Uncovering the functional diversity of rare CRISPR-Cas systems with deep terascale clustering-Reference-Cited by-全球学者库

Uncovering the functional diversity of rare CRISPR-Cas systems with deep terascale clustering

Published:2023-11-24 Issue:6673 Volume:382 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Altae-Tran Han¹²³⁴⁵^ORCID,Kannan Soumya¹²³⁴⁵^ORCID,Suberski Anthony J.¹²³⁴⁵,Mears Kepler S.¹²³⁴⁵,Demircioglu F. Esra¹²³⁴⁵^ORCID,Moeller Lukas¹²³⁴⁵^ORCID,Kocalar Selin¹²³⁴⁵^ORCID,Oshiro Rachel¹²³⁴⁵^ORCID,Makarova Kira S.⁶^ORCID,Macrae Rhiannon K.¹²³⁴⁵^ORCID,Koonin Eugene V.⁶^ORCID,Zhang Feng¹²³⁴⁵^ORCID

Affiliation:

1. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

2. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

3. McGovern Institute for Brain Research at MIT, Cambridge, MA 02139, USA.

4. Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

5. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

6. National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.adi1910

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