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Register a new userA branching process model for flow cytometry and budding index measurements in cell synchrony experiments
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Added by
Edwin S. Iversen Jr.
Publication date
2010
fields
Mathematical Statistics
and research's language is
English
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We present a flexible branching process model for cell population dynamics in synchrony/time-series experiments used to study important cellular processes. Its formulation is constructive, based on an accounting of the unique cohorts in the population as they arise and evolve over time, allowing it to be written in closed form. The model can attribute effects to subsets of the population, providing flexibility not available using the models historically applied to these populations. It provides a tool for in silico synchronization of the population and can be used to deconvolve population-level experimental measurements, such as temporal expression profiles. It also allows for the direct comparison of assay measurements made from multiple experiments. The model can be fit either to budding index or DNA content measurements, or both, and is easily adaptable to new forms of data. The ability to use DNA content data makes the model applicable to almost any organism. We describe the model and illustrate its utility and flexibility in a study of cell cycle progression in the yeast Saccharomyces cerevisiae.
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The ocean is filled with microscopic microalgae called phytoplankton, which together are responsible for as much photosynthesis as all plants on land combined. Our ability to predict their response to the warming ocean relies on understanding how the dynamics of phytoplankton populations is influenced by changes in environmental conditions. One powerful technique to study the dynamics of phytoplankton is flow cytometry, which measures the optical properties of thousands of individual cells per second. Today, oceanographers are able to collect flow cytometry data in real-time onboard a moving ship, providing them with fine-scale resolution of the distribution of phytoplankton across thousands of kilometers. One of the current challenges is to understand how these small and large scale variations relate to environmental conditions, such as nutrient availability, temperature, light and ocean currents. In this paper, we propose a novel sparse mixture of multivariate regressions model to estimate the time-varying phytoplankton subpopulations while simultaneously identifying the specific environmental covariates that are predictive of the observed changes to these subpopulations. We demonstrate the usefulness and interpretability of the approach using both synthetic data and real observations collected on an oceanographic cruise conducted in the north-east Pacific in the spring of 2017.
Flow cytometry is a technology that rapidly measures antigen-based markers associated to cells in a cell population. Although analysis of flow cytometry data has traditionally considered one or two markers at a time, there has been increasing interest in multidimensional analysis. However, flow cytometers are limited in the number of markers they can jointly observe, which is typically a fraction of the number of markers of interest. For this reason, practitioners often perform multiple assays based on different, overlapping combinations of markers. In this paper, we address the challenge of imputing the high dimensional jointly distributed values of marker attributes based on overlapping marginal observations. We show that simple nearest neighbor based imputation can lead to spurious subpopulations in the imputed data, and introduce an alternative approach based on nearest neighbor imputation restricted to a cells subpopulation. This requires us to perform clustering with missing data, which we address with a mixture model approach and novel EM algorithm. Since mixture model fitting may be ill-posed, we also develop techniques to initialize the EM algorithm using domain knowledge. We demonstrate our approach on real flow cytometry data.
Mass cytometry technology enables the simultaneous measurement of over 40 proteins on single cells. This has helped immunologists to increase their understanding of heterogeneity, complexity, and lineage relationships of white blood cells. Current statistical methods often collapse the rich single-cell data into summary statistics before proceeding with downstream analysis, discarding the information in these multivariate datasets. In this article, our aim is to exhibit the use of statistical analyses on the raw, uncompressed data thus improving replicability, and exposing multivariate patterns and their associated uncertainty profiles. We show that multivariate generative models are a valid alternative to univariate hypothesis testing. We propose two models: a multivariate Poisson log-normal mixed model and a logistic linear mixed model. We show that these models are complementary and that either model can account for different confounders. We use Hamiltonian Monte Carlo to provide Bayesian uncertainty quantification. Our models applied to a recent pregnancy study successfully reproduce key findings while quantifying increased overall protein-to-protein correlations between first and third trimester.
Robust estimation and variable selection procedure are developed for the extended t-process regression model with functional data. Statistical properties such as consistency of estimators and predictions are obtained. Numerical studies show that the proposed method performs well.
In medical research, continuous markers are widely employed in diagnostic tests to distinguish diseased and non-diseased subjects. The accuracy of such diagnostic tests is commonly assessed using the receiver operating characteristic (ROC) curve. To summarize an ROC curve and determine its optimal cut-point, the Youden index is popularly used. In literature, estimation of the Youden index has been widely studied via various statistical modeling strategies on the conditional density. This paper proposes a new model-free estimation method, which directly estimates the covariate-adjusted cut-point without estimating the conditional density. Consequently, covariate-adjusted Youden index can be estimated based on the estimated cutpoint. The proposed method formulates the estimation problem in a large margin classification framework, which allows flexible modeling of the covariate-adjusted Youden index through kernel machines. The advantage of the proposed method is demonstrated in a variety of simulated experiments as well as a real application to Pima Indians diabetes study.
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