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SUMMARY:Mapping regulatory variation in human cells - Daniel Gaffney\, San
 ger Institute
DTSTART:20170403T181500Z
DTEND:20170403T203000Z
UID:TALK65982@talks.cam.ac.uk
CONTACT:Peter Watson
DESCRIPTION:Association mapping of cellular traits such as gene expression
  can provide powerful insights into the functions of human genetic variati
 on. However\, until recently mapping studies have been limited to a very r
 estricted range of tissues or cell states. An additional limitation of ass
 ociation mapping is that\, depending on the structure of linkage disequili
 brium\, the causal variant that drives an association can be extremely dif
 ficult to pinpoint. I will discuss work from our group that attempts to ad
 dress some of these limitations. First I will discuss our work\, as part o
 f the Human Induced Pluripotent Stem Cells Initiative (HIPSCI: www.hipsci.
 org)\, to develop IPSCs as model systems for understanding the functions o
 f human genetic variation. I will show how variation due to the cell line 
 donor contributes to heterogeneity at the level of the epigenome\, transcr
 iptome and proteome of IPSCs\, and illustrate how individual quantitative 
 trait loci (QTLs) have confounded past studies of human pluripotent stem c
 ells. Second\, I will discuss a new statistical method (RASQUAL) that uses
  allele-specific signals to improve power and fine-mapping accuracy in ass
 ociation analysis of read-based phenotypes. I will show how RASQUAL handle
 s a range of technical and biological biases in allele-specific signals wi
 thout requiring data filtering or removal\, and significantly outperforms 
 all other existing methods. I will finish by discussing our application of
  RASQUAL to ATAC-seq data in human LCLs to pinpoint likely causal variants
  in disease\, and to uncover long-range interactions between different reg
 ulatory regions.
LOCATION:Institute of Public Health\, University Forvie Site\, Robinson Wa
 y\, Cambridge
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