Abstract
Orthogonal DNA barcode library design is an essential task in bioengineering. Here we present seqwalk, an efficient method for designing barcode libraries that satisfy a sequence symmetry minimization (SSM) heuristic for orthogonality, with theoretical guarantees of maximal or near-maximal library size under certain design constraints. Seqwalk encodes SSM constraints in a de Bruijn graph representation of sequence space, enabling the application of recent advances in discrete mathematics(1) to the problem of orthogonal sequence design. We demonstrate the scalability of seqwalk by designing a library of >10(6) SSM-satisfying barcode sequences in less than 20 s on a standard laptop.