Anti-CRISPRdb: a comprehensive online resource for anti-CRISPR proteins

Abstract

CRISPR-Cas is a tool that is widely used for gene editing. However, unexpected off-target effects may occur as a result of long-term nuclease activity. Anti-CRISPR proteins, which are powerful molecules that inhibit the CRISPR–Cas system, may have the potential to promote better utilization of the CRISPR-Cas system in gene editing, especially for gene therapy. Additionally, more in-depth research on these proteins would help researchers to better understand the co-evolution of bacteria and phages. Therefore, it is necessary to collect and integrate data on various types of anti-CRISPRs. Herein, data on these proteins were manually gathered through data screening of the literatures. Then, the first online resource, anti-CRISPRdb, was constructed for effectively organizing these proteins. It contains the available protein sequences, DNA sequences, coding regions, source organisms, taxonomy, virulence, protein interactors and their corresponding three-dimensional structures. Users can access our database at http://cefg.uestc.edu.cn/anti-CRISPRdb/ without registration. We believe that the anti-CRISPRdb can be used as a resource to facilitate research on anti-CRISPR proteins and in related fields.

CasLocusAnno: a web‐based server for annotating cas loci and their corresponding (sub)types

“…Therefore, the identification of cas loci and (sub)types can also help identify Acrs. Continuous works from scientific communities can enrich the overall number of Acr entries in public resources depending on emerging CRISPR‐Cas tools .…”

“…Therefore, the identification of cas loci and (sub)types can also help identify Acrs. Continuous works from scientific communities can enrich the overall number of Acr entries in public resources depending on emerging CRISPR-Cas tools [36,37]. Web-based servers [21,23] and standalone programs have been, in recent years, made available for CRISPR-Cas identification [22,35], nevertheless the constructed service and the developed standalone program can be still as complementary tools mainly because of the following reasons: Compared to other methods, CasLocusAnno facilitates selection of more reasonable Cas profile, because it chooses profiles with minimum e-values in each cluster.…”

Vast diversity of anti-CRISPR proteins predicted with a machine-learning approach

“…Our first step was therefore to assemble and quantify features that previously discovered Acrs appear to have in common. To keep track of the known Acrs, we relied on a combination of curated Acr databases 22,23 , and our own manual data curation ( Supplementary Table 1).…”

Machine Learning Predicts New Anti-CRISPR Proteins

“…To model the task of anti-CRISPR protein identification as a machine learning problem, a dataset consisting of examples from both positive (anti-CRISPR) and negative (non-anti-CRISPR) classes was needed. We collected anti-CRISPR information for proteins from the Anti-CRISPRdb (36). The database contained information for 432 anti-CRISPR proteins.…”

“…In this work, we have developed AcRanker, a machine learning model that accepts a proteome as input and ranks its constituent proteins in decreasing order of their expected Acr character. We have used EXtreme Gradient Boosting (XGBoost) based ranking (42) with 1, 2 and 3-mer amino acid composition as input features (38) to train on a dataset comprised of 20 experimentally verified Acrs taken from the anti-CRISPRdb (29,36) (Table S1) and their source proteomes. To evaluate the performance of AcRanker, we performed leave-one-out cross-validation as well as testing over an independent set of proteins.…”