Differential analysis of RNA structure probing experiments at nucleotide resolution: uncovering regulatory functions of RNA structure.
Differential analysis of RNA structure probing experiments at nucleotide resolution: uncovering regulatory functions of RNA structure.
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核苷酸分辨率下 RNA 结构探测实验的差异分析：揭示 RNA 结构的调控功能
DOI：
10.1038/s41467-022-31875-3
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发表时间：
2022-07-22
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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RNA通过形成特定的结构来执行其功能，这些结构可以在细胞条件下发生变化。结合下一代测序技术的结构探测实验使得能够在各种细胞条件下对RNA二级结构进行全转录组分析。对不同条件下的结构探针数据进行差异分析，可以揭示RNA的结构可变区，这对于理解RNA的功能具有重要意义。在这里，我们提出了DiffScan，一个计算框架的结构探测数据在高分辨率的归一化和差分分析。DiffScan预处理结构探测数据集以去除系统偏差，然后扫描转录本以识别SVR并自适应地确定其长度和位置。所提出的方法与大多数结构探测平台（例如，icSHAPE，DMS-seq）。当用模拟和基准数据集进行评估时，DiffScan以核苷酸分辨率识别结构可变区，与现有的SVR检测方法相比，准确性有了实质性的提高。此外，当在多个结构探测平台中测试时，改进是鲁棒的。DiffScan在多亚细胞RNA结构组数据集中的应用和随后的基序富集分析表明RNA结构变异和mRNA丰度的潜在联系，可能由RNA结合蛋白如富含丝氨酸/精氨酸的剪接因子介导。这一工作为RNA二级结构的差异分析提供了一个有效的工具，增强了结构探测实验在破译动态RNA结构组中的作用。作者介绍了DiffScan，一种用于RNA结构探测实验的标准化和差异分析的先进工具，结合了他们在破译动态RNA结构组和促进RNA调控功能发现方面的能力。
RNAs perform their function by forming specific structures, which can change across cellular conditions. Structure probing experiments combined with next generation sequencing technology have enabled transcriptome-wide analysis of RNA secondary structure in various cellular conditions. Differential analysis of structure probing data in different conditions can reveal the RNA structurally variable regions (SVRs), which is important for understanding RNA functions. Here, we propose DiffScan, a computational framework for normalization and differential analysis of structure probing data in high resolution. DiffScan preprocesses structure probing datasets to remove systematic bias, and then scans the transcripts to identify SVRs and adaptively determines their lengths and locations. The proposed approach is compatible with most structure probing platforms (e.g., icSHAPE, DMS-seq). When evaluated with simulated and benchmark datasets, DiffScan identifies structurally variable regions at nucleotide resolution, with substantial improvement in accuracy compared with existing SVR detection methods. Moreover, the improvement is robust when tested in multiple structure probing platforms. Application of DiffScan in a dataset of multi-subcellular RNA structurome and a subsequent motif enrichment analysis suggest potential links of RNA structural variation and mRNA abundance, possibly mediated by RNA binding proteins such as the serine/arginine rich splicing factors. This work provides an effective tool for differential analysis of RNA secondary structure, reinforcing the power of structure probing experiments in deciphering the dynamic RNA structurome. The authors present DiffScan, an advanced tool for normalization and differential analysis of RNA structure probing experiments, combining their power in deciphering the dynamic RNA structurome and facilitating the discovery of RNA regulatory functions.
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影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
DOI：
10.1093/database/baw035
发表时间：
2016-04-07
影响因子：
5.8
作者：
Giudice, Girolamo;Sanchez-Cabo, Fatima;Lara-Pezzi, Enrique
通讯作者：
Lara-Pezzi, Enrique
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影响因子：
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作者：
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通讯作者：
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影响因子：
14.9
作者：
Didiot, Marie-Cecile;Tian, Zhaoxia;Schaeffer, Celine;Subramanian, Murugan;Mandel, Jean-Louis;Moine, Herve
通讯作者：
Moine, Herve
影响因子：
14.8
作者：
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通讯作者：
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