Regardless of whether mutations in the FSC043 are neutral (fixed by genetic drift) or non-neutral (fixed by positive selection), it is interesting that the frequency of fixed disruptive mutations (INDELs) occurred at a frequency that greatly exceeded all other mutations (SNPs, VNTRs) in the strain FSC043.
Intriguingly, the frequency of FIX-specific PCs increased in the spleen of gene therapy-treated mice compared to saline- and LV-OVA treated controls (Fig 4B,E), although this increase did not affect the efficacy of gene therapy in reducing circulating anti-FIX Abs.
To evaluate whether FIX generated in vivo by LV-FIX gene therapy inhibits the activation or even deplete FIX-specific BMEM, we measured the frequency of FIX-specific BMEM (CD19+B220+IgM−IgD−) in LNs harvested from inhibitors-positive haemophilia B mice after LV-FIX gene therapy (Fig 5C,D).
The high frequency of fixed duplications in the glycolysis pathway may reflect the fact that it is the only cytoplasmic pathway in the system.
One is the computational cost necessary for clustering similar oligomers, and the other is the bias in the frequency of fixed-length oligomers, which complicates the detection of significant words.
Clearly, N had a significant effect on the frequencies of fixed mutation rates.
Figure 2 shows the change in the frequencies of fixed mutation rates with population size (N).
These attributes include the frequencies of fixed-length motifs in different windows in the -500 to +70 bps region.
Taking the influence of random factors in simulation studies into account, such small differences in frequencies of fixed mutation rates could be neglected.
In Figure 7, we show the change in the frequencies of fixed mutation rates in response to changes in the range of initial mutation rates assigned to subpopulations.
In Figure 8, we show the change in frequencies of fixed mutation rate given that the initial fitness of all individuals followed a normal or a gamma distribution.
