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

classical reaction equations, modified with nearest neighbor parameters and surface
attachment parameters [25]. However, any target genome not exactly similar to the
reference genome used in probe design is likely to diverge in unknown ways from the
sequence set expected [31]. Thus the precise interpretation of the values is an open
ended issue. Common problems that relate to managing specificity include:
a. Cross hybridization. Targets with near perfect sequence similarity to probes
have the potential to form sub-optimal but still stable duplexes that compete
with perfectly matched targets [29, 53]. The problem is exacerbated with
longer oligo probes because the greater stability of longer duplexes can
overcome a larger number of mismatches, but it is clear that sequence
composition effects can render this a problem even for quite short probes
[10]. The heading of cross-hybridization is understood to mean sequences
from other sites in the genome than the particular gene that the probe was
designed to target, and not variant alleles or alternate transcripts of the
intended gene. A complication when the probes are directly attached to the
array surface (absence of a spacer) is to determine which of the nucleotides
nearest the surface can actually bind the target. Evidence from Affymetrix
arrays suggests that the first 6 nucleotides are inaccessible to molecules in
the solution phase [10]. This is relevant to the cross-hybridization problem
because it results in a shorter string of nucleotides that must be matched, and
so a likelier cross-hybridization event.
b. SNPs. Alternate alleles are within-gene sequence variants, and their
significance to a DNA Microarray assay is that the intended probe may
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