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Introduction

modiff can either look for differentially methylated loci or check which regions in a pre-defined set are differentially methylated.

Differentially methylathed loci (DMLs)

TO find DMLs modiff does a two group tests by using a logistic regression with an intercept term and a group term followed by a test on the significance of the group term (via likelihood ratio).

Usage is as folllows:

modiff FILE

where FILE is a A TAB-separated file.

Input format

The columns are contig and genomic coordinate followed by depth and number of modified bases per each sample. For example with 2 samples an input line looks like the following:

chr1\t10471\t20\t7\t23\t19

modiff will read directly from stdin if the file name is -.

Columns after the genome coordinate by default are split in two equal parts corresponding to the two groups. Alternatively the option --ng1 can be used to specify the size of the first group.

Output format

column quantity comment
1 contig/chromosome reference sequence
2 start position (inclusive, 0-based)
3 end position (exclusive, 0-based)
4 mean methylation by group comma separated
5 total depth by group comma separated
6 b0 regression coeff.
7 b1 regression coeff.
8 statistics residual deviance of log reg
9 pvalue
10 adjusted pvalue BH-adjusted pvalue

Differentially methylathed regions (DMRs)

The regions to be checked have to be listed in a .BED fil, eg regions.bed. The first step is to run modiff normally to list all the DMLs in the available data. After that, and assuming the results from the first step are stored in dmls.bed one can run:

modiff --regions regions.bed dmls.bed

Output format

column quantity comment
1 contig/chromosome reference sequence
2 start position (inclusive, 0-based)
3 end position (exclusive, 0-based)
4 nCpGs number of CpGs in region
5 mean residual deviance averaged over the region
6 pvalue mean raw pvalue (computed from the average residual variance)

Contact

github issues and/or pull requests. email to emanuele dot raineri at cnag dot eu

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