Epistasis analysis.

<p>(A) MAPK pathway models depicting the secondary screen assays used to conduct the epistasis analysis. See <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001809#pbio.1001809.s020" target="_blank">Text S1</a> for full secondary assay information. (B) Epistasis screen results are shown for <i>bona fide</i> MAPK pathway components as well as a selection of candidates. Results are presented as pMAPK values normalized to <i>GFP</i> dsRNA treated controls. <i>Bona fide </i>MAPK pathway components are identified with an asterisk (*). Genes to which we have associated new gene symbols are marked with a cross (†). (C) Known pathway components (labeled) and experimental candidates are assigned to specific epistasis intervals. The calculated Pearson correlation <i>r</i> between the epistasis screen data profiles and the three predetermined profiles for epistasis intervals (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001809#s4" target="_blank">Methods</a>) are represented on three axes (<i>x</i>-axis, RAS-RAF; <i>y</i>-axis, MEK-MAPK; <i>z</i>-axis, RAF-MEK). Values near 0 represent poor correlation while values near 1 (negative regulators) or −1 (positive regulators) indicate high correlation with a given epistasis profile. Candidates were assigned to the RAS-RAF (orange), RAF-MEK (magenta), or MEK-MAPK (dark blue) interval on the basis of the highest distance value. Candidates that could not be assigned to a specific interval (distance values within [−0.5, 0.5]) are shown in grey. Detailed epistasis screen results are available in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001809#pbio.1001809.s014" target="_blank">Table S3</a>.