Clusters of 33 genes whose products have known protein-protein interactions copy changed among 34 (22%) of 154 patients with intellectual disability.

<p>These genes were those identified using two or more methods (from KEGG, GO and Gene Expression clustering) and that were found to contribute to a significant enrichment of interactions identified by the Dapple protein-protein interaction network (<i>p</i> < 1x10^–4).</p

Forty non-exclusive patient groups, each group’s patients sharing the same HPO term, amongst whom individual copy number variant candidate genes were each recurrently identified by multiple functional genomics methods and whose recurrently-identified candidate genes demonstrated a significant number of protein-protein interactions.

<p>The dendrogram displays the relationship between categories based upon the number of candidate genes identified by multiple methods that are shared between the phenotype-group patients. Categories are marked if there were significant enrichments using clustering in a gene expression network (Blue), GO (Green) or KEGG (yellow). No phenotype-grouped patients with candidate genes meeting these criteria were identified use mouse KO phenotype (MGI) associations.</p

Functional genomics enrichments significantly enriched in genes affected by <i>de novo</i> CNVs in 33 patients presenting with seizures.

<p><b>(A)</b> Significant functional genomics enrichments. Many of these functions have links to seizures or associated phenomena (synaptic deficits, receptor signaling, gustatory aura[<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005012#pgen.1005012.ref073" target="_blank">73</a>]) but also to regions prone to copy number variation[<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005012#pgen.1005012.ref074" target="_blank">74</a>]. <b>(B)</b> Genes disrupted by short CNVs in patients were also observed to cluster significantly in a brain-specific gene co-expression network. Here we display the strongest clusters (<i>r ></i> 0.92 for all co-expression similarities) of genes from seizure patients from this network. <b>(C)</b> Overall, the functional enrichments identified known (HPO-defined) seizure genes for 11 of the 33 patients, and proposed causal genes for 21 of the remaining 22 patients.</p