Co-occurrence of phosphorylation status can reflect known functional associations.

<p>(A) An example co-occurrence analysis on transcription factor c-Jun. There are four phosphosites (S58, T239, S243 and S249) on c-Jun. Their phosphorylation status (red: on, green: off) across 88 conditions are shown. For each pairwise combination of phosphosites, their joint phosphorylation status is summarized into a contingency table with four entries <i>n</i>_<i>ij</i> (<i>i,j</i> ∈ {0,1}), where <i>n</i>_<i>ij</i> denotes the number of times the site 1 is in state <i>i</i> site 2 is in state <i>j</i>. One-sided FET is used to test if two sites are phosphorylated together more often than expected. Consistent with the previous study that three sites (T239, S243 and S249) tend to be phosphorylated together to inhibit c-Jun’s activity in epithelial resting cells, their pairwise FET p-values are lower than their combination with S58. The most significant co-occurring pair is highlighted. (B) Cumulative distribution of co-occurrence FET p-values for 22 known cross-talk examples (red) are superimposed onto the p-values of all within-protein phosphosite pairs (blue). (C) Comparing the distribution co-occurrence FET p-values between 380 homo-functional pairs and 35 hetero-functional pairs.