A demonstration of DNA synthesis control at over 1000x higher density shows the path to large scale DNA data storage.
As global demand for digital storage capacity grows, storage technologies based on synthetic DNA have emerged as a dense and durable alternative to traditional media. Existing approaches leverage robust error correcting codes and precise molecular mechanisms to reliably retrieve specific files from large databases. Typically, files are retrieved using a pre-specified key, analogous to a filename. However, these approaches lack the ability to perform more complex computations over the stored data, such as similarity search: e.g., finding images that look similar to an image of interest without prior knowledge of their file names. Here we demonstrate a technique for executing similarity search over a DNA-based database of 1.6 million images. Queries are implemented as hybridization probes, and a key step in our approach was to learn an image-to-sequence encoding ensuring that queries preferentially bind to targets representing visually similar images. Experimental results show that our molecular implementation performs comparably to state-of-the-art in silico algorithms for similarity search.
DNA has emerged as an attractive medium for archival data storage due to its durability and high information density. Scalable parallel random access to information is a desirable property of any storage system. For DNA-based storage systems, however, this still needs to be robustly established. Here we report on a thermoconfined polymerase chain reaction, which enables multiplexed, repeated random access to compartmentalized DNA files. The strategy is based on localizing biotin-functionalized oligonucleotides inside thermoresponsive, semipermeable microcapsules. At low temperatures, microcapsules are permeable to enzymes, primers and amplified products, whereas at high temperatures, membrane collapse prevents molecular crosstalk during amplification. Our data show that the platform outperforms non-compartmentalized DNA storage compared with repeated random access and reduces amplification bias tenfold during multiplex polymerase chain reaction. Using fluorescent sorting, we also demonstrate sample pooling and data retrieval by microcapsule barcoding. Therefore, the thermoresponsive microcapsule technology offers a scalable, sequence-agnostic approach for repeated random access to archival DNA files.
Synthetic DNA has the potential to store the world’s continuously growing amount of data in an extremely dense and durable medium. Current proposals for DNA-based digital storage systems include the ability to retrieve individual files by their unique identifier, but not by their content. Here, we demonstrate content-based retrieval from a DNA database by learning a mapping from images to DNA sequences such that an encoded query image will retrieve visually similar images from the database via DNA hybridization. We encoded and synthesized a database of 1.6 million images and queried it with a variety of images, showing that each query retrieves a sample of the database containing visually similar images are retrieved at a rate much greater than chance. We compare our results with several algorithms for similarity search in electronic systems, and demonstrate that our molecular approach is competitive with state-of-the-art electronics.One Sentence SummaryLearned encodings enable content-based image similarity search from a database of 1.6 million images encoded in synthetic DNA.
With the rapidly decreasing cost of array-based oligo synthesis, large-scale oligo pools offer significant benefits for advanced applications including gene synthesis, CRISPR-based gene editing, and DNA data storage. The selective retrieval of specific oligos from these complex pools traditionally uses polymerase chain reaction (PCR). Designing a large number of primers to use in PCR presents a serious challenge, particularly for DNA data storage, where the size of an oligo pool is orders of magnitude larger than other applications. Although a nested primer address system was recently developed to increase the number of accessible files for DNA storage, it requires more complicated lab protocols and more expensive reagents to achieve high specificity, as well as more DNA address space. Here, we present a new combinatorial PCR method that has none of those drawbacks and outperforms in retrieval specificity. In experiments, we accessed three files that each comprised 1% of a DNA prototype database that contained 81 different files and enriched them to over 99.9% using our combinatorial primer method. Our method provides a viable path for scaling up DNA data storage systems and has broader utility whenever one must access a specific target oligo and can design their own primer regions.
Owing to its longevity and extremely high information density, DNA has emerged as an attractive medium for archival data storage. Scalable parallel random access of information is a desirable property of any storage system. For DNA-based storage systems, however, this yet has to be robustly established. Here we develop thermoconfined PCR, a novel method that enables multiplexed, repeated random access of compartmentalized DNA files. Our strategy is based on stable localization of biotin-functionalized oligonucleotides inside microcapsules with temperature-dependent membrane permeability. At low temperatures, microcapsules are permeable to enzymes, primers, and amplified products, while at high temperatures membrane collapse prevents molecular crosstalk during amplification. We demonstrate that our platform outperforms non-compartmentalized DNA storage with respect to repeated random access and reducing amplification bias during multiplex PCR. Using fluorescent sorting, we additionally demonstrate sample pooling and data retrieval by barcoding of microcapsules. Our thermoresponsive microcapsule technology offers a scalable, sequence-agnostic approach for repeated random access of archival DNA files.
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