Department of Computer Science, University of North Carolina at Chapel Hill, NC, USA.
College of Computer Science, Nankai University, Tianjin, China.
Nucleic Acids Res. 2020 Jul 2;48(W1):W358-W365. doi: 10.1093/nar/gkaa351.
Anti-CRISPR (Acr) proteins encoded by (pro)phages/(pro)viruses have a great potential to enable a more controllable genome editing. However, genome mining new Acr proteins is challenging due to the lack of a conserved functional domain and the low sequence similarity among experimentally characterized Acr proteins. We introduce here AcrFinder, a web server (http://bcb.unl.edu/AcrFinder) that combines three well-accepted ideas used by previous experimental studies to pre-screen genomic data for Acr candidates. These ideas include homology search, guilt-by-association (GBA), and CRISPR-Cas self-targeting spacers. Compared to existing bioinformatics tools, AcrFinder has the following unique functions: (i) it is the first online server specifically mining genomes for Acr-Aca operons; (ii) it provides a most comprehensive Acr and Aca (Acr-associated regulator) database (populated by GBA-based Acr and Aca datasets); (iii) it combines homology-based, GBA-based, and self-targeting approaches in one software package; and (iv) it provides a user-friendly web interface to take both nucleotide and protein sequence files as inputs, and output a result page with graphic representation of the genomic contexts of Acr-Aca operons. The leave-one-out cross-validation on experimentally characterized Acr-Aca operons showed that AcrFinder had a 100% recall. AcrFinder will be a valuable web resource to help experimental microbiologists discover new Anti-CRISPRs.
抗 CRISPR (Acr) 蛋白由 (前)噬菌体/ (前)病毒编码，具有很大的潜力使基因组编辑更可控。然而，由于缺乏保守的功能结构域和实验鉴定的 Acr 蛋白之间的低序列相似性，因此对新的 Acr 蛋白进行基因组挖掘具有挑战性。我们在此引入 AcrFinder，这是一个网络服务器 (http://bcb.unl.edu/AcrFinder)，它结合了以前的实验研究中使用的三个被广泛接受的想法，用于在基因组数据中预筛选 Acr 候选物。这些想法包括同源搜索、关联有罪 (GBA) 和 CRISPR-Cas 自我靶向间隔子。与现有的生物信息学工具相比，AcrFinder 具有以下独特功能：(i) 它是第一个专门用于挖掘 Acr-Aca 操纵子基因组的在线服务器；(ii) 它提供了最全面的 Acr 和 Aca（Acr 相关调节剂）数据库（由基于 GBA 的 Acr 和 Aca 数据集填充）；(iii) 它将基于同源性、基于 GBA 的和自我靶向方法结合在一个软件包中；和 (iv) 它提供了一个用户友好的网络界面，可接受核苷酸和蛋白质序列文件作为输入，并输出带有 Acr-Aca 操纵子基因组上下文的图形表示的结果页面。在实验鉴定的 Acr-Aca 操纵子上进行的留一法交叉验证表明，AcrFinder 的召回率为 100%。AcrFinder 将成为实验微生物学家发现新的抗 CRISPR 的有价值的网络资源。
