A Markov model approach shows a large variation in the length of S phase in MCF-7 breast cancer cells. |
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Authors: | Sara Larsson Maria Johansson Stina Oredsson Ulla Holst |
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Institution: | Centre for Mathematical Sciences, Division of Mathematical Statistics, Lund University, Lund, Sweden. sara@maths.lth.se |
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Abstract: | BACKGROUND: The potential doubling time of a tumor has been suggested to be a measurement of tumor aggressiveness; therefore, it is of interest to find reliable methods to estimate this time. Because of variability in length of the various cell cycle phases, stochastic modeling of the cell cycle might be a suitable approach. METHODS: The relative movement curve and the DNA synthesis time were estimated by using local polynomial regression methods. Further, the rate of nucleotide incorporation was estimated by using a Markov pure birth process with one absorbing state to model the progression of the DNA distribution through S phase. RESULTS: An estimate of the DNA synthesis time, with confidence intervals, was obtained from the relative movement curve. The Markov approach provided an estimate of the distribution of the time to complete S phase given the initial distribution. Using the Markov approach we also made an estimate of the mean number of active replicons during S phase. CONCLUSIONS: A Markov pure birth process has shown to be useful to model the progression of cells through S phase and to increase knowledge about the variability in the length of S phase and a large variation is shown. |
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