The Oral Tolerance as a Complex Network Phenomenon

Date of Acceptance: 23/05/2015 Funding: MSB acknowledges the Engineering and Physical Sciences Research Council (EPSRC) - UK grant EP/I032606/1. PJM and MD received regular scholarships from the Brazilian the following agency: Higher Education Personnel Training Coordination (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) CAPES http://www.fisica.uepg.br:7080/ppgfisica​/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Quantitative Predictive Modelling Approaches to Understanding Rheumatoid Arthritis:A Brief Review

Rheumatoid arthritis is a chronic autoimmune disease that is a major public health challenge. The disease is characterised by inflammation of synovial joints and cartilage erosion, which lead to chronic pain, poor life quality and, in some cases, mortality. Understanding the biological mechanisms behind the progression of the disease, as well as developing new methods for quantitative predictions of disease progression in the presence/absence of various therapies is important for the success of therapeutic approaches. The aim of this study is to review various quantitative predictive modelling approaches for understanding rheumatoid arthritis. To this end, we start by briefly discussing the biology of this disease and some current treatment approaches, as well as emphasising some of the open problems in the field. Then, we review various mathematical mechanistic models derived to address some of these open problems. We discuss models that investigate the biological mechanisms behind the progression of the disease, as well as pharmacokinetic and pharmacodynamic models for various drug therapies. Furthermore, we highlight models aimed at optimising the costs of the treatments while taking into consideration the evolution of the disease and potential complications.Publisher PDFPeer reviewe

Fitting stochastic epidemic models to gene genealogies using linear noise approximation

Phylodynamics is a set of population genetics tools that aim at reconstructing demographic history of a population based on molecular sequences of individuals sampled from the population of interest. One important task in phylodynamics is to estimate changes in (effective) population size. When applied to infectious disease sequences such estimation of population size trajectories can provide information about changes in the number of infections. To model changes in the number of infected individuals, current phylodynamic methods use non-parametric approaches, parametric approaches, and stochastic modeling in conjunction with likelihood-free Bayesian methods. The first class of methods yields results that are hard-to-interpret epidemiologically. The second class of methods provides estimates of important epidemiological parameters, such as infection and removal/recovery rates, but ignores variation in the dynamics of infectious disease spread. The third class of methods is the most advantageous statistically, but relies on computationally intensive particle filtering techniques that limits its applications. We propose a Bayesian model that combines phylodynamic inference and stochastic epidemic models, and achieves computational tractability by using a linear noise approximation (LNA) --- a technique that allows us to approximate probability densities of stochastic epidemic model trajectories. LNA opens the door for using modern Markov chain Monte Carlo tools to approximate the joint posterior distribution of the disease transmission parameters and of high dimensional vectors describing unobserved changes in the stochastic epidemic model compartment sizes (e.g., numbers of infectious and susceptible individuals). We apply our estimation technique to Ebola genealogies estimated using viral genetic data from the 2014 epidemic in Sierra Leone and Liberia.Comment: 43 pages, 6 figures in the main tex

An Immune Inspired Approach to Anomaly Detection

The immune system provides a rich metaphor for computer security: anomaly detection that works in nature should work for machines. However, early artificial immune system approaches for computer security had only limited success. Arguably, this was due to these artificial systems being based on too simplistic a view of the immune system. We present here a second generation artificial immune system for process anomaly detection. It improves on earlier systems by having different artificial cell types that process information. Following detailed information about how to build such second generation systems, we find that communication between cells types is key to performance. Through realistic testing and validation we show that second generation artificial immune systems are capable of anomaly detection beyond generic system policies. The paper concludes with a discussion and outline of the next steps in this exciting area of computer security.Comment: 19 pages, 4 tables, 2 figures, Handbook of Research on Information Security and Assuranc

Using process algebra to develop predator-prey models of within-host parasite dynamics

As a first approximation of immune-mediated within-host parasite dynamics we can consider the immune response as a predator, with the parasite as its prey. In the ecological literature of predator-prey interactions there are a number of different functional responses used to describe how a predator reproduces in response to consuming prey. Until recently most of the models of the immune system that have taken a predator-prey approach have used simple mass action dynamics to capture the interaction between the immune response and the parasite. More recently Fenton and Perkins (2010) employed three of the most commonly used functional response terms from the ecological literature. In this paper we make use of a technique from computing science, process algebra, to develop mathematical models. The novelty of the process algebra approach is to allow stochastic models of the population (parasite and immune cells) to be developed from rules of individual cell behaviour. By using this approach in which individual cellular behaviour is captured we have derived a ratio-dependent response similar to that seen in previous models of immune-mediated parasite dynamics, confirming that, whilst this type of term is controversial in ecological predator-prey models, it is appropriate for models of the immune system

How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements