Lack of human cytomegalovirus expression in single cells from glioblastoma tumors and cell lines
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The relationship between human cytomegalovirus (HCMV) and glioblastoma (GBM) is an ongoing debate with extensive evidence supporting or refuting its existence through molecular assays, pre-clinical studies, and clinical trials. We focus primarily on the crux of the debate, detection of HCMV in GBM samples using molecular assays. We propose that these differences in detection could be affected by cellular heterogeneity. To take this into account, we align the single-cell RNA sequencing (scRNA-seq) reads from five GBM tumors and two cell lines to HCMV and analyze the alignments for evidence of (i) complete viral transcripts and (ii) low-abundance viral reads. We found that neither tumor nor cell line samples showed conclusive evidence of full HCMV viral transcripts. We also identified low-abundance reads aligned across all tumors, with two tumors having higher alignment rates than the rest of the tumor samples. This work is meant to rigorously test for HCMV RNA expression at a single cell level in GBM samples and examine the possible utility of single cell data in tumor virology.
KeywordsGlioblastoma Cytomegalovirus scRNA-Seq Transcriptomics Sequence analysis
The authors acknowledge RGP0053 of the Human Frontier Science Program, National Library of Medicine Multi-Modeling and Integrative Data Analytics Training Program (T15LM011270-05), the Ohio Super Computer for computation resources and Yan Zhang acknowledges support from the Department of Biomedical Informatics at The Ohio State University.
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Conflict of interest
The authors declare that they have no conflict of interest.
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