Biomedical Engineering Reference
In-Depth Information
These queries include 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. These queries are 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. We describe two distinct methods for
processing logical queries: a surface-based primer-extension method, as well as
a solution-based PCR method. Query processing is executed with vast
molecular-level parallelism by a sequence of biochemical reactions requiring a
length of time that remains nearly invariant with respect to the size of the
database up to extremely large numbers (e.g., up to 10
15
). This is because the key
limitation is the time for DNA hybridization, which is done in parallel on all the
DNA. Output of the queries would be accomplished via DNA hybridization
array technology.
1.2.4. Computer Simulations and Software
We describe computer simulations and software that can be used for the
analysis and optimization of the experimental protocols. In particular, we de-
scribe the use of computer simulations for the design of hybridization targets for
readout of information tags and SAGE tags by microarray analysis. We also
discuss the scalability of these methods to do logical query processing within
Biomolecular Databases of various sizes.
1.2.5. Applications
The chapter also discusses applications of a Biomolecular Database system
to provide various genomic processing capabilities, including: (a) rapid identifi-
cation of subpopulations possessing a specific known genotype, (b) large-scale
gene expression profiling using Biomolecular Databases, and (c) streamlining
identification of susceptibility genes: high-throughput screening of candidate
genes to optimize genetic association analysis for complex diseases (see, e.g.,
this volume, Part III, section 6, on cancer). Such a Biomolecular Database sys-
tem provides a revolutionary change in the way that these genomic problems can
be solved, with the following advantages: (i) avoidance of sequencing for con-
version from genomic DNA to digital media, (ii) extreme compactness and port-
ability of storage media, (iii) use of vast molecular parallelism to execute
operations, and (iv) scalability of the technology, requiring a volume that scales
linearly with the size of the database, and a query time that is nearly invariant of
that size. These unique advantages may potentially provide a number of oppor-
tunities for a variety of applications beyond medicine, since they also impact
