Spontaneous emergence of cell polarity intrinsically lies at the localization of signaling molecules on a particular region of cell membrane. Such a process necessarily contains a positive feedback loop to amplify the localized cluster. To describe the polarizing process and explore different feedback functions involved, deterministic and stochastic models with non-local kinetics are discussed in this paper. Stochastic Simulation Algorithm (SSA) is used to numerically simulate the polarizing behavior and analytical analysis by the power spectrum is applied to approximate the parameter regime for the spontaneous emergence of cell polarity. Compared to the results from the deterministic model, we can understand how the stochastic effect extends the parameter regime for achieving cell polarization under different types of feedback, including the forms of quadratic function, linear function, and Hill function. Both deterministic and stochastic methods fail to yield the polarity at a low number of molecules. Our results suggest that the parameter region for cell polarization under the Hill function feedback is smaller than that with the quadratic function feedback. ©2021

Budding yeast, which undergoes polarized growth during budding and mating, has been a useful model system to study cell polarization. Bud sites are selected differently in haploid and diploid yeast cells: haploid cells bud in an axial manner, while diploid cells bud in a bipolar manner. While previous studies have been focused on the molecular details of the bud site selection and polarity establishment, not much is known about how different budding patterns give rise to different functions at the population level. In this paper, we develop a two-dimensional agent-based model to study budding yeast colonies with cell-type specific biological processes, such as budding, mating, mating type switch, consumption of nutrients, and cell death. The model demonstrates that the axial budding pattern enhances mating probability at an early stage and the bipolar budding pattern improves colony development under nutrient limitation. Our results suggest that the frequency of mating type switch might control the trade-off between diploidization and inbreeding. The effect of cellular aging is also studied through our model. Based on the simulations, colonies initiated by an aged haploid cell show declined mating probability at an early stage and recover as the rejuvenated offsprings become the majority. Colonies initiated with aged diploid cells do not show disadvantage in colony expansion possibly due to the fact that young cells contribute the most to colony expansion.

Randomness often plays an important role in the spatial and temporal dynamics of biological systems. General stochastic simulation methods may lead to excessive computational cost for a system in which a large number of molecules involved. Therefore, multi-scale hybrid simulation methods become important for stochastic simulations. Here we build a spatially hybrid method which couples two approaches: discrete stochastic simulation and continuous stochastic differential equations. In our method, the locations of the interfaces between the two approaches are changing according to the distribution of molecules in a one-dimensional domain. To balance the accuracy and efficiency, the time step of the numerical method for the continuous stochastic differential equations is adapted to the dynamics of the molecules near the adaptive interfaces. The simulation results for a linear system and two nonlinear biological systems in different one-dimensional domains demonstrate the effectiveness and advantage of our new hybrid method with the adaptive time step control.

High-throughput biological technologies (e.g. ChIPseq, RNA-seq and single-cell RNA-seq) rapidly accelerate the accumulation of genome-wide omics data in diverse interrelated biological scenarios (e.g. cells, tissues and conditions). Integration and differential analysis are two common paradigms for exploring and analyzing such data. However, current integrative methods usually ignore the differential part, and typical differential analysis methods either fail to identify combinatorial patterns of difference or require matched dimensions of the data. Here, we propose a flexible framework CSMF to combine them into one paradigm to simultaneously reveal Common and Specific patterns via Matrix Factorization from data generated under interrelated biological scenarios. We demonstrate the effectiveness of CSMF with four representative applications including pairwise ChIP-seq data describing the chromatin modification map between K562 and Huvec cell lines; pairwise RNA-seq data representing the expression profiles of two different cancers; RNA-seq data of three breast cancer subtypes; and single-cell RNA-seq data of human embryonic stem cell differentiation at six time points. Extensive analysis yields novel insights into hidden combinatorial patterns in these multi-modal data. Results demonstrate that CSMF is a powerful tool to uncover common and specific patterns with significant biological implications from data of interrelated biological scenarios.

We study the well-posedness of a unified system of coupled forward-backward stochastic differential equations (FB-SDEs) with Levy jumps and double completely-S skew reflections. Owing to the reflections, the solution to an embedded Skorohod problem may be not unique, i.e., bifurcations may occur at reflection boundaries, the well-known contraction mapping approach can not be extended directly to solve our problem. Thus, we develop a weak convergence method to prove the well-posedness of an adapted 6-tuple weak solution in the sense of distribution to the unified system. The proof heavily depends on newly established Malliavin calculus for vector-valued Levy processes together with a generalized linear growth and Lipschitz condition that guarantees the well-posedness of the unified system even under a random environment. Nevertheless, if a more strict boundary condition is imposed, i.e., the spectral radii in certain sense for the reflections are strictly less than the unity, a unique adapted 6-tuple strong solution in the sense of sample pathwise is concerned. In addition, as applications and economical studies of our unified system, we also develop new techniques including deriving a generalized mutual information formula for signal processing over possible non-Gaussian channels with multi-input multi-output (MIMO) antennas and dynamics driven by Levy processes.