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Bioinformatics Discovery of Anti-CRISPR Operons in Human Gut Microbiome

人类肠道微生物组中抗 CRISPR 操纵子的生物信息学发现

基本信息

批准号：
10509691
负责人：
Yanbin Yin
金额：
$ 21.78万
依托单位：
UNIVERSITY OF NEBRASKA LINCOLN
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-07 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10509691
关键词：
Algorithms Animals Archaeal Genome Bacteria Bacteriophages Basic Science Bioinformatics Biotechnology Clustered Regularly Interspaced Short Palindromic Repeats Communicable Diseases Computer software Data Databases Development Engineering Enterococcus Family Frequencies Genes Genetic Transcription Genome Genome engineering Genomics Human Iceberg Immune Listeria Machine Learning Methods Microbe Mining Molecular Nature Nucleic Acid Sequence Homology Operon Paper Plants Prokaryotic Cells Prophages Protein Family Proteins Proviruses Pseudomonas PubMed Publishing Reporting Running Scanning Sequence Homology Site Software Tools System Technology Training Variant Viral Viral Genome Virus Work applied biomedical research base bioinformatics tool combat computer program data mining genome editing genome-wide gut microbiome inhibitor innovation markov model metagenome microbial new technology novel open source pathogenic bacteria programs success tool user-friendly virome web server web site

项目摘要

PROJECT SUMMARY Various bacterial CRISPR-Cas systems and their variants have been engineered and repurposed for gene editing in animals, plants, and microbes since 2013. However, the current CRISPR-Cas genome editing tools are not perfectly safe to use. This is primarily due to the lack of an effective brake system and the off-target effect that may create unwanted cuts in the genome. Different strategies are being developed to reduce off- target effect and make CRISPR-Cas safer to use. A fact often overshadowed by the great success of genome editing is that, in the microbial world, CRISPR-Cas is an adaptive anti-viral immune mechanism present in ~50% of bacterial and ~90% of archaeal genomes. As a counterstrategy, anti-CRISPRs are produced by viruses and proviruses, as an anti-anti-viral mechanism, to inhibit the CRISPR-Cas systems of their prokaryote hosts. Thus, as the naturally occurring inhibitors of CRISPR-Cas, anti-CRISPR (Acr) proteins have obvious advantages to be used for developing safer and more controllable CRISPR-Cas genome editing technologies. The objective of this project is to develop a genomic context-based tool (AOMiner) for bioinformatics data mining of new Acr operons in human gut microbiome and virome. The significances of this project include: (i) it will enhance the experimental characterization of new anti-CRISPRs, which is fundamental to the understanding of phage-host interactions, and further to the development of novel phage-based technologies to combat pathogenic bacteria and infectious diseases; (ii) it will deliver new open source computer programs and online databases to provide novel anti-CRISPR candidates to be exploited for building safer and more controllable CRISPR-Cas genome editing tools. We recently developed AcrFinder (http://bcb.unl.edu/AcrFinder/), a bioinformatics software package for automated discovery of Acr operons, primarily based on sequence homology search. However, its ability to identify new Acrs is limited because it is largely based on homology search. The innovation of this project is that AOMiner (http://bcb.unl.edu/AOMiner) will implement a genomic context-based algorithm focusing on discovery of new Acr operons instead of Acr proteins. Additionally, this project will be the first large-scale genome mining for Acrs operons from human gut microbiome and virome, which will be developed into a gutAO database (http://bcb.unl.edu/gutAO). In summary, this project will deliver a suite of bioinformatics software tools in the form of open-source computer programs and online databases to assist the characterization of novel anti-CRISPRs.

项目总结