Uncovering Viral Signals Across Cell Populations in Colorectal Cancer

Cell-type-resolved viral reference-associated RNA signals in colorectal tissue differ by compartment and colon region, with random forest classification reaching macro-AUC 0.957 (SD 0.028) using HERV-K113.

• Why it matters: Viral sequences are reported in colorectal cancer, but where they appear across cell types and tissue conditions is unclear, limiting interpretation of virus–host biology and immune relevance.
• What they did: The study reprocessed human-unmapped reads from single-cell RNA-seq libraries from 10 public studies (547 libraries, 112 participants; ~415,000 cells), aligning to a curated human-associated viral reference and validating with participant-grouped repeated cross-validation plus an independent paired proteomics screen.
• The result: After Benjamini-Hochberg correction, 7 of 318 healthy-reference viral-load comparisons (6 virus–cell-type groups) remained significant, and proteomics found compatible peptide matches for 20 candidate viral groups.

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