Quantum biological insights into CRISPR-Cas9 sgRNA efficiency from explainable-AI driven feature engineering

Noshay, Jaclyn M.; Walker, Tyler; Alexander, William G.; Klingeman, Dawn M.; Romero, Jonathon; Walker, Angelica M.; Prates, Erica; Eckert, Carrie; Irle, Stephan; Kainer, David; Jacobson, Daniel A.

doi:10.1093/nar/gkad736

Quantum biological insights into CRISPR-Cas9 sgRNA efficiency from explainable-AI driven feature engineering

Journal Article · Wed Sep 20 00:00:00 EDT 2023 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkad736· OSTI ID:2004638

; Walker, Tyler; Alexander, William G.; Klingeman, Dawn M.; Romero, Jonathon; Walker, Angelica M.; Prates, Erica; Eckert, Carrie; Irle, Stephan; ;

Abstract

CRISPR-Cas9 tools have transformed genetic manipulation capabilities in the laboratory. Empirical rules-of-thumb have been developed for only a narrow range of model organisms, and mechanistic underpinnings for sgRNA efficiency remain poorly understood. This work establishes a novel feature set and new public resource, produced with quantum chemical tensors, for interpreting and predicting sgRNA efficiency. Feature engineering for sgRNA efficiency is performed using an explainable-artificial intelligence model: iterative Random Forest (iRF). By encoding quantitative attributes of position-specific sequences for Escherichia coli sgRNAs, we identify important traits for sgRNA design in bacterial species. Additionally, we show that expanding positional encoding to quantum descriptors of base-pair, dimer, trimer, and tetramer sequences captures intricate interactions in local and neighboring nucleotides of the target DNA. These features highlight variation in CRISPR-Cas9 sgRNA dynamics between E. coli and H. sapiens genomes. These novel encodings of sgRNAs enhance our understanding of the elaborate quantum biological processes involved in CRISPR-Cas9 machinery.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 2004638

Alternate ID(s):: OSTI ID: 2007740

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 19 Vol. 51; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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