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Fig. 2 | Genome Biology

Fig. 2

From: Endometrial tumorigenesis involves epigenetic plasticity demarcating non-coding somatic mutations and 3D-genome alterations

Fig. 2

3D genome landscape is remodeled during tumorigenesis. a Schematic of the Hi-C library preparation starting from fresh frozen tissues. Ten 30-µm-thick slices of flash-frozen tissue are cross-linked 25 min in 2% formaldehyde. Then, electronically homogenized tissues are filtered using a 75-µm cell strainer and subjected to Hi-C library preparation. Hi-C libraries are then sequenced and resulting reads are analyzed by the snHiC [24] pipeline. b On the left, 40-kb-resolution matrices of the average Hi-C score in tumor (n = 3) and healthy endometrial tissues (n = 3) at chromosome 6. On the right, differences of the scores shown on the left side (tumor − healthy). c Relative Hi-C contact probability (RCP) as function of the distance for each individual sample (40-kb resolution). d Violin plot of the distribution of the short-range (<2 Mb) over long-rage (>2 Mb) Hi-C contacts ratio in each individual sample (40-kb resolution). For each comparison, the Wilcoxon’s test P value is indicated. e Distribution of the Hi-C loop distance (10-kb resolution) for loops overlapping with tumor-depleted, tumor-enriched, or shared ERα consensus peaks in combined healthy (blue) or tumor (orange) endometrial tissues. f PE-SCAn results in healthy and tumor tissues at common, tumor-depleted, and tumor-enriched ERα binding sites. For each panel, top and middle rows depict the 3D and 2D, respectively, representation of the Hi-C contact frequency distribution in healthy (left) and tumor (right) tissues; lower row shows the difference of Hi-C contact frequencies between tumor (orange) and healthy (blue) tissue scores. g Compartment polarization ratio (100-kb resolution), defined as (AA + BB)/(AB + BA), for each individual sample. h Top: saddle plot of A/B compartments interactions as computed in g for each individual sample. Bottom: difference of saddle-score with the reference H.005.A2 (healthy tissue), where orange indicates a higher score in tumor samples while purple indicates a higher score in healthy tissues. i Sankey plot depicting the proportion of compartment state transition (100-kb resolution) of healthy compartments (left) upon tumorigenesis (right). j Upset plot showing the overlaps between different compartment transition states (100-kb resolution) in healthy compared to tumor as in g (A-to-A, B-to-B, A-to-B, B-to-A) and different categories of ERα consensus peaks. k Stacked bar plot of the proportion of compartment transition status as in g for individual genomic bins overlapping with only one of the different categories of ERα consensus peaks

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