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

Chapter 2: The BaFL Pipeline
Microarray technologies are high through-put platforms that measure some molecular fraction of
a sample [1-4]. Gene expression Microarrays assay the concentration of cellular transcripts at the
time samples were harvested [1]. Depending on the probe design, the technologies allow one to
quantify some fraction of the active genes’ transcript levels over the conditions of interest.
Accurate assessment of the transcriptional activity depends on how correctly one interprets the
source of a signal [5-8].
For example, a number of investigators have pointed out the cross-hybridization problem: many
of the probes in any given design do not uniquely bind to a single part of the genome, making
interpretation of any measurement arising from such a probe problematic [9, 10]. Elsewhere we
have pointed out that probes binding where SNPs are known to occur can result in an altered
extent of binding, depending on the alleles present, sometimes with large consequences for the
interpretation of the amount of a transcript [11]. We and others have shown that internally stable
structures in either the probe or the target that limit the accessibility of each to the other can
materially affect the extent of signal [12, 13]. The fluorescent response from the scanner or
imager is not consistent over the entire response range of the Microarray itself, so limits must be
imposed on the signal range from which the values are analyzed (outside the linear range of the
scanner bins must be used instead of fluorescent unit values) [14-16].
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