PMC5108817_01
Multi-layer approach to multi-omic data integration. Our approach consists of a three-layered model to compare cells in different conditions: the first layer represents the functional similarity of genes (according to the BP domain of GO) on which mutation data from the COSMIC database are mapped; the second layer represents the conformation of the chromatin in the nucleus (according to Hi-C data analyzed with NuChart) on which epigenetic information of cells are mapped, relying on MeDIP-seq experiments; the third layer represents a protein-protein interaction network (according to the STRING database) on which gene expression data are mapped.
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PMC5108817_01_fgene-07-00194-g0002.jpg
F2
As it can be seen from the comparison between Figures 3, 4, after the E2 stimulation the genes inside the nucleus achieve a closer conformation, becoming denser around the seed gene ESR1.
Multi-layer graph for the breast cancer cell line MCF-7 at time point 0 h, before E2 stimulation, considering ESR1 as seed gene. (A) represents the stacked multilayer (interlayer edges have been removed for readability), while (B) shows each single layer separately. In both panels, from left to right, the first layer represents the functional similarity of genes relying on the BP domain of GO, as computed by InteGO2. On this network, breast cancer mutation data are mapped, according to the COSMIC database (colors and dimensions of nodes indicate the number of samples with mutations in the COSMIC dataset for each gene). The second layer represents the conformation of the chromatin in the nucleus, according to Hi-C experiments analyzed using NuChart. Vertices are colored according to the methylation of genes, relying on MeDIP-seq experiments. The third layer represents a protein-protein interaction network according to the data reported in the STRING database. Gene expression data have been mapped on this graph and vertices are represented accordingly. Please note that in each layer genes are mapped always in the same positions, according to the representation achieved in the fourth level of (A), in which all genes are aggregated and the Fruchterman-Reingold is performed to achieve the optimal distribution of vertices.
fgene-07-00194-g0003.jpg
PMC5108817_01_fgene-07-00194-g0003.jpg
F3
In Figures 3, 4 we present two multi-layer graphs, as achieved with MuxViz, for the breast cancer cell line MCF-7 at time point 0 and 4 h after E2 stimulation (see Supplementary Tables 1, 2 for the full gene lists). The fourth level in Figures 3, 4 represents the aggregate layer, which shows the whole gene set staged in the other three layers (since, as discussed above, they can present different genes, due to the different connections that can be generated using the seed genes as input of the different tools). As it can be seen from the comparison between Figures 3, 4, after the E2 stimulation the genes inside the nucleus achieve a closer conformation, becoming denser around the seed gene ESR1.
Multi-layer graph for the breast cancer cell line MCF-7 at time point 4 h after E2 stimulation, considering ESR1 as seed gene. (A) represents the stacked multilayer (interlayer edges have been removed for readability), while (B) shows each single layer separately. In both panels, from left to right, the first layer represents the functional similarity of genes relying on the BP domain of GO, as computed by InteGO2. On this network, breast cancer mutation data are mapped, according to the COSMIC database (colors and dimensions of nodes indicate the number of samples with mutations in the COSMIC dataset for each gene). The second layer represents the conformation of the chromatin in the nucleus, according to Hi-C experiments analyzed using NuChart. Vertices are colored according to the methylayion of genes, relying on MeDIP-seq experiments. The third layer represents a protein-protein interaction network according to the data reported in the STRING database. Gene expression data have been mapped on this graph and vertices are represented accordingly. Please note that in each layer genes are mapped always in the same positions, according to the representation achieved in the fourth level of (A), in which all genes are aggregated and the Fruchterman-Reingold is performed to achieve the optimal distribution of vertices.
fgene-07-00194-g0004.jpg
PMC5108817_01_fgene-07-00194-g0004.jpg
F4
In Figures 3, 4 we present two multi-layer graphs, as achieved with MuxViz, for the breast cancer cell line MCF-7 at time point 0 and 4 h after E2 stimulation (see Supplementary Tables 1, 2 for the full gene lists). The fourth level in Figures 3, 4 represents the aggregate layer, which shows the whole gene set staged in the other three layers (since, as discussed above, they can present different genes, due to the different connections that can be generated using the seed genes as input of the different tools). As it can be seen from the comparison between Figures 3, 4, after the E2 stimulation the genes inside the nucleus achieve a closer conformation, becoming denser around the seed gene ESR1.