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Proteins with a high degree (connectivity) are involved in a large number of interactions and have been previously shown to be associated with essentiality [ 9- 11].
It has been shown that nodes that have high degree and/or betweenness centralities are frequently associated with essentiality [ 4, 5].
We used a broad variety of topological features, sequence characteristics and co-expression properties potentially associated with essentiality, such as flux deviations, centrality, codon frequencies of the sequences, co-regulation and phyletic retention.
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The results suggest that incomplete knowledge of the metabolic processes associated with essential genes and the immediately surrounding metabolic processes are driving forces in incorrect gene essentiality predictions.
Selecting features associated with gene essentiality is fundamental to predict essential genes in feature-based models.
Selecting features associated with gene essentiality is necessary to identify essential genes through machine learning approaches.
Thus, TR1 knockdown did not decrease the growth of DT cells, excluding the effects associated with TR1 essentiality for cell growth.
In protein interaction networks hubs and bottlenecks have both been associated with functional essentiality [ 24- 26].
In general, FWM provides a more effective way of integrating features associated with gene essentiality, and overcomes the impact of multicollinearity among features.
Consistent with the idea that changes in lifestyle are associated with flips in essentiality, we find that all the members of the large mitochondrial ribosomal subunit in C. albicans that have been experimentally tested are essential (fig. 4 C).
Finally, FBA using flux rates as additional constraints allowed us to identify gene essentialities associated with specific exchange fluxes in ccRCC cell lines.
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