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MethScope-MRMP

Generate an MRMP reference

MethScope includes pre-defined MRMP references, and you can also build your own from a methylation atlas.

Prerequisites

  1. Install YAME for .cg processing: https://zhou-lab.github.io/YAME/
  2. Prepare a reference methylation .cg file (for example, an atlas or merged reference panel)
  3. Install and load MethScope
library(MethScope)

Step 1: Binarize the reference .cg file

Convert methylation proportions into binary strings. The default threshold is 0.5; adjust with -b if needed.

yame rowop example.cg -o binstring > example_binstring

Step 2: Build MRMP pattern definitions

Use GenerateReference() to identify recurrent patterns.
min_CG controls the minimum CpGs per MRMP (default: 50).

GenerateReference(binary_file = "example_binstring", min_CG = 50)

This step generates a patterns.txt file.

Step 3: Pack patterns into a .cm reference

Pack patterns.txt into a .cm file that can be passed as reference_pattern in GenerateInput().

yame pack -f s patterns.txt patterns.cm

Build MRMP references from cell-type pseudobulks

If cell-type labels are available, pseudobulked profiles can produce robust cell-type-informed MRMP references.

Step 1: Create pseudobulk profiles per cell type

Prepare a text file (samples.txt) containing sample IDs for one cell type, then aggregate with musum.

yame subset -l samples.txt example.cg | yame rowop -o musum - example_pseudobulk.cg

Step 2: Repeat per cell type and build MRMPs

Run the same workflow above (binstring -> GenerateReference -> yame pack) on each pseudobulk or combined pseudobulk panel.

For running a full parallelized multi-cell-type script, please refer to: https://github.com/zhou-lab/MethScope/blob/main/analysis/GenerateReference.sh

After generating patterns.cm, use it as the custom MRMP reference in downstream MethScope analyses.

These binaries (installable software) and packages are in development.
They may not be fully stable and should be used with caution. We make no claims about them.
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