GuidePro: a multi-source ensemble predictor for prioritizing sgRNAs in CRISPR/Cas9 protein knockouts.
GuidePro: a multi-source ensemble predictor for prioritizing sgRNAs in CRISPR/Cas9 protein knockouts.
复制标题
GuidePro：一种多源集成预测器，用于在 CRISPR/Cas9 蛋白敲除中优先考虑 sgRNA。
DOI：
10.1093/bioinformatics/btaa1068
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Xu,Han
中科院分区：
文献类型：
--
作者：
He,Wei;Wang,Helen;Wei,Yanjun;Jiang,Zhiyun;Tang,Yitao;Chen,Yiwen;Xu,Han
CRISPR/ cas9介导的蛋白敲除效率由三个因素决定：序列特异性sgRNA活性、移码概率和靶向氨基酸的特性。许多计算方法从不同的角度预测sgRNA的效率。然而，目前还缺乏一种综合这三种因素来合理选择sgRNA的方法。我们开发了GuidePro，这是一个两层集合预测器，可以整合多个因素来确定蛋白质敲除中sgrna的优先级。在独立数据集上测试，GuidePro优于现有方法，并在预测蛋白质功能缺失引起的表型方面表现出一致的优越性能，表明其在CRISPR/Cas9敲除的各种应用中对sgrna进行优先排序的稳受性。可用性和实现：https://github.com/MDhewei/GuidePro。一个针对人类、猴子和小鼠基因组中蛋白质编码基因的sgrna优先排序的web应用程序可在https://bioinformatics.mdanderson.org/apps/GuidePro.Supplementary上获得。
MotivationThe efficiency of CRISPR/Cas9-mediated protein knockout is determined by three factors: sequence-specific sgRNA activity, frameshift probability and the characteristics of targeted amino acids. A number of computational methods have been developed for predicting sgRNA efficiency from different perspectives. However, an integrative method that combines all three factors for rational sgRNA selection is still lacking.ResultsWe developed GuidePro, a two-layer ensemble predictor that enables the integration of multiple factors for the prioritization of sgRNAs in protein knockouts. Tested on independent datasets, GuidePro outperforms existing methods and demonstrates consistent superior performance in predicting phenotypes caused by protein loss-of-function, suggesting its robustness for prioritizing sgRNAs in various applications of CRISPR/Cas9 knockouts.Availability and implementationGuidePro is available at https://github.com/MDhewei/GuidePro. A web application for prioritizing sgRNAs that target protein-coding genes in human, monkey and mouse genomes is available at https://bioinformatics.mdanderson.org/apps/GuidePro.Supplementary informationSupplementary data are available atBioinformaticsonline.