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SUMMARY:Bayesian Inference of Transmission Fidelity Rates of DNA Methylati
 on Patterns - Audrey Fu (University of Cambridge Systems Biology Center)
DTSTART:20090604T150000Z
DTEND:20090604T160000Z
UID:TALK18120@talks.cam.ac.uk
CONTACT:8047
DESCRIPTION: A central question in epigenetics is how faithfully DNA\nmeth
 ylation patterns are transmitted over cell generations. Our aim\nhere is t
 o estimate the rates of the maintenance and de novo\nmethylation events th
 at have occurred during the transmission process\nand have given rise to o
 bserved methylation patterns. A\nrecently-emerging type of epigenetic data
  consists of binary DNA\nmethylation patterns on double-stranded sequences
  in individual cells\,\neach sequence containing a parent-daughter pair. H
 owever\, parent and\ndaughter strand in each pair are unidentified\, the d
 ata are\ntechnically difficult and time-consuming to collect and they cont
 ain\nmeasurement error. We model these data at multiple sites jointly\, th
 us\nusing the whole-strand information\, and considerably reduce\nconfound
 ing between parameters. We also adopt a hierarchical structure\nthat allow
 s for variation in rates across sites without an explosion\nin the effecti
 ve number of parameters. Our context-specific priors\ncapture the expected
  stationarity\, or near-stationarity\, of the\nstochastic process that gen
 erated the data analyzed here. This\nexpected stationarity is further show
 n to greatly increase the precision of the estimation. Applying our model 
 to data collected at\nthe FMR1 locus on the hypermethylated X chromosome i
 n females\, we gain\nthe following novel insights impossible to obtain und
 er other existing\nanalyses: (i) not accounting for measurement error has 
 a large impact\non estimation\, leading to underestimation of maintenance 
 rates and\noverestimation of de novo rates\; and (ii) there is suggestive 
 evidence\nof de novo events occurring on both parent and daughter strands.
  This\nis joint work with Diane Genereux\, Charles Laird and Matthew Steph
 ens.\n\n
LOCATION:MR2\, CMS\, Wilberforce Road\, Cambridge\, CB3 0WB
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