Reverse engineering DNA origami nanostructure designs from raw scaffold and staple sequence lists

Designs for scaffolded DNA origami nanostructures are commonly and minimally published as the list of DNA staple and scaffold sequences required. In nearly all cases, high-level editable design files (e.g. caDNAno) which generated the low-level sequences are not made available. This de facto 'raw sequence' exchange format allows published origami designs to be re-attempted in the laboratory by other groups, but effectively stops designs from being significantly modified or re-purposed for new future applications. To make the raw sequence exchange format more accessible to further design and engineering, in this work we propose the first algorithmic solution to the inverse problem of converting staple/scaffold sequences back to a 'guide schematic' resembling the original origami schematic. The guide schematic can be used to aid the manual re-input of an origami into a CAD tool like caDNAno, hence recovering a high-level editable design file. Creation of a guide schematic can also be used to double check that a list of staple strand sequences does not have errors and indeed does assemble into a desired origami nanostructure prior to costly laboratory experimentation. We tested our reverse algorithm on 36 diverse origami designs from the literature and found that 29 origamis (81 %) had a good quality guide sche-matic recovered from raw sequences. Our software is made available at https://revnano.readthedocs.io.

Automated summary

Designs for scaffolded DNA origami nanostructures are commonly published as lists of required DNA staple and scaffold sequences, but the high-level editable design files are often not made available. In this work, we propose an algorithmic solution to convert staple/scaffold sequences back to a guide schematic resembling the original origami schematic. This guide schematic can aid manual re-input of origami designs into CAD tools and ensure accurate assembly before costly laboratory experiments. Testing our algorithm on 36 origami designs, we successfully recovered high-quality guide schematics from raw sequences for 29 origamis (81%). Our software is available at https://revnano.readthedocs.io.