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bioRxiv · 10.64898/2026.02.25.707904

Identification of different sequence properties between HIV-1 DNA and RNA across subtypes using the k-mer-based approach

Chen, H.-C.·Wisniewski, J.·Serwin, K.·Parczewski, M.·Kula-Pacurar, A.·Skums, P.·Kirpich, A.·Yakovlev, S.
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Abstract

Advanced analytical tools that enable mining of the masked features hidden in intricate datasets and strengthening the biological interpretation of multigenomic outputs hold paramount importance. At present, HIV-1 subtyping remains a challenging task in a great part due to analytical tool discordance. To tackle this issue, in this study, we present an updated version of a k-mer-based approach, PORT-EK-v2, a streamlined bioinformatic pipeline, allowing for a comparison of multiple genomic datasets and identification of over-represented genomic regions, k-mers, related to specific origins of datasets. Using PORT-EK-v2, we exemplified that intrinsic sequence patterns between HIV-1 DNA and RNA are distinct across group M HIV-1 subtypes. Furthermore, we showcased that "isolate k-mer count", a predictive variable computed in this work, could serve as a default choice in classifying the HIV-1 DNA versus RNA sequences across subtypes. Lastly, results based on network-based analyses and Markov chain Monte Carlo modeling unveiled a clear discontinuation of a random walk throughout the network properties corresponding to each tested group of HIV-1 subtypes, confirming the specificity of enriched k-mer retrieved by PORT-EK-v2 and the genomic diversity across group M HIV-1 subtypes. Source code for PORT-EK-v2 is at https://github.com/Quantitative-Virology-Research-Group/PORT-EK-version-2 and is freely available.

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Chen, H.-C., Wisniewski, J., Serwin, K., Parczewski, M., Kula-Pacurar, A., Skums, P., Kirpich, A., Yakovlev, S.. 2026-02-26. Identification of different sequence properties between HIV-1 DNA and RNA across subtypes using the k-mer-based approach. https://doi.org/10.64898/2026.02.25.707904

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