Sample A: Cover Page of Thesis, Project, or Dissertation Proposal

previously stated, rigorous reagent design, in a large number of experiments, has been scarce,
especially in comparison to the family of immunological assay technologies.
ELISAs use a similar biomolecule-based capture detection assay; however, ELISAs are made
quantitative by the nature and number of controls that are standard practice for the assays. As
quantitative assays ELISAs are performed with background controls, a dilution series standard,
sample replicates, and in addition, scanner limits are used to set boundaries on the measurements
when interpreting the results [7]. The majority of these features is absent or unrecognized in
commercial Microarray platforms and their associated analysis pipelines, although each has been
the subject of one or more studies by individual investigators and shown to have considerable
impact on the outcome [17-20].
The work reported here attempts to find a computational remedy for each of the weak design
points, in order to derive a more reliable representation of the transcript concentration. The
procedures developed are demonstrated in detail for the Affymetrix platform, but they are
extendable to any platform. The next sections present background material about the probe-target
reaction, the various measurement platforms, and gene expression experiments. Once the
apparent weak points have been identified, the important question is the extent to which they
change and whether they improve the interpretation of the data, which we approach in a number
of ways described in detail below. The final section lists the specific aims of the research
described in this dissertation.
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