The International Committee on Taxonomy of Viruses authorizes and organizes the taxonomic classification of viruses. Thus far, the detailed classifications for all viruses are neither complete nor free from dispute. For example, the current missing label rates in GenBank are 12.1% for family label and 30.0% for genus label. Using the proposed Natural Vector representation, all 2,044 single-segment referenced viral genomes in GenBank can be embedded in R^12. Unlike other approaches, this allows us to determine phylogenetic relations for all viruses at any level (e.g., Baltimore class, family, subfamily, genus, and species) in real time. Additionally, the proposed graphical representation for virus phylogeny provides a visualization of the distribution of viruses in R^12. Unlike the commonly used tree visualization methods which suffer from uniqueness and existence problems, our representation always exists and is unique. This approach is successfully used to predict and correct viral classification information, as well as to identify viral origins; e.g. a recent public health threat, the West Nile virus, is closer to the Japanese encephalitis antigenic complex based on our visualization. Based on cross validation results, the accuracy rates of our predictions are as high as 98.2% for Baltimore class labels, 96.6% for family labels, 99.7% for subfamily labels and 97.2% for genus labels.

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.

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

The stochasticity of gene expression is manifested in the fluctuations of mRNA and protein copy numbers within a cell lineage over time. While data of this type can be obtained for many generations, most mathematical models are unsuitable to interpret such data since they assume non-growing cells. Here we develop a theoretical approach that quantitatively links the frequency content of lineage data to subcellular dynamics. We elucidate how the position, height, and width of the peaks in the power spectrum provide a distinctive fingerprint that encodes a wealth of information about mechanisms controlling transcription, translation, replication, degradation, bursting, promoter switching, cell cycle duration, cell division, gene dosage compensation, and cell size homeostasis. Predictions are confirmed by analysis of single-cell Escherichia coli data obtained using fluorescence microscopy. Furthermore, by matching the experimental and theoretical power spectra, we infer the temperature-dependent gene expression parameters, without the need of measurements relating fluorescence intensities to molecule numbers.

Herein we describe new frontiers in mathematical modeling and statistical analysis of oscillatory biomedical signals, motivated by our recent studies of network formation in the human brain during the early stages of life and studies forty years ago on cardiorespiratory patterns during sleep in infants and animal models. The frontiers involve new nonlinear-type time-frequency analysis of signals with multiple oscillatory components, and efficient particle filters for joint state and parameter estimators together with uncertainty quantification in hidden Markov models and empirical Bayes inference.