CIF: NSF-BSF: Small: Collaborative Research: Characterization and Mitigation of Noise in a Live DNA Storage Channel

由于DNA合成和测序的最新进展，脱氧核糖核酸（DNA）正在成为日益增长的数据存储需求的潜在解决方案。与硅基存储相比，DNA提供了更高的密度和数据寿命。承载数据的DNA可以存储在非生物环境中（体外），也可以嵌入细菌或植物等活生物体的DNA中（体内）。体内DNA数据存储得益于天然的保护壳和可靠且经济高效的复制数据的方法。此外，体内存储与活细胞的兼容性为需要数据存储机制的合成生物学算法的进步创造了潜力。该项目的目标是开发和演示一种体内DNA数据存储系统，该系统能够适应测序和合成过程中出现的错误以及突变，同时实现最大可能的数据密度。为了实现其目标，该项目依赖于以下研究重点：1)活DNA通道的表征和2)错误缓解和纠正。众所周知，DNA存储中的错误依赖于上下文，即它们依赖于序列的局部结构。为了实现错误控制，将制定活DNA存储通道的数学模型，并将表征错误率对序列上下文的依赖性。该项目将利用基因编辑技术的新进展，特别是CRISPR/Cas系统，通过实验表征该通道。第二个重点是克服现有错误控制技术的局限性，这些技术要么不能提供足够的错误保护，要么是高度冗余的。该项目将开发半应变编码技术，用于限制高错误率模式的频率，以及用于对抗错误的高错误率纠错方案。将半应变和纠错方法应用于活DNA信道，并在实践中对其性能进行评价，以证明其优势。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Deoxyribonucleic acid (DNA) is emerging as a potential solution to growing data storage needs, due to recent advances in DNA synthesis and sequencing. Compared to silicon-based storage, DNA offers higher density and data longevity. Data-bearing DNA can be stored in non-biological environments (in vitro) or be embedded into the DNA of living organisms such as bacteria or plants (in vivo). In vivo DNA data storage benefits from a natural protective shell and a reliable and cost-efficient way to copy data. Furthermore, the compatibility of in vivo storage with living cells creates a potential for advances in synthetic-biology algorithms that require a mechanism for data storage. The goal of this project is to develop and demonstrate an in vivo DNA data storage system that is resilient to errors arising during sequencing and synthesis and from mutations, while achieving the maximum possible data density.To achieve its goal, the project relies on the following research thrusts: 1) Characterization of the live DNA channel and 2) Error mitigation and correction. Errors in DNA storage are known to be context-dependent, i.e., they depend on the local structure of the sequence. To enable error control, a mathematical model for the channel of live DNA storage will be formulated and the dependence of error rates on sequence context will be characterized. This project will take advantage of new advances in gene-editing technologies, in particular the CRISPR/Cas system, to characterize the channel through experiments. The second thrust aims to overcome the limitations of the existing error-control techniques, which either do not provide adequate error protection or are highly redundant. The project will develop semiconstrained-coding techniques for limiting the frequency of patterns with high error rates and high-rate error-correction schemes for combating errors. The semiconstrained and error-correction methods will be adapted to the live DNA channel and then implemented to evaluate their performance in practice and to demonstrate their advantages.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.