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Figure 3 | Genome Biology

Figure 3

From: Diverse modes of genomic alteration in hepatocellular carcinoma

Figure 3

Hepatitis B virus integration and chimeric transcription in hepatocellular carcinoma. (A) Viral integrations in 12 whole-genome sequenced samples were determined based on human-viral chimeric reads. Overlapping or nearby (within 500 bp) chimeric reads were clustered together, and the closest gene to the human-viral junction of each cluster was determined. In the plot, each point represents a chimeric read cluster, and the y-axis represents the total number of chimeric reads per cluster per gigabase of mapped human bases for that sample. The human junction is shown on the x-axis. For each sample, the cluster with the highest number of chimeric reads is labeled with the closest gene. (B) Two hotspots for viral breakpoints in viral-human chimeric transcripts. Human-viral chimeric RNA reads were clustered based on close vicinity (up to 500 bp). The scatter plot shows the mapping of the clusters on the viral genome (y-axis) versus the linearized human genome (x-axis). The size of the points is proportional to the number of reads belonging to the cluster. The histogram on the y-axis represents the frequency of chimera observed along the viral genome. Two hotspots are observable. The most frequent viral junction is the region at the 3' end of the X gene. A second, less frequent hotspot is seen at the S gene. (C) Chimeric transcripts show enrichment for viral promoter origin and human exon exclusion. Histograms representing chimeric RNA-Seq read counts are shown. Chimeric reads were classified as downstream, when the viral positive strand was 3' of the human sequence, or upstream, when the viral positive strand was 5' of the human sequence (consistent with viral promoter-driven transcription). They were further classified for inclusion or exclusion of human exon sequence. Specific enrichment of the chimeric transcripts can be seen when the viral sequence is upstream of the breakpoint, and human exons are excluded.

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