In order to gain insight into this discrepancy between the two organisms we examined the distribution of essentiality in small and large proteins in both organisms in the context of their phyletic retention.
Thus, even if protein abundance correlates with interaction properties, as the correlation between abundance and essentiality is very small, and as we do not observe a significant correlation between centrality and essentiality in protein complexes, we can conclude that protein abundance does not significantly influence our analyses.
Nutrient "dose response" relationships mainly cover intakes producing nutrient deficiencies, nutrient optimal activity, and preservation of nutrient safety with excess intakes rather than global, combined dose-responses that define nutrient essentiality as a small early portion of a mainly dose toxicity curve.
To confirm that the observed essentiality of the seven small proteins was specific to RNAi knockdown of the predicted transcript, we performed the following experiments.
We hypothesized that factor essentiality in highly-connected small-world networks might be better inferred by considering both expression data and multiple aspects of network architecture.
Since T. brucei undergoes extensive morphological and metabolic changes during its life cycle alternating between the mammalian (bloodstream) and insect (procyclic) hosts, it was of interest to gauge the essentiality of the seven small proteins in bloodstream forms.
Specifically, we observed that the nature of this relationship differed for E. coli and S. cerevisiae, with small protein size being indicative of essentiality in E. coli and the same being true of large proteins in S. cerevisiae.
In order to identify the set of organisms in which the retention of a gene is most predictive of essentiality, we first selected a small group of organisms likely to be predictive for the E. coli essential list, and then computed the accuracy for all subsets of this reduced set.
Although the fraction of technical failures was small, these observations reaffirm the need to confirm genetic essentiality by conditional methods, just as in conventional gene-by-gene studies.
One major difference was that our procedures included an analysis of the combined modifications (Step III in Figure 1, with details shown in Figure 5) to systematically eliminate undesirable effects, e.g., very small growth rates or new incorrect predictions of gene essentiality.
