Visual Representation of Our Approach.

<p>First, we summarize gene annotations made to functional terms in the Gene Ontology hierarchy as a gene-term bipartite graph. From these gene-term relationships, we project a term-term network. We partition this network into communities and compare those term communities to branches of terms in the DAG. Finally, we perform functional enrichment analysis on experimentally-defined gene sets using both the term communities and GO branches.</p

A Comparison of Branches in the GO DAG and Term Communities Found by Partitioning the Term Network.

<p>(a) Distribution of <i>J</i>_<i>m</i>, the maximum similarity a community or branch with ten or more members has compared to all other branches or communities with ten or more members, respectively. Although a small number of communities and branches have similar memberships, most are highly dissimilar. (b)-(c) Two example comparisons between communities and branches: (b) TC:0003876 compared to GO:0015298, and (c) TC:0011556 compared to GO:0090559. In each panel on the left hand side a community and its inter-community connections in the annotation-driven term network is shown and on the right hand side the branch with which that community has the the highest Jaccard similarity is illustrated. In the right panel edges represent the ontological associations defined by the Gene Ontology term hierarchy. Each term member of the community or branch is colored both by its associated primary domain (inner color—BP:yellow, MF:cyan, CC:magenta) and its community membership (outer color), determined at the same resolution value as the illustrated community. Terms common between each community and branch pair are circled. To read term-labels, please zoom in.</p

Biological Information in Term Communities.

<p>(a-d) Term Communities (TC:0000228, TC:0000227) and branches (GO:0050896, GO:0002376) summarized as word clouds. In each case the color of a word represents how often the term description containing that word belongs to each of the primary domains (BP:yellow, MF:cyan, CC:magenta, also see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004565#pcbi.1004565.g002" target="_blank">Fig 2</a> for mixed-domain coloration) and size represents that word’s statistical enrichment in that community/branch.</p

Functional Enrichment Analysis in Branches and Communities.

<p>(A) A plot of the percentage of branches and percent of communities found to be enriched at <i>p</i> < 0.01 in each gene signature. Although both communities and GO-branches have enrichment in these signatures, many signatures are only enriched in communities and not branches at the <i>p</i> < 0.01 significance. We chose a subset of signatures to investigate further, and note those with a blue dot. (b) A heat map showing the statistical enrichment of selected cancer signatures (noted in (a) with a blue dot), as measured by AEA, in both GO branches and term communities.</p

Visualization of Communities (Circles) of GO Terms Found at the Six Lowest Levels of Resolution (Rows), in Increasing Order (Top to Bottom).

<p>The width of the line connecting two communities is proportional to the percentage of terms in the child community that are also in the parent community. The size of communities is proportional to the log of the number of terms in the community. Color represents the normalized percentage of terms in the community which belong to the BP (yellow), MF (cyan) and CC (magenta) primary domains.</p

Pearson correlation vs. z-score.

<p>Gene pairs that are coregulated are represented by blue dots and those that are not coregulated are represented by red dots for <i>E. coli</i>.</p

AUC versus number of answers for the full model, position null model, and social influence null model for technical boards.

<p>AUC for (a) voting before an answer is accepted, (b) accepting an answer, and (c) voting after an answer is accepted versus the number of answers in technical boards (See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0173610#pone.0173610.s004" target="_blank">S4 Fig</a> for similar plots with non-technical and meta boards). Solid lines correspond to the full models, while the lighter dashed lines correspond to the position null model, in which the probability of picking answers decreases monotonically with the web page order. Finally, the dark dashed lines correspond to the “social influence” null model, in which social signals are the only attributes used in the model. Shaded regions correspond to standard deviations in values based on bootstrapping the test data.</p

The number of TFs, regulated genes and edges in our established TRI data set of known TRIs for <i>E. coli</i> and yeast.

<p>The number of TFs, regulated genes and edges in our established TRI data set of known TRIs for <i>E. coli</i> and yeast.</p

F-score vs. z-score cutoff.

<p>F-score versus z-score cutoff for prediction of coregulated gene pairs and TRIs are plotted in blue and red respectively. Also, the F-score curves for the prediction of coregulated gene pairs in coexpression gene pairs with at least one TF gene is plotted in green. The five subplots correspond to the five established TRI data sets for <i>E. coli</i> and yeast (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031969#pone-0031969-t001" target="_blank">Table 1</a>), A) RegulonDB, B) Lee et al. 2002 (Chip-chip), C) Harbison et al. 2004 (Chip-chip/sequence motif), D) Milo et al. 2002 (Compilation) and E) Lee et al. 2002 (Compilation).</p

Distribution of the final number of answers to each question and question popularity versus the final number of answers.

<p>(Top row) Complementary cumulative distribution of the final number of answers posted in reply to a question as of September, 2014, on (a) technical, (b) non-technical, and (c) meta sites. Shaded areas correspond to the standard deviation in the distributions made for each board. (Bottom row) Number of views per question as a function of the number of answers on (d) technical, (e) non-technical, and (f) meta sites. Boxes indicate 50% confidence intervals, with a red line to indicate the median view count, and a red dot to represent the mean viewcount.</p