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Ledidi: Designing genomic edits that induce functional activity

Jacob Schreiber, Yang Young Lu, William Stafford Noble
doi: https://doi.org/10.1101/2020.05.21.109686
Jacob Schreiber
1Department of Genome Science, University of Washington, Seattle, USA
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Yang Young Lu
1Department of Genome Science, University of Washington, Seattle, USA
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William Stafford Noble
1Department of Genome Science, University of Washington, Seattle, USA
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  • For correspondence: william-noble@uw.edu
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Abstract

The development of modern genome editing tools has enabled researchers to make edits with high precision, but has left unsolved the problem of designing these edits. We propose Ledidi, an approach that treats the design of genomic edits as an optimization problem where the goal is to produce the desired output from a predictive model. The discrete nature of biological sequences makes direct optimization challenging, but we overcome this by using the Gumbel-Softmax reparameterization trick. We validate Ledidi by pairing it with the Basenji model, which makes predictions for thousands of functional profiles, and designing edits that affect CTCF binding and induce cell type-specific binding of JUND.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 25, 2020.
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Ledidi: Designing genomic edits that induce functional activity
Jacob Schreiber, Yang Young Lu, William Stafford Noble
bioRxiv 2020.05.21.109686; doi: https://doi.org/10.1101/2020.05.21.109686
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Ledidi: Designing genomic edits that induce functional activity
Jacob Schreiber, Yang Young Lu, William Stafford Noble
bioRxiv 2020.05.21.109686; doi: https://doi.org/10.1101/2020.05.21.109686

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