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- Title
Predicting base editing outcomes with an attention-based deep learning algorithm trained on high-throughput target library screens.
- Authors
Marquart, Kim F.; Allam, Ahmed; Janjuha, Sharan; Sintsova, Anna; Villiger, Lukas; Frey, Nina; Krauthammer, Michael; Schwank, Gerald
- Abstract
Base editors are chimeric ribonucleoprotein complexes consisting of a DNA-targeting CRISPR-Cas module and a single-stranded DNA deaminase. They enable transition of C•G into T•A base pairs and vice versa on genomic DNA. While base editors have great potential as genome editing tools for basic research and gene therapy, their application has been hampered by a broad variation in editing efficiencies on different genomic loci. Here we perform an extensive analysis of adenine- and cytosine base editors on a library of 28,294 lentivirally integrated genetic sequences and establish BE-DICT, an attention-based deep learning algorithm capable of predicting base editing outcomes with high accuracy. BE-DICT is a versatile tool that in principle can be trained on any novel base editor variant, facilitating the application of base editing for research and therapy. Base editors enable precise genetic alterations but vary in efficiency at different loci. Here the authors analyse ABEs and CBEs at over 28,000 integrated sequences to train BE-DICT, a machine learning model capable of predicting base editing outcomes.
- Subjects
DEEP learning; MACHINE learning; SINGLE-stranded DNA; BASE pairs; GENOME editing; ADENINE; CRISPRS
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-25375-z