Site-specific genotypes and virome composition may be further shaped by the host’s immune response. Recent phylogenetic analysis also suggested that anatomical site predilection and tissue tropism by distinct HPV genotypes may be a result of viral niche adaptation to host ecosystems. The genetic differences in these oncogenes conferred disparate phenotypes and oncogenic potential. The PV genome backbone acquired oncogenes E6 and E7 and later E5 approximately 184 and 55 million years ago, respectively. The papillomavirus (PV) is a small 8000 base pair (bp) double-stranded, circular DNA virus that co-evolved with an ancestral host over 400 million years. The annual global burden of 570,000 new cervical and 120,000 other anogenital and oropharyngeal cancer cases have been attributed to HPV. Nonetheless, HPV is the second most prevalent primary infectious cause of cancer worldwide. The etiological role of HPV in breast and esophageal cancers has been postulated for several decades but remains controversial due to conflicting findings. Since then, the causal role of carcinogenic HPV in anogenital, oropharyngeal, and dermatological cancers (in patients with epidermodysplasia verruciformis) has been established and classified by the International Agency for Research on Cancer (IARC). Two thousand years elapsed before zur Hausen and his “papillomavirus crew” made the breakthrough discovery of identifying human papillomavirus (HPV)-16 in cervical, vulvar, and penile cancers in 1983. Hippocrates was the first to describe cervical cancer and its destructive nature around 400 BCE. The entire process named “HPV DeepSeq” provides a simple, accurate and practical means of NGS data analysis for a broad range of applications in viral research. Integrating clinically relevant, taxonomized HPV reference genomes within automated workflows proved to be an ultra-fast method of virome profiling. Biodiversity analysis between low- (LSIL) and high-grade squamous intraepithelial lesions (HSIL) revealed loss of species richness and gain of dominance by HPV-16 in HSIL. Tabular output conversion to visualizations entailed 1–2 keystrokes. Low-grade ( n = 95) and high-grade ( n = 60) Pap smears were tested with ensuing collective runtimes: Taxonomic Analysis (36 min) Alpha/Beta Diversities (5 s) Map Reads (45 min). HPV genomes from Papilloma Virus Episteme were customized and incorporated into CLC “ready-to-use” workflows for stepwise data processing to include: (1) Taxonomic Analysis, (2) Estimate Alpha/Beta Diversities, and (3) Map Reads to Reference. To address this, we developed and tested automated workflows for HPV taxonomic profiling and visualization using a customized papillomavirus database in the CLC Microbial Genomics Module. However, viral computational analysis remains a bottleneck due to semantic discrepancies between computational tools and curated reference genomes. Next-generation sequencing (NGS) has actualized the human papillomavirus (HPV) virome profiling for in-depth investigation of viral evolution and pathogenesis.
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