CasPEDIA Database: a functional classification system for class 2 CRISPR-Cas enzymes

Benjamin A Adler^{1

2}, Marena I Trinidad^{1

3}, Daniel Bellieny-Rabelo^{1

2}, Elaine Zhang^{1

3}, Hannah M Karp^{1

4}, Petr Skopintsev^{1

2}, Brittney W Thornton^{1

5}, Rachel F Weissman^{1

5}, Peter H Yoon^{1

5}, LinXing Chen^{1

6}, Tomas Hessler^{1

6

7

8}, Amy R Eggers^{1

5}, David Colognori^{1

5}, Ron Boger^{1

2}, Erin E Doherty^{1

2}, Connor A Tsuchida^{1

9}, Ryan V Tran⁴, Laura Hofman^{1

2

10}, Honglue Shi^{1

3}, Kevin M Wasko^{1

5}, Zehan Zhou^{1

5}, Chenglong Xia^{1

2}, Muntathar J Al-Shimary^{1

5}, Jaymin R Patel¹, Vienna C J X Thomas^{1

4}, Rithu Pattali^{1

5}, Matthew J Kan^{1

11}, Anna Vardapetyan¹, Alana Yang^{1

5}, Arushi Lahiri⁵, Micaela F Maxwell¹², Andrew G Murdock¹, Glenn C Ramit¹, Hope R Henderson¹, Roland W Calvert¹³, Rebecca S Bamert¹³, Gavin J Knott¹³, Audrone Lapinaite^{14

15

16}, Patrick Pausch¹⁷, Joshua C Cofsky¹⁸, Erik J Sontheimer^{19

20

21}, Blake Wiedenheft²², Peter C Fineran^{23

24

25

26}, Stan J J Brouns^{27

28}, Dipali G Sashital²⁹, Brian C Thomas³⁰, Christopher T Brown³⁰, Daniela S A Goltsman³⁰, Rodolphe Barrangou^{1

31}, Virginius Siksnys³², Jillian F Banfield^{1

6

7

8

33}, David F Savage^{1

3

5}, Jennifer A Doudna^{1

2

3

4

5

34

35}

Affiliations

¹ Innovative Genomics Institute, University of California, Berkeley, CA 94720, USA.
² California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720, USA.
³ Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
⁴ Department of Chemistry, University of California, Berkeley, CA 94720, USA.
⁵ Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
⁶ Department of Earth and Planetary Sciences, University of California, Berkeley, CA 94720, USA.
⁷ Department of Environmental Science, Policy, and Management, University of California, Berkeley, CA 94720, USA.
⁸ EGSB Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
⁹ University of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.
¹⁰ Graduate School of Life Sciences, Utrecht University, 3584 CS Utrecht, UT, The Netherlands.
¹¹ Department of Pediatrics, Division of Allergy, Immunology, and Bone Marrow Transplantation, University of California, San Francisco, CA 94158, USA.
¹² Department of Chemistry and Biochemistry, Hampton University, Hampton, VA 23668, USA.
¹³ Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3168, Australia.
¹⁴ School of Molecular Sciences, Arizona State University, Tempe, AZ 85281, USA.
¹⁵ Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA.
¹⁶ Center for Molecular Design and Biomimetics, The Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA.
¹⁷ LSC-EMBL Partnership Institute for Genome Editing Technologies, Life Sciences Center, Vilnius University, Vilnius 10257, Lithuania.
¹⁸ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
¹⁹ RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
²⁰ Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
²¹ Li Weibo Institute for Rare Diseases Research, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
²² Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA.
²³ Department of Microbiology and Immunology, University of Otago, Dunedin 9016, New Zealand.
²⁴ Genetics Otago, University of Otago, Dunedin 9016, New Zealand.
²⁵ Bioprotection Aotearoa, University of Otago, Dunedin 9016, New Zealand.
²⁶ Maurice Wilkins Centre for Molecular Biodiscovery, University of Otago, Dunedin 9016, New Zealand.
²⁷ Department of Bionanoscience, Delft University of Technology, 2629 HZ Delft, Netherlands.
²⁸ Kavli Institute of Nanoscience, 2629 HZ Delft, The Netherlands.
²⁹ Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
³⁰ Metagenomi, Inc., Emeryville, CA 94608, USA.
³¹ Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, NC 27606, USA.
³² Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius 10257, Lithuania.
³³ The University of Melbourne, Parkville, VIC 3052, Australia.
³⁴ MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
³⁵ Gladstone Institutes, University of California, San Francisco, CA 94158, USA.

PMID: 37889041
PMCID: PMC10767948
DOI: 10.1093/nar/gkad890

CasPEDIA Database: a functional classification system for class 2 CRISPR-Cas enzymes

Benjamin A Adler et al. Nucleic Acids Res. 2024.

. 2024 Jan 5;52(D1):D590-D596.

doi: 10.1093/nar/gkad890.

Authors

Affiliations

¹ Innovative Genomics Institute, University of California, Berkeley, CA 94720, USA.
² California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720, USA.
³ Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
⁴ Department of Chemistry, University of California, Berkeley, CA 94720, USA.
⁵ Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
⁶ Department of Earth and Planetary Sciences, University of California, Berkeley, CA 94720, USA.
⁷ Department of Environmental Science, Policy, and Management, University of California, Berkeley, CA 94720, USA.
⁸ EGSB Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
⁹ University of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.
¹⁰ Graduate School of Life Sciences, Utrecht University, 3584 CS Utrecht, UT, The Netherlands.
¹¹ Department of Pediatrics, Division of Allergy, Immunology, and Bone Marrow Transplantation, University of California, San Francisco, CA 94158, USA.
¹² Department of Chemistry and Biochemistry, Hampton University, Hampton, VA 23668, USA.
¹³ Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3168, Australia.
¹⁴ School of Molecular Sciences, Arizona State University, Tempe, AZ 85281, USA.
¹⁵ Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA.
¹⁶ Center for Molecular Design and Biomimetics, The Biodesign Institute, Arizona State University, Tempe, AZ 85281, USA.
¹⁷ LSC-EMBL Partnership Institute for Genome Editing Technologies, Life Sciences Center, Vilnius University, Vilnius 10257, Lithuania.
¹⁸ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
¹⁹ RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
²⁰ Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
²¹ Li Weibo Institute for Rare Diseases Research, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
²² Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA.
²³ Department of Microbiology and Immunology, University of Otago, Dunedin 9016, New Zealand.
²⁴ Genetics Otago, University of Otago, Dunedin 9016, New Zealand.
²⁵ Bioprotection Aotearoa, University of Otago, Dunedin 9016, New Zealand.
²⁶ Maurice Wilkins Centre for Molecular Biodiscovery, University of Otago, Dunedin 9016, New Zealand.
²⁷ Department of Bionanoscience, Delft University of Technology, 2629 HZ Delft, Netherlands.
²⁸ Kavli Institute of Nanoscience, 2629 HZ Delft, The Netherlands.
²⁹ Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
³⁰ Metagenomi, Inc., Emeryville, CA 94608, USA.
³¹ Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, NC 27606, USA.
³² Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius 10257, Lithuania.
³³ The University of Melbourne, Parkville, VIC 3052, Australia.
³⁴ MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
³⁵ Gladstone Institutes, University of California, San Francisco, CA 94158, USA.

PMID: 37889041
PMCID: PMC10767948
DOI: 10.1093/nar/gkad890

Erratum in

Correction to 'CasPEDIA Database: a functional classification system for class 2 CRISPR-Cas enzymes'.
[No authors listed] [No authors listed] Nucleic Acids Res. 2024 Jan 25;52(2):1002. doi: 10.1093/nar/gkad1228. Nucleic Acids Res. 2024. PMID: 38109298 Free PMC article. No abstract available.

Abstract

CRISPR-Cas enzymes enable RNA-guided bacterial immunity and are widely used for biotechnological applications including genome editing. In particular, the Class 2 CRISPR-associated enzymes (Cas9, Cas12 and Cas13 families), have been deployed for numerous research, clinical and agricultural applications. However, the immense genetic and biochemical diversity of these proteins in the public domain poses a barrier for researchers seeking to leverage their activities. We present CasPEDIA (http://caspedia.org), the Cas Protein Effector Database of Information and Assessment, a curated encyclopedia that integrates enzymatic classification for hundreds of different Cas enzymes across 27 phylogenetic groups spanning the Cas9, Cas12 and Cas13 families, as well as evolutionarily related IscB and TnpB proteins. All enzymes in CasPEDIA were annotated with a standard workflow based on their primary nuclease activity, target requirements and guide-RNA design constraints. Our functional classification scheme, CasID, is described alongside current phylogenetic classification, allowing users to search related orthologs by enzymatic function and sequence similarity. CasPEDIA is a comprehensive data portal that summarizes and contextualizes enzymatic properties of widely used Cas enzymes, equipping users with valuable resources to foster biotechnological development. CasPEDIA complements phylogenetic Cas nomenclature and enables researchers to leverage the multi-faceted nucleic-acid targeting rules of diverse Class 2 Cas enzymes.

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Figures

**Figure 1.**
CasID enzymatic labels for biotechnologically important Cas enzymes. Examples are shown for (A) SpyCas9a (1.1.1), (B) Cas9d (2.1.1), (C) AsCas12a (3.4.3), (D) UnCas12c2 (5.4.2), (E) LbuCas13a (6.5.3), (F) PspCas13b (6.2.3). For a complete description and list of CasID values and their definition, please refer to http://caspedia.org/.

**Figure 2.**
Overview of CasPEDIA Entry for SpyCas9a (1.1.1) from the database. (A) CasID diagram and functional description. (B) Resources for accessing native sequences and gRNA design for the Cas enzyme. (C) Functional and phylogenetic classification of SpyCas9 (CasID 1.1.1). (D) Biological properties of this Cas enzyme, including protein, gene and gRNA properties. (E) Overview of the Cas enzyme including a summary of the enzyme, applications, experimental considerations, protein structure and gene browser (below the visualized portion). (F) Link to homepage containing CasID Definitions and search bar, accommodating queries for Cas enzymes by CasID, protein name or protein family. (G) Icon for Tool Finder, where users can search CasPEDIA for enzymes with specific properties. (H) Redirects to Cas Phylogeny page for browsing the website by protein family. (I) Tool Glossary of common CRISPR-Cas systems. (J) Contact Page. (K) FAQ and general information.

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References

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CasPEDIA Database: a functional classification system for class 2 CRISPR-Cas enzymes

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CasPEDIA Database: a functional classification system for class 2 CRISPR-Cas enzymes

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