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coincidence of an increased transcription rate and a similarly increased transcript degradation
rate or from the coincidence of a decreased transcription rate and a similarly decreased
transcript degradation rate.
(12.17)
Again, to emphasize the importance of Statements 12.16 and 12.17, they may be
referred to as
the Second Law of Microarray Data Interpretation (SLMDI) and the
Third Law of Microarray Data Interpretation (TLMDI),
respectively. Violating
FLMDI leads to a false positive error (or Type 1 or
a
error), and violating SLMDI or
TLMDI results in a false negative error (or Type 2 or
b
error).
In summary, I have formulated three laws of
microarray data interpretation
(MDI) in this section, i.e., Statements 12.10, 12.16, and 12.17. It is truly surprising
to find that, even after almost one and a half decade following the invention of one of
the most revolutionary experimental techniques in biology, namely,
DNA
microarrays
, many workers in the field are still committing Types I and II errors
in interpreting the data measured with this technique. In December, 2009, I had
opportunities to attend two meetings, the
Regulatory Genomics, Systems Biology
and DREAM 2009
held at the Broad Institute in Cambridge and the 102nd Statistical
Mechanics Conference held at Rutgers, Piscataway. Having observed that several
prominent participants in these meetings violated one or more of the laws of MDI
described above, I was prompted to write several emails. I am taking the liberty of
attaching two of these emails and related documents as Appendices C-F at the end of
this topic in the hope of stimulating
worldwide discussions on ways to avoid
misinterpreting microarray data
, since misinterpreting microarray data can have
far-reaching consequences in both basic and applied researches in cell biology,
affecting drug discovery efforts in pharmaceutical industry and personalized medi-
12.7 The Mechanistic Modules of RNA Metabolism
Each plot or trajectory in Fig.
12.6
can be divided into five segments or “component
vectors” bound by two of the 6 time points labeled 1 through 6: First segment
between 0 and 5 min measured after the glucose-galactose shift, the second
segment between 5 and 120 min, the third segment between 120 and 360 min, the
fourth segment between 360 and 450 min, and the fifth segment between 450 and
850 min. Each segment can be characterized in terms of the angle measured
counterclockwise starting from the positive
x
-axis (see Fig.
12.8
). For example,
the segment between time points 5 and 6 in Fig.
12.6a
is approximately 45
and that
between time points 1 and 2 in Fig.
12.6b
is approximately 225
, etc. These angles
are conveniently divided into eight groups as explained in the legend to Fig.
12.8
.
Each group is associated with a distinct mechanism of RNA metabolism. For
example Group 2 (with angles in the range between 4
and 86
) is associated
with the mechanism in which both TL and TR increase (see the radial arrow in
Fig.
12.8
). In contrast, Group 8 (with angles in the range between 274
and 356
)
