Anti-CRISPRs are widespread amongst bacteriophage and promote bacteriophage infection by inactivating the bacterial host's CRISPR–Cas defence system. Identifying and characterizing anti-CRISPR proteins opens an avenue to explore and control CRISPR–Cas machineries for the development of new CRISPR–Cas based biotechnological and therapeutic tools. Past studies have identified anti-CRISPRs in several model phage genomes, but a challenge exists to comprehensively screen for anti-CRISPRs accurately and efficiently from genome and metagenome sequence data. Here, we have developed an ensemble learning based predictor, PaCRISPR, to accurately identify anti-CRISPRs from protein datasets derived from genome and metagenome sequencing projects. PaCRISPR employs different types of feature recognition united within an ensemble framework. Extensive cross-validation and independent tests show that PaCRISPR achieves a significantly more accurate performance compared with homology-based baseline predictors and an existing toolkit. The performance of PaCRISPR was further validated in discovering anti-CRISPRs that were not part of the training for PaCRISPR, but which were recently demonstrated to function as anti-CRISPRs for phage infections. Data visualization on anti-CRISPR relationships, highlighting sequence similarity and phylogenetic considerations, is part of the output from the PaCRISPR toolkit, which is freely available at http://pacrispr.erc.monash.edu/.

中文翻译：

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PaCRISPR：用于预测和可视化抗CRISPR蛋白的服务器。

Anti-CRISPRs在噬菌体中广泛存在，并通过灭活细菌宿主的CRISPR-Cas防御系统来促进噬菌体感染。鉴定和表征抗CRISPR蛋白为探索和控制CRISPR-Cas机器开辟了一条途径，以开发基于CRISPR-Cas的新型生物技术和治疗工具。过去的研究已经在几个模型噬菌体基因组中鉴定出了抗CRISPRs，但是从基因组和元基因组序列数据中准确，有效地全面筛选抗CRISPRs仍然是一个挑战。在这里，我们开发了基于集合学习的预测器PaCRISPR，以从基因组和元基因组测序项目衍生的蛋白质数据集中准确识别抗CRISPR。PaCRISPR采用不同类型的特征识别，并集成在一个整体框架中。广泛的交叉验证和独立测试表明，与基于同源性的基线预测因子和现有工具包相比，PaCRISPR实现了显着更准确的性能。PaCRISPR的性能在发现不属于PaCRISPR训练的一部分的抗CRISPR中得到了进一步验证，但最近被证明可作为噬菌体感染的抗CRISPR。PaCRISPR工具包输出的一部分包含有关反CRISPR关系的数据可视化，突出显示了序列相似性和系统发育考虑因素，该工具包可从http://pacrispr.erc.monash.edu/免费获得。PaCRISPR的性能在发现不属于PaCRISPR训练的一部分的抗CRISPR中得到了进一步验证，但最近被证明可作为噬菌体感染的抗CRISPR。PaCRISPR工具包输出的一部分包含有关反CRISPR关系的数据可视化，突出显示了序列相似性和系统发育考虑因素，该工具包可从http://pacrispr.erc.monash.edu/免费获得。PaCRISPR的性能在发现不属于PaCRISPR训练的一部分的抗CRISPR中得到了进一步验证，但最近被证明可作为噬菌体感染的抗CRISPR。PaCRISPR工具包输出的一部分包含有关反CRISPR关系的数据可视化，突出显示了序列相似性和系统发育考虑因素，该工具包可从http://pacrispr.erc.monash.edu/免费获得。