Motivation: As one of the most common and life-threatening diseases in humans, cancer is a result of the accumulation of somatic mutations throughout the life cycle. Somatic mutation is a joint result of DNA lesion, which is a result of damage on DNA caused by mutagen, and the failure of DNA repair mechanisms. Therefore, understanding the mechanism of DNA repair is important for the development of cancer pathology. Research on mutational signatures in cancer genomic data has given us insights into the relationship between DNA repair pathway and certain types of cancer. However, close-up studies on DNA repair pathways still need to be carried out to understand repair behaviour further. The CRISPR-Cas9 technique can create double-strand break in DNA. This paper extracts mutational signature to observe the characteristic of the pathway for the CRISPR-mediated double-strand break repairing in order to obtain a deeper understanding on DNA repair mechanisms.
Results: By analyzing the mutational signature extracted from CRISPR-Cas9 mediated targets, we found out that the mutational processes involved in double-strand break DNA repair processes are simple and predictable compared to mutational processes involved in the formation of cancer cells. When comparing the mutational processes in wildtype and cNHEJ-deficient cells, the latter show a much higher frequency of micro-homology related deletions. However, no significant difference between the two types of cells on the mutational process is able to be captured by the mutational signature extraction algorithm. The experiments also show that the selection of mutational features could significantly influence the final signature extraction results.