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

surface, while NimbleGen makes use of a polymer tether to build the probes upon [8, 11]. In any
design there must be not only resolution between spots but sufficient distance between probes
within a spot that they do not interact with one another (essentially a distance defined by the cone
that the tethered probe can sweep out [5]. This lesson was learned the hard way by the
commercial providers and is often violated by institutional core laboratories, which tend to use
very high concentrations of probe solution despite a number of reports indicating more linear
responses result from lower concentrations.
Affymetrix U95 Platform
Since the remainder of the research reported here utilized data obtained from experiments that
measured transcript levels on the Affymetrix U95 Microarray chip, details of the chip design are
included here. The probe design protocol is to perfectly align 25 nucleotide sequences against
known transcript regions of the experimental species and identify those that are unique to a single
location in the genome [9]. Gene models are matched with 11-16 of such probes, spanning an
approximate transcript region of 600 nucleotides at the 3’ terminus of the gene [9]. This regional
bias reflects the most common method for purifying eukaryotic mRNA, which uses the polyA tail
as a capture feature and the basis for the cDNA transformation step. Probes are distributed across
this region, but not in a very consistent fashion, since the sequence uniqueness requirement did
not allow homogeneous spacing to occur. While such composite or multiple-probe sets may
measure the same transcript, it is also possible that different isoforms will be assayed [9].
The Affymetrix company provides a reference Web-available resource
(http://www.affymetrix.com/analysis/index.affx) for acquiring information about the probe design
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