Biomedical Engineering Reference
In-Depth Information
tions described here. For example, false negative errors can prevent finding ex-
isting individuals with the desired genetic variant. This is less serious than a
false positive result, which could lead to sending a nonresistant individual into a
contaminated area, under the false belief that he is genetically protected from a
biological agent. A similar type of error could arise from database degradation
(as, for example, from repeated error-prone duplication of the database). This
type of error can be easily eliminated by follow-up confirmatory screening of
that single individual's DNA. In general, it would be best to use the Biomolecu-
lar Database for very powerful and rapid selections based on genetic informa-
tion, but then to confirm all results on individual DNA samples. This would
require maintenance of individual stocks of DNA for each individual. This is a
relatively large task, but well within current technology. An LIMS (laboratory
information maintenance software) system and robotic liquid handling capacity
are musts for this type of storage. There could also be errors of magnitude.
These errors result from preferential amplification of one DNA strand over an-
other. This kind of error is particularly troublesome, for it would skew allele
frequencies. It may be necessary for us to monitor the frequency and extent of
such errors and develop Boolean search strategies that minimize them. The final
type of error, based on an incomplete understanding of the human genome, can
only be rectified by continued research in other fields. This type of error could
result from incomplete knowledge of the way in which genetic variants are dis-
tributed among different racial and ethnic groups. For example, the well-
described
ccr5
variant that prevents HIV infection has been detected to date only
among white males. If one were to select for nonexistent African American fe-
males expressing this variant, one might well obtain a small number of false
positives. This type of error could also arise from mistaken assumptions. A
given genetic variant might protect Hispanic females from infection by a given
biologic agent, but oriental males carrying the same variant might be fully sus-
ceptible to infection because of another independent genetic variant.
3.11. Computer Simulations
Reif et al. (52,53) have made computer simulations of their methods for
DNA-based associative search. They constructed computer software (viewable
on the web) that provide a simulation of the entire experimental process, includ-
ing conversion of this attribute database into a DNA database using DNA chips,
the PCR method for associative search in the DNA database (using a software
simulation of the kinetics of DNA hybridization), and, finally, conversion of the
result of this query (using extensions of techniques described in (55)) into con-
ventional media by use of a DNA expression array. Our computer simulation
software to the above-described query processing provides a basis for future
