Deep learning and CRISPR-Cas13D ortholog discovery for optimized RNA targeting

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Abstract/Contents

Abstract
Effective mammalian transcriptome engineering technologies are needed to accelerate biological discovery and RNA therapeutics. Despite the promise of programmable CRISPR-Cas13 ribonucleases, their utility has been hampered by an incomplete understanding of guide RNA design rules and computational models for prediction of high efficiency guides. Here, we quantified the performance of 127,000 RfxCas13d (CasRx) guide RNAs and systematically evaluated seven machine learning models to build a guide efficiency prediction algorithm. I further validated the model across multiple genes and human cell types. Deep learning model interpretation revealed preferred sequence motifs and secondary features for highly efficient guides, elucidating CasRx targeting preferences and mechanisms.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2024; ©2024
Publication date 2024; 2024
Issuance monographic
Language English

Creators/Contributors

Author Wei, Jingyi, (Bioengineer)
Degree supervisor Konermann, Silvana
Thesis advisor Konermann, Silvana
Thesis advisor Bintu, Lacramioara
Thesis advisor Chang, Howard Y. (Howard Yuan-Hao), 1972-
Thesis advisor Quake, Stephen Ronald
Degree committee member Bintu, Lacramioara
Degree committee member Chang, Howard Y. (Howard Yuan-Hao), 1972-
Degree committee member Quake, Stephen Ronald
Associated with Stanford University, School of Engineering
Associated with Stanford University, Department of Bioengineering

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Jingyi Wei.
Note Submitted to the Department of Bioengineering.
Thesis Thesis Ph.D. Stanford University 2024.
Location https://purl.stanford.edu/cw868kk0098

Access conditions

Copyright
© 2024 by Jingyi Wei
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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