Open Access Open Badges Methodology article

Efficient design of meganucleases using a machine learning approach

Mikhail Zaslavskiy, Claudia Bertonati, Philippe Duchateau*, Aymeric Duclert and George H Silva

Author Affiliations

Research and Development department, Cellectis, 8 rue de la Croix Jarry, Paris 75013, France

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BMC Bioinformatics 2014, 15:191  doi:10.1186/1471-2105-15-191

Published: 17 June 2014



Meganucleases are important tools for genome engineering, providing an efficient way to generate DNA double-strand breaks at specific loci of interest. Numerous experimental efforts, ranging from in vivo selection to in silico modeling, have been made to re-engineer meganucleases to target relevant DNA sequences.


Here we present a novel in silico method for designing custom meganucleases that is based on the use of a machine learning approach. We compared it with existing in silico physical models and high-throughput experimental screening. The machine learning model was used to successfully predict active meganucleases for 53 new DNA targets.


This new method shows competitive performance compared with state-of-the-art in silico physical models, with up to a fourfold increase in terms of the design success rate. Compared to experimental high-throughput screening methods, it reduces the number of screening experiments needed by a factor of more than 100 without affecting final performance.