Scalable design of orthogonal DNA barcode libraries

IF 12 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS Nature computational science Pub Date : 2024-06-07 DOI:10.1038/s43588-024-00646-z
Gokul Gowri, Kuanwei Sheng, Peng Yin
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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 mathematics1 to the problem of orthogonal sequence design. We demonstrate the scalability of seqwalk by designing a library of >106 SSM-satisfying barcode sequences in less than 20 s on a standard laptop. Seqwalk is a scalable method for designing orthogonal DNA barcode libraries, producing one million barcodes in 20 s on a standard laptop.

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可扩展的正交 DNA 条形码库设计。
正交 DNA 条形码文库设计是生物工程中的一项重要任务。在此,我们介绍一种高效的条形码文库设计方法 Seqwalk,该方法满足序列对称性最小化(SSM)启发式正交性要求,理论上保证了在特定设计约束条件下最大或接近最大的文库规模。Seqwalk 将 SSM 约束条件编码为序列空间的 de Bruijn 图表示法,从而将离散数学1 的最新进展应用于正交序列设计问题。我们在一台标准笔记本电脑上用不到 20 秒的时间就设计出了大于 106 个满足 SSM 的条形码序列库,证明了 seqwalk 的可扩展性。
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