Negativeome in Early-Life Virome Studies: Characterization and Decontamination

Environmental contamination complicates the study of low-biomass microbial communities like the human gut virome. In 1,321 early-life gut viromes and 55 negative controls (NCs) from four datasets, we identified viral contaminants and their prevalence across studies. Samples and NCs were indistinguishable in genomic and ecological features, with 71.5% of samples sharing at least one identical strain with NCs. This work demonstrates the efficacy of strain-aware decontamination for preserving biological signals.