Characterization of phenotypic similarity by linear discrimination.

<p>(<b>a-c</b>) Images of cells in which <i>sfrp1, dvl2</i> or <i>fzd7</i> were knocked down, respectively. (<b>d</b>) First two principal components (PC 1 and PC 2) of the features for cells with knockdown of <i>sfrp1</i> and <i>dvl2</i>. (<b>e</b>) First two principal components of the features for cells with knockdown of <i>dvl2</i> and <i>fzd7</i>. Dotted lines sketch a linear separation.</p

Workflow.

<p>Images of a genome-wide cellular RNAi knockdown screen (the screening data was derived from the Mitocheck project, <a href="http://www.mitocheck.org" target="_blank">www.mitocheck.org</a>) were segmented and their features extracted to compile pairwise phenotype descriptors for a large set of gene pairs. These descriptors were used to train a machine learning system to discriminate activating and inhibiting PPIs taken from a reference. The performance was evaluated using cross-validation. The trained SVM models were used to predict the effects of uncharacterized PPIs. In addition, the SVM models were used to estimate similarity of the effects of proteins for all combinations of protein pairs in the network. Subsequently, this Effect Similarity Rate (ESR) was exemplarily used for clustering of functionally related protein sub-networks.</p

a) Receiver Operating Characteristics curves for the predictions of activation.

<p>Cross-validation results for all pathways combined (AUC  = 0.75, dashed line) and when training and validation was done for each set of pathways separately (AUC  = 0.82, solid line). <b>b</b>) Histogram of the votes for activating PPIs (green) and inhibiting PPIs (blue) when training and validation was done for each set of major signaling pathways separately. The thresholds for 80% confidence were set at 920 and 88 votes for activation and inhibition, respectively (dashed lines).</p

Clustering of the chemokine receptors and their interactors.

<p>Clustering of the chemokine receptors and their interactors.</p

Pairs of Pfam domain sets showing significant^* enrichment of predicted interactions.

<p>^*p≤0.1 only; t≥1 for both pos/neg - no zeroes.</p><p>Pairs of Pfam domain sets showing significant^{<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003814#nt101" target="_blank">*</a>} enrichment of predicted interactions.</p