Application of Biomolecular Computing to Medical Science: A Biomolecular Database System for Storage, Processing, and Retrieval of Genetic Information and Material

A key problem in medical science and genomics is that of the efficient storage, processing, and retrieval of genetic information and material. This chapter presents an architecture for a Biomolecular Database system that would provide a unique capability in genomics. It completely bypasses the usual transformation from biological material (genomic DNA and transcribed RNA) to digital media, as done in conventional bioinformatics. Instead, biotechnology techniques provide the needed capability of a Biomolecular Database system without ever transferring the biological information into digital media. The inputs to the system are DNA obtained from tissues: either genomic DNA, or reverse-transcript cDNA. The input DNA is then tagged with artificially synthesized DNA strands. These “information tags” encode essential information (e.g., identification of the DNA donor, as well as the date of the sample, gender, and date of birth) about the individual or cell type that the DNA was obtained from. The resulting Biomolecular Database is capable of containing a vast store of genomic DNA obtained from many individuals (multiple army divisions, etc.). For example, the DNA of a million individuals requires about 6 pedabits (6 × 1015 bits), but due to the compactness of DNA a volume the size of a conventional test tube with a few milliliters of solution could contain that entire Biomolecular Database. Known procedures for amplification and reproduction of the resulting Biomolecular Database are discussed. The Biomolecular Database system has the capability of retrieval of subsets of stored genetic material, which are specified by associative queries on the tags and/or the attached genomic DNA strands, as well as logical selection queries on the tags of the database. We describe how these queries can be executed by applying recombinant DNA operations on the Biomolecular Database, which have the effect of selection of subsets of the database as specified by the queries. In particular, we describe how to execute these queries on this Biomolecular Database by the use of biomolecular computing (also known as DNA computing) techniques, including execution of parallel associative search queries on DNA databases, and the execution of logical operations using recombinant DNA operations. We also utilize recent biotechnology developments (recombinant DNA technology, DNA hybridization arrays, DNA tagging methods, etc.), which are quickly being enhanced in scale (e.g., output via DNA hybridization array technology). The chapter also discusses applications of such a Biomolecular Database system to various medical sciences and genomic processing capabilities, including: (a) rapid identification of subpopulations possessing a specific known genotype, (b) large-scale gene expression profiling using DNA databases, and (c) streamlining identification of susceptibility genes (high-throughput screening of candidate genes to optimize genetic association analysis for complex diseases). Such a Biomolecular Database system may provide a revolutionary change in the way that these genomic problems are solved.