Single-cell parallel analysis of DNA damage and transcriptome reveals selective genome vulnerability

We used a new technology, named Paired-Damage-seq, to perform simultaneous profiling of DNA damage and mRNA on HeLa cells and mouse cortex at single-cell level. We developed Paired-Damage-seq for joint analysis of oxidative and single-stranded DNA damage with gene expression in single cells. We applied this approach to cultured HeLa cells and the mouse brain as a proof of concept. Our results indicated the associations between damage formation and epigenetic changes. The distribution of oxidative DNA damage hotspots exhibits cell-type-specific patterns; this selective genome vulnerability, in turn, can predict cell types and dysregulated molecular programs that contribute to disease risks.