Ontology highlight
ABSTRACT: Background
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.Results
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.Conclusions
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.
SUBMITTER: Zaslavskiy M
PROVIDER: S-EPMC4065607 | biostudies-literature | 2014 Jun
REPOSITORIES: biostudies-literature

Zaslavskiy Mikhail M Bertonati Claudia C Duchateau Philippe P Duclert Aymeric A Silva George H GH
BMC bioinformatics 20140617
<h4>Background</h4>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.<h4>Results</h4>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 wit ...[more]