HPV-KITE: sequence analysis software for rapid HPV genotype detection

Human papillomaviruses (HPVs) are among the most diverse viral families that infect humans. Fortunately, only a small number of closely related HPV types affect human health, most notably by causing nearly all cervical cancers, as well as some oral and other anogenital cancers, particularly when infections with high-risk HPV types become persistent. Numerous viral polymerase chain reaction-based diagnostic methods as well as sequencing protocols have been developed for accurate, rapid, and efficient HPV genotyping. However, due to the large number of closely related HPV genotypes and the abundance of nonviral DNA in human derived biological samples, it can be challenging to correctly detect HPV genotypes using high throughput deep sequencing. Here, we introduce a novel HPV detection algorithm, HPV-KITE (HPV K-mer Index Tversky Estimator), which leverages k-mer data analysis and utilizes Tversky indexing for DNA and RNA sequence data. This method offers a rapid and sensitive alternative for detecting HPV from both metagenomic and transcriptomic datasets. We assessed HPV-KITE using three previously analyzed HPV infection-related datasets, comprising a total of 1430 sequenced human samples. For benchmarking, we compared our method's performance with standard HPV sequencing analysis algorithms, including general sequence-based mapping, and k-mer-based classification methods. Parallelization demonstrated fast processing times achieved through shingling, and scalability analysis revealed optimal performance when employing multiple nodes. Our results showed that HPV-KITE is one of the fastest, most accurate, and easiest ways to detect HPV genotypes from virtually any next-generation sequencing data. Moreover, the method is also highly scalable and available to be optimized for any microorganism other than HPV.