DOI: http://dx.doi.org/10.7554/eLife.02935.016 To quantify whether the somatic mutational signature we have defined can fully explain the trinucleotide frequency of human mtDNA, we performed evolutionary simulations.
In the report summary, we stated, No single factor can fully explain the U.S. health disadvantage.
Having said that, it seems unlikely that these or other potential sources of bias can fully explain the substantial association we observed between the intervention programme and reduced incidence of sphincter tears.
The above discussion indicates that we cannot unequivocally determine if any one of the four mechanisms can fully explain our observations.
In their discussion of the Heinzle study, Raemaekers and colleagues noted a few differences in the methods and analyses, but ultimately concluded: "Whether this difference in methods can fully explain the difference in results is unclear…" We agree that there was considerable variability in the imaging and analytical approaches across all three studies (Heinzle's, Raemaekers', and ours).
However, we do not believe that the increased binding affinity for SII Ang II can fully explain the changes in potency/efficacy profiles for SII Ang II in the BRET vs. IP accumulation assay.
We therefore carried out further tests to establish whether changes in DNA composition can fully explain the observed variability in AAC.
Although we cannot rule out the possibility of residual confounding, it is unlikely that it can fully explain the observed strong associations.
To address the reviewer's point directly, we don't think the alternative of a limited capacity for motor control in pcd can fully explain our data.
If a system of equations is solvable, then the corresponding set of transcripts can fully explain the observed read coverage (see Supplementary Section G; for simplicity, we ignore statistical fluctuations and use exact, i.e. expected, quantities).
