Fig. 6
From: A practical guide for mutational signature analysis in hematological malignancies
Bleeding of signatures in CLLs. Summary of mutational signature analysis on 146 CLL cases. From the 96-mutational catalog (a) the Alexandrov et al.6,7 framework (NNMF) extracted different mutational processes. Signature 9 (nc-AID) was extracted also among U-CLL in contrast with their known pathogenesis (b). This is a typical example of inter-sample bleeding and it can be solved either running a fitting approach after the initial NNMF analysis using only the catalog of signatures extracted by NNMF (c), or analyzing M-CLL and U-CLLs in two different and independent runs (d, e). Using the 30 COSMIC signatures as reference, the first approach is usually the most appropriate in order to estimate the real contribution of each single mutational process. In fact, the NNMF extracted signatures may be over or under split, therefore preventing a precise estimation of their contribution. For example, in this analysis, Signature 1 and 5 were extracted as one single process and only by running a fitting approach we were able to differentiate these two processes (c). Sig. = signature. In b and c, red patient labels are used for U-CLL, green for M-CLL, and blue for unknown cases
