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Yuman Wang

Publications and source records attributed to Yuman Wang.

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Determining cell population size from cell fraction in cell plasticity models

Quantifying the size of cell populations is crucial for understanding biological processes such as growth, injury repair, and disease progression. Often, experimental data offer information in the form of relative frequencies of distinct cell types, rather than absolute cell counts. This emphasizes the need to devise effective strategies for estimating absolute cell quantities from fraction data. In response to this challenge, we present two computational approaches grounded in stochastic cell population models: the first-order moment method (FOM) and the second-order moment method (SOM). These methods explicitly establish mathematical mappings from cell fraction to cell population size using moment equations of the stochastic models. Notably, our investigation demonstrates that the SOM method obviates the requirement for a priori knowledge of the initial population size, highlighting the utility of incorporating variance details from cell proportions. The robustness of both the FOM and SOM methods was analyzed from different perspectives. Additionally, we extended the application of the FOM and SOM methods to various biological mechanisms within the context of cell plasticity models. Our methodologies not only assist in mitigating the inherent limitations of experimental techniques when only fraction data is available for detecting cell population size, but they also offer new insights into utilizing the stochastic characteristics of cell population dynamics to quantify interactions between different biomasses within the system.

q-bio.QM

Bayesian Inference of Phenotypic Plasticity of Cancer Cells Based on Dynamic Model for Temporal Cell Proportion Data

Mounting evidence underscores the prevalent hierarchical organization of cancer tissues. At the foundation of this hierarchy reside cancer stem cells, a subset of cells endowed with the pivotal role of engendering the entire cancer tissue through cell differentiation. In recent times, substantial attention has been directed towards the phenomenon of cancer cell plasticity, where the dynamic interconversion between cancer stem cells and non-stem cancer cells has garnered significant interest. Since the task of detecting cancer cell plasticity from empirical data remains a formidable challenge, we propose a Bayesian statistical framework designed to infer phenotypic plasticity within cancer cells, utilizing temporal data on cancer stem cell proportions. Our approach is grounded in a stochastic model, adept at capturing the dynamic behaviors of cells. Leveraging Bayesian analysis, we explore the moment equation governing cancer stem cell proportions, derived from the Kolmogorov forward equation of our stochastic model. With improved Euler method for ordinary differential equations, a new statistical method for parameter estimation in nonlinear ordinary differential equations models is developed, which also provides novel ideas for the study of compositional data. Extensive simulations robustly validate the efficacy of our proposed method. To further corroborate our findings, we apply our approach to analyze published data from SW620 colon cancer cell lines. Our results harmonize with \emph{in situ} experiments, thereby reinforcing the utility of our method in discerning and quantifying phenotypic plasticity within cancer cells.

stat.AP

Stochastic stem cell models with mutation: A comparison of asymmetric and symmetric divisions

In order to fulfill cell proliferation and differentiation through cellular hierarchy, stem cells can undergo either asymmetric or symmetric divisions. Recent studies pay special attention to the effect of different modes of stem cell division on the lifetime risk of cancer, and report that symmetric division is more beneficial to delay the onset of cancer. The fate uncertainty of symmetric division is considered to be the reason for the cancer-delaying effect. In this paper we compare asymmetric and symmetric divisions of stem cells via studying stochastic stem cell models with mutations. Specially, by using rigorous mathematical analysis we find that both asymmetric and symmetric models show the same statistical average, but symmetric model shows higher fluctuation than asymmetric model. We further show that the difference between the two models would be more remarkable for lower mutation rates. Our work quantifies the uncertainty of cell division and highlights the significance of stochasticity for distinguishing between different modes of stem cell division.

q-bio.PE