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alternative enzyme can restore the missing link between the separated nodes, and
supplementary pathways don't exist; otherwise the connection 'survives'. As for
the experimental side, a double mutation can be classified as 'essential' if the
double deletion causes the yeast death, or 'non essential' if the yeast survives.
Whereas single deletion knockouts data for
S. cerevisiae
are available from
SGDP, the experimental analysis of double mutations by means of an exhaustive
gene couples deletion is by now still largely incomplete. Thus, we made use of
two approaches in order to derive such information: the Segrè group theoretical
approach in which the essentiality of double mutations is obtained from the
application of a flux balance analysis model, and a full text mining meta-analysis
approach applied on the available literature on double mutants experiments.
Synthetic data from the Segrè group are available in many simulated different
growth conditions and their synthetic-lethality range goes from 0 (essential
couple) to 1 (non essential couple). Since many genes are relevant only under
particular growth conditions, literature studies have been analysed in which many
conditions have been tested. As an alternative, the lethality results of all the
experimental works available have been compared.
The agreement between Segrè group simulated results, experimental data and
our topological essentiality features is checked. This ended up with 25 couples of
genes singularly non essential.
Two different properties have been taken into consideration in order to
classify these couples: experimental essentiality/non essentiality (coded as
ES/NES) and presence/missing of alternatives (A/MA) to maintain network
connectivity in our topological analysis. Such alternatives can be, as already
stated in section 3.4:
i) other pathways,
ii) multiple genes synthesizing the same enzyme,
iii) supplementary enzymes participating in the reaction.
As clearly shown by Table 8.2, our conjecture (namely that essentiality arises
from the lack of alternative ways to link two or more nodes) is consistent with
the obtained results, given that only one couple out of 25 appears into the
'forbidden class' (namely essential even if in presence of alternatives). Moreover,
such inconsistency seems to be due to a lack of information. It is important to
keep in mind that the MA condition must be considered as a necessary but not
sufficient prerequisite for essentiality, since the corresponding missing
metabolite may be included in the culture medium, or its role may be played by
another one.
