Evalidating com

Associations of specific substitution and insertion/deletion (indel) signatures with mismatch repair (MMR) deficiency though conspicuous, have not been confirmed.Many other genes are also involved in the myriad DNA repair pathways in our cells, and it is not clear whether genetic defects in alternative, related genes could produce mutational signatures as well.

The concept of mutational signatures was postulated in 2012: The catalogue of somatic mutations uncovered through tumour sequencing is the outcome of one or more mutational processes that have been operative through the lifetime of a cancer patient, though each has its own mathematical idiosyncrasies leading to results that are broadly similar, but never identical.

Proliferation rates were also determined for each knockout cell line (Supplementary Fig. Moreover, potential off-target sites were also searched using COSMID ( a web-based tool to identify and validate CRISPR/CAS9 off-target sites (see Supplementary Data 2 for a ranked-list of potential off-target sites of the relevant guide RNA sequences generated by COSMID).

Furthermore, we also confirmed in all subclones, that no additional mutations were acquired in other DNA repair genes during the early clonal expansion phase (see Supplementary Data 3 for a list of DNA repair genes) that could affect the final mutational signature obtained in each subclone. Above the background mutations, subclones associated with particular gene knockouts also had greater numbers of specific classes of mutations, although effect sizes were notably variable.

This has caused some to question the robustness of the concept.

Nevertheless, as a field, mutational signature research has progressed remarkably.

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