Assessing microbiome engraftment extent following fecal microbiota transplant with q2-fmt
Fig 2
Schematic of PEDF permutation test.
To test if PEDF is capturing donor overlap caused by microbiome transfer versus general microbiome similarity that could be observed across any two microbiomes in the study, we developed the PEDF permutation test. The PEDF permutation test breaks connections between factual donor-recipient pairs and tests to see if the unrelated donor-recipient pairs are more similar than the related donor-recipient pairs (via FMT transplant). A) The combinations of actual donor-recipient pairs in this example. Note Donor 1 is a donor to two recipients, to illustrate how PEDF permutation handles repeated transfers from one donor. PEDF values would be calculated for each of these pairs, and these would be considered our factual PEDF values. B) To create a null (i.e., counterfactual) distribution to compare factual PEDF values against, donors are paired up with every recipient that they did not donate to, to form our counterfactual pairs. The counterfactual pairs are sampled 999 times, and PEDF is calculated for each counterfactual pair to provide a robust null distribution. If the recipients have significant donor similarity following the FMT, it is expected that our factual donor-recipient pairs will have higher PEDF than our counterfactual donor-recipient pairs. The fraction of counterfactual PEDF values that are greater than an individual factual donor-recipient pair PEDF value is the p-value representing the significance of the factual donor-recipient pair PEDF value. C) A distribution of factual donor-recipient pair PEDF p-values with no globally significant signal will be distributed uniformly. D) If factual donor-recipient PEDF p-values are clustered around significant values, this suggests global statistical significance. This figure is a schematic representation and all data is simulated. Created in BioRender.