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Negativeome characterization and decontamination in early-life virome studies

Author

Listed:
  • Nataliia Kuzub

    (University Medical Center Groningen)

  • Alexander Kurilshikov

    (University Medical Center Groningen)

  • Alexandra Zhernakova

    (University Medical Center Groningen)

  • Sanzhima Garmaeva

    (University Medical Center Groningen)

Abstract

Contaminant sequences of external origin complicate the study of host-associated viromes, particularly in low-biomass samples obtained through viral-like particle (VLP) enrichment. However, the prevalence and impact of external contaminants on low-biomass samples are under-studied. Here, we analyze 1321 gut virome samples and 55 negative controls (NCs) from four early-life virome studies. Virus sequences identified in NCs, termed negativeome, were used as a proxy for the contamination assessment. We show that 61% of samples share at least one identical strain with negativeome, likely representing external contamination. While the median abundance of contaminant strains in these samples is only 1%, it ranges from 0 to 99% and exceeds 10% in 11% of infant samples. We further demonstrate that contamination is largely study-specific and has a greater impact on infant samples than on maternal samples. Based on our results, we propose a contamination assessment method using a publicly available database of sequences detected in NCs and a strain-level decontamination strategy.

Suggested Citation

  • Nataliia Kuzub & Alexander Kurilshikov & Alexandra Zhernakova & Sanzhima Garmaeva, 2025. "Negativeome characterization and decontamination in early-life virome studies," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61478-7
    DOI: 10.1038/s41467-025-61478-7
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