Biology Reference
In-Depth Information
Fig. 12.7 The triadic
definition of the sign
“gene expression”
Gene Expression
(
Sign
)
Meaning
(
Object
)
Protocol
(
Interpretant
)
commercial media as the revolutionary tool for “measuring gene expression,”
interpreting “gene expression” arbitrarily as “transcription.” To emphasize its
importance, Statements 12.10 or 12.14 may be referred to as the
First Law of
Microarray Data Interpretation (FLMDI)
.
A survey of
the literature indicates that most
investigators employing
microarrays routinely violate FLMDI, since:
Most biologists conflate the terms “gene expression” and “mRNA levels,” or “transcrip-
tion” and “transcript levels”.
(12.15)
Statement 12.15 will be referred to as the “transcription-transcript level confla-
tion (TTLC).” The data obtained by Garcia-Martinez et al. (2004) and by Fan et al.
(2002) clearly demonstrate that the mixing of these two terms can lead to false
positive (Type I) and false negative (Type II) errors in interpreting microarray data
(Ji et al. 2009a; Ji and Yoo 2005).
A gene, commonly defined as a DNA segment encoding proteins, is an
equilibrium
structure
that is static (see Sect.
11.2
). On the other hand, the level of an
RNA molecule transcribed from its gene is a
dissipative structure
, because its
maintenance requires dissipation of free energy. Many studies employing
DNA arrays have been making the error of what may be referred to as “the gene-
to-transcript misinterpretation,” which would be equivalent to compressing both
transcriptomics
(the study of the whole set of the transcripts of a genome) and
genomics
(the study of the whole set of the genes of a genome) onto the same plane.
As alluded to above, two types of errors have resulted from the misuse of the phrase,
“gene expression.” The Type 1 error (also called the false positive error) is
committed when it is claimed that there is something when there actually is nothing;
Type 2 error (or the false negative error) is committed when it is claimed that there is
nothing when there actually is something. To help users of microarrays avoid
making Types I and II errors, I recommend the following rules:
It is impossible to identify a gene as a possible cause of a disease based only on the finding
that its mRNA level changed in the diseased state relative to the control state without
eliminating the possibility that the change in the mRNA level arose from the changes in
transcript degradation rates rather than from changes in the transcription rates.
(12.16)
Similarly:
It is impossible to exclude a gene as a possible cause of a disease based only on the finding
that its mRNA level did not change in the diseased state as compared to control without
eliminating the possibility that the lack of changes in the mRNA level arose from the
