radadjust - Correct p-values of individual CpGs

Synopsis

$ dnmtools radadjust [OPTIONS] <regression-output.bed>

Description

This program adjusts the p-value of individual CpGs in the output of radmeth. A typical application that takes the regression output as input and combines the p-values of 200 neighboring CpGs is done as follows.

$ dnmtools radadjust -bins 1:200:1 input.bed >output-adjusted.bed

Here, the only required parameter, besides the input file, is -bins whose value is set to 1:200:1 (which is also the default value). This means that for each n = 1, 2, ...199, radmeth-adjust computes the correlation between p-values of CpGs located at distance n from each other. These correlations are used during significance combination step. In addition, bin sizes determine the window for combining significance. In contrast, if -bins is set to 1:15:5, then the correlation is computed separately for p-values corresponding to CpGs at distances [1, 5), [5, 10), and [10, 15) from one another. The first five columns and the last four columns of radmeth-adjust have the same meaning as those output by radmeth regression. The 6th column gives the modified p-value based on the original p-value of the site and the p-values of its neighbors. The 7th column gives the FDR-corrected p-value. Then the last four columns correspond to the total read counts and methylated read counts of the case group and control group, respectively. Here is what the output-adjusted.bed file looks like for our example dataset:

chr1  108   +     CpG   0.157971    0.099290    0.353466    18     4    20    15
chr1  114   +     CpG   0.559191    0.099290    0.353466    21     3    41    10
chr1  160   +     CpG   0.095112    0.099290    0.353466    32    24    39    17
chr1  309   +     CpG   0.239772    0.122248    0.368902    33    17    19    13
chr1  499   +     CpG   0.770140    0.204467    0.419872    43    22    29    15

After completing the previous steps, individual differentially methy- lated sites can be obtained with 'awk'. To get all CpGs with FDR-corrected p-value below 0.01, run

$ awk '$7 <= 0.01' output-adjusted.bed >output-significant.bed

Options

 -o, -out

Name of the output file (default: stdout).

 -b, -bins

Correlation bin specification string (default is 1:200:1).

 -v, -verbose

Print more information while the command is running.