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A novel statistical analysis and interpretation of flow cytometry data.

Banks HT, Kapraun DF, Thompson WC, Peligero C, Argilaguet J, Meyerhans A - J Biol Dyn (2013)

Bottom Line: A recently developed class of models incorporating the cyton model of population generation structure into a conservation-based model of intracellular label dynamics is reviewed.Statistical aspects of the data collection process are quantified and incorporated into a parameter estimation scheme.This scheme is then applied to experimental data for PHA-stimulated CD4+T and CD8+T cells collected from two healthy donors.

View Article: PubMed Central - PubMed

Affiliation: Center for Research in Scientific Computation and Center for Quantitative Sciences in Biomedicine, North Carolina State University, Raleigh, NC 27695-8212, USA. htbanks@ncsu.edu

ABSTRACT
A recently developed class of models incorporating the cyton model of population generation structure into a conservation-based model of intracellular label dynamics is reviewed. Statistical aspects of the data collection process are quantified and incorporated into a parameter estimation scheme. This scheme is then applied to experimental data for PHA-stimulated CD4+T and CD8+T cells collected from two healthy donors. This novel mathematical and statistical framework is shown to form the basis for accurate, meaningful analysis of cellular behaviour for a population of cells labelled with the dye carboxyfluorescein succinimidyl ester and stimulated to divide.

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Calibrated model with CD8 cell data for a particular set of triplicates from Donor 1 (left) and Donor 2 (right). Shaded regions indicated a 4 standard deviation confidence region computed according to the theoretical statistical model (19), assuming the model is correctly specified.
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Figure 7: Calibrated model with CD8 cell data for a particular set of triplicates from Donor 1 (left) and Donor 2 (right). Shaded regions indicated a 4 standard deviation confidence region computed according to the theoretical statistical model (19), assuming the model is correctly specified.

Mentions: The primary shortcoming of the statistical model is the assumption of correct specification, i.e. E[Njk] = I[](tj, zk; ). There are clearly instances in Figures 6 and 7 where the data are not centred around the mathematical model, indicating that the mathematical model is systematically in error. As a result, the shaded regions do not contain 99.9% of the data points. From one perspective, this shortcoming of the statistical model is entirely mathematical – if an improved mathematical model were available, then it is possible that the assumption of correct specification would be accurate. Alternatively, it is possible to consider a more general statistical model which directly considers the effects of misspecification, for instance by assuming an autoregressive error structure [24]. This may provide a more accurate measure for model comparison in the absence of a more accurate mathematical model.


A novel statistical analysis and interpretation of flow cytometry data.

Banks HT, Kapraun DF, Thompson WC, Peligero C, Argilaguet J, Meyerhans A - J Biol Dyn (2013)

Calibrated model with CD8 cell data for a particular set of triplicates from Donor 1 (left) and Donor 2 (right). Shaded regions indicated a 4 standard deviation confidence region computed according to the theoretical statistical model (19), assuming the model is correctly specified.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3753657&req=5

Figure 7: Calibrated model with CD8 cell data for a particular set of triplicates from Donor 1 (left) and Donor 2 (right). Shaded regions indicated a 4 standard deviation confidence region computed according to the theoretical statistical model (19), assuming the model is correctly specified.
Mentions: The primary shortcoming of the statistical model is the assumption of correct specification, i.e. E[Njk] = I[](tj, zk; ). There are clearly instances in Figures 6 and 7 where the data are not centred around the mathematical model, indicating that the mathematical model is systematically in error. As a result, the shaded regions do not contain 99.9% of the data points. From one perspective, this shortcoming of the statistical model is entirely mathematical – if an improved mathematical model were available, then it is possible that the assumption of correct specification would be accurate. Alternatively, it is possible to consider a more general statistical model which directly considers the effects of misspecification, for instance by assuming an autoregressive error structure [24]. This may provide a more accurate measure for model comparison in the absence of a more accurate mathematical model.

Bottom Line: A recently developed class of models incorporating the cyton model of population generation structure into a conservation-based model of intracellular label dynamics is reviewed.Statistical aspects of the data collection process are quantified and incorporated into a parameter estimation scheme.This scheme is then applied to experimental data for PHA-stimulated CD4+T and CD8+T cells collected from two healthy donors.

View Article: PubMed Central - PubMed

Affiliation: Center for Research in Scientific Computation and Center for Quantitative Sciences in Biomedicine, North Carolina State University, Raleigh, NC 27695-8212, USA. htbanks@ncsu.edu

ABSTRACT
A recently developed class of models incorporating the cyton model of population generation structure into a conservation-based model of intracellular label dynamics is reviewed. Statistical aspects of the data collection process are quantified and incorporated into a parameter estimation scheme. This scheme is then applied to experimental data for PHA-stimulated CD4+T and CD8+T cells collected from two healthy donors. This novel mathematical and statistical framework is shown to form the basis for accurate, meaningful analysis of cellular behaviour for a population of cells labelled with the dye carboxyfluorescein succinimidyl ester and stimulated to divide.

Show MeSH