List of the 27 statistically overrepresented transcriptional regulators (TRs) as a response to the intervention.

<p><i>TR symbol</i> and <i>name</i> are indicated for each TR in the list. <i>Gene</i>:<i>Bg Ratio</i> indicates the number of target genes regulated by the TR (within the specific list of 4,772 out of 5,084 differential genes which appear in customized TR database obtained from Open Regulatory Annotation database) versus the number of target genes regulated by the TR within the background. Background considers 23,991 genes included in the customized database for TR Enrichment Analysis (TREA). TRs are sorted based on their <i>adj p-val</i> (FDR correction) coded as ***<0.001, ** < 0.01 and—in case > 0.05. Last column indicates the <i>adj p-val</i> obtained from Differential Gene Expression Analysis (DGEA).</p

Heatmap of the ranked transcript clusters (TCs) with stronger effect as response to the intervention.

<p>Heatmap of the TCs with stronger effect as response to completed distance in the Ultra Marathon Trail (UMT). Selection was based on β₂ values obtained in the linear model. Those TCs with <i>abs</i>(β₂) > were chosen corresponding to 1,115 among the 5,499 differential TCs.</p

Network of the overrepresented Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways listed in Table 9.

<p>Pathways are connected through their differential annotated genes for each Independent Component (IC) after removing first line of variance. (a) IC1 (b) IC2 (c) IC4 and (d) IC3. Pathway’s node size is proportional to the number of annotated genes (node degree). Genes annotated to each pathway are color-coded according to their type of regulation (green codes for down-regulation and red for up-regulation) together with its official gene symbol. SP stands for signalling pathway.</p

Main contributors of the independent components (ICs) after applying deflationary method to differential genes expression matrix.

<p>Main contributors were selected based on their highest weight values after subtracting one-dimensional data approximation (PC1) to differential genes expression matrix. Those located in the ninth decile were chosen, obtaining a total of 509 genes per IC. Table shows the number of matches between components and the elements that were unique per IC.</p

Network of the overrepresented Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways listed in Table 3 connected through their differential annotated genes.

<p>Statistically significant overrepresented KEGG pathways within the 5,084 distinct genes with marked differential expression level as a response to endurance exercise. Pathway’s circle size is proportional to the number of annotated genes (node degree). Pathway’s node color refers to their specific main category according to the KEGG structure. Genes annotated to each pathway are color-coded according to their type of regulation (green codes for down-regulation and red for up-regulation).</p

Principal component analysis (PCA) over the expression values of the ranked transcript clusters (TCs).

<p>(a) PCA over 25,272 TCs expression values targeting protein coding RNA molecules included in HuGene20st microarray. First principal component was aligned with the effect of participating in the Ultra Marathon Trail (UMT) (b) Proportion (in %) of captured variance per principal component.</p

Participants in the study–age, basic anthropometric and training regime.

<p>Participants in the study–age, basic anthropometric and training regime.</p

Down-regulated genes from the electron transport chain as a response to the intervention.

<p>Down-regulated genes from the electron transport chain as a response to the intervention.</p

Complete workflow implemented for the study.

<p>The differential genes list obtained from the differential gene expression analysis is taken as the initial step for the workflow. This represents the global response to intervention but can also be decomposed in independent components through an Independent Component Analysis (ICA) to obtain the independent block response. ICA is computed after applying a deflation method to the original expression data. Gene and transcriptional regulator (TR) enrichment analyses are computed over the global and independent response. Results are summarized in overrepresented pathway graphs and overrepresented TRs rankings.</p

List of the 42 overrepresented Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways as a response to the intervention.

<p><i>KEGG pathway identifier (ID)</i> and <i>description</i> is enclosed in the table. Pathway’s <i>main category</i> and <i>subcategory</i> are shown. <i>Gene</i>:<i>Bg Ratio</i> indicates the number of genes annotated to a pathway (within the specific list of 1,905 out of 5,084 differential genes which appear in KEGG database) versus the number of genes annotated to that specific pathway within the background. Background considers all genes included in the database which corresponds to 6,997 elements. Pathways are sorted based on their <i>adj p-val</i> (FDR correction) coded as *** < 0.001, ** < 0.01 and * < 0.05. <i>Up-reg[%]</i> indicates the percentage of differential genes annotated to the specific pathway being up-regulated.</p