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  • Software tools for comparing entire methylomes (WGBS)

    Software tools for comparing entire methylomes (WGBS)

    I am currently exploring the possibility of comparing entire methylomes of genets exposed to two different conditions.

    There seem to be a few options as for software tools to map bisulfite-seq reads (Bismark), but the options for comparing entire methylomes don't seem to exist as a tools as of yet.

    Essentially, I would like to model the work of Heyn et al. 2012. The details of their methods are available in supplemental materials.

    Is there a less cumbersome way of achieving what they are doing? Are there any tools capable of this? What is the most efficient way of identifying differential methylation between two samples?

    Thank you!
    Last edited by anth; 09-25-2013, 01:46 PM. Reason: My hasty post appeared to describe an experiment with an n of 1.

  • #2
    Do you really just have 2 samples? The normal reply would be to reference bsseq, but with just 2 samples I doubt any results would be meaningful. Why didn't you use biological replicates? You have absolutely no way of knowing if any differences are due to your treatment or are just normal variation.

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    • #3
      Thanks for your reply. The experiment has not been undertaken yet - but there will absolutely be biological replicates for each condition. I have edited the original post to correct this.

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      • #4
        Hi anth,

        My lab just published our WGBS toolbox and database, MethPipe/MethBase. We analyzed ~200 WGBS datasets (including the Heyn set you linked), calling single-base resolution methylation levels as well as identifying high-level methylation features like HMRs, allele-specific methylation, and PMDs. This should allow you to generate your own data, run it through our pipeline, and compare it to the public data knowing that you used the same methods.

        You can find the paper at
        DNA methylation is implicated in a surprising diversity of regulatory, evolutionary processes and diseases in eukaryotes. The introduction of whole-genome bisulfite sequencing has enabled the study of DNA methylation at a single-base resolution, revealing many new aspects of DNA methylation and highlighting the usefulness of methylome data in understanding a variety of genomic phenomena. As the number of publicly available whole-genome bisulfite sequencing studies reaches into the hundreds, reliable and convenient tools for comparing and analyzing methylomes become increasingly important. We present MethPipe, a pipeline for both low and high-level methylome analysis, and MethBase, an accompanying database of annotated methylomes from the public domain. Together these resources enable researchers to extract interesting features from methylomes and compare them with those identified in public methylomes in our database.


        The database and pipeline themselves (and a user manual) can be found here:




        Let me know if you give it a try/have any questions. Good luck!

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