Interestingly, mutation at some sites, such as F113 generated both responsive (F113L, c.337T>C) and nonresponsive mutant forms (F113S, c.338T>C).
Including the immediate sequence context allows better differentiation between different mutational processes; for example, distinguishing between C > T mutations due to the formation UV-light induced photodimers (i.e. C > T mutations at dipyrimidine sites such as Tp CpC or Cp CpC) from C > T mutations due to deamination of 5-methylcytosine (i.e. C > T mutations at CpG sites).
Excluding sites identified as translocation breakpoints (see above), there were 14 such mutation sites in QM9123 and 23 more in QM9414 (Tables 1 and 3).
Another possible explanation for clinical intrafamilial variability could arise in families carrying a splicing mutation that does not affect the canonical splice sites, such as the mutation in COL4A3 gene detected in family 253.
Although we cannot exclude the possibility that the ZFNs may have cleaved unknown off-target sites, such undesired mutations can subsequently be easily excluded from the genome of the carrier animals by backcrossing to the parental strain or another background strain.
During the curation process, curators frequently must consult additional articles, e.g. to disambiguate a gene symbol or to track down specific information such as the mutation sites in certain alleles.
On the other hand, selection-driven change at one site may cause an increase in selection at nearby sites, such as compensatory mutations.
In conclusion, our application of the machine learning technique to somatic mutations could predict some primary tumor sites, such as the large intestine, liver, skin, pancreas, and lung.
For example, mutations that alter transcription factor binding sites such that binding efficiency is reduced are hypothesized to lead to the down regulation of gene transcription, but the environments in which such down regulation will improve fitness are unknown.
In addition, mutations in gene regions responsible for crucial sites, such as folding sites or enzymatic active sites, can be more constrained than disordered segments of proteins [ 1].
