibody)-Convergent, a novel tool designed to assist users in quickly identifying candidate mutation hotspots of input antibody sequences in real human immune responses for subsequent antibody engineering. It uses antibody rearrangement features-based (V, D, J genes and CDR-H3 length) rather than traditional sequence-based strategies while ensuring the security of the original sequence. Combining more inclusive D-region identification and analysis methods, it can recognize and analyze the convergence of antibodies across various individuals. Additionally, given the limitations of obtaining antibody nucleotide sequences from academic literature, it provides an optimized approach for direct analysis and rapid comparison using amino acid sequences. hAb-Convergent bridges gaps in antibody engineering by linking natural evolution patterns to in vitro design, with implications for universal vaccine development. The tool can be freely accessed at https://nmdc.cn/zoe/.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"4 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103540","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}

引用次数: 0

Retroviral adapters hijack the RNA helicase UPF1 in a CRM1/XPO1-dependent manner and reveal proviral roles of UPF1 逆转录病毒适配器以依赖于CRM1/ xpo1的方式劫持RNA解旋酶UPF1，并揭示了UPF1的前体细胞作用

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-21 DOI: 10.1093/nar/gkaf434

Léa Prochasson, Makram Mghezzi-Habellah, Armelle Roisin, Martine Palma, Jean-Philippe Robin, Stève de Bossoreille, David Cluet, Malèke Mouelhi, Didier Decimo, Alexandra Desrames, Thibault Chaze, Mariette Matondo, Hélène Dutartre, Maria-Isabel Thoulouze, Fabrice Lejeune, Pierre Jalinot, Stephane Rety, Vincent Mocquet

{"title":"Retroviral adapters hijack the RNA helicase UPF1 in a CRM1/XPO1-dependent manner and reveal proviral roles of UPF1","authors":"Léa Prochasson, Makram Mghezzi-Habellah, Armelle Roisin, Martine Palma, Jean-Philippe Robin, Stève de Bossoreille, David Cluet, Malèke Mouelhi, Didier Decimo, Alexandra Desrames, Thibault Chaze, Mariette Matondo, Hélène Dutartre, Maria-Isabel Thoulouze, Fabrice Lejeune, Pierre Jalinot, Stephane Rety, Vincent Mocquet","doi":"10.1093/nar/gkaf434","DOIUrl":"https://doi.org/10.1093/nar/gkaf434","url":null,"abstract":"The hijacking of CRM1 export is an important step of the retroviral replication cycle. Here, we investigated the consequences of this hijacking for the host. During HTLV-1 infection, we identified that this hijacking by the viral protein Rex favours the association between CRM1 and the RNA helicase UPF1, leading to a decreased affinity of UPF1 for cellular RNA and its nuclear retention. As a consequence, we found that the nonsense-mediated mRNA decay (NMD), known to have an antiviral function, was inhibited. Corroborating these results, we described a similar process with Rev, the functional homolog of Rex from HIV-1. Unexpectedly, we also found that, for HTLV-1, this process is coupled with the specific loading of UPF1 onto vRNA, independently of NMD. In this latter context, UPF1 positively regulates several steps of the viral replication cycle, from the nuclear export of vRNA to the production of mature viral particles.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"127 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104660","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}

引用次数: 0

mRNAdesigner: an integrated web server for optimizing mRNA design and protein translation in eukaryotes. mRNAdesigner：一个用于优化真核生物mRNA设计和蛋白质翻译的集成web服务器。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-19 DOI: 10.1093/nar/gkaf410

Ouyang Mo,Zhuo Zhang,Xiang Cheng,Liqi Zhu,Kaixiang Zhang,Niubing Zhang,Justin Li,Honglin Li,Shixin Fan,Xuan Li,Pei Hao

{"title":"mRNAdesigner: an integrated web server for optimizing mRNA design and protein translation in eukaryotes.","authors":"Ouyang Mo,Zhuo Zhang,Xiang Cheng,Liqi Zhu,Kaixiang Zhang,Niubing Zhang,Justin Li,Honglin Li,Shixin Fan,Xuan Li,Pei Hao","doi":"10.1093/nar/gkaf410","DOIUrl":"https://doi.org/10.1093/nar/gkaf410","url":null,"abstract":"Messenger RNA (mRNA) therapy has revolutionized modern medicine through its rapid development capabilities and ability to induce effective immune responses, becoming a powerful weapon against infectious diseases. The expression level of target proteins from mRNA sequences is primarily influenced by translational efficiency and stability, which can be significantly enhanced by modifying the 5' and 3' untranslated regions (UTRs), codon adaptation index, GC content, and secondary structure. To address the challenges of optimizing mRNA design, we have developed mRNAdesigner (https://www.biosino.org/mRNAdesigner/), a web server specifically designed to improve mRNA stability and translational efficiency in eukaryotes. Users can input a coding sequence (CDS) along with optional 5' UTR and 3' UTR, and the tool optimizes the CDS by reducing unpaired regions, minimizing complex stem-loop structures, and mitigating the use of rare codons while adhering to user-defined GC content preferences. Additionally, mRNAdesigner identifies optimal UTR sequences to enhance translation efficiency and stability. As an open-access computational resource, mRNAdesigner supports full-length mRNA design, enabling researchers to generate high-expression mRNA sequences for efficient protein production in eukaryotic expression systems, providing extra support for vaccine development and protein therapeutics. This is the first such tool that was made open accessible to the public.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"32 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087605","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}

引用次数: 0

PrankWeb 4: a modular web server for protein-ligand binding site prediction and downstream analysis. prankweb4：蛋白质配体结合位点预测和下游分析的模块化web服务器。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-19 DOI: 10.1093/nar/gkaf421

Lukáš Polák,Petr Škoda,Kamila Riedlová,Radoslav Krivák,Marian Novotný,David Hoksza

{"title":"PrankWeb 4: a modular web server for protein-ligand binding site prediction and downstream analysis.","authors":"Lukáš Polák,Petr Škoda,Kamila Riedlová,Radoslav Krivák,Marian Novotný,David Hoksza","doi":"10.1093/nar/gkaf421","DOIUrl":"https://doi.org/10.1093/nar/gkaf421","url":null,"abstract":"Knowledge of protein-ligand binding sites (LBSs) is crucial for advancing our understanding of biology and developing practical applications in fields such as medicine or biotechnology. PrankWeb is a web server that allows users to predict LBSs from a given three-dimensional structure. It provides access to P2Rank, a state-of-the-art machine learning tool for binding site prediction. Here, we present a new version of PrankWeb enabling the development of both client- and server-side modules acting as postprocessing tasks on the predicted pockets. Furthermore, each module can be associated with a visualization module that acts on the results provided by both client- and server-side modules. This newly developed system was utilized to implement the ability to dock user-provided molecules into the predicted pockets using AutoDock Vina (server-side module) and to interactively visualize the predicted poses (visualization module). In addition to introducing a modular architecture, we revamped PrankWeb's interface to better support the modules and enhance user interaction between the 1D and 3D viewers. We introduced a new, faster P2Rank backend or user-friendly exports, including ChimeraX visualization.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"17 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087659","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}

引用次数: 0

BEscreen: a versatile toolkit to design base editing libraries. 一个设计基本编辑库的多功能工具包。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-19 DOI: 10.1093/nar/gkaf406

Philipp G Schneider,Shuang Liu,Lars Bullinger,Benjamin N Ostendorf

{"title":"BEscreen: a versatile toolkit to design base editing libraries.","authors":"Philipp G Schneider,Shuang Liu,Lars Bullinger,Benjamin N Ostendorf","doi":"10.1093/nar/gkaf406","DOIUrl":"https://doi.org/10.1093/nar/gkaf406","url":null,"abstract":"Base editing enables the high-throughput screening of genetic variants for phenotypic effects. Base editing screens require the design of single guide RNA (sgRNA) libraries to enable either gene- or variant-centric approaches. While computational tools supporting the design of sgRNAs exist, no solution offers versatile and scalable library design enabling all major use cases. Here, we introduce BEscreen, a comprehensive base editing guide design tool provided as a web server (bescreen.ostendorflab.org) and as a command line tool. BEscreen provides variant-, gene-, and region-centric modes to accommodate various screening approaches. The variant mode accepts genomic coordinates, amino acid changes, or rsIDs as input. The gene mode designs near-saturation libraries covering the entire coding sequence of given genes or transcripts, and the region mode designs all possible guides for given genomic regions. BEscreen enables selection of guides by biological consequence, it features comprehensive customization of base editor characteristics, and it offers optional annotation using Ensembl's Variant Effect Predictor. In sum, BEscreen is a highly versatile tool to design base editing screens for a wide range of use cases with seamless scalability from individual variants to large, near-saturation libraries.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"41 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087606","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}

引用次数: 0

ClusterONE Web: a tool for discovering and analyzing overlapping protein complexes. ClusterONE Web：一个发现和分析重叠蛋白复合物的工具。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-16 DOI: 10.1093/nar/gkaf368

Marcelo Baez,Ruben Jimenez,Luca Cernuzzi,Alberto Paccanaro

引用次数: 0

Onkopus: precise interpretation and prioritization of sequence variants for biomedical research and precision medicine. Onkopus：生物医学研究和精准医学序列变异的精确解释和优先排序。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-16 DOI: 10.1093/nar/gkaf376

Nadine S Kurz,Kevin Kornrumpf,Tim Tucholski,Klara Drofenik,Alexander König,Tim Beißbarth,Jürgen Dönitz

{"title":"Onkopus: precise interpretation and prioritization of sequence variants for biomedical research and precision medicine.","authors":"Nadine S Kurz,Kevin Kornrumpf,Tim Tucholski,Klara Drofenik,Alexander König,Tim Beißbarth,Jürgen Dönitz","doi":"10.1093/nar/gkaf376","DOIUrl":"https://doi.org/10.1093/nar/gkaf376","url":null,"abstract":"One of the major challenges in precision oncology is the identification of pathogenic, actionable variants and the selection of personalized treatments. We present Onkopus, a variant interpretation framework based on a modular architecture, for interpreting and prioritizing genetic alterations in cancer patients. A multitude of tools and databases are integrated into Onkopus to provide a comprehensive overview about the consequences of a variant, each with its own semantic, including pathogenicity predictions, allele frequency, biochemical and protein features, and therapeutic options. We present the characteristics of variants and personalized therapies in a clear and concise form, supported by interactive plots. To support the interpretation of variants of unknown significance (VUS), we present a protein analysis based on protein structures, which allows variants to be analyzed within the context of the entire protein, thereby serving as a starting point for understanding the underlying causes of variant pathogenicity. Onkopus has the potential to significantly enhance variant interpretation and the selection of actionable variants for identifying new targets, drug screens, drug testing using organoids, or personalized treatments in molecular tumor boards. We provide a free public instance of Onkopus at https://mtb.bioinf.med.uni-goettingen.de/onkopus.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"8 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065762","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}

引用次数: 0

ASOptimizer: optimizing chemical diversity of antisense oligonucleotides through deep learning. ASOptimizer：通过深度学习优化反义寡核苷酸的化学多样性。

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-05-16 DOI: 10.1093/nar/gkaf392

Seokjun Kang,Daehwan Lee,Gyeongjo Hwang,Kiwon Lee,Mingeun Kang

引用次数: 0