Looking first at figure S3, nothing stands out. The most important figures here are A, B, and G-I. G-I are showing the % of sequencing runs that gave an unexpected base at I-Ppol cut sites, I-Ppol alternative cut sites, and 100,000 randomly selected sites. There’s a little bit of variation in the ICE samples at canonical sites, but I consider this pretty convincing evidence that the ICE system is not particularly mutagenic.
You should reconsider that conclusion. Double-strand breaks cause an increase in mutation rate. This is a known fact.
The experiment design is weird and the supposed results contradict a lot of other things.
I don’t think the experiment design is that weird. This is not the first iDSB system, and the TAM dose was 1.9mg/kg of bodyweight, 2 OOM less than other IDSB papers, administered orally as opposed to intraperitoneally.
And you don’t see zero mutagenesis, which I agree would be weird, you see a slight increase in mutagenesis specifically at I-Ppol cut sites, (which are, with a single exception non-coding). I’d have to look at accelerated aging via mutagenesis papers to see exactly how much lower the mutation increase here is vs standard, but I’d expect the rate in this paper to be a lot lower.
Could you be specific about what things, exactly, these results contradict?
You should reconsider that conclusion. Double-strand breaks cause an increase in mutation rate. This is a known fact.
The experiment design is weird and the supposed results contradict a lot of other things.
I don’t think the experiment design is that weird. This is not the first iDSB system, and the TAM dose was 1.9mg/kg of bodyweight, 2 OOM less than other IDSB papers, administered orally as opposed to intraperitoneally.
And you don’t see zero mutagenesis, which I agree would be weird, you see a slight increase in mutagenesis specifically at I-Ppol cut sites, (which are, with a single exception non-coding). I’d have to look at accelerated aging via mutagenesis papers to see exactly how much lower the mutation increase here is vs standard, but I’d expect the rate in this paper to be a lot lower.
Could you be specific about what things, exactly, these results contradict?