Extended Data Fig. 7: Mapping SVs with low-coverage Hi-C and Giemsa staining.
From: Chromosome evolution screens recapitulate tissue-specific tumor aneuploidy patterns
(a) Top: Copy number plot for clone CQ-ev-H. Bottom: raw read mapping data from deep WGS analysis showing evidence for an 11q-17q translocation breakpoint, which facilitates copy number gains of 11p and 17q. (b) Hi-C plots for chromosomes 11 and 17 in the CQ-ev-H clone (top triangle of diamond) and diploid control (bottom triangle of diamond). Each pixel represents the log2 observed vs expected interaction between a pair of 1 Mb bins (see Methods). Only bins with >1 read are included in the analysis. Since the average number of bin interactions in trans-chromosome interaction space is less than 1, all colored pixels in trans-chromosome interaction space have a positive value. Log2 ratios are capped at +3 or −3. The two diamonds to the right are zoom-ins of the 1 Mb region centered on the known translocation, re-binned at 10 kb. The known translocation is indicated by the dotted line. The chromosome 11-17 translocation is automatically detected from Hi-C data by a modified version of the HiNT algorithm (far right panel). ES = enrichment score (HiNT score of mutant/ HiNT score of diploid control). (c) Sparse Hi-C mapping of two centromeric translocations in the evolved HMEC FQ lineage. (d) Sparse Hi-C mapping of a centromeric translocation in the evolved HMEC FY lineage. (e) Schematic diagram of fold-back inversion identified by deep WGS resulting in an imbalance on chromosomes 1 and 3 in clone FX-ev2-A. (f) Giemsa staining and karyotyping of the normal diploid HMEC clone bq. A karyotype summary of five profiled cells from each is shown on the right. (g) Giemsa staining and karyotyping of the evolved 2N-range aneuploid clone dc-ev2 that gained two copies of 8q. (h) Giemsa staining and karyotyping of an evolved 4N-range aneuploid from the CQ series that gained 4 copies of 1q. Isochromosomes were suspected based on 1q gain dynamics (occurring in multiples of two) and a lack of evidence of trans-fusions in Hi-C. Copy number plots based on WGS for each line are shown as bars above the G-banding images.
