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Abstract Diversity indices are useful single-number metrics for characterizing a complex distribution of a set of attributes across a population of interest. The utility of these different metrics or sets of metrics depends on the context and application, and whether a predictive mechanistic model exists. In this topical review, we first summarize the relevant mathematical principles underlying heterogeneity in a large population, before outlining the various definitions of ‘diversity’ and providing examples of scientific topics in which its quantification plays an important role. We then review how diversity has been a ubiquitous concept across multiple fields, including ecology, immunology, cellular barcoding experiments, and socioeconomic studies. Since many of these applications involve sampling of populations, we also review how diversity in small samples is related to the diversity in the entire population. Features that arise in each of these applications are highlighted. 

Antibodies are important biomolecules that are often designed to recognize target antigens. However, they are expensive to produce and their relatively large size prevents their transport across lipid membranes. An alternative to antibodies is aptamers, short ([Formula: see text] bp) oligonucleotides (and amino acid sequences) with specific secondary and tertiary structures that govern their affinity to specific target molecules. Aptamers are typically generated via solid phase oligonucleotide synthesis before selection and amplification through Systematic Evolution of Ligands by EXponential enrichment (SELEX), a process based on competitive binding that enriches the population of certain strands while removing unwanted sequences, yielding aptamers with high specificity and affinity to a target molecule. Mathematical analyses of SELEX have been formulated in the mass action limit, which assumes large system sizes and/or high aptamer and target molecule concentrations. In this paper, we develop a fully discrete stochastic model of SELEX. While converging to a mass-action model in the large system-size limit, our stochastic model allows us to study statistical quantities when the system size is small, such as the probability of losing the best-binding aptamer during each round of selection. Specifically, we find that optimal SELEX protocols in the stochastic model differ from those predicted by a deterministic model. 

We consider age-structured models with an imposed refractory period between births. These models can be used to formulate alternative population control strategies to China’s one-child policy. By allowing any number of births, but with an imposed delay between births, we show how the total population can be decreased and how a relatively older age distribution can be generated. This delay represents a more ‘continuous’ form of population management for which the strict one-child policy is a limiting case. Such a policy approach could be more easily accepted by society. Our analyses provide an initial framework for studying demographics and how social constraints influence population structure. 

The specificity of T cells is that each T cell has only one T cell receptor (TCR). A T cell clone represents a collection of T cells with the same TCR sequence. Thus, the number of different T cell clones in an organism reflects the number of different T cell receptors (TCRs) that arise from recombination of the V(D)J gene segments during T cell development in the thymus. TCR diversity and more specifically, the clone abundance distribution, are important factors in immune functions. Specific recombination patterns occur more frequently than others while subsequent interactions between TCRs and self-antigens are known to trigger proliferation and sustain naive T cell survival. These processes are TCR-dependent, leading to clone-dependent thymic export and naive T cell proliferation rates. We describe the heterogeneous steady-state population of naive T cells (those that have not yet been antigenically triggered) by using a mean-field model of a regulated birth-death-immigration process. After accounting for random sampling, we investigate how TCR-dependent heterogeneities in immigration and proliferation rates affect the shape of clone abundance distributions (the number of different clones that are represented by a specific number of cells, or “clone counts”). By using reasonable physiological parameter values and fitting predicted clone counts to experimentally sampled clone abundances, we show that realistic levels of heterogeneity in immigration rates cause very little change to predicted clone-counts, but that modest heterogeneity in proliferation rates can generate the observed clone abundances. Our analysis provides constraints among physiological parameters that are necessary to yield predictions that qualitatively match the data. Assumptions of the model and potentially other important mechanistic factors are discussed. 

Abstract Backtracking of RNA polymerase (RNAP) is an important pausing mechanism during DNA transcription that is part of the error correction process that enhances transcription fidelity. We model the backtracking mechanism of RNAP, which usually happens when the polymerase tries to incorporate a noncognate or ‘mismatched’ nucleotide triphosphate. Previous models have made simplifying assumptions such as neglecting the trailing polymerase behind the backtracking polymerase or assuming that the trailing polymerase is stationary. We derive exact analytic solutions of a stochastic model that includes locally interacting RNAPs by explicitly showing how a trailing RNAP influences the probability that an error is corrected or incorporated by the leading backtracking RNAP. We also provide two related methods for computing the mean times for error correction and incorporation given an initial local RNAP configuration. Using these results, we propose an effective interacting-RNAP lattice that can be readily simulated.