In silico design of DNA sequences for in vivo nucleosome positioning
Routhier, E.; Pierre, E.; Joubert, A.; Lancrey, A.; Boule, J.-B.; Mozziconacci, J.
Show abstract
The computational design of synthetic DNA sequences with desired in vivo properties is gaining traction in the field of synthetic genomics. We propose here a computational method which combines a kinetic Monte Carlo framework with a deep mutational screening based on deep learning predictions. We apply our method to build regular nucleosome arrays with tailored nucleosomal repeat lengths (NRL) in yeast. Our design is validated in vivo by successfully engineering and integrating thousands of kilobases long tandem arrays of computationally optimized sequences which could accommodate NRLs much larger than the yeast natural NRL. This method delineates the key sequence rules for nucleosome positioning in yeast and is readily applicable to other sequence properties and other genomes.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Deciphering Multi-way Interactions in the Human Genome 94%
- Hi-C-LSTM: Learning representations of chromatin contacts using a recurrent neural network identifies genomic drivers of conformation 93%
- Higher resolution pooled genome-wide CRISPR knockout screening in Drosophila cells using integration and anti-CRISPR (IntAC) 93%
Similar papers in this journal
- Structural interplay between DNA-shape proteinrecognition and supercoiling: the case of IHF 93%
- Dissecting the binding mechanisms of transcription factors to DNA using a statistical thermodynamics framework. 92%
- Abasy Atlas v2.2: The most comprehensive and up-to-date inventory of meta-curated, historical, bacterial regulatory networks, their completeness and system-level characterization 92%
Similar papers in this journal
- Nucleosome positioning on large tandem DNA repeats of the '601' sequence engineered in Saccharomyces cerevisiae 97%
- Modular cloning of multigene vectors for the baculovirus system and yeast 93%
- The role of XPB/Ssl2 double-stranded DNA translocase processivity in transcription start-site scanning. 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.