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

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

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hybridization and multiple dye strategies, so the procedures developed in this research do not<br />

handle this class <strong>of</strong> problems.<br />

Gene Structure Fact<strong>or</strong>s<br />

A probe covers only a small fraction <strong>of</strong> the possible target sequence, and the investigat<strong>or</strong> should<br />

be, but <strong>of</strong>ten is not, wary <strong>of</strong> drawing conclusions about the expression <strong>of</strong> the ‘gene’ that, in fact,<br />

are true only f<strong>or</strong> a particular is<strong>of</strong><strong>or</strong>m <strong>of</strong> the gene. Current chip designs are attempting to account<br />

better f<strong>or</strong> exon coverage and alternative transcript events across sample comparisons by<br />

increasing the number <strong>of</strong> probes and diversifying their placement [9]. Is<strong>of</strong><strong>or</strong>m-sensitive analysis<br />

does depend on an underlying gene model [43, 44]. While the results <strong>of</strong> the research presented<br />

here are sensitive to probe position and gene models, the resolution <strong>of</strong> competing models requires<br />

wet-lab methods not available to us, so the results shown present likely alternatives rather than<br />

absolute outcomes.<br />

Commonly Recognized Confounding Fact<strong>or</strong>s<br />

The underlying goal <strong>of</strong> Microarray technologies is to detect and quantify biological compounds.<br />

Any such molecular assay faces the sensitivity challenge <strong>of</strong> augmenting the signal <strong>of</strong> very rare<br />

events, setting conditions that optimize the specificity <strong>of</strong> interactions, minimizing background<br />

contributions, and respecting device limitations, ideally by including external and internal<br />

calibration standards. To date, standard platf<strong>or</strong>ms f<strong>or</strong> Microarray analysis have not focused on<br />

robust and standardized wholesale technical solutions to these problems, but instead have focused<br />

on one particular technical aspect in which to specialize (and segment from the competition) and<br />

then relied on statistical methods embodied in alg<strong>or</strong>ithmic analysis pipelines f<strong>or</strong> signal<br />

9

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