Calibrating MR-link p values

After a first pass of MR-link and if you have at least 100 and preferably 1,000 uncalibrated p values for different genes, it is possible to calibrate them using the script located in ./mr_link/p_value_calibration.py.

for this you require the PYMC3 package and the gcc C++ compiler g++. You can install this package using

pip3 install pymc3

Running a single p value calibration will take up to 30 minutes, but should only have to be performed at the end of an analysis, when all the genes are run.

p value calibration example

After installation of PYMC3 It is possible to run the p value calibration script using the following commands

#Run this from the ./mr_link/ directory
python3 p_value_calibration.py --input_file example_files/uncalibrated_p_values_example.txt --output_file calibrated_p_values.txt

Which will output calibrated p values in the calibrated_p_values.txt file, and accept uncalibrated p values from the uncalibrated_p_values_example.txt file.

If you want to calibrate p values without computing the beta distribution coefficients, you specify the alpha and beta parameters combined with the --only_calibrate option in the following way:

#Run this from the ./mr_link/ directory
python3 p_value_calibration.py \
    --input_file example_files/uncalibrated_p_values_example.txt \
    --output_file calibrated_p_values.txt \
    --only_calibrate \
    --alpha_parameter 3.9703 \
    --beta_parameter 0.6106

If you use simulated datasets, it’s important to calibrate on the null scenarios, then use these parameters on the non-null scenarios.

p_value_calibration.py specifications

The --input_file from which p values are calibrated should be a tab separated file with two columns:

1. exposure_name
2. uncalibrated_p_value

The --output_file is the same file, but with an extra column appended to it:

1. exposure_name
2. uncalibrated_p_value
3. calibrated_p_value