据介绍，微生物系统是包括CRISPR在内的许多生物技术的基础，但序列数据库的指数增长使得很难找到以前未识别的系统。
研究人员开发了FLSHcluster算法，该算法在线性时间内对海量数据集进行深度聚类。研究人员将FLSHcluster纳入CRISPR发现管道，并鉴定了188个以前未报道的CRISPR连接基因模块，揭示了许多与适应性免疫相关的额外生化功能。研究人员对三个含有HNH核酸酶的CRISPR系统进行了实验表征，包括第一个具有特定干扰机制的IV型系统，并将其用于基因组编辑。研究人员还鉴定并表征了一个候选的VII型系统，并展示了它对RNA的作用。
总之，这项工作为利用CRISPR和更广泛地探索微生物蛋白质的巨大功能多样性开辟了新的途径。
附：英文原文
Title: Uncovering the functional diversity of rare CRISPR-Cas systems with deep terascale clustering
Author: Han Altae-Tran, Soumya Kannan, Anthony J. Suberski, Kepler S. Mears, F. Esra Demircioglu, Lukas Moeller, Selin Kocalar, Rachel Oshiro, Kira S. Makarova, Rhiannon K. Macrae, Eugene V. Koonin, Feng Zhang
Issue&Volume: 2023-11-24
Abstract: Microbial systems underpin many biotechnologies, including CRISPR, but the exponential growth of sequence databases makes it difficult to find previously unidentified systems. In this work, we develop the fast locality-sensitive hashing–based clustering (FLSHclust) algorithm, which performs deep clustering on massive datasets in linearithmic time. We incorporated FLSHclust into a CRISPR discovery pipeline and identified 188 previously unreported CRISPR-linked gene modules, revealing many additional biochemical functions coupled to adaptive immunity. We experimentally characterized three HNH nuclease–containing CRISPR systems, including the first type IV system with a specified interference mechanism, and engineered them for genome editing. We also identified and characterized a candidate type VII system, which we show acts on RNA. This work opens new avenues for harnessing CRISPR and for the broader exploration of the vast functional diversity of microbial proteins.
DOI: adi1910
Source: https://www.science.org/doi/10.1126/science.adi1910