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TransmiR v3.0: an updated transcription factor-microRNA regulation database TransmiR v3.0:最新转录因子--microRNA调控数据库
IF 14.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-12 DOI: 10.1093/nar/gkae1081
Maodi Liang, Chenhao Zhang, Yang Yang, Qinghua Cui, Jun Zhang, Chunmei Cui
microRNAs (miRNAs) are active in various biological processes by mediating gene expression, and the full investigation of miRNA transcription is crucial for understanding the mechanisms underlying miRNA deregulation in pathological conditions. Here an updated TransmiR v3.0 database is presented with more comprehensive miRNA transcription regulation information, which contains 5095 transcription factor (TF) -miRNA regulations curated from 2285 papers and >6 million TF–miRNA regulations derived from ChIP-seq data. Currently, TransmiR v3.0 covers 3260 TFs, 4253 miRNAs and 514 433 TF–miRNA regulation pairs across 29 organisms. Additionally, motif scanning of TF loci on promoter sequences of miRNAs from multiple species is employed to predict TF–miRNA regulations, generating 284 527 predicted TF–miRNA regulations. Besides the significant growth of data volume, we also improve the annotations for TFs and miRNAs by introducing the TF family, TFBS motif, and expression profiles for several species. Moreover, the functionality of the TransmiR v3.0 online database is enhanced, including allowing batch search for flexible queries and offering more extensive disease-specific, as well as newly sex-specific TF–miRNA regulation networks in the ‘Network’ module. TransmiR v3.0 provides a useful resource for studying miRNA biogenesis regulation and can be freely accessed at http://www.cuilab.cn/transmir.
microRNA(miRNA)通过介导基因表达活跃于各种生物过程,全面研究miRNA的转录对于了解病理情况下miRNA失调的机制至关重要。本文介绍了更新的 TransmiR v3.0 数据库,其中包含更全面的 miRNA 转录调控信息,包括从 2285 篇论文中筛选出的 5095 条转录因子(TF)-miRNA 调控信息,以及从 ChIP-seq 数据中筛选出的 >600 万条 TF-miRNA 调控信息。目前,TransmiR v3.0 涵盖了 29 种生物的 3260 个 TF、4253 个 miRNA 和 514 433 个 TF-miRNA 调控对。此外,通过对多个物种的 miRNA 启动子序列上的 TF 位点进行主题扫描来预测 TF-miRNA 调控,预测出 284 527 个 TF-miRNA 调控。除了数据量的大幅增长,我们还通过引入 TF 家族、TFBS 主题和多个物种的表达谱,改进了 TF 和 miRNA 的注释。此外,TransmiR v3.0 在线数据库的功能也得到了增强,包括允许批量搜索灵活查询,在 "网络 "模块中提供更广泛的疾病特异性和新的性别特异性 TF-miRNA 调控网络。TransmiR v3.0 为研究 miRNA 生物发生调控提供了有用的资源,可通过 http://www.cuilab.cn/transmir 免费访问。
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引用次数: 0
The evolution of dbSNP: 25 years of impact in genomic research dbSNP 的演变:25 年来对基因组研究的影响
IF 14.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-12 DOI: 10.1093/nar/gkae977
Lon Phan, Hua Zhang, Qiang Wang, Ricardo Villamarin, Tim Hefferon, Aravinthan Ramanathan, Brandi Kattman
The Single Nucleotide Polymorphism Database (dbSNP), established in 1998 by the National Center for Biotechnology Information (NCBI), has been a critical resource in genomics for cataloging small genetic variations. Originally focused on single nucleotide polymorphisms (SNPs), dbSNP has since expanded to include a variety of genetic variants, playing a key role in genome-wide association studies (GWAS), population genetics, pharmacogenomics, and cancer research. Over 25 years, dbSNP has grown to include more than 4.4 billion submitted SNPs and 1.1 billion unique reference SNPs, providing essential data for identifying disease-related genetic variants and studying human diversity. Integrating large-scale projects like 1000 Genomes, gnomAD, TOPMed, and ALFA has expanded dbSNP’s catalog of human genetic variation, increasing its usefulness for research and clinical applications. Keeping up with advancements such as next-generation sequencing and cloud-based infrastructure, dbSNP remains a cornerstone of genetic research supporting continued discoveries in precision medicine and population genomics. DATABASE URL: https://www.ncbi.nlm.nih.gov/snp.
单核苷酸多态性数据库(dbSNP)由美国国家生物技术信息中心(NCBI)于 1998 年建立,一直是基因组学中对微小遗传变异进行编目的重要资源。dbSNP 最初侧重于单核苷酸多态性 (SNP),后来扩展到包括各种遗传变异,在全基因组关联研究 (GWAS)、群体遗传学、药物基因组学和癌症研究中发挥了关键作用。25 年来,dbSNP 已收录了超过 44 亿个提交的 SNP 和 11 亿个独特的参考 SNP,为确定与疾病相关的遗传变异和研究人类多样性提供了重要数据。整合 1000 Genomes、gnomAD、TOPMed 和 ALFA 等大型项目扩大了 dbSNP 的人类基因变异目录,提高了其在研究和临床应用中的实用性。随着下一代测序和基于云的基础设施等技术的不断进步,dbSNP 仍是基因研究的基石,为精准医学和群体基因组学的不断发现提供支持。数据库网址:https://www.ncbi.nlm.nih.gov/snp。
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引用次数: 0
PolyASite v3.0: a multi-species atlas of polyadenylation sites inferred from single-cell RNA-sequencing data. PolyASite v3.0:从单细胞 RNA 序列数据推断出的多腺苷酸化位点多物种图谱。
IF 16.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-12 DOI: 10.1093/nar/gkae1043
Youngbin Moon, Christina J Herrmann, Aleksei Mironov, Mihaela Zavolan

The broadly used 10X Genomics technology for single-cell RNA sequencing (scRNA-seq) captures RNA 3' ends. Thus, some reads contain part of the non-templated polyadenosine tails, providing direct evidence for the sites of 3' end cleavage and polyadenylation on the respective RNAs. Taking advantage of this property, we recently developed the SCINPAS workflow to infer polyadenylation sites (PASs) from scRNA-seq data. Here, we used this workflow to construct version 3.0 (v3.0, https://polyasite.unibas.ch/) of the PolyASite Atlas from a big compendium of publicly available human, mouse and worm scRNA-seq datasets obtained from healthy tissues. As the resolution of scRNA-seq was too low for robust detection of cell-level differences in PAS usage, we aggregated samples based on their tissue-of-origin to construct tissue-level catalogs of PASs. These provide qualitatively new information about PAS usage, in comparison to the previous PAS catalogs that were based on bulk 3' end sequencing experiments primarily in cell lines. In the new version, we document stringency levels associated with each PAS so that users can balance sensitivity and specificity in their analysis. We also upgraded the integration with the UCSC Genome Browser and developed track hubs conveniently displaying pooled and tissue-specific expression of PASs.

广泛使用的 10X Genomics 单细胞 RNA 测序(scRNA-seq)技术可捕获 RNA 3' 端。因此,一些读数包含了部分非模板多聚腺苷尾,为相应 RNA 的 3' 端裂解和多聚腺苷化位点提供了直接证据。利用这一特性,我们最近开发了 SCINPAS 工作流程,从 scRNA-seq 数据中推断多腺苷酸化位点(PAS)。在这里,我们利用这一工作流程,从从健康组织中获取的大量公开可用的人类、小鼠和蠕虫scRNA-seq数据集中构建了PolyASite Atlas的3.0版本(v3.0,https://polyasite.unibas.ch/)。由于 scRNA-seq 的分辨率太低,无法稳健地检测 PAS 使用的细胞级差异,因此我们根据样本的原生组织对样本进行了汇总,以构建组织级的 PAS 目录。与之前基于主要在细胞系中进行的大量 3' 端测序实验的 PAS 目录相比,这些目录提供了有关 PAS 使用情况的新的定性信息。在新版本中,我们记录了与每个 PAS 相关的严格程度,以便用户在分析中平衡灵敏度和特异性。我们还升级了与 UCSC 基因组浏览器的整合,并开发了跟踪中心,方便显示 PAS 的集合表达和组织特异性表达。
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引用次数: 0
Single-molecule visualization of sequence-specific RNA binding by a designer PPR protein 单分子可视化设计 PPR 蛋白与序列特异性 RNA 的结合
IF 14.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-12 DOI: 10.1093/nar/gkae984
Nicholas Marzano, Brady Johnston, Bishnu P Paudel, Jason Schmidberger, Slobodan Jergic, Till Böcking, Mark Agostino, Ian Small, Antoine M van Oijen, Charles S Bond
Pentatricopeptide repeat proteins (PPR) are a large family of modular RNA-binding proteins, whereby each module can be modified to bind to a specific ssRNA nucleobase. As such, there is interest in developing ‘designer’ PPRs (dPPRs) for a range of biotechnology applications, including diagnostics or in vivo localization of ssRNA species; however, the mechanistic details regarding how PPRs search for and bind to target sequences is unclear. To address this, we determined the structure of a dPPR bound to its target sequence and used two- and three-color single-molecule fluorescence resonance energy transfer to interrogate the mechanism of ssRNA binding to individual dPPRs in real time. We demonstrate that dPPRs are slower to bind longer ssRNA sequences (or could not bind at all) and that this is, in part, due to their propensity to form stable secondary structures that sequester the target sequence from dPPR. Importantly, dPPR binds only to its target sequence (i.e. it does not associate with non-target ssRNA sequences) and does not ‘scan’ longer ssRNA oligonucleotides for the target sequence. The kinetic constraints imposed by random 3D diffusion may explain the long-standing conundrum of why PPR proteins are abundant in organelles, but almost unknown outside them (i.e. in the cytosol and nucleus).
五肽重复蛋白(PPR)是一个庞大的模块化 RNA 结合蛋白家族,其中的每个模块都可以进行修饰以结合到特定的 ssRNA 核碱基上。因此,人们有兴趣开发 "设计型 "PPR(dPPR),用于一系列生物技术应用,包括诊断或 ssRNA 的体内定位;然而,有关 PPR 如何搜索目标序列并与之结合的机理细节尚不清楚。为了解决这个问题,我们确定了 dPPR 与其目标序列结合的结构,并使用双色和三色单分子荧光共振能量转移来实时检测 ssRNA 与单个 dPPR 结合的机制。我们证明,dPPRs 结合较长 ssRNA 序列的速度较慢(或根本无法结合),部分原因是它们倾向于形成稳定的二级结构,将目标序列从 dPPR 中封存起来。重要的是,dPPR 只与其目标序列结合(即不与非目标 ssRNA 序列结合),不会 "扫描 "较长的 ssRNA 寡核苷酸以寻找目标序列。随机三维扩散所带来的动力学限制或许可以解释为什么 PPR 蛋白在细胞器中含量丰富,而在细胞器外(即在细胞质和细胞核中)却几乎无人知晓这一长期存在的难题。
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引用次数: 0
Transfer RNA supplementation rescues HARS deficiency in a humanized yeast model of Charcot-Marie-Tooth disease 补充转运核糖核酸可挽救夏科-玛丽-牙病人源化酵母模型中的 HARS 缺乏症
IF 14.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-12 DOI: 10.1093/nar/gkae996
Sarah D P Wilhelm, Jenica H Kakadia, Aruun Beharry, Rosan Kenana, Kyle S Hoffman, Patrick O’Donoghue, Ilka U Heinemann
Aminoacyl-tRNA synthetases are indispensable enzymes in all cells, ensuring the correct pairing of amino acids to their cognate tRNAs to maintain translation fidelity. Autosomal dominant mutations V133F and Y330C in histidyl-tRNA synthetase (HARS) cause the genetic disorder Charcot-Marie-Tooth type 2W (CMT2W). Treatments are currently restricted to symptom relief, with no therapeutic available that targets the cause of disease. We previously found that histidine supplementation alleviated phenotypic defects in a humanized yeast model of CMT2W caused by HARS V155G and S356N that also unexpectedly exacerbated the phenotype of the two HARS mutants V133F and Y330C. Here, we show that V133F destabilizes recombinant HARS protein, which is rescued in the presence of tRNAHis. HARS V133F and Y330C cause mistranslation and cause changes to the proteome without activating the integrated stress response as validated by mass spectrometry and growth defects that persist with histidine supplementation. The growth defects and reduced translation fidelity caused by V133F and Y330C mutants were rescued by supplementation with human tRNAHis in a humanized yeast model. Our results demonstrate the feasibility of cognate tRNA as a therapeutic that rescues HARS deficiency and ameliorates toxic mistranslation generated by causative alleles for CMT.
氨基酰-tRNA 合成酶是所有细胞中不可或缺的酶,它能确保氨基酸与其同源的 tRNA 正确配对,从而保持翻译的保真度。组氨酰-tRNA 合成酶(HARS)中的常染色体显性突变 V133F 和 Y330C 导致遗传性疾病 Charcot-Marie-Tooth 2W 型(CMT2W)。目前的治疗仅限于缓解症状,还没有针对病因的治疗方法。我们以前曾发现,组氨酸补充可减轻由 HARS V155G 和 S356N 引起的 CMT2W 人源化酵母模型的表型缺陷,这也意外地加剧了两个 HARS 突变体 V133F 和 Y330C 的表型。在这里,我们发现 V133F 会破坏重组 HARS 蛋白的稳定性,而在有 tRNAHis 存在的情况下,这种稳定性会被挽救。HARS V133F 和 Y330C 会导致翻译错误,并引起蛋白质组的变化,但不会激活综合应激反应,质谱分析和生长缺陷验证了这一点。在人源化酵母模型中,V133F 和 Y330C 突变体导致的生长缺陷和翻译保真度降低可通过补充人类 tRNAHis 得到挽救。我们的研究结果证明了同源 tRNA 作为一种治疗方法的可行性,它能挽救 HARS 缺乏症并改善 CMT 致病等位基因产生的毒性错误翻译。
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引用次数: 0
Overcoming nucleotide bias in the nonenzymatic copying of RNA templates 克服 RNA 模板非酶复制过程中的核苷酸偏差
IF 14.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-12 DOI: 10.1093/nar/gkae982
Daniel Duzdevich, Christopher E Carr, Ben W F Colville, Harry R M Aitken, Jack W Szostak
The RNA World hypothesis posits that RNA was the molecule of both heredity and function during the emergence of life. This hypothesis implies that RNA templates can be copied, and ultimately replicated, without the catalytic aid of evolved enzymes. A major problem with nonenzymatic template-directed polymerization has been the very poor copying of sequences containing rA and rU. Here, we overcome that problem by using a prebiotically plausible mixture of RNA mononucleotides and random-sequence oligonucleotides, all activated by methyl isocyanide chemistry, that direct the uniform copying of arbitrary-sequence templates, including those harboring rA and rU. We further show that the use of this mixture in copying reactions suppresses copying errors while also generating a more uniform distribution of mismatches than observed for simpler systems. We find that oligonucleotide competition for template binding sites, oligonucleotide ligation and the template binding properties of reactant intermediates work together to reduce product sequence bias and errors. Finally, we show that iterative cycling of templated polymerization and activation chemistry improves the yields of random-sequence products. These results for random-sequence template copying are a significant advance in the pursuit of nonenzymatic RNA replication.
RNA 世界假说认为,在生命出现的过程中,RNA 是遗传和功能的分子。这一假说意味着,在没有进化酶的催化帮助下,RNA 模板可以被复制,并最终被复制。非酶模板定向聚合的一个主要问题是含有 rA 和 rU 的序列的复制能力很差。在这里,我们克服了这一问题,使用了一种生物学上可信的 RNA 单核苷酸和随机序列寡核苷酸的混合物,所有这些都通过甲基异氰化物化学反应激活,可以指导任意序列模板(包括含有 rA 和 rU 的模板)的均匀复制。我们进一步发现,在复制反应中使用这种混合物可以抑制复制错误,同时产生的错配分布也比在更简单的系统中观察到的更均匀。我们发现,寡核苷酸对模板结合位点的竞争、寡核苷酸连接以及反应物中间体的模板结合特性共同作用,减少了产物序列偏差和错误。最后,我们发现模板聚合和活化化学的迭代循环提高了随机序列产物的产量。这些关于随机序列模板复制的研究成果是非酶 RNA 复制领域的重大进展。
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引用次数: 0
TranscriptDB: a transcript-centric database to study eukaryotic transcript conservation and evolution. TranscriptDB:以转录本为中心的数据库,用于研究真核生物转录本的保存和进化。
IF 16.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-12 DOI: 10.1093/nar/gkae995
Wend Yam D D Ouedraogo, Aida Ouangraoua

Eukaryotic genes can encode multiple distinct transcripts through the alternative splicing (AS) of genes. Interest in the AS mechanism and its evolution across different species has stimulated numerous studies, leading to several databases that provide information on AS and transcriptome data across multiple eukaryotic species. However, existing resources do not offer information on transcript conservation and evolution between genes of multiple species. Similarly to genes, identifying conserved transcripts-those from homologous genes that have retained a similar exon composition-is useful for determining transcript homology relationships, studying transcript functions and reconstructing transcript phylogenies. To address this gap, we have developed TranscriptDB, a database dedicated to studying the conservation and evolution of transcripts within gene families. TranscriptDB offers an extensive catalog of conserved transcripts and phylogenies for 317 annotated eukaryotic species, sourced from Ensembl database version 111. It serves multiple purposes, including the exploration of gene and transcript evolution. Users can access TranscriptDB through various browsing and querying tools, including a user-friendly web interface. The incorporated web servers enable users to retrieve information on transcript evolution using their own data as input. Additionally, a REST application programming interface is available for programmatic data retrieval. A data directory is also available for bulk downloads. TranscriptDB and its resources are freely accessible at https://transcriptdb.cobius.usherbrooke.ca.

真核生物基因可以通过基因的替代剪接(AS)编码多种不同的转录本。人们对替代剪接机制及其在不同物种间的进化产生了浓厚的兴趣,由此产生了多个数据库,提供真核生物多个物种的替代剪接信息和转录组数据。然而,现有资源并不能提供多个物种基因间转录本的保护和进化信息。与基因类似,识别保守的转录本--那些来自同源基因且保留了相似外显子组成的转录本--对于确定转录本同源性关系、研究转录本功能和重建转录本系统发育非常有用。为了填补这一空白,我们开发了转录本数据库(TranscriptDB),这是一个专门研究基因家族内转录本保护和进化的数据库。TranscriptDB 为 317 个已注释的真核生物物种提供了广泛的保守转录本和系统发育目录,其来源是 Ensembl 数据库第 111 版。它有多种用途,包括探索基因和转录本的进化。用户可以通过各种浏览和查询工具访问 TranscriptDB,包括一个用户友好的网络界面。内置的网络服务器可让用户使用自己的数据作为输入检索转录本进化信息。此外,REST 应用程序编程接口可用于程序化数据检索。数据目录也可用于批量下载。TranscriptDB 及其资源可通过 https://transcriptdb.cobius.usherbrooke.ca 免费访问。
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引用次数: 0
CRISPRepi: a multi-omic atlas for CRISPR-based epigenome editing CRISPRepi:基于 CRISPR 的表观基因组编辑的多组图谱
IF 14.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-12 DOI: 10.1093/nar/gkae1039
Leisheng Shi, Shasha Li, Rongyi Zhu, Chenyang Lu, Xintian Xu, Changzhi Li, Xinyue Huang, Xiaolu Zhao, Fengbiao Mao, Kailong Li
CRISPR-based epigenome editing integrates the precision of CRISPR with the capability of epigenetic mark rewriting, offering a tunable and reversible gene regulation strategy without altering the DNA sequences. Various epigenome editing systems have been developed and applied in different organisms and cell types; however, the detailed information is discrete, making it challenging to evaluate the precision of different editing systems and design the optimal sgRNAs for further functional studies. Herein, we developed CRISPRepi (http://crisprepi.maolab.org/ or http://crisprepi.lilab-pkuhsc.org/), a pioneering platform that consolidates extensive sequencing data from 671 meticulously curated RNA-seq, ChIP-seq, Bisulfite-seq and ATAC-seq datasets in 87 cell types manipulated by 74 epigenome editing systems. In total, we have curated 5962 sgRNAs associated with 283 target genes from 2277 samples across six species. CRISPRepi incorporates tools for analyzing editing outcomes and assessing off-target effects by analyzing gene expression changes pre- and post-editing, along with the details of multi-omic epigenetic landscapes. Moreover, CRISPRepi supports the investigation of editing potentials for newly designed sgRNA sequences in a cell/tissue-specific context. By providing a user-friendly interface for searching and selecting optimal editing designs across multiple organisms, CRISPRepi serves as an integrated resource for researchers to evaluate editing efficiency and off-target effects among diverse CRISPR-based epigenome editing systems.
基于CRISPR的表观基因组编辑整合了CRISPR的精确性和表观遗传标记重写的能力,在不改变DNA序列的情况下提供了一种可调且可逆的基因调控策略。各种表观基因组编辑系统已被开发出来并应用于不同的生物和细胞类型;然而,详细的信息是不连续的,这使得评估不同编辑系统的精确性和为进一步的功能研究设计最佳的sgRNA具有挑战性。在此,我们开发了 CRISPRepi(http://crisprepi.maolab.org/ 或 http://crisprepi.lilab-pkuhsc.org/),这是一个开创性的平台,它整合了来自 671 个精心策划的 RNA-seq、ChIP-seq、Bisulfite-seq 和 ATAC-seq 数据集的大量测序数据,这些数据集由 74 种表观基因组编辑系统对 87 种细胞类型进行了操作。我们总共从 6 个物种的 2277 个样本中筛选出了与 283 个目标基因相关的 5962 个 sgRNA。CRISPRepi 通过分析编辑前后的基因表达变化以及多组表观遗传景观的细节,整合了分析编辑结果和评估脱靶效应的工具。此外,CRISPRepi 还支持在细胞/组织特异性背景下研究新设计的 sgRNA 序列的编辑潜力。CRISPRepi 提供了一个用户友好界面,用于搜索和选择多个生物体的最佳编辑设计,是研究人员评估基于 CRISPR 的各种表观遗传组编辑系统的编辑效率和脱靶效应的综合资源。
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引用次数: 0
ASpdb: an integrative knowledgebase of human protein isoforms from experimental and AI-predicted structures ASpdb:根据实验和人工智能预测结构建立的人类蛋白质同工酶综合知识库
IF 14.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-12 DOI: 10.1093/nar/gkae1018
Yuntao Yang, Himansu Kumar, Yuhan Xie, Zhao Li, Rongbin Li, Wenbo Chen, Chiamaka S Diala, Meer A Ali, Yi Xu, Albon Wu, Sayed-Rzgar Hosseini, Erfei Bi, Hongyu Zhao, Pora Kim, W Jim Zheng
Alternative splicing is a crucial cellular process in eukaryotes, enabling the generation of multiple protein isoforms with diverse functions from a single gene. To better understand the impact of alternative splicing on protein structures, protein–protein interaction and human diseases, we developed ASpdb (https://biodataai.uth.edu/ASpdb/), a comprehensive database integrating experimentally determined structures and AlphaFold 2-predicted models for human protein isoforms. ASpdb includes over 3400 canonical isoforms, each represented by both experimentally resolved and predicted structures, and &gt;7200 alternative isoforms with AlphaFold 2 predictions. In addition to detailed splicing events, 3D structures, sequence variations and functional annotations, ASpdb uniquely offers comparative analyses and visualization of structural alterations among isoforms. This resource is invaluable for advancing research in alternative splicing, structural biology and disease mechanisms.
在真核生物中,替代剪接是一个关键的细胞过程,它能使单个基因产生多种具有不同功能的蛋白质异构体。为了更好地了解替代剪接对蛋白质结构、蛋白质-蛋白质相互作用和人类疾病的影响,我们开发了 ASpdb (https://biodataai.uth.edu/ASpdb/),这是一个整合了实验测定的结构和 AlphaFold 2 预测的人类蛋白质同工酶模型的综合数据库。ASpdb 包括 3400 多种典型同工酶,每种酶都有实验测定的结构和预测的结构,以及 7200 种带有 AlphaFold 2 预测的替代同工酶。除了详细的剪接事件、三维结构、序列变化和功能注释外,ASpdb 还提供了独特的比较分析和同工酶结构变化的可视化。该资源对于推进替代剪接、结构生物学和疾病机制方面的研究非常有价值。
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引用次数: 0
The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity NHGRI-EBI GWAS 目录:可重用性、可持续性和多样性标准
IF 14.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-12 DOI: 10.1093/nar/gkae1070
Maria Cerezo, Elliot Sollis, Yue Ji, Elizabeth Lewis, Ala Abid, Karatuğ Ozan Bircan, Peggy Hall, James Hayhurst, Sajo John, Abayomi Mosaku, Santhi Ramachandran, Amy Foreman, Arwa Ibrahim, James McLaughlin, Zoë Pendlington, Ray Stefancsik, Samuel A Lambert, Aoife McMahon, Joannella Morales, Thomas Keane, Michael Inouye, Helen Parkinson, Laura W Harris
The NHGRI-EBI GWAS Catalog serves as a vital resource for the genetic research community, providing access to the most comprehensive database of human GWAS results. Currently, it contains close to 7 000 publications for &gt;15 000 traits, from which more than 625 000 lead associations have been curated. Additionally, 85 000 full genome-wide summary statistics datasets—containing association data for all variants in the analysis—are available for downstream analyses such as meta-analysis, fine-mapping, Mendelian randomisation or development of polygenic risk scores. As a centralised repository for GWAS results, the GWAS Catalog sets and implements standards for data submission and harmonisation, and encourages the use of consistent descriptors for traits, samples and methodologies. We share processes and vocabulary with the PGS Catalog, improving interoperability for a growing user group. Here, we describe the latest changes in data content, improvements in our user interface, and the implementation of the GWAS-SSF standard format for summary statistics. We address the challenges of handling the rapid increase in large-scale molecular quantitative trait GWAS and the need for sensitivity in the use of population and cohort descriptors while maintaining data interoperability and reusability.
NHGRI-EBI GWAS 目录是遗传研究界的重要资源,提供了最全面的人类 GWAS 结果数据库。目前,该数据库收录了近 7000 篇关于 15000 个性状的论文,从中筛选出了 625000 多条相关线索。此外,85000 个全基因组汇总统计数据集(包含分析中所有变异的关联数据)可用于荟萃分析、精细图谱、孟德尔随机化或多基因风险评分等下游分析。作为 GWAS 结果的集中存储库,GWAS 目录制定并实施了数据提交和统一的标准,并鼓励对性状、样本和方法使用一致的描述符。我们与 PGS 目录共享流程和词汇,为不断增长的用户群提高互操作性。在此,我们将介绍数据内容的最新变化、用户界面的改进以及 GWAS-SSF 统计摘要标准格式的实施情况。我们将应对处理大规模分子定量性状 GWAS 快速增长所带来的挑战,以及在保持数据互操作性和可重用性的同时对使用群体和队列描述符的敏感性的需求。
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引用次数: 0
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