225 research outputs found
Modeling cumulative biological phenomena with Suppes-Bayes Causal Networks
Several diseases related to cell proliferation are characterized by the
accumulation of somatic DNA changes, with respect to wildtype conditions.
Cancer and HIV are two common examples of such diseases, where the mutational
load in the cancerous/viral population increases over time. In these cases,
selective pressures are often observed along with competition, cooperation and
parasitism among distinct cellular clones. Recently, we presented a
mathematical framework to model these phenomena, based on a combination of
Bayesian inference and Suppes' theory of probabilistic causation, depicted in
graphical structures dubbed Suppes-Bayes Causal Networks (SBCNs). SBCNs are
generative probabilistic graphical models that recapitulate the potential
ordering of accumulation of such DNA changes during the progression of the
disease. Such models can be inferred from data by exploiting likelihood-based
model-selection strategies with regularization. In this paper we discuss the
theoretical foundations of our approach and we investigate in depth the
influence on the model-selection task of: (i) the poset based on Suppes' theory
and (ii) different regularization strategies. Furthermore, we provide an
example of application of our framework to HIV genetic data highlighting the
valuable insights provided by the inferred
Modeling biological systems with delays in Bio-PEPA
Delays in biological systems may be used to model events for which the
underlying dynamics cannot be precisely observed, or to provide abstraction of
some behavior of the system resulting more compact models. In this paper we
enrich the stochastic process algebra Bio-PEPA, with the possibility of
assigning delays to actions, yielding a new non-Markovian process algebra:
Bio-PEPAd. This is a conservative extension meaning that the original syntax of
Bio-PEPA is retained and the delay specification which can now be associated
with actions may be added to existing Bio-PEPA models. The semantics of the
firing of the actions with delays is the delay-as-duration approach, earlier
presented in papers on the stochastic simulation of biological systems with
delays. These semantics of the algebra are given in the Starting-Terminating
style, meaning that the state and the completion of an action are observed as
two separate events, as required by delays. Furthermore we outline how to
perform stochastic simulation of Bio-PEPAd systems and how to automatically
translate a Bio-PEPAd system into a set of Delay Differential Equations, the
deterministic framework for modeling of biological systems with delays. We end
the paper with two example models of biological systems with delays to
illustrate the approach.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005
GPU-powered Simulation Methodologies for Biological Systems
The study of biological systems witnessed a pervasive cross-fertilization
between experimental investigation and computational methods. This gave rise to
the development of new methodologies, able to tackle the complexity of
biological systems in a quantitative manner. Computer algorithms allow to
faithfully reproduce the dynamics of the corresponding biological system, and,
at the price of a large number of simulations, it is possible to extensively
investigate the system functioning across a wide spectrum of natural
conditions. To enable multiple analysis in parallel, using cheap, diffused and
highly efficient multi-core devices we developed GPU-powered simulation
algorithms for stochastic, deterministic and hybrid modeling approaches, so
that also users with no knowledge of GPUs hardware and programming can easily
access the computing power of graphics engines.Comment: In Proceedings Wivace 2013, arXiv:1309.712
Fine-tuning anti-tumor immunotherapies via stochastic simulations
Background: Anti-tumor therapies aim at reducing to zero the number of tumor cells in a host within their end or, at least, aim at leaving the patient with a sufficiently small number of tumor cells so that the residual tumor can be eradicated by the immune system. Besides severe side-effects, a key problem of such therapies is finding a suitable scheduling of their administration to the patients. In this paper we study the effect of varying therapy-related parameters on the final outcome of the interplay between a tumor and the immune system.Results: This work generalizes our previous study on hybrid models of such an interplay where interleukins are modeled as a continuous variable, and the tumor and the immune system as a discrete-state continuous-time stochastic process. The hybrid model we use is obtained by modifying the corresponding deterministic model, originally proposed by Kirschner and Panetta. We consider Adoptive Cellular Immunotherapies and Interleukin-based therapies, as well as their combination. By asymptotic and transitory analyses of the corresponding deterministic model we find conditions guaranteeing tumor eradication, and we tune the parameters of the hybrid model accordingly. We then perform stochastic simulations of the hybrid model under various therapeutic settings: constant, piece-wise constant or impulsive infusion and daily or weekly delivery schedules.Conclusions: Results suggest that, in some cases, the delivery schedule may deeply impact on the therapy-induced tumor eradication time. Indeed, our model suggests that Interleukin-based therapies may not be effective for every patient, and that the piece-wise constant is the most effective delivery to stimulate the immune-response. For Adoptive Cellular Immunotherapies a metronomic delivery seems more effective, as it happens for other anti-angiogenesis therapies and chemotherapies, and the impulsive delivery seems more effective than the piece-wise constant. The expected synergistic effects have been observed when the therapies are combined. \ua9 2012 Caravagna et al.; licensee BioMed Central Ltd
Stochastic Hybrid Automata with delayed transitions to model biochemical systems with delays
To study the effects of a delayed immune-response on the growth of an immuno- genic neoplasm we introduce Stochastic Hybrid Automata with delayed transi- tions as a representation of hybrid biochemical systems with delays. These tran- sitions abstractly model unknown dynamics for which a constant duration can be estimated, i.e. a delay. These automata are inspired by standard Stochastic Hybrid Automata, and their semantics is given in terms of Piecewise Determin- istic Markov Processes. The approach is general and can be applied to systems where (i) components at low concentrations are modeled discretely (so to retain their intrinsic stochastic fluctuations), (ii) abundant component, e.g., chemical signals, are well approximated by mean-field equations (so to simulate them efficiently) and (iii) missing components are abstracted with delays. Via sim- ulations we show in our application that interesting delay-induced phenomena arise, whose quantification is possible in this new quantitative framewor
On the Interpretation of Delays in Delay Stochastic Simulation of Biological Systems
Delays in biological systems may be used to model events for which the
underlying dynamics cannot be precisely observed. Mathematical modeling of
biological systems with delays is usually based on Delay Differential Equations
(DDEs), a kind of differential equations in which the derivative of the unknown
function at a certain time is given in terms of the values of the function at
previous times. In the literature, delay stochastic simulation algorithms have
been proposed. These algorithms follow a "delay as duration" approach, namely
they are based on an interpretation of a delay as the elapsing time between the
start and the termination of a chemical reaction. This interpretation is not
suitable for some classes of biological systems in which species involved in a
delayed interaction can be involved at the same time in other interactions. We
show on a DDE model of tumor growth that the delay as duration approach for
stochastic simulation is not precise, and we propose a simulation algorithm
based on a ``purely delayed'' interpretation of delays which provides better
results on the considered model
Analysis of the spatial and dynamical properties of a multiscale model of intestinal crypts
The preliminary analyses on a multiscale model of intestinal crypt dynamics are here presented. The model combines a morphological model, based on the Cellular Potts Model (CPM), and a gene regulatory network model, based on Noisy Random Boolean Networks (NRBNs). Simulations suggest that the stochastic differentiation process is itself sufficient to ensure the general homeostasis in the asymptotic states, as proven by several measures
- …