Clustergram of Top Enriched Pathway, TF, and GO terms.

<p>Concatenated enrichment profiles for GO, C2, and TF gene set collections, similar to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143563#pone.0143563.g003" target="_blank">Fig 3</a>, ordered by hierarchical clustering of Euclidean distance between rows. Rows have been normalized by dividing by the row sum for visualization, intensity is proportional to normalized enrichment. Heatmap is partitioned into groups A-E based on hierarchical clustering. Clusters A, B, and C are primarily involved in the immune response and are enriched in gene subsets that include more genes. Clusters D and E are predominantly related to developmental and transcriptional regulation processes.</p

DE genes by significance.

<p>DE genes by significance.</p

DAVID functional clustering.

<p>Cluster Function labels were assigned manually by inspecting the terms within the cluster but generally correspond to the name of the most enriched term within the cluster. The (1) Immune response cluster contained 27 distinct terms from across the default genesets used by DAVID.</p

HD sample statistics.

<p>HD sample statistics.</p

Control sample statistics.

<p>Control sample statistics.</p

Detailed GO enrichment.

<p>Top 25 enriched GO categories across all three GO namespaces identified by topGO for different numbers of DE genes. X-axis indicates the number of top genes used for the enrichment in each GO category, e.g. the first column uses the top 25 genes, the second column uses the top 50, and so on. The intensity is proportional to–log10(p-value) from topGO. White dots indicate the gene set with the most significant p-value, concordant with <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143563#pone.0143563.t005" target="_blank">Table 5</a>. This figure shows that the first three GO Categories are defined by genes that are among the top 25 to 150 DE genes in the dataset. GO Categories further down the list are defined by genes whose differential expression is less pronounced between HD and controls.</p

DE genes by DES.

<p>Differential Expression Score (DES) is calculated as (overall mean counts) x abs(log2 FC) x–log10(adjusted p-value)</p

Protein coding genes associated with clinical covariates.

<p>P-values are nominal.</p

DAVID functional clustering network.

<p>Network representation of the DAVID clusters from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143563#pone.0143563.t005" target="_blank">Table 5</a>. Nodes represent clusters, the size of the node is proportional to the number of unique genes that make up the cluster and numbers within nodes are the number of unique genes mapped to terms in the cluster. Edges between nodes indicate the existence of overlapping genes, where the width is proportional to the percent overlap of genes in the smaller of two connected nodes. The color of nodes and edges is proportional to the average fold change of the genes in the node or edge.</p

Differentially expressed miRNAs in HD are located in Hox genes clusters.

<p>Schematic representation of Hox clusters. Hox genes are represented as numbered boxes (labeled 1–13), miRNA are represented by triangles and other genes in the regions (functional lncRNA, <i>PRAC</i>) are represented by rectangles. Antisense transcripts and pseudogenes are not pictured. Nineteen genes within Hox cluster regions were found significantly differentially expressed in HD prefrontal cortex using mRNA-sequencing (FDR-adjusted p-value<0.05). Four miRNAs, one lncRNA, and fourteen Hox genes were significantly up-regulated in HD (indicated by red), many of which are adjacent to differentially expressed miRNAs. A single Hox gene (<i>HOXD1</i>) was down-regulated in HD (indicated by blue). (HD = Huntington's disease).</p