854 research outputs found
An in-host model of HIV incorporating latent infection and viral mutation
We construct a seven-component model of the in-host dynamics of the Human
Immunodeficiency Virus Type-1 (i.e, HIV) that accounts for latent infection and
the propensity of viral mutation. A dynamical analysis is conducted and a
theorem is presented which characterizes the long time behavior of the model.
Finally, we study the effects of an antiretroviral drug and treatment
implications.Comment: 10 pages, 7 figures, Proceedings of AIMS Conference on Differential
Equations and Dynamical Systems (2015
Inferring HIV escape rates from multi-locus genotype data
Cytotoxic T-lymphocytes (CTLs) recognize viral protein fragments displayed by
major histocompatibility complex (MHC) molecules on the surface of virally
infected cells and generate an anti-viral response that can kill the infected
cells. Virus variants whose protein fragments are not efficiently presented on
infected cells or whose fragments are presented but not recognized by CTLs
therefore have a competitive advantage and spread rapidly through the
population. We present a method that allows a more robust estimation of these
escape rates from serially sampled sequence data. The proposed method accounts
for competition between multiple escapes by explicitly modeling the
accumulation of escape mutations and the stochastic effects of rare multiple
mutants. Applying our method to serially sampled HIV sequence data, we estimate
rates of HIV escape that are substantially larger than those previously
reported. The method can be extended to complex escapes that require
compensatory mutations. We expect our method to be applicable in other contexts
such as cancer evolution where time series data is also available
StochKit-FF: Efficient Systems Biology on Multicore Architectures
The stochastic modelling of biological systems is an informative, and in some
cases, very adequate technique, which may however result in being more
expensive than other modelling approaches, such as differential equations. We
present StochKit-FF, a parallel version of StochKit, a reference toolkit for
stochastic simulations. StochKit-FF is based on the FastFlow programming
toolkit for multicores and exploits the novel concept of selective memory. We
experiment StochKit-FF on a model of HIV infection dynamics, with the aim of
extracting information from efficiently run experiments, here in terms of
average and variance and, on a longer term, of more structured data.Comment: 14 pages + cover pag
Specific protein-protein binding in many-component mixtures of proteins
Proteins must bind to specific other proteins in vivo in order to function.
The proteins must bind only to one or a few other proteins of the of order a
thousand proteins typically present in vivo. Using a simple model of a protein,
specific binding in many component mixtures is studied. It is found to be a
demanding function in the sense that it demands that the binding sites of the
proteins be encoded by long sequences of bits, and the requirement for specific
binding then strongly constrains these sequences. This is quantified by the
capacity of proteins of a given size (sequence length), which is the maximum
number of specific-binding interactions possible in a mixture. This calculation
of the maximum number possible is in the same spirit as the work of Shannon and
others on the maximum rate of communication through noisy channels.Comment: 13 pages, 3 figures (changes for v2 mainly notational - to be more in
line with notation in information theory literature
Agent-Based Modeling of Host-Pathogen Systems: The Successes and Challenges
Agent-based models have been employed to describe numerous processes in
immunology. Simulations based on these types of models have been used to
enhance our understanding of immunology and disease pathology. We review
various agent-based models relevant to host-pathogen systems and discuss their
contributions to our understanding of biological processes. We then point out
some limitations and challenges of agent-based models and encourage efforts
towards reproducibility and model validation.Comment: LaTeX, 12 pages, 1 EPS figure, uses document class REVTeX 4, and
packages hyperref, xspace, graphics, amsmath, verbatim, and SIunit
Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo
The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity
Stable States of Biological Organisms
A novel model of biological organisms is advanced, treating an organism as a
self-consistent system subject to a pathogen flux. The principal novelty of the
model is that it describes not some parts, but a biological organism as a
whole. The organism is modeled by a five-dimensional dynamical system. The
organism homeostasis is described by the evolution equations for five
interacting components: healthy cells, ill cells, innate immune cells, specific
immune cells, and pathogens. The stability analysis demonstrates that, in a
wide domain of the parameter space, the system exhibits robust structural
stability. There always exist four stable stationary solutions characterizing
four qualitatively differing states of the organism: alive state, boundary
state, critical state, and dead state.Comment: Latex file, 12 pages, 4 figure
Global stability for a class of virus models with CTL immune response and antigenic variation
We study the global stability of a class of models for in-vivo virus
dynamics, that take into account the CTL immune response and display antigenic
variation. This class includes a number of models that have been extensively
used to model HIV dynamics. We show that models in this class are globally
asymptotically stable, under mild hypothesis, by using appropriate Lyapunov
functions. We also characterise the stable equilibrium points for the entire
biologically relevant parameter range. As a byproduct, we are able to determine
what is the diversity of the persistent strains.Comment: 15 page
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