Advances in computational immunology

Published versio

Challenges in interpreting allergen microarrays in relation to clinical symptoms: a machine learning approach.

Identifying different patterns of allergens and understanding their predictive ability in relation to asthma and other allergic diseases is crucial for the design of personalized diagnostic tools.Allergen-IgE screening using ImmunoCAP ISAC(®) assay was performed at age 11 yrs in children participating a population-based birth cohort. Logistic regression (LR) and nonlinear statistical learning models, including random forests (RF) and Bayesian networks (BN), coupled with feature selection approaches, were used to identify patterns of allergen responses associated with asthma, rhino-conjunctivitis, wheeze, eczema and airway hyper-reactivity (AHR, positive methacholine challenge). Sensitivity/specificity and area under the receiver operating characteristic (AUROC) were used to assess model performance via repeated validation.Serum sample for IgE measurement was obtained from 461 of 822 (56.1%) participants. Two hundred and thirty-eight of 461 (51.6%) children had at least one of 112 allergen components IgE > 0 ISU. The binary threshold >0.3 ISU performed less well than using continuous IgE values, discretizing data or using other data transformations, but not significantly (p = 0.1). With the exception of eczema (AUROC~0.5), LR, RF and BN achieved comparable AUROC, ranging from 0.76 to 0.82. Dust mite, pollens and pet allergens were highly associated with asthma, whilst pollens and dust mite with rhino-conjunctivitis. Egg/bovine allergens were associated with eczema.After validation, LR, RF and BN demonstrated reasonable discrimination ability for asthma, rhino-conjunctivitis, wheeze and AHR, but not for eczema. However, further improvements in threshold ascertainment and/or value transformation for different components, and better interpretation algorithms are needed to fully capitalize on the potential of the technology

SIMMUNE, a tool for simulating and analyzing immune system behavior

We present a new approach to the simulation and analysis of immune system behavior. The simulations that can be done with our software package called SIMMUNE are based on immunological data that describe the behavior of immune system agents (cells, molecules) on a microscopial (i.e. agent-agent interaction) scale by defining cellular stimulus-response mechanisms. Since the behavior of the agents in SIMMUNE can be very flexibly configured, its application is not limited to immune system simulations. We outline the principles of SIMMUNE's multiscale analysis of emergent structure within the simulated immune system that allow the identification of immunological contexts using minimal a priori assumptions about the higher level organization of the immune system.Comment: 23 pages, 10 figure

Evaluation of HIV infected Cells

In this paper, Human Immunodeficiency Virus (HIV) infected cells is found out using a Simulink model. The Simulink solution is equivalent or very close to the exact solution of the problem. Accuracy of the Simulink solution to this problem is better than the existing numerical methods. The main advantage of Simulink model is that solution of any dynamicalproblem can be obtained by anybody without writing any codes. Anillustrative numerical example is presented for the proposed method

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology.

Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose-concentration-effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future

The Rules of Human T Cell Fate in vivo.

The processes governing lymphocyte fate (division, differentiation, and death), are typically assumed to be independent of cell age. This assumption has been challenged by a series of elegant studies which clearly show that, for murine cells in vitro, lymphocyte fate is age-dependent and that younger cells (i.e., cells which have recently divided) are less likely to divide or die. Here we investigate whether the same rules determine human T cell fate in vivo. We combined data from in vivo stable isotope labeling in healthy humans with stochastic, agent-based mathematical modeling. We show firstly that the choice of model paradigm has a large impact on parameter estimates obtained using stable isotope labeling i.e., different models fitted to the same data can yield very different estimates of T cell lifespan. Secondly, we found no evidence in humans in vivo to support the model in which younger T cells are less likely to divide or die. This age-dependent model never provided the best description of isotope labeling; this was true for naïve and memory, CD4+ and CD8+ T cells. Furthermore, this age-dependent model also failed to predict an independent data set in which the link between division and death was explored using Annexin V and deuterated glucose. In contrast, the age-independent model provided the best description of both naïve and memory T cell dynamics and was also able to predict the independent dataset