Detection of viral infection in cell lines using ViralCellDetector

ABSTRACT Cell lines are commonly used in research to study biology, including gene expression regulation, cancer progression, and drug responses. However, cross-contaminations with bacteria, mycoplasma, and viruses are common issues in cell line experiments. Detection of bacteria and mycoplasma infections in cell lines is relatively easy but identifying viral infections in cell lines is difficult. Currently, there are no established methods or tools available for detecting viral infections in cell lines. To address this challenge, we developed a tool called ViralCellDetector that detects viruses through mapping RNA-seq data to a library of virus genome. Using this tool, we observed that around 10% of experiments with the MCF7 cell line were likely infected with viruses. Furthermore, to facilitate the detection of samples with unknown sources of viral infection, we identified the differentially expressed genes involved in viral infection from two different cell lines and used these genes in a machine learning approach to classify infected samples based on the host response gene expression biomarkers. Our model reclassifies the infected and non-infected samples with an AUC of 0.91 and an accuracy of 0.93. Overall, our mapping- and marker-based approaches can detect viral infections in any cell line simply based on readily accessible RNA-seq data, allowing researchers to avoid the use of unintentionally infected cell lines in their studies.