Mutational signatures <i>in vivo</i>, <i>in vitro</i> and through reprogramming.

<p><b>a</b>. Schematic showing the longitudinal progression from <i>in vivo</i> development, <i>in vitro</i> culture of somatic cells through reprogramming and finally through to the experimental set-up used to calculate the mutation rate in iPSC maintenance culture. <b>b</b>. Mutational spectrum of SNVs found in the EPCs (top), and primary (middle) and sub-cloned (bottom) S7-RE14 iPSC lines. Clonal (left) and sub-clonal (right) mutations were shown separately. <b>c</b>. Contribution of mutational processes identified by the NNMF analysis. The germ line mutations described in ref 18 were analysed [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005932#pgen.1005932.ref018" target="_blank">18</a>]. The NNMF analysis was not performed for the mutations in sub-clonal S7-EPC due to the limited number of mutations available.