Computational Integration of HSV-1 Multi-omics Data

Functional genomics techniques based on next-generation sequencing provide new avenues for studying host responses to viral infections at multiple levels, including transcriptional and translational processes and chromatin organization. This chapter provides an overview on the computational integration of multiple types of "omics" data on lytic herpes simplex virus 1 (HSV-1) infection. It summarizes methods developed and applied in two publications that combined 4sU-seq for studying de novo transcription, ribosome profiling for investigating active translation, RNA-seq of subcellular RNA fractions for determining subcellular location of transcripts, and ATAC-seq for profiling chromatin accessibility genome-wide. These studies revealed an unprecedented disruption of transcription termination in HSV-1 infection resulting in widespread read-through transcription beyond poly(A) sites for most but not all host genes. This impacts chromatin architecture by increasing chromatin accessibility selectively in downstream regions of affected genes. In this way, computational integration of multi-omics data identified novel and unsuspected mechanisms at play in lytic HSV-1 infection.