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Genes with a high hierarchical position would have more power to determine whether the genes are enriched in a certain pathway.
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Proteins with high out-degrees (i.e., modulating a high number of other proteins), low in-degrees (i.e., modulated by a few or no other proteins), and/or high H values (i.e., with a high number of proteins acting downstream of it) can be considered to occupy high hierarchical positions in the network.
Power was measured by who had a higher hierarchical position and who had the lower position in the storyline -- boss versus secretary, teacher versus student, etc.
This is to be expected under a model in which upstream genes, owing to their higher hierarchical position, have a higher impact on the function of the pathway.
In biosynthetic pathways, upstream genes usually evolve under higher levels of selective constraint than those acting at the downstream part, as a result of their higher hierarchical position.
This finding seems striking, as these proteins, owing to their higher hierarchical position, may be capable of regulating the activity of a higher number of downstream proteins.
At EDF-GDF, occupational grade is an internal company classification in which all jobs are classified into 23 grades arranged on a 1 60 scale, where higher values represent a higher hierarchical position, associated with a larger salary, greater autonomy and responsibility in work tasks and higher status within the company (CFDT, 2013).
Studies on safety climate, for example, repeatedly report more positive ratings from individuals in higher hierarchical positions [ 34].
The interviewees were of higher hierarchical positions (directors, project managers, leading researchers, and division leaders), as we were interested in the institutional and organizational strategy and the stakeholders' experiences over time.
Surprisingly, no evidence was found supporting that upstream genes (those occupying higher hierarchical positions) are subject to increased levels of selective constraint.
This suggests that genes occupying higher hierarchical positions are not more relevant for the function of the signaling network, or to the organism's fitness, than downstream genes.
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