Statistical Inference on Chemotherapy Effects from Flow Cytometry Data- Our preliminary studies have resulted in a stochastic model of clonal growth of oligodendrocyte progenitor cells in vitro. The model has been applied to several sets of experimental data and validated in independent time-lapse experiments. New estimation techniques built on this model allow analysis of the underlying processes of cell proliferation and differentiation in terms of biologically meaningful parameters. However, the ability of practitioners to benefit from the proposed methodology is limited because clonal analyses are very laborious and difficult to conduct in an automated fashion. By contrast, in vitro experiments with DNA, protein, or cell surface markers are readily amenable to automatization by resorting to flow cytometry. Some labeling techniques (BrdU) provide the needed information on the structure of cell cycle under in vivo conditions. These practical considerations motivate an in-depth study of cell kinetics using flow cytometry data.
The specific aims of this project are: (1) To develop a stochastic framework for modeling cell kinetics during flow cytometry experiments;(2) To design new methods of statistical inference for the quantitative analysis of flow cytometry data by building on the proposed stochastic models;(3) To validate the proposed methods in specially designed biological experiments;(4) To assess the utility of these methods to study effects of chemotherapeutic drugs on normal and neoplastic tissues. Specific applications will be focused on responses of oligodendrocyte precursors the myelin-forming cells of the central nervous system - and leukemic progenitor cells to chemotherapeutic drugs used for leukemia treatment.

Public Health Relevance

This project is concerned with the effects of chemotherapy on normal and neoplastic tissues, which has obvious clinical and public health implications for oncology in general and for leukemia treatment in particular.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA134839-05
Application #
8320725
Study Section
Biostatistical Methods and Research Design Study Section (BMRD)
Program Officer
Forry, Suzanne L
Project Start
2008-09-23
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$227,432
Indirect Cost
$79,749
Name
University of Rochester
Department
Biostatistics & Other Math Sci
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Hyrien, O; Peslak, S A; Yanev, N M et al. (2015) Stochastic modeling of stress erythropoiesis using a two-type age-dependent branching process with immigration. J Math Biol 70:1485-521
Chen, Rui; Hyrien, Ollivier (2011) Quasi- and pseudo-maximum likelihood estimators for discretely observed continuous-time Markov branching processes. J Stat Plan Inference 141:2209-2227
Chen, Rui; Hyrien, Ollivier; Noble, Mark et al. (2011) A composite likelihood approach to the analysis of longitudinal clonal data on multitype cellular systems under an age-dependent branching process. Biostatistics 12:173-91
Hyrien, Ollivier; Dietrich, Jorg; Noble, Mark (2010) Mathematical and experimental approaches to identify and predict the effects of chemotherapy on neuroglial precursors. Cancer Res 70:10051-9
Hyrien, Ollivier; Chen, Rui; Zand, Martin S (2010) An age-dependent branching process model for the analysis of CFSE-labeling experiments. Biol Direct 5:41
Hyrien, O; Chen, R; Mayer-Proschel, M et al. (2010) Saddlepoint approximations to the moments of multitype age-dependent branching processes, with applications. Biometrics 66:567-77
Hocde, Sandrine A; Hyrien, Ollivier; Waugh, Richard E (2009) Molecular accessibility in relation to cell surface topography and compression against a flat substrate. Biophys J 97:369-78
Hocde, Sandrine A; Hyrien, Ollivier; Waugh, Richard E (2009) Cell adhesion molecule distribution relative to neutrophil surface topography assessed by TIRFM. Biophys J 97:379-87