Variability in the 3D Genome

Caleb Lareau
bit.ly/Aug23HSPH

Overview


  • Experimental Assays
  • Importance
  • Advances
  • On the stove

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

ChIA-PET

Hi-C

What do they look like?

Why do we care?

A Story


  • Certain gliomas have a nonsynonymous IDH1 mutation
    • 2-Hydroxyglutarate -> Inhibition of DNA demethylase
    • 3D-Rearrangement -> Oncogenesis

Flavahan et al. 2016–Nature

Types of loops

  • ~60% of enhancers affect a gene that isn't the most proximal

Hnisz et al. 2016–Science

Okay, so these are important...


  • But then why aren't these data more widely used?


dnalandscaper.aryeelab.org


Compression


  • ~ 1000x compression gain using sparse matrices and variable resolutions

diffloop


Advances


On the stove...

CRISPR Screen: Joung Lab @ MGH


Translocations: Bernstein Lab @ MGH



Differentiation: Frankael/Young Labs @ MIT




Acquired Immunity: O'Shea Lab @ NIH




eQTL: Aryee Lab



Tang et al. 2016

Shout outs


  • Martin Aryee, PhD
    • Research Advisor

  • Sarah Johnstone, MD, PhD
  • Pat Gaffney, MD, PhD
  • Rusty Ryan, MD
  • Prathik Naidu
  • Sarah Shareef

  • Many others!

Thank You!


  • bit.ly/Aug23HSPH

  • dnalandscaper.aryeelab.org
  • bioconductor.org/packages/release/bioc/html/diffloop.html
  • github.com/aryeelab/sparseHiC