泥者在多重复合的CLIP数据中检测到组合RNA结合蛋白相互作用
Hsuanlin Her1, Katherine L Rothamel2, Grady G Nguyen2
1Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Sanford Stem Cell Institute Innovation Center and Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
Cell genomics
|July 2, 2024
概括
Mudskipper通过改进多重交联和免疫沉降 (CLIP) 实验的数据分析来增强RNA结合蛋白 (RBP) 站点映射. 这种计算工具可以提高RBP绑定位点识别的精度和回忆.
科学领域:
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
- 基因组学就是基因组学.
背景情况:
- 了解蛋白质-RNA相互作用对于破译RNA处理和调节至关重要.
- 多重交联和免疫沉 (CLIP) 技术,如抗体条形编码的eCLIP (ABC),已经推进了RNA结合蛋白 (RBP) 结合部位的高通量映射.
- 现有的多重CLIP数据集由于其多变量性质和不同RBPs的可变信号噪声比率而存在挑战.
研究的目的:
- 开发一个计算套件,Mudskipper,用于改进多重CLIP数据集的分析.
- 为了应对多变量数据和非统一的信号噪声比在绘制RBP绑定站点的挑战.
- 提高RBP结合位点识别的精度和回忆,特别是对于低信号噪声比的RBP.
主要方法:
- 开发Mudskipper,一个计算套件,有两个核心组件.
- 实施迪里克莱多项混合模型来处理ABC数据集的多变量特征.
- 应用软掩盖方法来识别和去除非特异性蛋白质-RNA相互作用.
主要成果:
- 与多重CLIP数据集上的现有工具相比,Mudskipper表现出更高的精度和回忆能力.
- 该计算套件有效地分析重复元素和小型非编码RNA.
- 泥者有助于解开拼接结果和变异相关的破坏.
结论:
- Mudskipper提供了一种多功能和有效的计算解决方案,用于分析复杂的多重Clip数据.
- 该工具增强了对RNA结合蛋白质介导调节和疾病机制的调查.
- Mudskipper 能够对蛋白质-RNA 相互作用进行更高吞吐量和更准确的研究.
相关概念视频
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
01:53RNA Stability
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
02:53CRISPR and crRNAs
Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
02:57Southern Blot
Agarose gel electrophoresis is very useful in separating DNA fragments by size. Running a DNA ladder containing fragments of the known length alongside the sample helps determine the approximate length of the sample DNA fragments. However, additional steps are needed to verify the sequence identity of the sample DNA fragments.
Denatured DNA fragments must be transferred onto a carrier membrane from the gel to make it accessible to a probe - a small ssDNA fragment complementary to the target DNA...
Denatured DNA fragments must be transferred onto a carrier membrane from the gel to make it accessible to a probe - a small ssDNA fragment complementary to the target DNA...
03:21RNA-seq
RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases.
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while microarray-based...
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while microarray-based...