Scalable design of orthogonal DNA barcode libraries.

Gowri, Gokul; Sheng, Kuanwei; Yin, Peng · Nat Comput Sci · 2024

basic_science · Level V

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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<sup>1</sup> to the problem of orthogonal sequence design. We demonstrate the scalability of seqwalk by designing a library of >10<sup>6</sup> SSM-satisfying barcode sequences in less than 20 s on a standard laptop.

Medical subject headings