Federico Buti

BioShape: a spatial shape-based scale-independent simulation environment for biological systems

Abstract The simulation and visualization of biological system models is becoming more and more important both in clinical use and in basic research. Since many systems are characterized by interactions involving different scales at the same time, several approaches have been defined to handle such complex systems at different spatial and temporal scale. In this context, we propose BioShape, a 3D particle-based spatial simulator whose novelty consists of providing a uniform and geometry-oriented multiscale modeling environment. These features make BioShape “scaleindependent”, able to express geometric and positional information, and able to support transformations between scales simply defined as mappings between different granularity model instances. To highlight BioShape peculiarities, we sketch a multiscale model of human aortic valve where shapes are used at the cell scale for describing the interaction between a single valvular interstitial cell and its surrounding matrix, at the tissue scale for modeling the valve leaflet tissue mechanical behaviour, and at the organ scale for reproducing, as a 3D structure with fluid-structure interaction, the motion of the valve, blood, and surrounding tissue.

Bone Remodelling in BioShape

Many biological phenomena are inherently multiscale, i.e. they are characterised by interactions involving different scales at the same time. This is the case of bone remodelling, where macroscopic behaviour (at organ and tissue scale) and microstructure (at cell scale) strongly influence each other. Consequently, several approaches have been defined to model such a process at different spatial and temporal levels and, in particular, in terms of continuum properties, abstracting in this way from a realistic - and more complex - cellular scenario. While a large amount of information is available to validate such models separately, more work is needed to integrate all levels fully in a faithful multiscale model. In this scenario, we propose the use of BioShape, a 3D particle-based, scale-independent, geometry and space oriented simulator. It is used to define and integrate a cell and tissue scale model for bone remodelling in terms of shapes equipped with perception, interaction and movement capabilities. Their in-silico simulation allows for tuning continuum-based tissutal and cellular models, as well as for better understanding - both in qualitative and in quantitative terms - the blurry synergy between mechanical and metabolic factors triggering bone remodelling.

An Individual-based Probabilistic Model for Fish Stock Simulation

We define an individual-based probabilistic model of a sole (Solea solea) behaviour. The individual model is given in terms of an Extended Probabilistic Discrete Timed Automaton (EPDTA), a new formalism that is introduced in the paper and that is shown to be interpretable as a Markov decision process. A given EPDTA model can be probabilistically model-checked by giving a suitable translation into syntax accepted by existing model-checkers. In order to simulate the dynamics of a given population of soles in different environmental scenarios, an agent-based simulation environment is defined in which each agent implements the behaviour of the given EPDTA model. By varying the probabilities and the characteristic functions embedded in the EPDTA model it is possible to represent different scenarios and to tune the model itself by comparing the results of the simulations with real data about the sole stock in the North Adriatic sea, available from the recent project SoleMon. The simulator is presented and made available for its adaptation to other species.

BIOSHAPE: end-user development for simulating biological systems

The simulation and visualization of biological system models are becoming more and more important, in both clinical and research activities. Many tools help biologists and bioengineers to analyse and to study complex biological phenomena, such as disease spreading, tissue development and neurological reactivity. We present ongoing work on BioShape, a bio-inspired 3D simulation tool whose novelty consists of providing a 3D geometry-oriented modelling environment. Unlike most of the other tools, BioShape development aims to improve usability by taking advantage of End-User Development techniques. While the user can easily understand the basic features of the tool, he is also made capable of extending them at different levels of complexity, for specific simulation purposes.

Automated Analysis of MUTEX Algorithms with FASE

In this paper we study the liveness of several MUTEX solutions by representing them as processes in PAFASs, a CCS-like process algebra with a specific operator for modelling non-blocking reading behaviours. Verification is carried out using the tool FASE, exploiting a correspondence between violations of the liveness property and a special kind of cycles (called catastrophic cycles) in some transition system. We also compare our approach with others in the literature. The aim of this paper is twofold: on the one hand, we want to demonstrate the applicability of FASE to some concrete, meaningful examples; on the other hand, we want to study the impact of introducing non-blocking behaviours in modelling concurrent systems.

A Geometrical Refinement of Shape Calculus Enabling Direct Simulation

The Shape Calculus is a bio-inspired timed and spatial calculus for describing 3D geometrical shapes moving in a space. Its purpose is twofold: i) modelling and formally verifying (not only) biological systems, and ii) simulating the models for validation and hypothesis testing. The original geometric primitives of the calculus are highly abstract: the associated simulator needs to attach a lot of code to the model specification in order to perform an effective simulation. In this work we propose a calculus refinement in which a detailed 3D characterization of the geometric primitives is injected into the syntax of the calculus. In this way, models written with the new syntax can be directly simulated.

A Uniform Multiscale Meta-model of BioShape

Existing approaches in multiscale (MS) science and engineering have evolved from a range of ideas and solutions that are reflective of their original problem domains. As a result, research in MS science has followed widely diverse and disjoint paths, which present a barrier to cross pollination of ideas and application of methods outside their application domains. The status of the research environment calls for a methodological framework able to (i) provide a common language to modelling and simulating MS problems across a range of scientific and engineering disciplines and, consequently, (ii) characterize critical common issues arising in MS problems in an uniform setting. In this paper, we contribute in this sense. Taking inspiration from the Complex Automata (CxA) MS approach, we formally define and enrich the meta-model of BioShape - put forward as a scale-independent MS simulation environment - and we exploit it to give a uniform treatment of generally defined coupling schemes, in particular the micro-macro one applied to the bone remodelling process. Similarly to CxA, also the BioShape meta-model enjoys two important features: namely, (i) a MS system can be decomposed in uniform single-scale models, each one described by a generic sequence of calls to well-defined operators, and (ii) the link between any two single-scale models can be expressed as a flow of data between a pair of these operators by well-defined coupling schemes. As a consequence, such features not only enforce and formally prove the scale-independence property of the BioShape simulator, but also makes the BioShape meta-model a common and uniform MS modelling paradigm across a range of heterogeneous application domains.

Towards Abstraction-Based Verification of Shape Calculus

The Shape Calculus is a bio-inspired timed and spatial calculus for describing 3D geometrical shapes moving in a space. Shapes, combined with a behaviour, form 3D processes, i.e., individual entities able to bind with other processes on compatible spatial channels and to split over previously established bonds. Due to geometrical space, timed behaviours, a wide degree of freedom in defining motion laws and usual nondeterminism, 3D processes typically exhibits an infinite behaviour that prevents any decidable analysis. Shape Calculus models are currently used only for simulation and, thus, validation of models and hypothesis testing. In this work we introduce a complementary, and synergetic, way of using the calculus for systems biology purposes: we define a first abstract interpretation that can be used to verify untimed and unspatial safety properties of a given model. Such an abstraction focuses on the possible interactions that, during the evolution of the system, can occur among processes yielding new composed processes and, thus, new species. Other possible abstract domains for the verification of more expressive properties are also discussed.