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

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statistical criterion, but it appears to be unable to classify the adenocarcinomas because the<br />

Euclidean Sum <strong>of</strong> Squares is two fold larger than f<strong>or</strong> the (smaller N) squamous and n<strong>or</strong>mal<br />

clusters. The ProbeSets KRT17, EMP2 and MFAP4 which were selected by both criteria,<br />

demonstrate that one method by which to avoid such false positives: that is, select an average<br />

probe gain threshold criteria <strong>of</strong> ProbeSets whose aggregate gain improves on the average probe<br />

gain. Thirteen <strong>of</strong> 29 ProbeSets demonstrating an average probe gain had an aggregate gain ratio<br />

that improved on the average probe gain ratio. In contrast to the average probe gain list <strong>of</strong> 29<br />

genes, half <strong>of</strong> this list (6 <strong>of</strong> 13) demonstrates enhanced ProbeSet inf<strong>or</strong>mation gain; having a<br />

ProbeSet gain ratio greater than 0.8. The 7 additional genes f<strong>or</strong> demonstrate a close relationship<br />

to the underlying biology.<br />

Such effective down selection, at the ProbeSet level, may be a reasonable endpoint if the goal is<br />

to produce an effective and simple diagnostic test. However, this is a limited approach if the goal<br />

is to understand the biological mechanisms <strong>of</strong> disease. Based upon the classification<br />

perf<strong>or</strong>mances, presented in Figure 5.1, 18 Genes were identified were selected as a candidate list<br />

(Table 5.1) to expl<strong>or</strong>e the biological function with respect to NSCLC.<br />

Literature Validation <strong>of</strong> Biological Process<br />

We observed significant down regulation <strong>of</strong> TACC1 in both f<strong>or</strong>ms <strong>of</strong> NSCLC, which is supp<strong>or</strong>ted<br />

by the literature [15-17]. There are 3 TACC human genes, which appear to be imp<strong>or</strong>tant f<strong>or</strong><br />

cellular division and <strong>or</strong>ganization [18], with <strong>or</strong>thologues rep<strong>or</strong>ted in Mus. musculus, Drosophila<br />

melangaster, and Xenopus laevis [18]. Proper localization <strong>of</strong> TACC during cytokinesis appears<br />

to be dependent upon phosph<strong>or</strong>ylation by aur<strong>or</strong>a kinases [15, 19] and may posses a critical<br />

function in cell cycle control [17]. Appropriate cell division is a prerequisite in the propagation<br />

125

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