Matstat seminarium fredagen 14 september 13.15 i MH:227

Statistical estimation cell cycle kinetic parameters
Sara Larsson

Abstract

When treating cancer it can be considered important to estimate the growth rate
of the tumour. Of basic interest in this context is to estimate the time for
the DNA synthesis, i.e. the time it takes for the DNA in the nucleus
of the cell to duplicate, T_S 

Using a bromodeoxyuridine (BrdUrd)-DNA flowcytometry (FCM)-method it is
possible to measure the relative DNA content in the cell and separate the cells
in the DNA synthesis phase at time zero from the rest of the population. The
DNA distributions for these cells can then be followed through the cell
cycle. 

An established way to describe the movement through the DNA synthesis
phase is the
Relative Movement curve (RM). When all BrdUrd-labelled DNA is
replicated the RM value should 
theoretically reach one and then remain there. Since this is not
normally the case in practice, we have interpretated T_S
as the time when the RM curve reaches its maximum and used local
polynomial kernel regression to estimate the derivative of the curve.

A simple Markov model approach to the estimation of T_S
is also suggested. A state in the Markov model
corresponds to an interval of DNA content.
Divided BrdUrd-labelled cells are moved
back to the last state and an absorbing state is created. The
intensity matrix will contain the estimated rates of the DNA
replication and when an initial DNA distribution is estimated the time to
absorption and a distribution for that time are estimated. An
estimate of T_S will now be the estimated mean
time to absorption.