• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

评估分支点预测工具以预测生理分支点及其变体的改变。

Assessment of branch point prediction tools to predict physiological branch points and their alteration by variants.

机构信息

Laboratoire de Biologie Clinique et Oncologique, Centre François Baclesse, Caen, France.

Inserm U1245, Normandy Center for Genomic and Personalized Medicine, Rouen, UNIROUEN, Normandy University, Caen, France.

出版信息

BMC Genomics. 2020 Jan 28;21(1):86. doi: 10.1186/s12864-020-6484-5.

DOI:10.1186/s12864-020-6484-5
PMID:31992191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6988378/
Abstract

BACKGROUND

Branch points (BPs) map within short motifs upstream of acceptor splice sites (3'ss) and are essential for splicing of pre-mature mRNA. Several BP-dedicated bioinformatics tools, including HSF, SVM-BPfinder, BPP, Branchpointer, LaBranchoR and RNABPS were developed during the last decade. Here, we evaluated their capability to detect the position of BPs, and also to predict the impact on splicing of variants occurring upstream of 3'ss.

RESULTS

We used a large set of constitutive and alternative human 3'ss collected from Ensembl (n = 264,787 3'ss) and from in-house RNAseq experiments (n = 51,986 3'ss). We also gathered an unprecedented collection of functional splicing data for 120 variants (62 unpublished) occurring in BP areas of disease-causing genes. Branchpointer showed the best performance to detect the relevant BPs upstream of constitutive and alternative 3'ss (99.48 and 65.84% accuracies, respectively). For variants occurring in a BP area, BPP emerged as having the best performance to predict effects on mRNA splicing, with an accuracy of 89.17%.

CONCLUSIONS

Our investigations revealed that Branchpointer was optimal to detect BPs upstream of 3'ss, and that BPP was most relevant to predict splicing alteration due to variants in the BP area.

摘要

背景

分支点 (BP) 位于接受体剪接位点 (3' ss) 上游的短基序内，是成熟 mRNA 剪接所必需的。在过去的十年中，已经开发了几种专门用于 BP 的生物信息学工具，包括 HSF、SVM-BPfinder、BPP、Branchpointer、LaBranchoR 和 RNABPS。在这里，我们评估了它们检测 BP 位置的能力，以及预测 3' ss 上游变体对剪接影响的能力。

结果

我们使用了从 Ensembl（n=264787 个 3' ss）和内部 RNAseq 实验（n=51986 个 3' ss）收集的大量组成型和替代人类 3' ss。我们还收集了 120 个变体（62 个未发表）在致病基因的 BP 区域的功能剪接数据，这是前所未有的。Branchpointer 在检测组成型和替代 3' ss 上游的相关 BP 方面表现最佳（准确性分别为 99.48%和 65.84%）。对于发生在 BP 区域的变体，BPP 是预测 mRNA 剪接效应的最佳工具，准确率为 89.17%。

结论

我们的研究表明，Branchpointer 是检测 3' ss 上游 BP 的最佳工具，而 BPP 是预测 BP 区域变体对剪接改变最相关的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e127/6988378/84ac00f02f11/12864_2020_6484_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e127/6988378/20e8f977ae96/12864_2020_6484_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e127/6988378/94ee060673c6/12864_2020_6484_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e127/6988378/231e712d83cd/12864_2020_6484_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e127/6988378/84ac00f02f11/12864_2020_6484_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e127/6988378/20e8f977ae96/12864_2020_6484_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e127/6988378/94ee060673c6/12864_2020_6484_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e127/6988378/231e712d83cd/12864_2020_6484_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e127/6988378/84ac00f02f11/12864_2020_6484_Fig4_HTML.jpg

相似文献

1
Assessment of branch point prediction tools to predict physiological branch points and their alteration by variants.评估分支点预测工具以预测生理分支点及其变体的改变。
BMC Genomics. 2020 Jan 28;21(1):86. doi: 10.1186/s12864-020-6484-5.
2
Splicing Enhancers at Intron-Exon Borders Participate in Acceptor Splice Sites Recognition.剪接增强子在内含子-外显子边界参与供体位点识别。
Int J Mol Sci. 2020 Sep 8;21(18):6553. doi: 10.3390/ijms21186553.
3
Identification of new branch points and unconventional introns in Saccharomyces cerevisiae.酿酒酵母中新分支点和非常规内含子的鉴定
RNA. 2016 Oct;22(10):1522-34. doi: 10.1261/rna.057216.116. Epub 2016 Jul 29.
4
Impact of acceptor splice site NAGTAG motif on exon recognition.接受子剪接位点 NAGTAG 基序对exon 识别的影响。
Mol Biol Rep. 2019 Jun;46(3):2877-2884. doi: 10.1007/s11033-019-04734-6. Epub 2019 Mar 6.
5
Aberrant 3' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.人类疾病基因中的异常3'剪接位点：突变模式、核苷酸结构及预测其使用情况的计算工具比较
Nucleic Acids Res. 2006;34(16):4630-41. doi: 10.1093/nar/gkl535. Epub 2006 Sep 8.
6
Biased exon/intron distribution of cryptic and de novo 3' splice sites.隐蔽型和新生3'剪接位点的外显子/内含子分布偏差
Nucleic Acids Res. 2005 Sep 1;33(15):4882-98. doi: 10.1093/nar/gki811. Print 2005.
7
Secondary structure is required for 3' splice site recognition in yeast.二级结构是酵母 3' 剪接位点识别所必需的。
Nucleic Acids Res. 2011 Dec;39(22):9759-67. doi: 10.1093/nar/gkr662. Epub 2011 Sep 5.
8
RNA secondary structure mediates alternative 3'ss selection in Saccharomyces cerevisiae.RNA 二级结构介导酿酒酵母中可变 3'剪接位点的选择。
RNA. 2012 Jun;18(6):1103-15. doi: 10.1261/rna.030767.111. Epub 2012 Apr 26.
9
Deciphering 3'ss selection in the yeast genome reveals an RNA thermosensor that mediates alternative splicing.解析酵母基因组中的 3'ss 选择揭示了一种介导选择性剪接的 RNA 热传感器。
Mol Cell. 2011 Sep 16;43(6):1033-9. doi: 10.1016/j.molcel.2011.07.030.
10
AG-exclusion zone revisited: Lessons to learn from 91 intronic NF1 3' splice site mutations outside the canonical AG-dinucleotides.重新审视 AG 外显子缺失区：从 91 个 NF1 外显子 3'剪接位点突变中非典型 AG 二核苷酸中吸取的教训。
Hum Mutat. 2020 Jun;41(6):1145-1156. doi: 10.1002/humu.24005. Epub 2020 Mar 11.

引用本文的文献

1
New genetic diagnoses for inherited retinal dystrophies by integrating splicing tools into NGS pipelines.通过将剪接工具整合到二代测序流程中实现遗传性视网膜营养不良的新基因诊断
NPJ Genom Med. 2025 Jul 2;10(1):52. doi: 10.1038/s41525-025-00500-9.
2
Data-driven insights to inform splice-altering variant assessment.基于数据的见解为剪接改变变异评估提供信息。
Am J Hum Genet. 2025 Apr 3;112(4):764-778. doi: 10.1016/j.ajhg.2025.02.012. Epub 2025 Mar 7.
3
DeepSplice: a deep learning approach for accurate prediction of alternative splicing events in the human genome.

本文引用的文献

1
SpliceLauncher: a tool for detection, annotation and relative quantification of alternative junctions from RNAseq data.SpliceLauncher：一种从 RNAseq 数据中检测、注释和相对定量替代剪接的工具。
Bioinformatics. 2020 Mar 1;36(5):1634-1636. doi: 10.1093/bioinformatics/btz784.
2
A systems view of spliceosomal assembly and branchpoints with iCLIP.基于 iCLIP 的剪接体组装和分支点的系统观
Nat Struct Mol Biol. 2019 Oct;26(10):930-940. doi: 10.1038/s41594-019-0300-4. Epub 2019 Sep 30.
3
MMSplice: modular modeling improves the predictions of genetic variant effects on splicing.
DeepSplice：一种用于准确预测人类基因组中可变剪接事件的深度学习方法。
Front Genet. 2024 Jun 21;15:1349546. doi: 10.3389/fgene.2024.1349546. eCollection 2024.
4
SpliceAPP: an interactive web server to predict splicing errors arising from human mutations.SpliceAPP：一个交互式网络服务器，用于预测由人类突变引起的剪接错误。
BMC Genomics. 2024 Jun 15;25(1):600. doi: 10.1186/s12864-024-10512-x.
5
Refining clinically relevant parameters for mis-splicing risk in shortened introns with donor-to-branchpoint space constraint.针对具有供体到分支点空间限制的缩短内含子中的错配剪接风险，优化临床相关参数。
Eur J Hum Genet. 2024 Aug;32(8):972-979. doi: 10.1038/s41431-024-01632-9. Epub 2024 May 27.
6
Exonic splicing code and coordination of divalent metals in proteins.外显子剪接代码和蛋白质中二价金属的协调。
Nucleic Acids Res. 2024 Feb 9;52(3):1090-1106. doi: 10.1093/nar/gkad1161.
7
Exploiting public databases of genomic variation to quantify evolutionary constraint on the branch point sequence in 30 plant and animal species.利用基因组变异的公共数据库来量化 30 种植物和动物物种分支点序列的进化约束。
Nucleic Acids Res. 2023 Dec 11;51(22):12069-12075. doi: 10.1093/nar/gkad970.
8
Variations of intronic branchpoint motif: identification and functional implications in splicing and disease.内含子分支点基序的变异：剪接和疾病中的鉴定及功能意义。
Commun Biol. 2023 Nov 10;6(1):1142. doi: 10.1038/s42003-023-05513-7.
9
Computational prediction of human deep intronic variation.人类深内含子变异的计算预测。
Gigascience. 2022 Dec 28;12. doi: 10.1093/gigascience/giad085. Epub 2023 Oct 25.
10
c.6480-35A>G, a novel branchpoint variant associated with Stargardt disease.c.6480-35A>G，一种与斯塔加特病相关的新型分支点变异。
Front Genet. 2023 Sep 7;14:1234032. doi: 10.3389/fgene.2023.1234032. eCollection 2023.
MMSplice：模块化建模提高了对剪接中遗传变异影响的预测。
Genome Biol. 2019 Mar 1;20(1):48. doi: 10.1186/s13059-019-1653-z.
4
Corrigendum: Novel diagnostic tool for prediction of variant spliceogenicity derived from a set of 395 combined in silico/in vitro studies: an international collaborative effort.勘误：基于395项计算机模拟/体外研究组合得出的预测变异剪接原性的新型诊断工具：一项国际合作成果。
Nucleic Acids Res. 2018 Nov 30;46(21):11656-11657. doi: 10.1093/nar/gky979.
5
A sequence-based, deep learning model accurately predicts RNA splicing branchpoints.基于序列的深度学习模型可准确预测 RNA 剪接分支点。
RNA. 2018 Dec;24(12):1647-1658. doi: 10.1261/rna.066290.118. Epub 2018 Sep 17.
6
Vex-seq: high-throughput identification of the impact of genetic variation on pre-mRNA splicing efficiency.Vex-seq：高通量鉴定遗传变异对前体 mRNA 剪接效率的影响。
Genome Biol. 2018 Jun 1;19(1):71. doi: 10.1186/s13059-018-1437-x.
7
Splicing mutations in human genetic disorders: examples, detection, and confirmation.人类遗传疾病中的剪接突变：实例、检测与确认
J Appl Genet. 2018 Aug;59(3):253-268. doi: 10.1007/s13353-018-0444-7. Epub 2018 Apr 21.
8
Most human introns are recognized via multiple and tissue-specific branchpoints.大多数人类内含子通过多个组织特异性分支点被识别。
Genes Dev. 2018 Apr 1;32(7-8):577-591. doi: 10.1101/gad.312058.118. Epub 2018 Apr 17.
9
Ensembl 2018.Ensembl 2018.
Nucleic Acids Res. 2018 Jan 4;46(D1):D754-D761. doi: 10.1093/nar/gkx1098.
10
Machine learning annotation of human branchpoints.基于机器学习的人类分支点标注。
Bioinformatics. 2018 Mar 15;34(6):920-927. doi: 10.1093/bioinformatics/btx688.