Fast estimation of genetic relatedness between members of heterogeneous populations of closely related genomic variants.

Background: Many biological analysis tasks require extraction of families of genetically similar sequences from large datasets produced by Next-generation Sequencing (NGS). Such tasks include detection of viral transmissions by analysis of all genetically close pairs of sequences from viral datasets sampled from infected individuals or studying of evolution of viruses or immune repertoires by analysis of network of intra-host viral variants or antibody clonotypes formed by genetically close sequences. The most obvious naïeve algorithms to extract such sequence families are impractical in light of the massive size of modern NGS datasets.

Results: In this paper, we present fast and scalable k-mer-based framework to perform such sequence similarity queries efficiently, which specifically targets data produced by deep sequencing of heterogeneous populations such as viruses. It shows better filtering quality and time performance when comparing to other tools. The tool is freely available for download at https://github.com/vyacheslav-tsivina/signature-sj CONCLUSION: The proposed tool allows for efficient detection of genetic relatedness between genomic samples produced by deep sequencing of heterogeneous populations. It should be especially useful for analysis of relatedness of genomes of viruses with unevenly distributed variable genomic regions, such as HIV and HCV. For the future we envision, that besides applications in molecular epidemiology the tool can also be adapted to immunosequencing and metagenomics data.