687 research outputs found
Process Calculi Abstractions for Biology
Several approaches have been proposed to model biological systems by means of the formal techniques and tools available in computer science. To mention just a few of them, some representations are inspired by Petri Nets theory, and some other by stochastic processes. A most recent approach consists in interpreting the living entities as terms of process calculi where the behavior of the represented systems can be inferred by applying syntax-driven rules. A comprehensive picture of the state of the art of the process calculi approach to biological modeling is still missing. This paper goes in the direction of providing such a picture by presenting a comparative survey of the process calculi that have been used and proposed to describe the behavior of living entities. This is the preliminary version of a paper that was published in Algorithmic Bioprocesses. The original publication is available at http://www.springer.com/computer/foundations/book/978-3-540-88868-
Enhanced Operational Semantics in Systems Biology
We are faced with a great challenge: the cross-fertilization between the fields of formal methods for concurrency, in the computer science domain, and systems biology in the biological realm
BlenX-based compositional modeling of complex reaction mechanisms
Molecular interactions are wired in a fascinating way resulting in complex
behavior of biological systems. Theoretical modeling provides a useful
framework for understanding the dynamics and the function of such networks. The
complexity of the biological networks calls for conceptual tools that manage
the combinatorial explosion of the set of possible interactions. A suitable
conceptual tool to attack complexity is compositionality, already successfully
used in the process algebra field to model computer systems. We rely on the
BlenX programming language, originated by the beta-binders process calculus, to
specify and simulate high-level descriptions of biological circuits. The
Gillespie's stochastic framework of BlenX requires the decomposition of
phenomenological functions into basic elementary reactions. Systematic
unpacking of complex reaction mechanisms into BlenX templates is shown in this
study. The estimation/derivation of missing parameters and the challenges
emerging from compositional model building in stochastic process algebras are
discussed. A biological example on circadian clock is presented as a case study
of BlenX compositionality
The role of concurrency in an evolutionary view of programming abstractions
In this paper we examine how concurrency has been embodied in mainstream
programming languages. In particular, we rely on the evolutionary talking
borrowed from biology to discuss major historical landmarks and crucial
concepts that shaped the development of programming languages. We examine the
general development process, occasionally deepening into some language, trying
to uncover evolutionary lineages related to specific programming traits. We
mainly focus on concurrency, discussing the different abstraction levels
involved in present-day concurrent programming and emphasizing the fact that
they correspond to different levels of explanation. We then comment on the role
of theoretical research on the quest for suitable programming abstractions,
recalling the importance of changing the working framework and the way of
looking every so often. This paper is not meant to be a survey of modern
mainstream programming languages: it would be very incomplete in that sense. It
aims instead at pointing out a number of remarks and connect them under an
evolutionary perspective, in order to grasp a unifying, but not simplistic,
view of the programming languages development process
A framework for protein and membrane interactions
We introduce the BioBeta Framework, a meta-model for both protein-level and
membrane-level interactions of living cells. This formalism aims to provide a
formal setting where to encode, compare and merge models at different
abstraction levels; in particular, higher-level (e.g. membrane) activities can
be given a formal biological justification in terms of low-level (i.e.,
protein) interactions. A BioBeta specification provides a protein signature
together a set of protein reactions, in the spirit of the kappa-calculus.
Moreover, the specification describes when a protein configuration triggers one
of the only two membrane interaction allowed, that is "pinch" and "fuse". In
this paper we define the syntax and semantics of BioBeta, analyse its
properties, give it an interpretation as biobigraphical reactive systems, and
discuss its expressivity by comparing with kappa-calculus and modelling
significant examples. Notably, BioBeta has been designed after a bigraphical
metamodel for the same purposes. Hence, each instance of the calculus
corresponds to a bigraphical reactive system, and vice versa (almost).
Therefore, we can inherith the rich theory of bigraphs, such as the automatic
construction of labelled transition systems and behavioural congruences
A Process Calculus for Molecular Interaction Maps
We present the MIM calculus, a modeling formalism with a strong biological
basis, which provides biologically-meaningful operators for representing the
interaction capabilities of molecular species. The operators of the calculus
are inspired by the reaction symbols used in Molecular Interaction Maps (MIMs),
a diagrammatic notation used by biologists. Models of the calculus can be
easily derived from MIM diagrams, for which an unambiguous and executable
interpretation is thus obtained. We give a formal definition of the syntax and
semantics of the MIM calculus, and we study properties of the formalism. A case
study is also presented to show the use of the calculus for modeling
biomolecular networks.Comment: 15 pages; 8 figures; To be published on EPTCS, proceedings of MeCBIC
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Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway.
BACKGROUND: Appropriately formulated quantitative computational models can support researchers in understanding the dynamic behaviour of biological pathways and support hypothesis formulation and selection by "in silico" experimentation. An obstacle to widespread adoption of this approach is the requirement to formulate a biological pathway as machine executable computer code. We have recently proposed a novel, biologically intuitive, narrative-style modelling language for biologists to formulate the pathway which is then automatically translated into an executable format and is, thus, usable for analysis via existing simulation techniques. RESULTS: Here we use a high-level narrative language in designing a computational model of the gp130/JAK/STAT signalling pathway and show that the model reproduces the dynamic behaviour of the pathway derived by biological observation. We then "experiment" on the model by simulation and sensitivity analysis to define those parameters which dominate the dynamic behaviour of the pathway. The model predicts that nuclear compartmentalisation and phosphorylation status of STAT are key determinants of the pathway and that alternative mechanisms of signal attenuation exert their influence on different timescales. CONCLUSION: The described narrative model of the gp130/JAK/STAT pathway represents an interesting case study showing how, by using this approach, researchers can model biological systems without explicitly dealing with formal notations and mathematical expressions (typically used for biochemical modelling), nevertheless being able to obtain simulation and analysis results. We present the model and the sensitivity analysis results we have obtained, that allow us to identify the parameters which are most sensitive to perturbations. The results, which are shown to be in agreement with existing mathematical models of the gp130/JAK/STAT pathway, serve us as a form of validation of the model and of the approach itself
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