HPViewer

HPViewer identifies and genotypes human papillomavirus (HPV) directly from metagenomic short-read sequencing data to improve sensitivity and specificity of HPV detection in complex samples.

Key Features:

• Custom reference databases: Two custom-built HPV reference databases—one masking simple repeats and one masking homologous sequences—to minimize misidentification due to sequence similarity with human and prokaryotic genomes.
• Homology distance matrix: A homology distance matrix hybridizes the two reference databases to enhance accurate identification from short DNA reads without assembly.
• Direct short-read analysis: Identification and genotyping are performed directly on short DNA reads without requiring assembly into contigs to preserve sensitivity for low-abundance HPV.
• Validation on simulated and clinical samples: Validated on 100 simulated samples and 12 shotgun sequencing samples from respiratory papillomatosis, demonstrating detection across varying read abundances.
• Comparative performance: Matched the specificity of VirusTAP and Vipie and outperformed HPVDetector for HPV types 6 and 11, exhibiting superior sensitivity for those types.
• Large-scale body-site detection: Applied to 1573 sample sets from 18 human body sites, identifying 104 distinct HPV types with site-specific patterns and detecting co-occurrences of 89 HPV types within individual samples.

Scientific Applications:

• Viral epidemiology: Precise genotyping of diverse HPV types across large-scale and multi-site metagenomic datasets.
• Pathogenesis research: Investigation of HPV involvement in diseases, including respiratory papillomatosis, through accurate type-specific detection.
• Metagenomic surveillance: Detection of low-abundance HPV within complex microbial communities and mixed-host samples.

Methodology:

Uses two custom HPV reference databases (one masking simple repeats, one masking homologous sequences) and a homology distance matrix to hybridize the databases, and performs direct analysis of short DNA reads without assembly into contigs.