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Reading and writing digital data in DNA

Nature Protocols volume 15, pages 86–101 (2020)Cite this article

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Abstract

Because of its longevity and enormous information density, DNA is considered a promising data storage medium. In this work, we provide instructions for archiving digital information in the form of DNA and for subsequently retrieving it from the DNA. In principle, information can be represented in DNA by simply mapping the digital information to DNA and synthesizing it. However, imperfections in synthesis, sequencing, storage and handling of the DNA induce errors within the molecules, making error-free information storage challenging. The procedure discussed here enables error-free storage by protecting the information using error-correcting codes. Specifically, in this protocol, we provide the technical details and precise instructions for translating digital information to DNA sequences, physically handling the biomolecules, storing them and subsequently re-obtaining the information by sequencing the DNA. Along with the protocol, we provide computer code that automatically encodes digital information to DNA sequences and decodes the information back from DNA to a digital file. The required software is provided on a Github repository. The protocol relies on commercial DNA synthesis and DNA sequencing via Illumina dye sequencing, and requires 1–2 h of preparation time, 1/2 d for sequencing preparation and 2–4 h for data analysis. This protocol focuses on storage scales of ~100 kB to 15 MB, offering an ideal starting point for small experiments. It can be augmented to enable higher data volumes and random access to the data and also allows for future sequencing and synthesis technologies, by changing the parameters of the encoder/decoder to account for the corresponding error rates.

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Fig. 1: Process overview of DNA data storage.
Fig. 2: Reed–Solomon-based error-correcting coding scheme from file to DNA.
Fig. 3: Sequencing preparation scheme from synthesized DNA to DNA ready for Illumina sequencing with quality control.

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Data and code availability

Supplementary Software containing the code version used in the protocol, together with all test data and documentation, can be found in the following GitHub and Figshare repositories: https://github.com/reinhardh/dna_rs_coding and https://doi.org/10.6084/m9.figshare.c.4546937.

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Acknowledgements

We thank ICB/ETH Zurich for funding and the Beat Christen Group at ETH for giving access to the iSeq 100 sequencer.

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Authors and Affiliations

  1. Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland

    Linda C. Meiser, Philipp L. Antkowiak, Julian Koch, Weida D. Chen, A. Xavier Kohll, Wendelin J. Stark & Robert N. Grass

  2. Department of Electrical and Computer Engineering, Rice University, Houston, TX, USA

    Reinhard Heckel

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Contributions

R.N.G. initiated and supervised the project with input from W.J.S. R.H. designed and developed the code and coding scheme. P.L.A. and J.K. performed the experiments. A.X.K., W.D.C. and L.C.M. prepared illustrations. L.C.M., R.H. and R.N.G. wrote the manuscript with input and approval from all authors.

Corresponding authors

Correspondence to Reinhard Heckel or Robert N. Grass.

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Competing interests

The authors declare no competing interests.

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Related links

Key references using this protocol

Grass, R. et al. Angew. Chem. Int. Ed. 54, 2552–2555 (2015): https://doi.org/10.1002/anie.201411378

Chen, W. et al. Adv. Funct. Mater. 29, 1–8 (2019): https://doi.org/10.1002/adfm.201901672

Heckel, R. et al. Sci. Rep. 9, 9663 (2019): https://doi.org/10.1038/s41598-019-45832-6

Supplementary information

Supplementary Manual

README file. Description of coding scheme with additional explanations of coding parameters and examples for how to utilize the code. Additionally, code installation instructions are given for Windows, Linux, and macOS.

Reporting Summary

Supplementary Software

Error-correcting code (C++). Error-correcting scheme for storing information in DNA using Reed–Solomon codes.

Supplementary Data 1

Coding parameters. File to aid parameter selection by choosing redundancy, file size, number of sequences to be synthesized, and the sequence.

Supplementary Data 2

Files to be encoded. Sample file to be encoded as an illustrative example of the protocol’s procedure. Here the first five protocols published in Nature Protocols were chosen.

Supplementary Data 3

The output of the decoder using Supplementary Data 2 as input, executed on a macOS operating system with default parameters as given in the Anticipated results (K = 32, N = 34, l = 4, nuss = 12, n = 12,472, k = 9,000, resulting in sequences of length 102 nt each).

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Meiser, L.C., Antkowiak, P.L., Koch, J. et al. Reading and writing digital data in DNA. Nat Protoc 15, 86–101 (2020). https://doi.org/10.1038/s41596-019-0244-5

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