Functional variants of human papillomavirus type 16 demonstrate host genome integration and transcriptional alterations corresponding to their unique cancer epidemiology

Table 1 Integration loci detected by ViralFusionSeq

Sample	Mapped human transcript†	Gene description	Chromosome location	HPV transcript breakpoint(s)‡
AAE6	SLC26A2	Solute carrier family 26, member 2	5q32	E1, L1
AAE6	PDE6A	Cyclic GMP- Phosphodiesterase 6A alpha subunit	5q32	E1, L1
EPE6	None	–	–	–
NIKS	None	–	–	–

Viral-human fusion transcripts were discovered using ViralFusionSeq’s [61]: clipped-sequence (CS) and read-pair (RP) modules. Detected by at least 1 RP and CS event (†). As detected by CS method (‡). VFS uses two methods to detect viral-human fusion transcripts. The Clipped-Seq (CS) method detects viral fusion transcript breakpoints with a read that maps to both viral and human sequences, while the Read-Pair (RP) analysis detects transcripts with read ends mapped separately to the viral and human genome [61]. We required candidate viral fusion transcripts to be supported by at least 1 CS and 1 RP event in order to improve its stringency [64]. Although RP events were more abundant in our samples, CS analysis provided single-base resolution of viral-human fusion transcript breakpoints. In particular, we identified an average of 1.33 +/− 1.53 CS transcripts in EPE6 and 7.66 +/− 6.66 in AAE6. We detected no RP transcripts in EPE6, while 118.66 +/− 7.23 were found in AAE6 rafts. While one RP transcript was detected in a NIKS control culture, this read was not confirmed by the CS method of VFS and therefore not considered as a valid event

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