Demography and the genetics of age-related diseases.

<p>A schematic representation of the effect of birth cohort and chronological age on the genetic risk of age-related diseases is depicted. The interaction between demographic, environmental, and aging factors allows a genetic risk to emerge (LOCUS green becomes LOCUS X red) only in the presence of a unique combination of chronological age and birth cohort, due to the combined effect of changes in the environmental pressures and the physiopathological remodelling that occurs with age.</p

DRYAD_journal.pone.0032678.s004

The archive contains files (tab delimited values format; protein list files, protein interaction list files and README files) relative to the proteins datasets and protein-protein interaction data related to, and described in the original article, i.e. DI, UI, MCI, UNION, DG and FEEDBACK datasets

summary of main network parameters of NF-κB upstream protein interactomes DI, UI, MCI and UNION and overrepresented KEGG pathways (p<0.05).

<p>See main text for further comments and explanations. Complete datasets available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032678#pone.0032678.s003" target="_blank">Table S3</a>.</p

The UNION interactome is composed by 622 proteins, including the five NF-κB subunits.

<p>NF-κB is able to regulate the expression of 426 proteins (DG set, see main text). A subset (384 proteins, present in the APID database, out of 426) has been checked for PPIs (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032678#pone.0032678.s004" target="_blank">Dataset S1</a>). Forty nine proteins are shared by both the UNION and the DG sets, establishing a feedback loop: “<i>interaction with NF-κB pathway → transcription factor activation → transcriptional regulation → interaction with NF-κB pathway</i>”, meaning that 13% of the identified NF-κB-regulated genes express proteins that play a direct role in the UNION interactome.</p

First 25 most central proteins (betweenness centrality) in UNION interactome (in bold the NF-κB components).

<p>First 25 most central proteins (betweenness centrality) in UNION interactome (in bold the NF-κB components).</p

The three interactomes DI (a), UI (b) and MCI (c) and the resulting UNION interactome (d) as from Cytoscape layout, available in the Dataset S1 as .<i>cys</i> file.

<p>Datasets and interactomes have been reconstructed following procedures described in materials and methods section. Nodes represent proteins and links are evidence-based physical interactions. Node size and color are proportional to betweenness centrality values (red: high, green: low; not comparable among different interactomes). Isolated proteins show no evidence of physical interactions with any other proteins within the same dataset.</p

Overrepresented pathways in DG (p<0.05), first 20 terms ranked for percentage of DG proteins present in KEGG pathway (“% of set” column).

<p>Overrepresented pathways in DG (p<0.05), first 20 terms ranked for percentage of DG proteins present in KEGG pathway (“% of set” column).</p

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Correlation analysis reveals the emergence of coherence in the gene expression dynamics following system perturbation-4

<p><b>Copyright information:</b></p><p>Taken from "Correlation analysis reveals the emergence of coherence in the gene expression dynamics following system perturbation"</p><p>http://www.biomedcentral.com/1471-2105/8/S1/S16</p><p>BMC Bioinformatics 2007;8(Suppl 1):S16-S16.</p><p>Published online 8 Mar 2007</p><p>PMCID:PMC1885845.</p><p></p>butions between Y-treatment and NY-control is qualitatively the same as the one observed in the entire pool of genes selected with the change point analysis (Figure 2)

Correlation analysis reveals the emergence of coherence in the gene expression dynamics following system perturbation-2

<p><b>Copyright information:</b></p><p>Taken from "Correlation analysis reveals the emergence of coherence in the gene expression dynamics following system perturbation"</p><p>http://www.biomedcentral.com/1471-2105/8/S1/S16</p><p>BMC Bioinformatics 2007;8(Suppl 1):S16-S16.</p><p>Published online 8 Mar 2007</p><p>PMCID:PMC1885845.</p><p></p>with one-way ANOVA, P value < 0.01. The picture on the right (B) is the histogram of the correlation coefficients for a set of 768 probesets randomly sampled from the whole dataset of 14688 probesets. A single-gene time reshuffling applied onto each dataset produces a Gaussian distribution (data not shown)