Service Project: "CRISPR Bioinformatics"

服务项目：“CRISPR生物信息学”

• 批准号: 405939317
• 负责人: Professor Dr. Rolf Backofen
• 金额: --
• 依托单位: Lehrstuhl für Bioinformatik
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/405939317?language=en
• 关键词: Service; Project; CRISPR; Bioinformatics

Bioinformatics analysis has always played a key role in the history of the CRISPR-Cas system. The characteristic repetitive structure of CRISPR loci has been known since 1987 but it was only in 2005 when a computational analysis revealed that spacers could match bacteriophage genomes, leading to the later-confirmed hypothesis that the CRISPR-Cas system acts as an immune system. Bioinformatic approaches have always been instrumental in the detection of new functions and applications, one prominent example being the in-silico detection of endogenous targets of CRISPR-Cas systems which hinted towards endogenous regulatory mechanisms. The discovery of new and unusual CRISPR-Cas elements and functions by computational analyses, however, requires careful definition of the different standard elements of a CRISPR-Cas system. Only a precise and comprehensive classification can avoid the detection of too many false positives, which occur only due to an incomplete detection of all standard elements.Thus, we wish to support the experimental groups of the SPP 2141 in the detection of new functions for CRISPR-Cas systems by setting up a thorough classification of all the major elements of the CRISPR-Cas system. These classification tools will then be employed in the detection of novel elements and functions in collaboration with the aforementioned experimental groups. This will comprise new and comprehensive detection and classification approaches for: 1) CRISPR arrays and their associated elements such as protospacers and PAM; 2) Cas proteins and complete CRISPR-Cas systems in genomic and metagenomic data; and 3) CRISPR-related sRNAs like tracRNA and scaRNAs. We will use this information to search for CRISPR-Cas systems with unusual composition, such as orphan Cas proteins and CRISPR arrays. However we expect to find many other unusual compositions, especially within metagenomic data, which have not yet been screened for previously in any CRISPR-Cas systems so far. In addition, we will actively assist the experimental groups in the analysis of CRISPR-related NGS data.

生物信息学分析在CRISPR-CAS系统的历史上一直扮演着关键的角色。CRISPR基因座特有的重复结构从1987年就已为人所知，但直到2005年，一项计算分析才发现，间隔区可以与噬菌体基因组匹配，导致后来证实的假设，即CRISPR-Cas系统起到免疫系统的作用。生物信息学方法一直有助于检测新的功能和应用，其中一个突出的例子是对CRISPR-CAS系统内源性靶点的电子检测，这暗示了内源性调控机制。然而，通过计算分析发现新的和不寻常的CRISPR-CAS元素和功能，需要仔细定义CRISPR-CAS系统的不同标准元素。只有准确和全面的分类才能避免检测到太多的假阳性，而误阳性是由于对所有标准元素的不完全检测而造成的。因此，我们希望通过对CRISPR-CAS系统的所有主要元素建立彻底的分类，来支持SPP 2141的试验组对CRISPR-CAS系统的新功能进行检测。然后，这些分类工具将与上述实验小组合作，用于检测新的元素和功能。这将包括新的和全面的检测和分类方法：1)CRISPR阵列及其相关元件，如ProtSpacers和PAM；2)基因组和元基因组数据中的Cas蛋白和完整的CRISPR-Cas系统；以及3)与CRISPR相关的sRNA，如trRNA和scaRNAs。我们将使用这些信息来搜索具有不寻常组成的CRISPR-Cas系统，例如孤儿Cas蛋白和CRISPR阵列。然而，我们预计会发现许多其他不寻常的成分，特别是在元基因组数据中，到目前为止，这些成分还没有在任何CRISPR-CAS系统中进行筛选。此外，我们将积极协助试验组分析与CRISPR相关的NGS数据。