14 Maio 2018, 14:41 - Fátima Sampaio
Candidate: Pedro do Nascimento Barata Leal Varela N.º 42342
Title: Efficient attractor characterisation in large discrete event systems: application to biological regulatory networks
Location: Room 0.19, Pavilhão de Informática II, Alameda
Advisors: Professor Pedro Tiago Gonçalves Monteiro / Doutora Claudine Chaouiya
Abstract: Cellular processes are governed by complex molecular regulatory networks. To understand the dynamics emerging from these networks, a popular approach relies on a Boolean abstraction. These Boolean regulatory networks define qualitative models with discrete dynamics in which properties of interest relate to the so-called attractors and their reachability. Attractors are of the utmost importance as they relate to long term behaviours of the modelled processes.When considering multicellular systems, cell-cell communication must be accounted by properly inter-connecting cellular network models. This is done through logical composition rules that define cell-cell communication, leading to a (composed) model of the regulatory contrai of the whole.The goal of this thesis is to develop and implement formal methods to characterise multicellular stable states, henceforth known as stable patterns. ldentification of these stable patterns is a challenging problem due to the combinatorial explosion of the dimensions of the model state space and to the potentially huge number of solutions.Typically cells are represented as hexagons, and a simple epithelial tissue as an hexagonal grid. Epilog, a Java software tool was developed to simulate and visualise pattern formation on simple epithelial tissue, combining logical formalism and Cellular Automata.Another contribution of this thesis, was the development of a SAT-based approach to identify stable patterns, by composing stable patterns from the cellular models stable states. This approach provided further insights on the complexity of the problem, particularly on the huge number of reachable stable pattens. To escape from the constraints of the classical Cellular Automata, it was explored the influence of boundary conditions, update schemes, and neighbourhood relationship on stable patterns and their reachability properties. A simple lateral inhibition process, present in many developmental systems, is used as a case study for ali theoretical approaches. Lateral inhibition is known to be involved in the emergence of "salt-and-pepper" patterns.