Defiant: (DMRs: Easy, fast, identification and ANnoTation) identifies differentially Methylated regions from iron-deficient rat hippocampus

David E. Condon, Phu V. Tran, Yu Chin Lien, Jonathan Schug, Michael K. Georgieff, Rebecca A. Simmons, Kyoung Jae Won

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background: Identification of differentially methylated regions (DMRs) is the initial step towards the study of DNA methylation-mediated gene regulation. Previous approaches to call DMRs suffer from false prediction, use extreme resources, and/or require library installation and input conversion. Results: We developed a new approach called Defiant to identify DMRs. Employing Weighted Welch Expansion (WWE), Defiant showed superior performance to other predictors in the series of benchmarking tests on artificial and real data. Defiant was subsequently used to investigate DNA methylation changes in iron-deficient rat hippocampus. Defiant identified DMRs close to genes associated with neuronal development and plasticity, which were not identified by its competitor. Importantly, Defiant runs between 5 to 479 times faster than currently available software packages. Also, Defiant accepts 10 different input formats widely used for DNA methylation data. Conclusions: Defiant effectively identifies DMRs for whole-genome bisulfite sequencing (WGBS), reduced-representation bisulfite sequencing (RRBS), Tet-assisted bisulfite sequencing (TAB-seq), and HpaII tiny fragment enrichment by ligation-mediated PCR-tag (HELP) assays.

Original languageEnglish (US)
Article number31
JournalBMC bioinformatics
Volume19
Issue number1
DOIs
StatePublished - Feb 5 2018

Bibliographical note

Funding Information:
We thank the Functional Genomics Core of the Penn Diabetes Research Center (P30-DK19525). This work is supported by NIH grant (R01 DK106027 to KJW and R01 HD029421 to MG).

Publisher Copyright:
© 2018 The Author(s).

Keywords

  • Bisulfite sequencing
  • DNA Methylation
  • Differentially Methylated regions (DMR)
  • Epigenetics
  • RRBS
  • WGBS

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