Identifying and Visualizing Differential Topological Features in DNA

Caleb Lareau
24 June 2016

Generating 3D Data

  • Chromatin Capture (e.g. Hi-C) methods reveal 3D proximity
  • ChIA-PET enables discovery of specific protein-mediated 3D loops
    Shlyueva et al. 2014



  • Q: Do topological loops in DNA change between cell types?




  • Q: Do topological loops in DNA change between cell types?


  • A: Use diffloop to find out!

Bioconductor Package: diffloop


  • Handles pre-processed ChIA-PET data
    • mango: *.fastq -> *.interactions.all.mango
    • diffloop: *.interactions.all.mango -> loops( )

  • Suit of tools to perform QC, Visualization, and Association
    • edgeR:RNA-Seq < > diffloop:ChIA-PET


  • Integration of other -omics data

Visualization

Implementation: New S4 loops( ) object


  • anchors– GRanges
  • interactions– int matrix
  • counts– int matrix
  • rowData– data.frame
  • colData– data.frame

Why does the 3D genome matter?


  • DNA methylation change the 3D lanscape
    • (Flavahan et al. 2016–Nature)

  • Common variants change the 3D landscape

    • (Tang et al. 2015–Cell)


  • 3D landscape changes gene expression

Enhancer-Promoter Looping

Cavalli & Misteli 2013.



Differential Loops & Differential Expression

plot of chunk unnamed-chunk-1

  • 232 unique differential (FDR < 0.05) enhancer-promoter loops w/ a unique T.S.S. that was differentially expressed (FDR < 0.05)
    • 224 (97%) pairs had a similar direction of transcription logFC as loop logFC.

Interactive viewing


New Shiny App: DNAlandscapeR dnalandscaper.aryeelab.org

Acknowledgements


  • Martin Morgan & BioConductor Team
    • Reviewed diffloop source code
    • Aided in my trip to BioC 2016

  • Martin Aryee, PhD
    • Research Advisor

Questions?