Biology Reference
In-Depth Information
Table 19.3
A theoretical comparison between the current and the new methods for analyzing
microarray data
Methods and theories underlying microarray data analysis
Categories of comparison
Currently fashionable
Ribonoscopic
Changes in
RNA levels
in
time
(time series),
or across
individual
sequences
at a
given time (
structure series
)
Changes in
RNA levels
in time
(time series),
or across
individual
sequences
at a
given time (
structure series
)
1. Objects measured with
microarrays
2. Changes are interpreted
in terms of
Genes
The whole cell under the
influence of its environment
3. Assumption: the level
of an RNA molecule
inside the cell is
determined by
Its structural gene
Its structural gene plus dozens
of proteins coded by other
structural genes and
regulatory DNA regions
4. Role of RNA
degradation
Not taken into account
Taken into account
10-10
4
due
to alternative splicing
5. The “structural gene:
RNA ratio”
1:1
1:N, where N
¼
6. The goal of analysis
To discover sets of genes
responsible for phenotypes
To discover the ribons
(i.e., the patterns of RNA
level changes) responsible
for phenotypes
7. The category to which
the sought-after object
belong
Static, stable structures
(equilibrium structures
or equilibrons)
Dynamic, transient structures
(dissipative structures
or dissipatons)
ribonoscopic approach
to microarray data analysis being advocated here and the
approach widely adopted by contemporary investigators in microarray technology
as summarized in Table
19.3
. One of the main differences is that, whereas
ribonoscopy is centered on RNA levels (as its name indicates) as regulated by the
whole cell, the currently widely used approach is centered on DNA or genes, that is,
on discovering the genes responsible for the phenotypes under investigation (see
Rows 2, 3, and 6 in Table
19.3
). The following excerpts from a leading journal
article are good examples of what is here referred to as the
gene-centric approach
:
This study was undertaken to indentify genes that could predict response to doxorubicin-
based primary chemotherapy in breast cancer patients
...
(Folgueira et al. 2005, p. 7434)
...
A set of three gene,
PRSS11, MTSS1, and CLPTM1,
could correctly classify 95% of the
samples
...
(Folgueira et al. 2005, p. 7442)
The gene-centric approach to microarray data analysis is untenable for two main
reasons:
1. Since the level of an RNAmolecule inside the cell is determined by two opposing
processes,
transcription
and
transcript degradation
(see Row 4 in Table
19.3
and
catalyzed by a set of enzymes numbering up to several dozens, it is erroneous to
