Skip to main content

DiMmer: Discovery of Differentially Methylated Regions in Epigenome-Wide Association Study (EWAS) Data

  • Protocol
  • First Online:
Book cover Data Mining for Systems Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1807))

  • 1476 Accesses

Abstract

DNA-methylation has a strong influence on gene expression such that differences in methylation are associated with a wide range of diseases. Array-based approaches like the Illumina 450 K or 850 K EPIC chips have been used in a wide range of studies mostly comparing a disease group with healthy control, but also to correlate with survival times, for instance. Processing, normalization, and analysis of raw data require extensive knowledge in statistics and programming languages such as R. Here we introduce DiMmer, an easy-to-use Java tool for the analysis of EWAS. A graphical user interface guides the user through preprocessing, normalization, testing for differentially methylated CpGs, and finally the discovery of differentially methylated regions (DMRs). The software performs randomization tests to compute empirical P-values, corrects for multiple testing, and requires no prior knowledge in programming. All computed results are provided as plots or tables and can be easily exported. DiMmer is thus a powerful one-stop-shop for EWAS data analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Almeida D, Skov I, Silva A, Vandin F, Tan Q, Röttger R, Baumbach J (2016) Efficient detection of differentially methylated regions using dimmer. Bioinformatics 33(4):549–551

    Google Scholar 

  2. Aryee MJ, Jaffe AE, Corrada-Bravo H, Ladd-Acosta C, Feinberg AP, Hansen KD, Irizarry RA (2014) Minfi: a flexible and comprehensive bioconductor package for the analysis of infinium DNA methylation microarrays. Bioinformatics 30(10):1363–1369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bock C (2012) Analysing and interpreting DNA methylation data. Nat Rev Genet 13(10):705

    Article  CAS  PubMed  Google Scholar 

  4. Frigola J, Song J, Stirzaker C, Hinshelwood RA, Peinado MA, Clark SJ (2006) Epigenetic remodeling in colorectal cancer results in coordinate gene suppression across an entire chromosome band. Nat Genet 38(5):540

    Article  CAS  PubMed  Google Scholar 

  5. Gardiner-Garden M, Frommer M (1987) CpG islands in vertebrate genomes. J Mol Biol 196(2):261–282

    Article  CAS  PubMed  Google Scholar 

  6. Hastie T, Tibshirani R, Friedman J (2003) The elements of statistical learning, corrected edn. Springer, Berlin

    Google Scholar 

  7. Houseman EA, Accomando WP, Koestler DC, Christensen BC, Marsit CJ, Nelson HH, Wiencke JK, Kelsey KT (2012) DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinf 13(1):86

    Article  Google Scholar 

  8. Jaffe AE, Irizarry RA (2014) Accounting for cellular heterogeneity is critical in epigenome-wide association studies. Genome Biol 15(2):R31

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ji L, Sasaki T, Sun X, Ma P, Lewis ZA, Schmitz RJ (2014) Methylated DNA is over-represented in whole-genome bisulfite sequencing data. Front Genet 5:341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Karlić R, Chung HR, Lasserre J, Vlahoviček K, Vingron M (2010) Histone modification levels are predictive for gene expression. Proc Natl Acad Sci 107(7):2926–2931

    Article  PubMed  Google Scholar 

  11. Karolchik D, Baertsch R, Diekhans M, Furey TS, Hinrichs A, Lu Y, Roskin KM, Schwartz M, Sugnet CW, Thomas DJ et al (2003) The UCSC genome browser database. Nucleic Acids Res 31(1):51–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Oracle (2014) Java 8. http://www.oracle. com/technetwork/java/javase/overview/java 8-2100321.html. Accessed 06 Nov 2017

  13. Plongthongkum N, Diep DH, Zhang K (2014) Advances in the profiling of DNA modifications: cytosine methylation and beyond. Nat Rev Genet 15(10):647

    Article  CAS  PubMed  Google Scholar 

  14. Rakyan VK, Down TA, Balding DJ, Beck S (2011) Epigenome-wide association studies for common human diseases. Nat Rev Genet 12(8):529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wilhelm-Benartzi CS, Koestler DC, Karagas MR, Flanagan JM, Christensen BC, Kelsey KT, Marsit CJ, Houseman EA, Brown R (2013) Review of processing and analysis methods for DNA methylation array data. Br J Cancer 109(6):1394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Jan Baumbach and Tobias Frisch are grateful for financial support from the VILLUM foundation (Young Investigator Grant nr. 13154).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tobias Frisch .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Frisch, T., Gøttcke, J., Röttger, R., Tan, Q., Baumbach, J. (2018). DiMmer: Discovery of Differentially Methylated Regions in Epigenome-Wide Association Study (EWAS) Data. In: Mamitsuka, H. (eds) Data Mining for Systems Biology. Methods in Molecular Biology, vol 1807. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8561-6_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8561-6_5

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8560-9

  • Online ISBN: 978-1-4939-8561-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics