Topological characteristics of the evolvable core and robust neighbor sub-network.

<p>(<b>A</b>) Number of self-loops. (<b>B</b>) Number of two-node feedbacks. (<b>C</b>) Number of three-node feedbacks of the original network, evolvable core sub-network, random-deletion sub-network, robust neighbor sub-network, and random-selection sub-network. (<b>D</b>) Degree heterogeneity of the original network, evolvable core sub-network, and random-deletion sub-network. (<b>E</b>) Degree distribution of the original network and evolvable core sub-network. (<b>F</b>) The ratio of robust neighbor links to the whole links for the low-degree, middle-degree, and high-degree nodes, respectively. (<b>G</b>) Characteristic path length of the original network, evolvable core sub-network, and random-deletion sub-network. (<b>H</b>) Number of connected components of the robust neighbor and random-selection sub-network. (<b>I</b>) Characteristic path lengths of the robust neighbor and random-selection sub-network. Error bars denote the standard errors of the average values.</p

Decomposition of the human signaling network.

<p>(<b>A</b>) Human signaling network. (<b>B</b>) Evolvable core. (<b>C</b>) Robust neighbor. (<b>D</b>) Attractor landscape of the human signaling network. (<b>E</b>) Attractor landscape of the evolvable core.</p

A conceptual framework of the evolvable core and robust neighbor in biomolecular regulatory networks.

<p>This figure shows that deletion of an evolvable core link causes acquiring a new phenotype, whereas deletion of a robust neighbor link causes cryptic genetic variation for the biological system represented by the attractor landscape.</p

Perturbation experiments of the evolvable core and robust neighbor.

<p>(<b>A</b>) Average of absolute log2 fold change of each output node activity over three repetitions obtained from each perturbation experiments of the evolvable core. (<b>B</b>) Average of absolute log2 fold change of each output node activity over three repetitions obtained from each perturbation experiments of the robust neighbor. (<b>C</b>) Average of all the experimental results (three repetitions×four output nodes×eight perturbation experiments) with respect to perturbation of the evolvable core elements and average of all the experimental results (three repetitions×four output nodes×five perturbation experiments) with respect to perturbation of the robust neighbor elements. Error bars denote the standard errors of the average values. The red numbers and blue numbers in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003763#pcbi-1003763-g002" target="_blank">Figs. 2A and 2B</a> denote the evolvability scores and the robustness scores, respectively.</p

Genetic properties of the network nodes in terms of evolvability and robustness scores.

<p>(<b>A</b>) The correlation between evolutionary rate and evolvability score. (<b>B</b>) The correlation between species broadness and evolvability score. (<b>C</b>) The normalized average evolvability and robustness scores of the genes related to immune system. (<b>D</b>) The normalized average evolvability and robustness scores of the oncogenes.</p

Additional file 1 of Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial

Additional file 1: Supplementary Methods, Results, Tables and Figures