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

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

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

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In summary, each probe demonstrates its own binding affinities, and, since on Affymetrix arrays<br />

there is no replication <strong>of</strong> individual probes, variation per hybridization reaction cannot be<br />

assessed. Replication is represented solely in the probeset’s (transcript level) distribution <strong>of</strong> signal<br />

intensities, and this distribution <strong>of</strong> the probe intensities then is represented with any <strong>of</strong> a number<br />

<strong>of</strong> statistical estimat<strong>or</strong>s [52]. The aggregation <strong>of</strong> these probesets into a scalar value representing<br />

the transcript concentration can be perf<strong>or</strong>med by mean analysis, trimmed mean analysis, median<br />

analysis, etc., and there exists considerable debate about the appropriate methodology and<br />

whether the mismatch probe inf<strong>or</strong>mation should be used, and how [45, 46, 48]. However, one<br />

must acknowledge the dubious nature <strong>of</strong> a simple interpretation <strong>of</strong> these ‘measurements’ f<strong>or</strong><br />

transcript levels when they are only pixel summarizations <strong>of</strong> flu<strong>or</strong>escence <strong>of</strong> sequence subsets <strong>of</strong><br />

the transcript, where no replication <strong>of</strong> spots occurs.<br />

Data Analysis and the Impact <strong>of</strong> the Data Cleansing Methods on<br />

Interpretation<br />

The end result <strong>of</strong> a half-million individual Microarray reactions is the flu<strong>or</strong>escent intensity <strong>of</strong> a<br />

grid <strong>of</strong> spots, which the scanner (<strong>or</strong> imager) rec<strong>or</strong>ds as a Microarray image. S<strong>of</strong>tware and<br />

alg<strong>or</strong>ithms continue to be developed to accommodate adjustments f<strong>or</strong> local and global<br />

background spotting intensities and to extract intensities and merge them into scalar gene values<br />

[52]. This interpretation <strong>of</strong> the signal represents a semi-quantitative measurement <strong>of</strong> the<br />

transcript region’s concentration [7]. The investigat<strong>or</strong> is then left to make decisions as to how to<br />

aggregate individual probes into probesets, including whether to combine probesets that measure<br />

the same transcript and/<strong>or</strong> the same gene [9]. An unexpl<strong>or</strong>ed aspect <strong>of</strong> these experiments is<br />

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