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scDEcrypter: Uncertainty-aware differential expression analysis for viral infection in scRNA-seq

Zhong, L.; Ensberg, K.; Tibbetts, S.; Molstad, A. J.; Bacher, R.

2026-03-11 genomics
10.64898/2026.03.09.710583 bioRxiv
Show abstract

Single-cell RNA-seq studies of viral infection are limited by sparse viral reads, under-labeled infected cells, and bystander responses that confound differential expression (DE) analysis. We introduce scDEcrypter, a penalized two-way mixture model that leverages partial labels for infection status and additional variables such as cell type. Our approach employs data-splitting to avoid double-dipping and enables fast, likelihood-based inference for DE analysis. Through simulations and applications on two different viral infection datasets, scDE-crypter demonstrated improved recovery of infected cell states and identified more biologically coherent infection-associated genes and enriched pathways.

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