JSM 2005 - Toronto

Abstract #302664

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Legend: = Applied Session, = Theme Session, = Presenter
Activity Number: 118
Type: Invited
Date/Time: Monday, August 8, 2005 : 10:30 AM to 12:20 PM
Sponsor: Section on Bayesian Statistical Science
Abstract - #302664
Title: Posterior Inference on the Stem Cell Population of the Human Colon through Analysis of Methylation Patterns
Author(s): Simon Tavare*+ and P. Nicolas and D. Shibata
Companies: University of Southern California and University of Southern California and University of Southern California
Address: Program in Molecular and Computational Biology, Los Angeles, CA, 90089-1340, United States
Keywords: methylation ; Markov chain Monte Carlo ; colon crypts ; context-dependent mutation ; stem cells ; coalescent
Abstract:

Colon crypts are believed to be maintained by a small number of stem cells that produce functionally differentiated cells after a small number of cell divisions. These latter cells are known to be short-lived, and are continuously replaced by new differentiated cells. We use the methylation patterns to track mitotic divisions within an individual. We have collected data from nine CpG sites in a 130 basepair locus upstream of the BGN gene on the X chromosome in a sample of 57 colon crypts taken from seven males. We have developed a coalescent-like model for the evolution of the methylation patterns within crypts of an individual, and have used it to infer the number of stem cells within a crypt. A novel feature of our analysis is a context-dependent model for methylation and demethylation within a crypt. Bayesian inference is performed by a Markov chain Monte Carlo approach. Model fit is assessed by comparing the distribution of several intercrypt statistics with their actual values. Qualitative and quantitative conclusions from the analysis will be presented.

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Revised March 2005