Heatmaps representing, across the different subcompartments A1-B4, the domain average excess interactions over background within single chromosomes (<i>in-cis</i>, Panel a) and between chromosomes (<i>in-trans</i>, Panel b).

<p>Intra-chromosomal contacts (a) especially occur between homologous subcompartments (diagonal), while inter-chromosomal contacts (b) are particularly frequent with subcompartment A1, rich in highly expressed genes, hinting to a functional role.</p

The heatmap of the overall contacts between chromosome pairs.

<p>While different chromosomal pairs have different degrees of interactions, the RSS analysis points out that there are no significant isolated subgroups and the system forms a single nuclear network.</p

Distribution of the sizes of genomic regions where <i>DR</i> is coherent in sign in the random bootstrapped (red) and Hi-C real data (blue), as a function of the number of domains or, correspondingly, in Mb (the average length of each contact domain is 320Kb).

<p>The superimposed curves are exponential fits.</p

The distribution of intra-chromosomal interactions between contact domains (here in a <i>log</i>₁₀ − <i>log</i>₁₀ plot) decays as a power law, <i>P</i>(<i>I</i>) ≃ <i>I</i>^−<i>γ</i>, with an exponent close to <i>γ</i> ≃ 2 (dashed line), which appear to be ‘universal’ across different chromosomes.

<p>So, the structures of their contact networks exhibit similar quantitative features. <i>I</i>₀ and <i>P</i>₀ are factors to rescale on top of each other the data from different chromosomes.</p

Our analysis of Hi-C genomic interactions shows that the nucleus of human GM12878 cells is structured as a net of networks.

<p>Each individual chromosome form a strong intra-chromosomal network of contacts, consistent with the ‘chromosomal territories’ seen by microscopy. Yet, chromosomes intermingle via weaker, yet non-random and functionally important contacts, whereby distinct chromosomal networks form a global nuclear network. Panel a: A pictorial representation of the 3D organization of chromosomes (colored spheres) within the nucleus, as emerging from our network analysis. Panel b: A real network reconstruction (using the visualization tool described in [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0188201#pone.0188201.ref014" target="_blank">14</a>]) of chromosomal contacts of chromosomes 19 and 20. For clarity of presentation, each sphere inside a chromosome represents ∼ 1<i>Mb</i> (5 contact domains) and a high threshold is set for link visualization.</p

Heatmap of the normalized in-situ Hi-C interactions between the contact domains of chromosomes 19 and 22.

<p>Bands of regions with above background signal are visible, in contrast to the corresponding random matrix (top-right, see details in the text). The differential interaction score, <i>DR</i>, of the domains of chromosome 22 with 19 (rightmost panel) quantifies the dissimilarity with the random control and highlights the clustering of genomic locations enriched in contacts with domains on the other chromosome.</p

Heatmap representing the average frequency of interactions between ‘top interacting’ contact domains (see text).

<p>Panel a: <i>in-cis</i> and Panel b: <i>in-trans</i>, belonging to the different subcompartments.</p

The major issue of oncological treatment administration at the end of life: a retrospective study - supplementary material

Supplementary table S1: Clinicopathological features of study case seriesSupplementary Table S3: Univariate analysis of variable potential predicting end-of-life therapy</p