A Characterization of the DNA Data Storage Channel
Open accessAbstract
Owing to its longevity and enormous information density, DNA, the molecule encoding biological information, has emerged as a promising archival storage medium. However, due to technological constraints, data can only be written onto many short DNA molecules that are stored in an unordered way, and can only be read by sampling from this DNA pool. Moreover, imperfections in writing (synthesis), reading (sequencing), storage, and handling of the DNA, in particular amplification via PCR, lead to a loss of DNA molecules and induce errors within the molecules. In order to design DNA storage systems, a qualitative and quantitative understanding of the errors and the loss of molecules is crucial. In this paper, we characterize those error probabilities by analyzing data from our own experiments as well as from experiments of two different groups. We find that errors within molecules are mainly due to synthesis and sequencing, while imperfections in handling and storage lead to a significant loss of sequences. The aim of our study is to help guide the design of future DNA data storage systems by providing a quantitative and qualitative understanding of the DNA data storage channel.
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De novo synthesis of long sequences of DNA remains challenging, so sequences must be broken into smaller fragments of ∼200 bases, requiring massive numbers of unique DNA sequences.
“Because the de novo synthesis of long sequences of DNA remains challenging,20 these sequences must be broken into smaller fragments (∼200 bases), which requires massive numbers of unique DNA sequences to be made.”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [20]
It is likely unpractical to scale random access by PCR-based addressing indefinitely because of the difficulty of orthogonal primer design and the requirement for many amplification cycles given PCR bias.
“While this does not appear to be a hard limit,6 it is likely unpractical to scale random access by PCR-based addressing indefinitely because of the aforementioned difficulty of orthogonal primer design and the requirement for many amplification cycles given the associated impact of PCR bias.20”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [20]
Synthesis dominantly causes deletions at a final rate of around 0.2-1% per nucleotide.
“synthesis dominantly causes deletions (e.g., missing a base) at a final rate of around 0.2–1% per nt.”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [20]
Amplification and SBS-based platforms mainly introduce substitution errors.
“While amplification and SBS-based platforms mainly introduce substitution errors (reading a C instead of a G, for example),”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [20]
Insertions are uncommon and usually occur at less than 0.1% per nucleotide, mainly because of synthesis.
“Insertions (addition of extra bases) are uncommon and usually occur at less than 0.1% per nt, mainly because of synthesis.”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [20]
Increasing physical redundancy to cluster sequence information alleviates the problem of sequence loss and errors but is undesirable and inefficient because it drastically lowers information density.
“While an increase of physical redundancy to cluster sequence information alleviates this problem, doing so is undesirable and inefficient because it drastically lowers the information density.”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [20]
Storage mainly contributes to shifts in the copy number distribution of sequences, leading to unrecoverable loss of individual sequences over time, e.g., 8% after 94% of the DNA has decayed (four half-lives).
“storage mainly contributes to shifts in the copy number distribution of the sequences, which leads to the unrecoverable loss of individual sequences over time, e.g., 8% after 94% of the DNA has decayed (i.e., four half-lives).”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [20]
The nonideal yield was probably owing to incomplete deprotection and insufficient reaction between phosphoramidite and hydroxyl group, leading to deletion errors in DNA synthesis.
“The nonideal yield was probably owing to incomplete deprotection and the insufficient reaction between the phosphoramidite and the hydroxyl group, leading to deletion errors in the DNA synthesis (39).”
From Electrochemical DNA synthesis and sequencing on a single electrode with scalability for integrated data storage (2021) · cites this paper as [39]
Homopolymer can lead to low coupling efficiency in DNA synthesis, especially for G and C, and quantification of the number of identical nucleotides in DNA sequencing can also be problematic.
“The homopolymer can lead to low coupling efficiency in DNA synthesis (especially for G and C), and quantification of the number of identical nucleotides in DNA sequencing can also be problematic (39, 53).”
From Electrochemical DNA synthesis and sequencing on a single electrode with scalability for integrated data storage (2021) · cites this paper as [39]
As these errors stem from synthesis and subsequent PCR steps, the prevalence of these errors depends on synthesis technique and employed PCR enzymes.
“As these errors stem from synthesis and subsequent PCR steps, the prevalence of these errors depends on synthesis technique and employed PCR enzymes.[33]”
From Integrating DNA Encapsulates and Digital Microfluidics for Automated Data Storage in DNA (2022) · cites this paper as [33]
During synthesis of DNA, growing strands may be terminated before reaching desired length and thus induce a bias to the pool.
“During synthesis of DNA, growing strands may be terminated before having reached the desired length and thus induce a bias to the pool36,37.”
From DNA synthesis for true random number generation (2020) · cites this paper as [37]
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- Authors
- Heckel, R., Mikutis, G., & Grass, R. N.
- Affiliations
- Rice University (US)
- ETH Zurich (CH)
- Corresponding author
- Heckel, Reinhard
- Venue
- Scientific Reports
- Published
- 2019-07-04
- Volume
- 9
- Issue
- 1
- Pages
- 9663-9663
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6609604
- OpenAlex
- W2791679619
- Cited by
- 9
- References
- 41
- Citations by year
- 2023: 1 · 2021: 2 · 2020: 3 · 2019: 3
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- arXiv (Cornell University)
- ETH Zürich Research Collection (cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Biological Computing
- Physical Sciences › Computer Science › Computer Networks and Communications › Advanced Data Storage Technologies
- Physical Sciences › Computer Science › Artificial Intelligence › Algorithms and Data Compression
- Keywords
- DNA data storage, error probability, sequencing errors, archival storage, information density
- MeSH terms
- Algorithms, Diagnostic Tests, Routine, DNA, Humans, Research Design, Specimen Handling, Information Storage and Retrieval, Sequence Analysis, DNA, High-Throughput Nucleotide Sequencing
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