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To evaluate the relationship between membrane content and the CLR, we developed a nonparametric measure, the Index of Degree and Essentiality (Indess).

Large DRA-divergence is thus a strong indicator of essentiality.

Instead, large DRA-divergence was a better indicator of essentiality.

Hence, an FVA score for genes was computed (see Methods) and used as a metric alongside the druggability index and in silico gene essentiality analysis to prioritize L. major targets.

The fraction of metabolisms of a given size in which a reaction is essential is a useful quantifier of the reaction's essentiality, which we have called the reaction's superessentiality index [ 13].

In a previous attempt to link gene essentiality with the gene expression level, the codon adaptation index (CAI, [ 30]) was used as an approximation for gene expression [ 18] which is based on the assumption that highly expressed genes are generally optimized for translation speed and accuracy [ 31].

We investigated the major parameters correlated with mRNA stability, by modeling all mRNA half-lives statistically, taking into account, without the a priori selection of parameters, both qualitative (e.g. gene function, gene essentiality) and quantitative (e.g. mRNA concentration, codon adaptation index (CAI, a measure of synonymous codon usage bias [ 18])) biological factors.

Figure 6: In silico elucidation of the mechanisms of essentiality for the five genes selectively essential in ccRCC.

Not only transcriptional abundance (codon adaptation index and expression level), but also protein-protein associations (PPAs), essentiality (ESS), subcellular localization of cytoplasmic membrane (SLM), transmembrane helices (TMH) and hydropathicity score (HS) independently and significantly affected the ERs of bacterial proteins.

However, sequence-related features (codon adaptation index (CAI), ORF length, GC content, polycistronic mRNA), gene function and essentiality also affected mRNA lifetime at all growth rates.

Essentiality tests suggested that neither sig1 nor sig2 is essential under all conditions.

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