Modular modelling of signalling pathways and their crosstalk

Signalling pathways are well-known abstractions that explain the mechanisms whereby cells respond to signals. Collections of pathways form networks, and interactions between pathways in a network, known as cross-talk, enables further complex signalling behaviours. While there are several formal modelling approaches for signalling pathways, none make cross-talk explicit; the aim of this paper is to define and categorise cross-talk in a rigorous way. We define a modular approach to pathway and network modelling, based on the module construct in the PRISM modelling language, and a set of generic signalling modules. Five different types of cross-talk are defined according to various biologically meaningful combinations of variable sharing, synchronisation labels and reaction renaming. The approach is illustrated with a case-study analysis of cross-talk between the TGF-β, WNT and MAPK pathways

A knowledge representation meta-model for rule-based modelling of signalling networks

The study of cellular signalling pathways and their deregulation in disease states, such as cancer, is a large and extremely complex task. Indeed, these systems involve many parts and processes but are studied piecewise and their literatures and data are consequently fragmented, distributed and sometimes--at least apparently--inconsistent. This makes it extremely difficult to build significant explanatory models with the result that effects in these systems that are brought about by many interacting factors are poorly understood. The rule-based approach to modelling has shown some promise for the representation of the highly combinatorial systems typically found in signalling where many of the proteins are composed of multiple binding domains, capable of simultaneous interactions, and/or peptide motifs controlled by post-translational modifications. However, the rule-based approach requires highly detailed information about the precise conditions for each and every interaction which is rarely available from any one single source. Rather, these conditions must be painstakingly inferred and curated, by hand, from information contained in many papers--each of which contains only part of the story. In this paper, we introduce a graph-based meta-model, attuned to the representation of cellular signalling networks, which aims to ease this massive cognitive burden on the rule-based curation process. This meta-model is a generalization of that used by Kappa and BNGL which allows for the flexible representation of knowledge at various levels of granularity. In particular, it allows us to deal with information which has either too little, or too much, detail with respect to the strict rule-based meta-model. Our approach provides a basis for the gradual aggregation of fragmented biological knowledge extracted from the literature into an instance of the meta-model from which we can define an automated translation into executable Kappa programs.Comment: In Proceedings DCM 2015, arXiv:1603.0053

Modelling the acquisition of syntactic categories

This research represents an attempt to model the child’s acquisition of syntactic categories. A computational model, based on the EPAM theory of perception and learning, is developed. The basic assumptions are that (1) syntactic categories are actively constructed by the child using distributional learning abilities; and (2) cognitive constraints in learning rate and memory capacity limit these learning abilities. We present simulations of the syntax acquisition of a single subject, where the model learns to build up multi-word utterances by scanning a sample of the speech addressed to the subject by his mother

Creativity as Cognitive design \ud The case of mesoscopic variables in Meta-Structures\ud

Creativity is an open problem which has been differently approached by several disciplines since a long time. In this contribution we consider as creative the constructivist design an observer does on the description levels of complex phenomena, such as the self-organized and emergent ones ( e.g., Bènard rollers, Belousov-Zhabotinsky reactions, flocks, swarms, and more radical cognitive and social emergences). We consider this design as related to the Gestaltian creation of a language fit for representing natural processes and the observer in an integrated way. Organised systems, both artificial and most of the natural ones are designed/ modelled according to a logical closed model which masters all the inter-relation between their constitutive elements, and which can be described by an algorithm or a single formal model. We will show there that logical openness and DYSAM (Dynamical Usage of Models) are the proper tools for those phenomena which cannot be described by algorithms or by a single formal model. The strong correlation between emergence and creativity suggests that an open model is the best way to provide a formal definition of creativity. A specific application relates to the possibility to shape the emergence of Collective Behaviours. Different modelling approaches have been introduced, based on symbolic as well as sub-symbolic rules of interaction to simulate collective phenomena by means of computational emergence. Another approach is based on modelling collective phenomena as sequences of Multiple Systems established by percentages of conceptually interchangeable agents taking on the same roles at different times and different roles at the same time. In the Meta-Structures project we propose to use mesoscopic variables as creative design, invention, good continuity and imitation of the description level. In the project we propose to define the coherence of sequences of Multiple Systems by using the values taken on by the dynamic mesoscopic clusters of its constitutive elements, such as the instantaneous number of elements having, in a flock, the same speed, distance from their nearest neighbours, direction and altitude. In Meta-Structures the collective behaviour’s coherence corresponds, for instance, to the scalar values taken by speed, distance, direction and altitude along time, through statistical strategies of interpolation, quasi-periodicity, levels of ergodicity and their reciprocal relationship. In this case the constructivist role of the observer is considered creative as it relates to neither non-linear replication nor transposition of levels of description and models used for artificial systems, like reductionism. Creativity rather lies in inventing new mesoscopic variables able to identify coherent patterns in complex systems. As it is known, mesoscopic variables represent partial macroscopic properties of a system by using some of the microscopic degrees of freedom possessed by composing elements. Such partial usage of microscopic as well as macroscopic properties allows a kind of Gestaltian continuity and imitation between levels of descriptions for mesoscopic modelling. \ud \u

Modelling potential movement in constrained travel environments using rough space-time prisms

The widespread adoption of location-aware technologies (LATs) has afforded analysts new opportunities for efficiently collecting trajectory data of moving individuals. These technologies enable measuring trajectories as a finite sample set of time-stamped locations. The uncertainty related to both finite sampling and measurement errors makes it often difficult to reconstruct and represent a trajectory followed by an individual in space-time. Time geography offers an interesting framework to deal with the potential path of an individual in between two sample locations. Although this potential path may be easily delineated for travels along networks, this will be less straightforward for more nonnetwork-constrained environments. Current models, however, have mostly concentrated on network environments on the one hand and do not account for the spatiotemporal uncertainties of input data on the other hand. This article simultaneously addresses both issues by developing a novel methodology to capture potential movement between uncertain space-time points in obstacle-constrained travel environments

Self-Evaluation Applied Mathematics 2003-2008 University of Twente

This report contains the self-study for the research assessment of the Department of Applied Mathematics (AM) of the Faculty of Electrical Engineering, Mathematics and Computer Science (EEMCS) at the University of Twente (UT). The report provides the information for the Research Assessment Committee for Applied Mathematics, dealing with mathematical sciences at the three universities of technology in the Netherlands. It describes the state of affairs pertaining to the period 1 January 2003 to 31 December 2008

Learning feedforward controller for a mobile robot vehicle

This paper describes the design and realisation of an on-line learning posetracking controller for a three-wheeled mobile robot vehicle. The controller consists of two components. The first is a constant-gain feedback component, designed on the basis of a second-order model. The second is a learning feedforward component, containing a single-layer neural network, that generates a control contribution on the basis of the desired trajectory of the vehicle. The neural network uses B-spline basis functions, enabling a computationally fast implementation and fast learning. The resulting control system is able to correct for errors due to parameter mismatches and classes of structural errors in the model used for the controller design. After sufficient learning, an existing static gain controller designed on the basis of an extensive model has been outperformed in terms of tracking accuracy