Abstract A12: Web-based tools for visualization of the Human Papilloma Virus genome dynamics: A computational approach to cancer prevention and control

Abstract

Abstract The implementation and widespread use of prophylactic Human Papilloma Virus (HPV) vaccines targeting the most common oncogenic HPV types (HPV 16/18), is expected to change the prevalence of high risk types in populations with high vaccination rates. The projected loss in the Positive Predictive Value (PPV) of cytology in the post vaccination era suggests a need to rely on molecular markers of HPV infection and technologies, such as HPV genotyping. FDA approval of HPV genotyping tests has led to concerns about how typing can assist cervical cancer screening and clinical decisions in a cost-effective manner. Computational tools to visualize the dynamics of genetic material across related HPV genomes are lacking. Web-and Mobile-based tools, which make sequencing results easily accessible to clinicians, investigators, and patients, can be created to facilitate functional interpretations, spur biomarker development, and advance the deployment of medical devices for cancer prevention and control. To facilitate the visualization and functional interpretation of high risk genotypes in hpv-associated cancer patients we downloaded 21 HPV genomes from the NCBI public repository (http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=151340&lvl=3&lin=f&keep=1&srchmode=1&unlock) and created two proof-of-principle Web-based tools, which allow the comparative view of 11 high risk HPV types and 9 low risk HPV types against a reference genome (hpv16). All the 20 genomes play a role in HPV-associated benign or malignant lesions. The Enterix-HPV web servers (http://enterix.cbcb.umd.edu/enteric/enteric-hpv.html), (http://enterix.cbcb.umd.edu/menteric/menteric-hpv.html) allow comparative views of twenty human papilloma virus (HPV) genomes (hpv18, hpv45, hpv68b, hpv53, hpv31, hpv52, hpv6, hpv54, hpv33, hpv56, hpv11, hpv61, hpv35, hpv58, hpv42, hpv72, hpv39, hpv59, hpv44, hpv81) against a reference genome (hpv16), in two formats: large-scale and close-up. The large-scale view (Enteric) displays pair wise alignments and annotations of genome rearrangement events in a 9KB region surrounding an address in the reference genome, whereas the close-up view (Menteric) shows nucleotide-level multiple alignments of the genomes and annotations of conserved and functional regions in a 1KB region. Hyperlinks embedded in the graphical features link to web resources such as the Entrez Gene pages, provide additional information about the feature, or allow downloading sequence data for local analyses. It is anticipated that screening for oncogenic HPV genotypes, followed by cytological triage, may be useful in a post-vaccination era. Genotyping for specific oncogenic HPV types has been shown to increase the PPV and specificity in predicting CIN2/3 and carcinoma in women with ASCUS and LSIL, thus possibly tailoring clinical management of these women in a post vaccination era. Enterix-HPV can be a useful tool for the new wave of Next generation sequencing-based approaches to HPV genotyping for cervical cancer clinical management, prevention and control. Computational tools, such as Enterix-HPV, that create Web- and Mobile-based visualization solutions can be used to spur innovation in HPV-related cancer prevention and clinical care. As HPV genotyping becomes the standard of care in screening and clinical management of HPV related tumors, interactive Web- and Mobile-based genomic visualization tools will become valuable assets for clinicians, research scientists, and patients. Citation Format: Rafael Guerrero-Preston, Michael McClelland, David Sidransky, Liliana Florea. Web-based tools for visualization of the human papillomavirus genome dynamics: A computational approach to cancer prevention and control. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A12.