Estimating the Total Rate of DNA Replication Using Branching Processes |
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Authors: | Sara Larsson Tobias Rydén Ulla Holst Stina Oredsson Maria Johansson |
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Institution: | (1) Centre for Mathematical Sciences, Lund University, Box 118, 221 00 Lund, Sweden;(2) Department of Cell and Organism Biology, Lund University, Box 118, 221 00 Lund, Sweden;(3) Department of Oncology, Clinical Sciences, Lund University Hospital, 221 85 Lund, Sweden |
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Abstract: | Increasing the knowledge of various cell cycle kinetic parameters, such as the length of the cell cycle and its different
phases, is of considerable importance for several purposes including tumor diagnostics and treatment in clinical health care
and a deepened understanding of tumor growth mechanisms. Of particular interest as a prognostic factor in different cancer
forms is the S phase, during which DNA is replicated. In the present paper, we estimate the DNA replication rate and the S
phase length from bromodeoxyuridine-DNA flow cytometry data. The mathematical analysis is based on a branching process model,
paired with an assumed gamma distribution for the S phase duration, with which the DNA distribution of S phase cells can be
expressed in terms of the DNA replication rate. Flow cytometry data typically contains rather large measurement variations,
however, and we employ nonparametric deconvolution to estimate the underlying DNA distribution of S phase cells; an estimate
of the DNA replication rate is then provided by this distribution and the mathematical model. |
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Keywords: | Branching process Cell cycle kinetics DNA replication rate Flow cytometry Nonparametric deconvolution |
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