Figure 4.

Reprogramming enriches for putatively actionable mutations in genes connected to cell cycling, cell death, or pluripotency, and in curated OG and TSGs

The nature of donor-specific category C, potentially GVAs detected in iPSC clones was characterized. (A) Mutational spectra of the collective of donor-specific GAVs, enriched GAVs, and GAVs unique to 1 iPSC clone. n = 10 donors. (B) Percentage of putatively actionable GAVs, defined by harmful designation predicted by a consensus of in silico prediction of Condel, FATHMM, CADD, and SnpEff impact (red), as well as proportion of neutral GAVs (blue). The percentage of variants that affect genes involved in control of cell cycling, cell death, and pluripotency is depicted in dark red or blue, respectively. The proportion of variants in genes with other cellular functions is plotted in light red or blue. n = 10 donors. (C) Total number of putative actionable enriched GAVs and GAVs unique to only 1 iPSC clone per iPSC clone. Mean ± SD; n = 18 iPSC clones of neonatal donors, 12 of aged donors; discrepancy of samples was assessed applying two-tailed Mann Whitney test. (D) Percentage of curated OGs or TSGs as found in the human genome (calculated based on COSMIC cancer gene census and OncoKB database), or affected by neutral or putatively actionable, donor-specific GAVs, enriched GAVs, or GAVs in 1 iPSC clone. n = 10 donors.