Medical Science : A Biomolecular Database System for Storage , Processing & Retrieval of Genetic Information & Material

نویسندگان

  • John H Reif
  • Michael Hauser
  • Thomas LaBean
  • Michael Pirrung
چکیده

A key problem in medical science and genomics is that of the efficient storage, processing and retrieval of genetic information and material. This paper presents an architecture for a Biomolecular Database system which 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 bio-informatics. Instead, biotechnology techniques provide the needed capability of a Biomolecular Database system, without ever transferring the biological information into a 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 individual from which the DNA was obtained, as well as the date of the sample, gender, date of birth, etc.) 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 (e.g., multiple divisions of an army, etc.). For example the DNA of a million individuals requires about 6 pedabits (6x10 bits); but due to the compactness of DNA, a volume the size of a conventional test tube with a few milliliters of solution contains 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 the 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 this 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 the 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.) that are quickly being enhanced in scale (e.g., output is via DNA hybridization array technology). The paper also discusses applications of such a Biomolecular Database System to various medical science 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.

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تاریخ انتشار 2004