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)正在成为一种潜在的解决方案，以满足日益增长的数据存储需求。与硅基存储相比，DNA提供了更高的密度和数据寿命。携带数据的DNA可以储存在非生物环境中(体外)，也可以嵌入细菌或植物等活生物的DNA中(体内)。在体内，DNA数据存储得益于天然的保护壳和可靠且经济高效的数据复制方式。此外，体内存储与活细胞的兼容性为合成生物学算法的进步创造了潜力，合成生物学算法需要一种数据存储机制。该项目的目标是开发和展示一种体内DNA数据存储系统，该系统对测序和合成过程中以及由突变引起的错误具有弹性，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推动力：1)活DNA通道的特征；2)错误的缓解和纠正。众所周知，DNA存储中的错误是与上下文相关的，即它们依赖于序列的局部结构。为了实现差错控制，将建立活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关系。该项目将利用基因编辑技术的新进展，特别是CRISPR/CAS系统，通过实验来描述该频道的特征。第二个推力旨在克服现有差错控制技术的局限性，这些技术要么不能提供足够的差错保护，要么高度冗余。该项目将开发半约束编码技术，以限制具有高错误率的模式的频率，并开发用于消除错误的高错误率纠错方案。半约束和纠错方法将适应现场DNA通道，然后实施以评估其在实践中的表现并展示其优势。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.