Article

# A composite likelihood approach to the analysis of longitudinal clonal data on multitype cellular systems under an age-dependent branching process.

Department of Biostatistics and Computational Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.

Biostatistics (Impact Factor: 2.24). 01/2011; 12(1):173-91. DOI: 10.1093/biostatistics/kxq050 Source: PubMed

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**ABSTRACT:**Stem and precursor cells play a critical role in tissue development, maintenance, and repair throughout the life. Often, experimental limitations prevent direct observation of the stem cell compartment, thereby posing substantial challenges to the analysis of such cellular systems. Two-type age-dependent branching processes with immigration are proposed to model populations of progenitor cells and their differentiated progenies. Immigration of cells into the pool of progenitor cells is formulated as a non-homogeneous Poisson process. The asymptotic behavior of the process is governed by the largest of two Malthusian parameters associated with embedded Bellman-Harris processes. Asymptotic approximations to the expectations of the total cell counts are improved by Markov compensators.Mathematical Population Studies 10/2012; 19(4):164-176. · 0.38 Impact Factor - [Show abstract] [Hide abstract]

**ABSTRACT:**Two-type reducible age-dependent branching processes with inhomogeneous immigration are considered to describe the kinetics of renewing cell populations. This class of processes can be used to model the generation of oligodendrocytes in the central nervous system in vivo or the kinetics of leukemia cells. The asymptotic behavior of the first and second moments, including the correlation, of the process is investigated.Pliska. Pliiska. 01/2011; 20:81-108. -
##### Article: Quantifying T lymphocyte turnover.

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**ABSTRACT:**Peripheral T cell populations are maintained by production of naive T cells in the thymus, clonal expansion of activated cells, cellular self-renewal (or homeostatic proliferation), and density dependent cell life spans. A variety of experimental techniques have been employed to quantify the relative contributions of these processes. In modern studies lymphocytes are typically labeled with 5-bromo-2'-deoxyuridine (BrdU), deuterium, or the fluorescent dye carboxy-fluorescein diacetate succinimidyl ester (CFSE), their division history has been studied by monitoring telomere shortening and the dilution of T cell receptor excision circles (TRECs) or the dye CFSE, and clonal expansion has been documented by recording changes in the population densities of antigen specific cells. Proper interpretation of such data in terms of the underlying rates of T cell production, division, and death has proven to be notoriously difficult and involves mathematical modeling. We review the various models that have been developed for each of these techniques, discuss which models seem most appropriate for what type of data, reveal open problems that require better models, and pinpoint how the assumptions underlying a mathematical model may influence the interpretation of data. Elaborating various successful cases where modeling has delivered new insights in T cell population dynamics, this review provides quantitative estimates of several processes involved in the maintenance of naive and memory, CD4(+) and CD8(+) T cell pools in mice and men.Journal of Theoretical Biology 01/2013; · 2.35 Impact Factor

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