Fig 1.
Hi-C as a new technique for detecting large-scale SVs.
(A) The expected alteration to chromatin interaction frequencies for different types of SVs. (B) The Hi-C map is shown a validated deletion event in K562 cell line. (C) The significances of interaction frequencies of stripes, TADs and SV boundaries on chromosome 4 in K562 cell line.
Fig 2.
HiSV has the three major steps: (1) Distance normalization: HiSV normalized the interactions based on linear genomic distance; (2) Saliency measure: the saliency value of each bin pair is measured by calculating the dissimilarity between its interactions and that of neighboring bin pairs; (3) Segmentation: HiSV used two-dimensional segmentation method to group the sparse data into several subgroups called segments, and a segment will be reported as a SVs event if the segmented interactions greater than a predefined cutoff.
Fig 3.
Performance comparison of SVs callers.
(A) The precision and recall rates of SVs detected by HiSV, HiC_breakfinder, HiCtrans and HiNT-TL in the simulation sample at different sequencing depths. Black contours show harmonic means of precision and recall rates (F1-score). (B) The precise and recall rates of SVs detected by the above methods in HCC1954, K562 and T47D cell lines. (C) The number of validated SVs with different types detected by existing methods. (D) The number of different ranges of SVs detected by HiSV and HiC_breakfinder with validation by groundtruth.
Fig 4.
Complex SVs were detected by HiSV.
Intra-chromosomal complex SVs were detected in K562 (A) and T47D (B) by HiSV. The top shows the Hi-C maps with complex SVs and boxes represent the SVs event detected by HiSV. The plot in the middle depicts breakpoint connections that are detected from long-read sequencing data. The bottom panel shows the genome structure of the complex SVs. Inter-chromosomal complex SVs were detected in T47D (C) and K562 (D) by HiSV. The top panel shows Hi-C maps with complex SVs. The circos plot in the below, from outside to inside, depicts the chromosome ideogram, copy number profiles and breakpoint connections. The black arcs are the SVs detected from long reads data and red arcs represent the inter-chromosomal rearrangements detected by all Hi-C methods.
Fig 5.
Effects of SVs on gene expression in K562 cell line.
(A) Volcano plot showing differentially expressed genes (DEGs); red dots represent upregulated genes; blue dots represent downregulated genes and gray dots represent genes with no expression changes. (B) Comparison of the genes in SV regions with DEGs. (C) The overlap counts of DEGs in novel SV regions and common SV regions. (D) The differential expression of GPC5 is associated with neo-loops. (E) The upregulated expression of DLGAP1 is associated with an enhancer hijacking event.
Fig 6.
HiSV complements the detection of SVs by the WGS method.
(A) The detection results of WGS method and HiSV for different types of large-scale SVs in K562 (left) and T47D (right) cell lines. (B) Circos plot visualizing the detection of novel SVs in K562 (left) and T47D (right). Tracks from outer to inner circles are the chromosome ideogram, duplication (red) and deletion (blue), and positional rearrangements including inversions (green), intra-chromosomal translocation (orange), and inter-chromosomal translocation (purple).