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

CRISPR-Cas Systems / genetics Gene Editing Humans HEK293 Cells Cluster Analysis Algorithms CRISPR-Associated Proteins / chemistry DNA Cleavage RNA, Guide, CRISPR-Cas Systems Datasets as Topic Data Mining / methods

Journal

Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511

Informations de publication

Date de publication:
24 11 2023
Historique:
medline: 27 11 2023
pubmed: 23 11 2023
entrez: 23 11 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1126/science.adi1910 PMID: 37995242
pubmed: 37995242
doi: 10.1126/science.adi1910
doi:

Substances chimiques

CRISPR-Associated Proteins 0
RNA, Guide, CRISPR-Cas Systems 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

eadi1910

Auteurs

Han Altae-Tran (H)

Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
McGovern Institute for Brain Research at MIT, Cambridge, MA 02139, USA.
Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
ORCID: 0000-0003-1083-4802

Soumya Kannan (S)

Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
McGovern Institute for Brain Research at MIT, Cambridge, MA 02139, USA.
Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
ORCID: 0000-0002-7332-9662

Anthony J Suberski (AJ)

Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
McGovern Institute for Brain Research at MIT, Cambridge, MA 02139, USA.
Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Kepler S Mears (KS)

Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
McGovern Institute for Brain Research at MIT, Cambridge, MA 02139, USA.
Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

F Esra Demircioglu (FE)

Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
McGovern Institute for Brain Research at MIT, Cambridge, MA 02139, USA.
Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
ORCID: 0000-0002-3866-2742

Lukas Moeller (L)

Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
McGovern Institute for Brain Research at MIT, Cambridge, MA 02139, USA.
Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
ORCID: 0000-0002-4375-8837

Selin Kocalar (S)

Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
McGovern Institute for Brain Research at MIT, Cambridge, MA 02139, USA.
Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
ORCID: 0000-0003-4521-8647

Rachel Oshiro (R)

Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
McGovern Institute for Brain Research at MIT, Cambridge, MA 02139, USA.
Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
ORCID: 0000-0003-0948-6361

Kira S Makarova (KS)

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
ORCID: 0000-0002-8174-2844

Rhiannon K Macrae (RK)

Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
McGovern Institute for Brain Research at MIT, Cambridge, MA 02139, USA.
Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
ORCID: 0000-0002-7850-9056

Eugene V Koonin (EV)

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
ORCID: 0000-0003-3943-8299

Feng Zhang (F)

Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
McGovern Institute for Brain Research at MIT, Cambridge, MA 02139, USA.
Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
ORCID: 0000-0003-0178-7995

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Systèmes CRISPR-Cas › Uncovering the functional diversity of rare...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Édition de gène › Uncovering the functional diversity of rare...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Uncovering the functional diversity of rare...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Uncovering the functional diversity of rare...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de regroupements › Uncovering the functional diversity of rare...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Algorithmes › Uncovering the functional diversity of rare...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées aux CRISPR › Uncovering the functional diversity of rare...
questionsmedicales.fr › Phénomènes génétiques › Clivage de l'ADN › Uncovering the functional diversity of rare...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › Systèmes CRISPR-Cas, ARN, guide › Uncovering the functional diversity of rare...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Jeux de données comme sujet › Uncovering the functional diversity of rare...
questionsmedicales.fr › Sciences de l'information › Mémorisation et recherche des informations › Fouille de données › Uncovering the functional diversity of rare...