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A Model-Based Approach to Identify Binding Sites in CLIP-Seq Data

机译:一种基于模型的方法来识别CLIP-Seq数据中的结合位点

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摘要

Cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-Seq) has made it possible to identify the targeting sites of RNA-binding proteins in various cell culture systems and tissue types on a genome-wide scale. Here we present a novel model-based approach (MiClip) to identify high-confidence protein-RNA binding sites from CLIP-seq datasets. This approach assigns a probability score for each potential binding site to help prioritize subsequent validation experiments. The MiClip algorithm has been tested in both HITS-CLIP and PAR-CLIP datasets. In the HITS-CLIP dataset, the signaloise ratios of miRNA seed motif enrichment produced by the MiClip approach are between 17% and 301% higher than those by the ad hoc method for the top 10 most enriched miRNAs. In the PAR-CLIP dataset, the MiClip approach can identify ∼50% more validated binding targets than the original ad hoc method and two recently published methods. To facilitate the application of the algorithm, we have released an R package, MiClip ( ), and a public web-based graphical user interface software () for customized analysis.
机译:交联免疫沉淀与高通量测序(CLIP-Seq)结合在一起,使得在全基因组范围内鉴定各种细胞培养系统和组织类型中RNA结合蛋白的靶向位点成为可能。在这里,我们提出了一种新颖的基于模型的方法(MiClip),用于从CLIP-seq数据集中识别高可信度的蛋白质-RNA结合位点。该方法为每个潜在的结合位点分配概率得分,以帮助确定后续验证实验的优先级。 MiClip算法已在HITS-CLIP和PAR-CLIP数据集中进行了测试。在HITS-CLIP数据集中,通过MiClip方法产生的miRNA种子基序富集的信噪比比通过ad hoc方法产生的前10个最富集的miRNA高出17%至301%。在PAR-CLIP数据集中,与原始的ad hoc方法和两个最近发布的方法相比,MiClip方法可识别约50%的有效结合靶标。为了促进算法的应用,我们发布了R包,MiClip()和基于Web的公共图形用户界面软件(),用于自定义分析。

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