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使用 VAST-TOOLS 和 VastDB 框架进行可变剪接的计算分析。

Computational Analysis of Alternative Splicing Using VAST-TOOLS and the VastDB Framework.

机构信息

Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.

Universitat Pompeu Fabra, Barcelona, Spain.

出版信息

Methods Mol Biol. 2022;2537:97-128. doi: 10.1007/978-1-0716-2521-7_7.

DOI:10.1007/978-1-0716-2521-7_7
PMID:35895261
Abstract

Alternative splicing (AS) can vastly expand animal transcriptomes and proteomes. Two main open questions in the field are how AS is regulated across cell/tissue types and disease, and what roles different AS events play. To facilitate AS research, we have created the computational VastDB framework, which comprises a series of complementary software and resources that we describe in this chapter. The VastDB framework is especially designed to aid biomedical researchers without a strong computational background. It offers tools and resources to: (a) quantify AS and identify differentially spliced AS events using RNA-seq data (vast-tools), (b) perform multiple genomic and sequence analyses for investigating AS events (Matt), (c) identify AS events with genomic and regulatory conservation among species (ExOrthist), and (d) help with the biological interpretation of the results, and, ultimately, with the identification of interesting AS events to design wet-lab experiments (VastDB and PastDB).

摘要

可变剪接 (AS) 可以极大地扩展动物的转录组和蛋白质组。该领域的两个主要问题是 AS 如何在细胞/组织类型和疾病中被调控,以及不同的 AS 事件扮演何种角色。为了促进 AS 研究,我们创建了计算性的 VastDB 框架,该框架包括一系列互补的软件和资源,我们将在本章中进行介绍。VastDB 框架是专门为没有强大计算背景的生物医学研究人员设计的。它提供了工具和资源,用于:(a) 使用 RNA-seq 数据定量 AS 和识别差异剪接的 AS 事件(vast-tools),(b) 进行多种基因组和序列分析以研究 AS 事件(Matt),(c) 在物种间识别具有基因组和调控保守性的 AS 事件(ExOrthist),以及 (d) 帮助对结果进行生物学解释,并最终识别有趣的 AS 事件以设计湿实验(VastDB 和 PastDB)。

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本文引用的文献

1
ExOrthist: a tool to infer exon orthologies at any evolutionary distance.ExOrthist:一种能够推断任意进化距离上外显子直系同源性的工具。
Genome Biol. 2021 Aug 20;22(1):239. doi: 10.1186/s13059-021-02441-9.
2
Alternative splicing landscapes in Arabidopsis thaliana across tissues and stress conditions highlight major functional differences with animals.拟南芥不同组织和胁迫条件下的选择性剪接图谱突出了与动物的主要功能差异。
Genome Biol. 2021 Jan 14;22(1):35. doi: 10.1186/s13059-020-02258-y.
3
Broccoli: Combining Phylogenetic and Network Analyses for Orthology Assignment.
Mol Cell. 2024 Jul 11;84(13):2553-2572.e19. doi: 10.1016/j.molcel.2024.05.024. Epub 2024 Jun 24.
西兰花:结合系统发育分析和网络分析进行直系同源物分配
Mol Biol Evol. 2020 Nov 1;37(11):3389-3396. doi: 10.1093/molbev/msaa159.
4
Genetic interaction mapping and exon-resolution functional genomics with a hybrid Cas9-Cas12a platform.利用杂交 Cas9-Cas12a 平台进行遗传互作作图和外显子分辨率功能基因组学研究。
Nat Biotechnol. 2020 May;38(5):638-648. doi: 10.1038/s41587-020-0437-z. Epub 2020 Mar 16.
5
RNA isoform screens uncover the essentiality and tumor-suppressor activity of ultraconserved poison exons.RNA 异构体筛选揭示超保守“毒”外显子的必需性和肿瘤抑制活性。
Nat Genet. 2020 Jan;52(1):84-94. doi: 10.1038/s41588-019-0555-z. Epub 2020 Jan 7.
6
OrthoFinder: phylogenetic orthology inference for comparative genomics.OrthoFinder:用于比较基因组学的系统发育直系同源推断。
Genome Biol. 2019 Nov 14;20(1):238. doi: 10.1186/s13059-019-1832-y.
7
ELM-the eukaryotic linear motif resource in 2020.ELM-the eukaryotic linear motif resource in 2020. ELM-the 2020 eukaryotic linear motif resource.
Nucleic Acids Res. 2020 Jan 8;48(D1):D296-D306. doi: 10.1093/nar/gkz1030.
8
A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons.一个古老剪接因子中的新蛋白结构域驱动了神经微外显子的演化。
Nat Ecol Evol. 2019 Apr;3(4):691-701. doi: 10.1038/s41559-019-0813-6. Epub 2019 Mar 4.
9
Efficient and Accurate Quantitative Profiling of Alternative Splicing Patterns of Any Complexity on a Laptop.在笔记本电脑上高效、准确地定量分析任何复杂度的可变剪接模式。
Mol Cell. 2018 Oct 4;72(1):187-200.e6. doi: 10.1016/j.molcel.2018.08.018. Epub 2018 Sep 13.
10
Systematic evaluation of isoform function in literature reports of alternative splicing.系统评价文献中可变剪接报告的异构体功能。
BMC Genomics. 2018 Aug 28;19(1):637. doi: 10.1186/s12864-018-5013-2.