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Random access DNA memory using Boolean search in an archival file storage system
Open accessPublished version of a preprint
Abstract
DNA is an ultrahigh-density storage medium that could meet exponentially growing worldwide demand for archival data storage if DNA synthesis costs declined sufficiently and if random access of files within exabyte-to-yottabyte-scale DNA data pools were feasible. Here, we demonstrate a path to overcome the second barrier by encapsulating data-encoding DNA file sequences within impervious silica capsules that are surface labelled with single-stranded DNA barcodes. Barcodes are chosen to represent file metadata, enabling selection of sets of files with Boolean logic directly, without use of amplification. We demonstrate random access of image files from a prototypical 2-kilobyte image database using fluorescence sorting with selection sensitivity of one in 106 files, which thereby enables one in 106N selection capability using N optical channels. Our strategy thereby offers a scalable concept for random access of archival files in large-scale molecular datasets. Silica beads encapsulating DNA information and functionalized with DNA labels create an alternative DNA data storage system, where direct random access and data retrieval are enabled by complementary fluorescent strands that identify beads for separation in fluorescence-activated sorting.
Overview
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Written from the paper’s full text.
TL;DR
The paper demonstrates a random-access DNA archival file system that encapsulates DNA-encoded image files in silica capsules surface-labeled with ssDNA barcodes, enabling Boolean search and fluorescence-activated sorting without PCR amplification. It retrieves files from a 20-image proof-of-concept database with selection sensitivity of 1 in 10^6 files per channel and shows AND/OR/NOT queries.
Key findings
- Encapsulated 20 image files, each ~0.1 kB encoded in a 3,000-base-pair plasmid, within 6-µm silica particles labeled with up to three 25-mer ssDNA barcodes chosen from 240,000 orthogonal primers, allowing up to ~10^15 possible distinct files using three barcodes per file.
- Demonstrated direct random access by fluorescence-activated sorting without amplification: single-file selection sensitivity of 1 in 10^6 files, scaling to 1 in 10^6N with N optical channels; 60–95% of Airplane files sorted into the flying gate.
- Implemented Boolean AND, OR, and NOT queries, including president AND (NOT 18th century) and dog AND wild, with sequencing validation; selected single files could be transformed, amplified, and re-encapsulated for a write-store-access-read cycle.
- Estimated 10^6 plasmids per capsule and 10^8 barcodes per file; the data pool contained at least ~10^6 copies of each file; proof-of-concept search rate was ~1 kB per second, with a theoretical ~1 GB per second if data per capsule were increased, or ~15 days to search 1 PB.
Methods
- Proof-of-principle file system: 20 26 × 26-pixel black-and-white icon images were run-length encoded, converted to DNA, cloned into pUC19-based plasmids, amplified in bacteria, and validated by sequencing.
- Encapsulation and barcoding: plasmid DNA was condensed on fluorescein-core 5-µm silica particles, encapsulated with TMAPS/TEOS, surface-functionalized, and conjugated to 25-mer ssDNA barcodes representing metadata; files were pooled at ~2.0 mg/mL in 10 mL saline TAE buffer.
- Selection and readout: fluorescently labeled complementary probes hybridized to barcodes; FAS was performed on a BD FACSAria III with sorting gates; DNA was released using buffered oxide etch and sequenced with Illumina MiniSeq/MiSeq; sort probability/enrichment was calculated as the count for a file in a fraction divided by the sum of counts for that file across all fractions.
Limitations
- Stated: silica encapsulation lowers overall data storage density compared with bare DNA memory; encapsulation and barcoding latency is currently days and may limit archival use unless reduced to hours or less; FAS retrieval scales linearly with pool size, with proof-of-concept sorting rate ~1 kB per second; unprotected DNA barcodes and linkers are susceptible to hydrolysis and require periodic renewal or protection; sort probabilities were typically below 100%, with possible contamination or random FAS errors, though repeated selection cycles may mitigate this.
- Evident from the text: the demonstration is limited to 20 icon-resolution 26 × 26 black-and-white images and a small proof-of-concept pool, not exabyte- or yottabyte-scale storage; scalability depends on high-throughput silica encapsulation and surface DNA labeling that were not demonstrated here.
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22 Own result · 19 Not checked yet · 10 Own interpretation · 8 Own method · 7 No basis given · 1 Partly supported · 1 Couldn’t confirm · accuracy not yet measured
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In the paper
“We also demonstrate Boolean AND, OR, NOT logic to select arbitrary subsets of files with combinations of distinct barcodes to query the data pool, similar to conventional Boolean logic applied in text and file searches on solid-state silicon devices.”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
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In the paper
“Using hybridization assays with fluorescently-labelled probes35–37, we estimated the number of barcodes available for hybridization on each file to be on the order of 108 (Supplementary Fig. 7).”
§ Random access DNA memory using Boolean search in an archival file storage system > File Synthesis
What the sources say
- Not checked yetcites [35] Pillai, P. P., Reisewitz, S., Schroeder, H. & Niemeyer, C. M. Quantum-dot-encoded silica nanospheres for nucleic acid hybridization. Small 6, 2130–2134 (2010). source
- Not checked yetcites [36] Leidner, A. et al. Biopebbles: DNA-functionalized core–shell silica nanospheres for cellular uptake and cell guidance studies. Adv. Funct. Mater. 28, 1707572 (2018). source
- Not checked yetcites [37] Sun, P. et al. Biopebble containers: DNA-directed surface assembly of mesoporous silica nanoparticles for cell studies. Small 15, 1900083 (2019). source
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In the paper
“Quantitative PCR (qPCR) of the reaction supernatant after encapsulation (Supplementary Fig. 4) showed full encapsulation of plasmids without residual DNA in solution.”
§ Random access DNA memory using Boolean search in an archival file storage system > File Synthesis
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In the paper
“We were able to detect and select the desired Airplane file through FAS even at a relative abundance of 10−6 compared with each other file (Fig. 3c).”
§ Random access DNA memory using Boolean search in an archival file storage system > File Selection
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In the paper
“Notably, the sizes of bare, hydroxy-terminated silica particles representing capsules without barcodes were comparable with complete files consisting of capsules with barcodes attached, confirmed using scanning electron microscopy (Fig. 2d and 2e, left).”
§ Random access DNA memory using Boolean search in an archival file storage system > File Synthesis
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In the paper
“Using qPCR to measure released DNA after de-encapsulation, we estimated 106 plasmids per capsule (Supplementary Fig. 5 and Supplementary Table 3).”
§ Random access DNA memory using Boolean search in an archival file storage system > File Synthesis
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In the paper
“The data pool contains at least ~106 copies of each file based on the mass of silica used during encapsulation (Supplementary Section 5).”
§ Random access DNA memory using Boolean search in an archival file storage system > File Synthesis
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In the paper
“In cases where single images were selected (Figs. 4c, 5a), we were able to transform competent bacteria from each search query that resulted in a single file (Supplementary Fig. 27).”
§ Random access DNA memory using Boolean search in an archival file storage system > Boolean Search
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In the paper
“Release of the encapsulated file sequence and subsequent sequencing of each gated population from the dog versus wild 2D plot validated sorting (Fig. 5b, right; Supplementary Fig. 26).”
§ Random access DNA memory using Boolean search in an archival file storage system > Boolean Search
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In the paper
“We introduced a direct random access molecular file system for the retrieval of arbitrary files and file-subsets from an archival DNA data store.”
§ Random access DNA memory using Boolean search in an archival file storage system > Discussion & Outlook
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- Probably not a substantial claim. 22
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In the paper
“Demonstrations of its viability as a general information storage medium include the storage and retrieval of books, images, computer programs, audio clips, works of art, and Shakespeare’s sonnets using a variety of encoding schemes6–12, with data size limited primarily by the cost of DNA synthesis.”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
What the sources say
- Not checked yetcites [6] Church, G. M., Gao, Y. & Kosuri, S. Next-generation digital information storage in DNA. Science 337, 1628–1628 (2012). source
- Partly supportedcites [7] Goldman, N. et al. Towards practical, high-capacity, low-maintenance information storage in synthesized DNA. Nature 494, 77–80 (2013). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [8] Yazdi, S. M. H. T., Yuan, Y., Ma, J., Zhao, H. & Milenkovic, O. A rewritable, random-access DNA-based storage system. Sci. Rep. 5, 14138 (2015). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked yetcites [9] Grass, R. N., Heckel, R., Puddu, M., Paunescu, D. & Stark, W. J. Robust chemical preservation of digital information on DNA in silica with error-correcting codes. Angew. Chem. Int. Ed. 54, 2552–2555 (2015). source
- Partly supportedcites [10] Yazdi, S. M. H. T., Gabrys, R. & Milenkovic, O. Portable and error-free DNA-based data storage. Sci. Rep. 7, 5011 (2017). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [11] Erlich, Y. & Zielinski, D. DNA Fountain enables a robust and efficient storage architecture. Science 355, 950–954 (2017). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [12] Organick, L. et al. Random access in large-scale DNA data storage. Nat. Biotechnol. 36, 242–248 (2018). sourceExperimental — accuracy not yet measured
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The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Finally, avoiding spurious amplification of off-target files due to crosstalk of PCR primers with incorrect barcodes or main file sequences requires careful primer design20.”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
What the sources say
- Could not verifycites [20] Xu, Q., Schlabach, M. R., Hannon, G. J. & Elledge, S. J. Design of 240,000 orthogonal 25mer DNA barcode probes. Proc. Natl Acad. Sci. USA 106, 2289–2294 (2009). sourceExperimental — accuracy not yet measured
The paper’s introduction (p. 1) mentions PCR as a step in barcode-based screening, and its Results (p. 1) describe designing barcode probes to minimize cross-hybridization. Neither passage addresses PCR primer crosstalk with incorrect barcodes or file sequences, or spurious amplification of off-target files; searches for those terms found no such discussion. (LLM, conf=0.76)
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In the paper
“To realize this file system, we first encapsulate DNA-based files physically within discrete, impervious silica capsules9,23,24, which we subsequently surface-label with unique single-stranded DNA barcodes that offer Boolean logic based selection on the entire data pool via simple hybridization.”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
What the sources say
- Not checked yetcites [9] Grass, R. N., Heckel, R., Puddu, M., Paunescu, D. & Stark, W. J. Robust chemical preservation of digital information on DNA in silica with error-correcting codes. Angew. Chem. Int. Ed. 54, 2552–2555 (2015). source
- Not checked yetcites [23] Paunescu, D., Puddu, M., Soellner, J. O. B., Stoessel, P. R. & Grass, R. N. Reversible DNA encapsulation in silica to produce ROS-resistant and heat-resistant synthetic DNA ‘fossils’. Nat. Protoc. 8, 2440–2448 (2013). source
- Not checked yetcites [24] Paunescu, D., Fuhrer, R. & Grass, R. N. Protection and deprotection of DNA—high-temperature stability of nucleic acid barcodes for polymer labeling. Angew. Chem. Int. Ed. 52, 4269–4272 (2013). source
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In the paper
“As an alternative to PCR-based approaches, here we introduce a direct random access memory approach that retrieves specific files, or arbitrary subsets of files, directly using physical sorting, without a need for amplification, and without any potential for barcode-memory crosstalk, while also preserving non-selected files intact by recycling them into the original memory pool.”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
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- The authors state this as an assumption: DNA synthesis costs will decline sufficiently for DNA storage to meet exponentially growing worldwide demand for archival data storage.
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In the paper
“We also observed systematic shifts in the surface charge of the silica particles as different functional groups were introduced onto their surfaces (Fig. 2e).”
§ Random access DNA memory using Boolean search in an archival file storage system > File Synthesis
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In the paper
“Digital information in the form of 20 icon-resolution images was stored in a data pool, with each image encoded into DNA and synthesized on a plasmid.”
§ Random access DNA memory using Boolean search in an archival file storage system > File Synthesis
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In the paper
“All capsules synthesized in the presence of both DNA and TO-PRO showed a distinct fluorescence signal, consistent with the presence of plasmid DNA in the majority of capsules, compared with a silica particle negative control that contained no DNA.”
§ Random access DNA memory using Boolean search in an archival file storage system > File Synthesis
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In the paper
“To demonstrate the feasibility of performing Boolean search using more than three fluorescence channels for sorting, we also selected the Wolf file from the data pool using the query dog AND wild, and used the black & white probe to validate the selected file (Fig. 5b, left).”
§ Random access DNA memory using Boolean search in an archival file storage system > Boolean Search
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In the paper
“Besides single file selection, our approach allows for repeated rounds of FAS selection, as well as Boolean logic, described below.”
§ Random access DNA memory using Boolean search in an archival file storage system > File Selection
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In the paper
“To demonstrate a NOT query, we added to the data pool an AFDye 647-labelled ssDNA probe that hybridized to files that contained the cat barcode. Files that did not show AFDye 647 signal were sorted into the NOT cat subset (Fig. 4a, Supplementary Fig. 14a).”
§ Random access DNA memory using Boolean search in an archival file storage system > Boolean Search
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In the paper
“For example, in our proof-of-concept system, data reconstruction was successful with 100 copies of a file (Figure 3 and Supplementary Figure 13), so that our file size of 0.1 kB and search rate of 1,000 files per second yield a final sorting rate of only ~1 kB per second.”
§ Random access DNA memory using Boolean search in an archival file storage system > Discussion & Outlook
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In the paper
“We note that the internal agitator in the flow cytometer with a 300 rpm agitation speed was not sufficient to prevent the silica particles from sedimenting over time”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Fluorescence-activated sorting.
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In the paper
“We found that performing sorting at a flow rate that exceeds this events rate clogged the FAS instrument intermittently.”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Fluorescence-activated sorting.
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“we found that periodically agitating the sample tube every 5 minutes with a vortex mixer was more effective.”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Fluorescence-activated sorting.
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In the paper
“Recent progress in nucleic acid synthesis and sequencing technologies continue to reduce the cost of writing and reading DNA, foreshadowing future commercially competitive DNA-based information storage1,3–5.”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
What the sources say
- Not checked yetcites [1] Zhirnov, V., Zadegan, R. M., Sandhu, G. S., Church, G. M. & Hughes, W. L. Nucleic acid memory. Nat. Mater. 15, 366–370 (2016). source
- Not checked yetcites [3] Kosuri, S. & Church, G. M. Large-scale de novo DNA synthesis: technologies and applications. Nat. Methods 11, 499–507 (2014). source
- Not checked yetcites [4] Palluk, S. et al. De novo DNA synthesis using polymerase-nucleotide conjugates. Nat. Biotechnol. 36, 645–650 (2018). source
- Not checked yetcites [5] Lee, H. H., Kalhor, R., Goela, N., Bolot, J. & Church, G. M. Terminator-free template-independent enzymatic DNA synthesis for digital information storage. Nat. Commun. 10, 2383 (2019). source
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In the paper
“While DNA is the polymer selected by evolution for the storage and transmission of genetic information in biology, it can also be used for the storage of arbitrary digital information at densities far exceeding conventional data storage technologies such as flash and tape memory, at scales well beyond the capacity of the largest existing data centers1,2.”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
What the sources say
- Not checked yetcites [1] Zhirnov, V., Zadegan, R. M., Sandhu, G. S., Church, G. M. & Hughes, W. L. Nucleic acid memory. Nat. Mater. 15, 366–370 (2016). source
- Not checked yetcites [2] Ceze, L., Nivala, J. & Strauss, K. Molecular digital data storage using DNA. Nat. Rev. Genet. 20, 456–466 (2019). source
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In the paper
“To date, molecular random access has largely relied on conventional polymerase chain reaction (PCR)8,10,12,13, which uses up to ~20–30 heating and cooling cycles with DNA polymerase to selectively amplify specific DNA sequences from a DNA data pool using primers.”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
What the sources say
- Not checked yetcites [8] Yazdi, S. M. H. T., Yuan, Y., Ma, J., Zhao, H. & Milenkovic, O. A rewritable, random-access DNA-based storage system. Sci. Rep. 5, 14138 (2015). source
- Not checked yetcites [10] Yazdi, S. M. H. T., Gabrys, R. & Milenkovic, O. Portable and error-free DNA-based data storage. Sci. Rep. 7, 5011 (2017). source
- Not checked yetcites [12] Organick, L. et al. Random access in large-scale DNA data storage. Nat. Biotechnol. 36, 242–248 (2018). source
- Not checked yetcites [13] Ranu, N., Villani, A.-C., Hacohen, N. & Blainey, P. C. Targeting individual cells by barcode in pooled sequence libraries. Nucleic Acids Res. 47, e4 (2018). source
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In the paper
“Nested addressing barcodes14–16 have also been used to uniquely identify a greater number of files, as well as biochemical affinity tags to selectively pull down oligos for targeted amplification17.”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
What the sources say
- Not checked yetcites [14] Kashiwamura, S., Yamamoto, M., Kameda, A., Shiba, T. & Ohuchi, A. Hierarchical DNA memory based on nested PCR. In 8th International Workshop on DNA-Based Computers (DNA8) (eds Hagiya, M. & Ohuchi, A.) 112–123 (Springer, 2003). source
- Not checked yetcites [15] Yamamoto, M., Kashiwamura, S., Ohuchi, A. & Furukawa, M. Large-scale DNA memory based on the nested PCR. Nat. Comput. 7, 335–346 (2008). source
- Not checked yetcites [16] Yamamoto, M., Kashiwamura, S. & Ohuchi, A. DNA memory with 16.8M addresses. In 13th International Meeting on DNA Computing (DNA13) (eds Garzon, M. H. & Yan, H.) 99–108 (Springer, 2008). source
- Not checked yetcites [17] Tomek, K. J. et al. Driving the scalability of DNA-based information storage systems. ACS Synth. Biol. 8, 1241–1248 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, for an exabyte-scale data pool, each file requires at least three barcodes17, or up to sixty nucleotides in total barcode sequence length, thereby reducing the number of nucleotides that can be used for data encoding.”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
What the sources say
- Not checked yetcites [17] Tomek, K. J. et al. Driving the scalability of DNA-based information storage systems. ACS Synth. Biol. 8, 1241–1248 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Because physical encapsulation separates file sequences from external barcodes that are used to describe the encapsulated information, our file system offers long-term environmental protection of encoded file sequences via silica encapsulation for permanent archival storage9,23,24, where external barcodes may be renewed periodically, further protected with secondary encapsulation, or data pools”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
What the sources say
- Not checked yetcites [9] Grass, R. N., Heckel, R., Puddu, M., Paunescu, D. & Stark, W. J. Robust chemical preservation of digital information on DNA in silica with error-correcting codes. Angew. Chem. Int. Ed. 54, 2552–2555 (2015). source
- Not checked yetcites [23] Paunescu, D., Puddu, M., Soellner, J. O. B., Stoessel, P. R. & Grass, R. N. Reversible DNA encapsulation in silica to produce ROS-resistant and heat-resistant synthetic DNA ‘fossils’. Nat. Protoc. 8, 2440–2448 (2013). source
- Not checked yetcites [24] Paunescu, D., Fuhrer, R. & Grass, R. N. Protection and deprotection of DNA—high-temperature stability of nucleic acid barcodes for polymer labeling. Angew. Chem. Int. Ed. 52, 4269–4272 (2013). source
- Not checked yetcites [21] Newman, S. et al. High density DNA data storage library via dehydration with digital microfluidic retrieval. Nat. Commun. 10, 1706 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Second, PCR-based retrieval requires an aliquot of the entire data pool to be irreversibly consumed for random access, and therefore additional PCR amplification of the entire data pool may periodically be needed to restore this loss of data.”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
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In the paper
“While strategies exist to circumvent these preceding challenges, they generally reduce data density and might not be easily scalable to exabyte and larger file-systems.”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“While only twenty icon-resolution images were chosen as our image database, representing diverse subject matter including animals, plants, transportation, and buildings (Supplementary Fig. 1), our file system may in principle be scaled to considerably larger sets of images, limited primarily by the cost of DNA synthesis and the need to develop strategies for high-throughput silica encapsulation of”
§ Random access DNA memory using Boolean search in an archival file storage system > INTRODUCTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- The authors state this as an assumption: DNA synthesis costs will decline sufficiently for DNA storage to meet exponentially growing worldwide demand for archival data storage.
In the paper
“While comparable in sensitivity to a nested PCR barcoding data indexing approach17, unlike PCR that requires 20–30 of rounds of heating and cooling to selectively amplify the selected sequence, our approach selects files directly without need for thermal cycling and amplification.”
§ Random access DNA memory using Boolean search in an archival file storage system > File Selection
What the sources say
- Not checked yetcites [17] Tomek, K. J. et al. Driving the scalability of DNA-based information storage systems. ACS Synth. Biol. 8, 1241–1248 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Because encapsulation of the DNA file sequence relies only on electrostatic interactions between positively-charged silica and the phosphate backbone of DNA, our approach can equally encapsulate any molecular weight of DNA molecule applicable to MB and larger file sizes, as demonstrated previously23, and is compatible with alternative DNA file compositions such as 100–200-mer oligonucleotides that”
§ Random access DNA memory using Boolean search in an archival file storage system > File Synthesis
What the sources say
- Not checked yetcites [23] Paunescu, D., Puddu, M., Soellner, J. O. B., Stoessel, P. R. & Grass, R. N. Reversible DNA encapsulation in silica to produce ROS-resistant and heat-resistant synthetic DNA ‘fossils’. Nat. Protoc. 8, 2440–2448 (2013). source
- Not checked yetcites [2] Ceze, L., Nivala, J. & Strauss, K. Molecular digital data storage using DNA. Nat. Rev. Genet. 20, 456–466 (2019). source
- Not checked yetcites [6] Church, G. M., Gao, Y. & Kosuri, S. Next-generation digital information storage in DNA. Science 337, 1628–1628 (2012). source
- Not checked yetcites [7] Goldman, N. et al. Towards practical, high-capacity, low-maintenance information storage in synthesized DNA. Nature 494, 77–80 (2013). source
- Not checked yetcites [11] Erlich, Y. & Zielinski, D. DNA Fountain enables a robust and efficient storage architecture. Science 355, 950–954 (2017). source
- Not checked yetcites [12] Organick, L. et al. Random access in large-scale DNA data storage. Nat. Biotechnol. 36, 242–248 (2018). source
- Not checked yetcites [17] Tomek, K. J. et al. Driving the scalability of DNA-based information storage systems. ACS Synth. Biol. 8, 1241–1248 (2019). source
- Not checked yetcites [34] Chen, W. D. et al. Combining data longevity with high storage capacity—layer-by-layer DNA encapsulated in magnetic nanoparticles. Adv. Funct. Mater. 29, 1901672 (2019). source
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: Encapsulation of the DNA file sequence relies only on electrostatic interactions between positively-charged silica and the phosphate backbone of DNA.
None of the sources cited for this claim have been checked yet.
In the paper
“This strategy also applies to gating of N barcodes simultaneously in parallel optical channels, which offers file selection sensitivity of 1 in 106N total files, where common commercial FAS systems offer up to N = 17 channels38,39.”
§ Random access DNA memory using Boolean search in an archival file storage system > File Selection
What the sources say
- Not checked yetcites [38] Perfetto, S. P., Chattopadhyay, P. K. & Roederer, M. Seventeen-colour flow cytometry: unravelling the immune system. Nat. Rev. Immunol. 4, 648–655 (2004). source
- Not checked yetcites [39] Chattopadhyay, P. K. et al. Quantum dot semiconductor nanocrystals for immunophenotyping by polychromatic flow cytometry. Nat. Med. 12, 972–977 (2006). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Amplified material was pure and ready for re-encapsulation into silica particles, which could be re-introduced directly back into the data pool and thereby represents a complete write-store-access-read cycle that in principle may be applied larger-scale datasets, with periodic renewal of single-stranded DNA barcodes and bacterial replication of DNA data following reading25–27.”
§ Random access DNA memory using Boolean search in an archival file storage system > Boolean Search
What the sources say
- Not checked yetcites [25] Farzadfard, F. et al. Single-nucleotide-resolution computing and memory in living cells. Mol. Cell 75, 769–780.E4 (2019). source
- Not checked yetcites [26] Farzadfard, F. & Lu, T. K. Genomically encoded analog memory with precise in vivo DNA writing in living cell populations. Science 346, 1256272 (2014). source
- Not checked yetcites [27] Farzadfard, F. & Lu, T. K. Emerging applications for DNA writers and molecular recorders. Science 361, 870–875 (2018). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, in a practical implementation of our file system, only the selected files must be restored via amplification, encapsulation, and barcoding, because files that are not selected can be returned to the data pool immediately following FAS.”
§ Random access DNA memory using Boolean search in an archival file storage system > Boolean Search
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Our file system overcomes several challenges associated with pre-existing PCR-based file systems, including obviating the need for numerous heating and cooling cycles and enzymatic synthesis, and eliminating non-specific crosstalk between file sequences and barcodes17,19,21, while enabling arbitrary Boolean logical search queries.”
§ Random access DNA memory using Boolean search in an archival file storage system > Discussion & Outlook
What the sources say
- Not checked yetcites [17] Tomek, K. J. et al. Driving the scalability of DNA-based information storage systems. ACS Synth. Biol. 8, 1241–1248 (2019). source
- Not checked yetcites [19] Chen, Y.-J. et al. Quantifying molecular bias in DNA data storage. Nat. Commun. 11, 3264 (2020). source
- Not checked yetcites [21] Newman, S. et al. High density DNA data storage library via dehydration with digital microfluidic retrieval. Nat. Commun. 10, 1706 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“First, while our file system supports theoretical storage densities that are orders of magnitude higher than archival file storage systems based on hard disk, magnetic tape, or similar archival media1,40 commonly used today, silica encapsulation of DNA file sequences lowers overall data storage density compared with bare DNA memory (Supplementary Section 6).”
§ Random access DNA memory using Boolean search in an archival file storage system > Discussion & Outlook
What the sources say
- Not checked yetcites [1] Zhirnov, V., Zadegan, R. M., Sandhu, G. S., Church, G. M. & Hughes, W. L. Nucleic acid memory. Nat. Mater. 15, 366–370 (2016). source
- Not checked yetcites [40] Fontana, R. E.Jr & Decad, G. M. Moore’s law realities for recording systems and memory storage components: HDD, tape, NAND, and optical. AIP Adv. 8, 056506 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, because our proof-of-concept system did not make use of the vast majority of DNA stored in each capsule, the data stored in each capsule can in theory be significantly increased to yield a search rate of ~1 GB per second, or ~15 days to search through 1 PB of data (Supplementary Section 10).”
§ Random access DNA memory using Boolean search in an archival file storage system > Discussion & Outlook
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, because our system is not limited to synthetic DNA, it also applies to compact and energy-efficient long-term archival storage of bacterial, human, and other genomes for archival sample preservation and retrieval.”
§ Random access DNA memory using Boolean search in an archival file storage system > Discussion & Outlook
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
- Rests on an assumption: The file system is not limited to synthetic DNA.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“PCR bias was checked by qPCR (Supplementary Fig. 3).”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Generating file sequences.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Each master primer and hash barcode pairs were verified by PCR and agarose gel analysis”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Generating file sequences.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Finally, while DNA file protection by silica encapsulation offers millennium-scale protection and storage9 of the encapsulated file, unprotected DNA barcodes and their covalent linkers are susceptible to hydrolysis and will therefore require either periodic renewal or additional protection, as noted at the outset of this article.”
§ Random access DNA memory using Boolean search in an archival file storage system > Discussion & Outlook
What the sources say
- Not checked yetcites [9] Grass, R. N., Heckel, R., Puddu, M., Paunescu, D. & Stark, W. J. Robust chemical preservation of digital information on DNA in silica with error-correcting codes. Angew. Chem. Int. Ed. 54, 2552–2555 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Unprotected DNA barcodes and their covalent linkers are susceptible to hydrolysis.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Generated DNA sequences were ordered as custom genes synthesized, cloned, sequenced, and validated by Integrated DNA Technologies into pUC19-based vector.”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Generating file sequences.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The final sequence was checked for problematic subsequences, specifically, GGGG, CCCC, AAAAA, TTTTT, and the restriction enzyme recognition sites GAATTC and CTGCAG. If any of these subsequences were found outside of expected occurrences in the constant flanking regions, the entire sequence was regenerated with a new random seed until no such subsequences appeared.”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Generating file sequences.
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasmid preparations were verified by PCR, Sanger sequencing, and short-read sequencing using Illumina MiniSeq for quality control (Supplementary Fig. 3).”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Generating file sequences.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The latency times associated with file selection and recovery of DNA from files renders our file system ideally suited to archival data storage in which data are written once, stored for decades or longer, and accessed rarely, file protection by silica encapsulation offers millennium-scale storage9 of immutable data, such as astronomical image databases48, high-energy physics datasets49, or high”
§ Random access DNA memory using Boolean search in an archival file storage system > Discussion & Outlook
What the sources say
- Not checked yetcites [9] Grass, R. N., Heckel, R., Puddu, M., Paunescu, D. & Stark, W. J. Robust chemical preservation of digital information on DNA in silica with error-correcting codes. Angew. Chem. Int. Ed. 54, 2552–2555 (2015). source
- Not checked yetcites [48] Broekema, P. C., van Nieuwpoort, R. V. & Bal, H. E. In Proceedings of the 2012 Workshop on High-Performance Computing for Astronomy Date 9–16 (Association for Computing Machinery, 2012).
- Not checked yetcites [49] Gaillard, M. & Pandolfi, S. CERN Data Centre passes the 200-petabyte milestone. CERN https://cds.cern.ch/record/2276551 (2017).
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“all particles were gated by default using the ‘FITC’ laser and detector settings, which is defined by gating the majority population in the ‘FITC-A’ channel histogram, in addition to standard FSC and SSC gates to minimize sorting of doublets”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Fluorescence-activated sorting.
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“As also noted there, similar to PCR-based approaches, barcodes can be protected by dehydrating the data pool or immersing files in hydrophobic liquids21.”
§ Random access DNA memory using Boolean search in an archival file storage system > Discussion & Outlook
What the sources say
- Not checked yetcites [21] Newman, S. et al. High density DNA data storage library via dehydration with digital microfluidic retrieval. Nat. Commun. 10, 1706 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The sequence containing image hash, seed, and image encoding, was additionally flanked on the 5’ and 3’ ends by sequences (5′-CGTCGTCGTCCCCTCAAACT-3′ and 5′-GCTGAAAAGGTGGCATCAAT-3′, respectively) that allow amplification from a “master primer” pair that would amplify every sequence in the molecular plasmid database”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Generating file sequences.
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Samples were filtered through a Corning® 70-µm cell strainer (Fisher Scientific; catalog number: 07–201-431) prior to particle sorts.”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Fluorescence-activated sorting.
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The authors state this as an assumption.
DNA synthesis costs will decline sufficiently for DNA storage to meet exponentially growing worldwide demand for archival data storage.
“DNA is an ultra-high-density storage medium that could meet exponentially growing worldwide demand for archival data storage if DNA synthesis costs declined sufficiently and random access of files within exabyte-to-yottabyte-scale DNA data pools were feasible.”
The paper relies on this without support.
FAS scales linearly with the size of the data pool.
“Third, retrieval time is currently limiting for our system in an exabyte-scale data pool because FAS scales linearly with the size of the pool.”
The paper relies on this without support.
Unprotected DNA barcodes and their covalent linkers are susceptible to hydrolysis.
“unprotected DNA barcodes and their covalent linkers are susceptible to hydrolysis and will therefore require either periodic renewal or additional protection”
The paper relies on this without support.
Encapsulation of the DNA file sequence relies only on electrostatic interactions between positively-charged silica and the phosphate backbone of DNA.
“Because encapsulation of the DNA file sequence relies only on electrostatic interactions between positively-charged silica and the phosphate backbone of DNA, our approach can equally encapsulate any molecular weight of DNA molecule applicable to MB and larger file sizes”
The paper relies on this without support.
The file system is not limited to synthetic DNA.
“Finally, because our system is not limited to synthetic DNA, it also applies to compact and energy-efficient long-term archival storage of bacterial, human, and other genomes for archival sample preservation and retrieval.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“First, the incorporation of random-access priming regions into each oligo decreases the available space for data-encoding bases, thereby also decreasing the storage density (currently by about 15% per address region).71,75”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [75]
Experimental — accuracy not yet measuredIn the citing paper
“Second, PCR-based random access irreversibly removes oligos from the pool, which necessitates potentially lossy reamplification of the entire pool after repeated data retrieval.75,76”
From Emerging Approaches to DNA Data Storage: Challenges and Prospects (2022) · cites this paper as [75]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Random access DNA memory using Boolean search in an archival file storage system > File Synthesis
“Condensation of 3-aminopropyltriethoxysilane with the hydroxy-terminated surface of the encapsulated plasmid DNA provided a primary amine chemical handle”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > DNA encapsulation.
“A volume of 20 µL of 2-aminopropyltriethoxysilane (Millipore Sigma; catalog number: 440140), was then added”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Querying molecular file database using fluorescently-labelled probes.
“| 1:1 | 500 [a] | 0 |”
§ Random access DNA memory using Boolean search in an archival file storage system > Methods > Querying molecular file database using fluorescently-labelled probes.
“| Ratio of Airplane:19other files | Volume of Airplane stocksolution [µL] | Volume of stock solution of 19 other files[µL] [a] |”
Citations
Cites
Next-Generation Digital Information Storage in DNA
Church, G. M., Gao, Y., & Kosuri, S. (2012) · Science · doi:10.1126/science.1226355 · Cited by 1,441
Towards Practical, High-Capacity, Low-Maintenance Information Storage in Synthesized DNA
Goldman, N., Bertone, P., Chen, S., Dessimoz, C., LeProust, E. M., Sipos, B., & Birney, E. (2013) · Nature · doi:10.1038/nature11875 · Cited by 1,220
cGAS in action: Expanding roles in immunity and inflammation
Ablasser, A., & Chen, Z. J. (2019) · Science · doi:10.1126/science.aat8657 · Cited by 1,077
Seventeen-colour flow cytometry: unravelling the immune system
Perfetto, S. P., Chattopadhyay, P. K., & Roederer, M. (2004) · Nature Reviews Immunology · doi:10.1038/nri1416 · Cited by 1,019
DNA Fountain enables a robust and efficient storage architecture
Erlich, Y., & Zielinski, D. (2017) · Science · doi:10.1126/science.aaj2038 · Cited by 898
Large-scale de novo DNA synthesis: technologies and applications
Kosuri, S., & Church, G. M. (2014) · Nature Methods · doi:10.1038/nmeth.2918 · Cited by 869
Random access in large-scale DNA data storage
Organick, L., Ang, S. D., Chen, Y.-J., Lopez, R., Yekhanin, S., Makarychev, K., Racz, M. Z., Kamath, G., Gopalan, P., Nguyen, B., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4079 · Cited by 775
Robust Chemical Preservation of Digital Information on DNA in Silica with Error-Correcting Codes
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Metadata
- Authors
- Banal, J. L., Shepherd, T. R., Berleant, J., Huang, H., Reyes, M., Ackerman, C. M., Blainey, P. C., & Bathe, M.
- Affiliations
- Massachusetts Institute of Technology (US)
- Broad Institute (US)
- Corresponding author
- Bathe, Mark
- ORCID
- Venue
- Nature Materials
- Published
- 2021-06-10
- Volume
- 20
- Issue
- 9
- Pages
- 1272-1280
- ISSN
- 1476-1122 (ISSN-L)
- 1476-4660
- PMC
- PMC8564878
- OpenAlex
- W3168942844
- Semantic Scholar
- 083dd616930e4422e552abc9463db66be0db32df
- Cited by
- 143
- References
- 60
- Citations by year
- 2026: 18 · 2025: 34 · 2024: 32 · 2023: 31 · 2022: 20 · 2021: 6
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Materials (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- United States Department of Defense | United States Navy | Office of Naval Research (N00014-17-1-2609, N00014-12-1-0621, N00014-18-1-2290)
- National Science Foundation (CCF-1564025, CCF-1956054, CBET-1729397, Grant # 1122374)
- United States Department of Defense | United States Army | U.S. Army Research, Development and Engineering Command | Army Research Office (W911NF-19-2-0026)
- U.S. Department of Health & Human Services | National Institutes of Health (F32CA236425)
- Burroughs Wellcome Fund
- Topics
- Physical Sciences › Mathematics › Theoretical Computer Science › DNA and Biological Computing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Physical Sciences › Computer Science › Computer Networks and Communications › Advanced Data Storage Technologies
- Keywords
- DNA data storage, Boolean search, DNA barcodes, data archiving, DNA synthesis, molecular databases
- MeSH terms
- Archives, DNA, Fluorescence, Plasmids, Silicon Dioxide, Polymerase Chain Reaction, Information Storage and Retrieval, Synthetic Biology
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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