CasPEDIA Database: A Functional Classification System for Class 2 CRISPR-Cas Enzymes

This is a Preprint and has not been peer reviewed. The published version of this Preprint is available: https://doi.org/10.1093/nar/gkad890. This is version 1 of this Preprint.

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Authors

Benjamin A Adler, Marena I Trinidad, Daniel Bellieny-Rabelo, Elaine Zhang, Hannah M Karp, Petr Skopintsev, Brittney Thornton, Rachel F Weissman, Peter H Yoon, Linxing Chen, Tomas Hessler, Amy R Eggers, David A Colognori, Ron Boger, Erin E Doherty, Connor A Tsuchida, Ryan V Tran, Laura Hofman, Honglue Shi, Kevin M Wasko, Zehan Zhou, Chenglong Xia, Muntathar Al-Shimary, Jaymin Patel, Vienna Thomas, Rithu Pattali, Matthew J Kan, Anna Vardapetyan, Alana Yang, Arushi Lahiri, Michaela F Maxwell, Andrew Murdock, Glenn Ramit, Hope R Henderson, Roland W Calvert, Rebecca S Bamert, Audrone Lapinaite, Patrick Pausch, Joshua C Cofsky, Erik J Sontheimer, Blake Wiedenheft, Peter C Fineran, Stan Brouns, Dipali Sashital, Brian C Thomas, Christopher T Brown, Daniela S Goltsman, Rodolphe Barrangou, Virginius Siksnys, Jillian F Banfield, David F Savage, Jennifer A Doudna

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.

DOI

https://doi.org/10.32942/X2C31F

Subjects

Biochemistry, Biophysics, and Structural Biology, Bioinformatics, Life Sciences

Keywords

CRISPR, Cas, Class 2, Enzyme, Database

Dates

Published: 2023-08-17 20:27

Last Updated: 2023-08-18 00:27

License

CC-By Attribution-ShareAlike 4.0 International

Additional Metadata

Language:
English

Conflict of interest statement:
The authors and their respective institutions have filed for patent protection for some of the technology discussed in this manuscript. C.A.T. and the Regents of the University of California have patents pending or issued related to the use of CRISPR genome editing technologies. The Regents of the University of California have patents pending for CRISPR technologies on which G.J.K. and P.P. are inventors. E.J.S. is a co-founder and scientific advisory board member of Intellia Therapeutics and a scientific advisory board member of Tessera Therapeutics. B.W. is the founder of SurGene LLC and VIRIS Detection Systems Inc. and is an inventor on patent applications related to CRISPR-Cas systems and applications thereof. P.C.F. is an inventor on patent applications related to CRISPR-Cas systems and applications thereof. B.C.T., C.T.B., and D.S.A.G. are employees of and receive salary from Metagenomi, Inc., and might own equity in Metagenomi Technologies, LLC. R.B. is a co-founder of Intellia Therapeutics, Locus Biosciences, Ancilia Biosciences and TreeCo and a shareholder of Caribou Biosciences, Inari Ag, Tune Therapeutics and CRISPR QC. V.S. is a chairman and co-founder of CasZyme. J.F.B. is a co-founder of Metagenomi, Inc. D.F.S. is a co-founder and scientific advisory board member of Scribe Therapeutics. The Regents of the University of California have patents issued and pending for CRISPR technologies on which J.A.D. is an inventor. J.A.D. is a co-founder of Caribou Biosciences, Editas Medicine, Scribe Therapeutics, Intellia Therapeutics, and Mammoth Biosciences. J.A.D. is a scientific advisory board member of Vertex, Caribou Biosciences, Intellia Therapeutics, Scribe Therapeutics, Mammoth Biosciences, Algen Biotechnologies, Felix Biosciences, The Column Group and Inari. J.A.D. is Chief Science Advisor to Sixth Street, a Director at Johnson & Johnson, Altos and Tempus, and has research projects sponsored by Apple Tree Partners and Roche. All other authors declare no competing interests.

Data and Code Availability Statement:
CasPEDIA is freely accessible at http://caspedia.org, and data is licensed under Creative Commons Attribution 4.0 International License (CC BY 4.0). The website is compatible with all devices, including tablets and mobile phones. A complete inventory of enzymes in CasPEDIA, along with CasID numbers, can be downloaded on the Tool Finder page. Text content for the wikis is available upon request, with more information provided on the Contact page of the website. Illustrations from CasPEDIA are available for non-commercial use under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0). Please credit "Innovative Genomics Institute, University of California, Berkeley."