Sc-Seq of polyploid hepatocytes reveal increasing CNV with the basal ploidy state

Single-cell whole genome sequencing of wt and caspase-2 deficient murine hepatocytes before and after regeneration reveals increasing levels of copy number variation with basal ploidy. Polyploid hepatocytes from wt and caspase-2 deficient mice were analyzed using single-cell whole genome sequencing. We addressed the question whether caspase-2, the polyploid state or the liver regeneration process impact on the degree of aneuploidy in the liver. We sequenced the ploidy states of 4c, 8c and 16c nuclei isolated form livers of these mice before and 7 days after 2/3 partial hepatectomy (PH). The data was analyzed using the R package AneuFinder (developer version 1.10.1) to call copy number variations (Bakker et al., 2016, van den Bos et al., 2019). The following settings for AneuFinder were used: Fixed ground ploidy for the respective ploidy state of the sample, variable bins (average size of 2Mb), 500kb step size, significance level < 0.05 and R = 20. Breakpoints located within 5 Mb from each other across libraries were grouped and centered using custom made R functions. We introduced an additional data curation step based on total read cound and spikiness of the data. The following cut offs were used: total read count >250kb, spikiness >= 0.11. The data deposited here includes all single profile plots of the sequenced and analyzed nuclei before and after curation based on spikiness and read count.