Caryoscope

Unlike the other display methods discussed, Caryoscope developed by Christian Rees of
the Botstein laboratory at Stanford, is not primarily intended to summarize
and display gene expression data but, rather, to display the results of array
comparative genomic hybridizations (aCGH). The essential idea of array-based
CGH is that, instead of cDNA produced from mRNA, genomic DNA (gDNA)
can be directly used in array experiments. Comparative gDNA hybridization
can therefore be used for gene copy estimation (9). As with gene expression
studies, two genomic DNA samples are hybridized at once to the same array,
each having been labeled with a different fl uorophore. Typically, these genomic
DNA samples are obtained from either a normal and a diseased tissue (i.e.,
channel one measures a sample from a cancerous tissue, which may have
undergone gene duplications or deletions, while channel two measures a sample
from a normal tissue) (9,10), or from two closely related species, such as
recently evolutionarily diverged strains of yeast or bacteria (11,12). In either
case, obtaining a log ratio that signifi cantly deviates from zero is presumptive
evidence that either a gene amplifi cation has occurred in one of the tissues, or
that the gene copy number has been increased in the other tissue. Caryoscope is
designed to display these data in a genome-ordered fashion. Separate versions
are available for both yeast and human physical map data. The ability to display
aCGH ratio data in the context of a physical map is particularly useful given that
deletions or duplications often occur on a larger scale than individual genes;
indeed, amplifi cations or deletions often occur in large contiguous regions, and
this is immediately evident on examination of the data with Caryoscope.
A very nice feature of Caryoscope is that a separate diagram is produced
for each of the chromosomes of the organism of interest. As shown in Fig. 3,
Caryoscope displays ratios of greater than zero as red bars to the right of the
line representing the chromosome, while green bars representing ratios of less
than zero are displayed to the left of the line. In this case, color is used only to
indicate the sign of the ratio, while the actual deviation of the log ratio from
zero is proportional to the height of the bar representing a particular locus. In
the example shown, the lines drawn to the right of the main line indicate the
ratio associated with a hypothetical bar of that length. Clearly, most of the
bars in Fig. 3 are of a length consistent with fl uctuation within the “noise” of
the expression ratios, but with notable peaks corresponding to areas of copy
number variation.