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CRISPRpred: A flexible and efficient tool for sgRNAs on-target activity prediction in CRISPR/Cas9 systems

机译:CRISPRpred:一种灵活高效的工具用于在CRISPR / Cas9系统中预测sgRNA的靶标活性

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摘要

The CRISPR/Cas9-sgRNA system has recently become a popular tool for genome editing and a very hot topic in the field of medical research. In this system, Cas9 protein is directed to a desired location for gene engineering and cleaves target DNA sequence which is complementary to a 20-nucleotide guide sequence found within the sgRNA. A lot of experimental efforts, ranging from in vivo selection to in silico modeling, have been made for efficient designing of sgRNAs in CRISPR/Cas9 system. In this article, we present a novel tool, called CRISPRpred, for efficient in silico prediction of sgRNAs on-target activity which is based on the applications of Support Vector Machine (SVM) model. To conduct experiments, we have used a benchmark dataset of 17 genes and 5310 guide sequences where there are only 20% true values. CRISPRpred achieves Area Under Receiver Operating Characteristics Curve (AUROC-Curve), Area Under Precision Recall Curve (AUPR-Curve) and maximum Matthews Correlation Coefficient (MCC) as 0.85, 0.56 and 0.48, respectively. Our tool shows approximately 5% improvement in AUPR-Curve and after analyzing all evaluation metrics, we find that CRISPRpred is better than the current state-of-the-art. CRISPRpred is enough flexible to extract relevant features and use them in a learning algorithm. The source code of our entire software with relevant dataset can be found in the following link: .
机译:CRISPR / Cas9-sgRNA系统最近已成为基因组编辑的流行工具,并且在医学研究领域是非常热门的话题。在该系统中,Cas9蛋白被引导至基因工程所需的位置,并切割与sgRNA中的20个核苷酸的引导序列互补的目标DNA序列。为了在CRISPR / Cas9系统中高效设计sgRNA,已经进行了许多实验努力,从体内选择到计算机模拟。在本文中,我们基于支持向量机(SVM)模型的应用,提出了一种名为CRISPRpred的新型工具,用于有效地计算机模拟sgRNA的靶标活性。为了进行实验,我们使用了包含17个基因和5310个指导序列的基准数据集,其中真实值只有20%。 CRISPRpred的接收器工作特性曲线下面积(AUROC-Curve),精确召回曲线下面积(AUPR-Curve)和最大Matthews相关系数(MCC)分别为0.85、0.56和0.48。我们的工具显示出AUPR曲线大约提高了5%,并且在分析了所有评估指标之后,我们发现CRISPRpred优于当前的最新技术。 CRISPRpred具有足够的灵活性来提取相关特征并将其用于学习算法中。包含相关数据集的整个软件的源代码可以在以下链接中找到:。

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  • 年(卷),期 -1(12),8
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  • 页码 e0181943
  • 总页数 14
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