Model Revision from Temporal Logic Properties in Computational Systems Biology

International audienceSystems biologists build models of bio-molecular processes from knowledge acquired both at the gene and protein levels, and at the phenotype level through experiments done in wildlife and mutated organisms. In this chapter, we present qualitative and quantitative logic learning tools, and illustrate how they can be useful to the modeler. We focus on biochemical reaction models written in the Systems Biology Markup Language SBML, and interpreted in the Biochemical Abstract Machine BIOCHAM. We first present a model revision algorithm for inferring reaction rules from biological properties expressed in temporal logic. Then we discuss the representations of kinetic models with ordinary differential equations (ODEs) and with stochastic logic programs (SLPs), and describe a parameter search algorithm for finding parameter values satisfying quantitative temporal properties. These methods are illustrated by a simple model of the cell cycle control, and by an application to the modelling of the conditions of synchronization in period of the cell cycle by the circadian cycle

Geospatial Narratives and their Spatio-Temporal Dynamics: Commonsense Reasoning for High-level Analyses in Geographic Information Systems

The modelling, analysis, and visualisation of dynamic geospatial phenomena has been identified as a key developmental challenge for next-generation Geographic Information Systems (GIS). In this context, the envisaged paradigmatic extensions to contemporary foundational GIS technology raises fundamental questions concerning the ontological, formal representational, and (analytical) computational methods that would underlie their spatial information theoretic underpinnings. We present the conceptual overview and architecture for the development of high-level semantic and qualitative analytical capabilities for dynamic geospatial domains. Building on formal methods in the areas of commonsense reasoning, qualitative reasoning, spatial and temporal representation and reasoning, reasoning about actions and change, and computational models of narrative, we identify concrete theoretical and practical challenges that accrue in the context of formal reasoning about `space, events, actions, and change'. With this as a basis, and within the backdrop of an illustrated scenario involving the spatio-temporal dynamics of urban narratives, we address specific problems and solutions techniques chiefly involving `qualitative abstraction', `data integration and spatial consistency', and `practical geospatial abduction'. From a broad topical viewpoint, we propose that next-generation dynamic GIS technology demands a transdisciplinary scientific perspective that brings together Geography, Artificial Intelligence, and Cognitive Science. Keywords: artificial intelligence; cognitive systems; human-computer interaction; geographic information systems; spatio-temporal dynamics; computational models of narrative; geospatial analysis; geospatial modelling; ontology; qualitative spatial modelling and reasoning; spatial assistance systemsComment: ISPRS International Journal of Geo-Information (ISSN 2220-9964); Special Issue on: Geospatial Monitoring and Modelling of Environmental Change}. IJGI. Editor: Duccio Rocchini. (pre-print of article in press

Contracts and Behavioral Patterns for SoS: The EU IP DANSE approach

This paper presents some of the results of the first year of DANSE, one of the first EU IP projects dedicated to SoS. Concretely, we offer a tool chain that allows to specify SoS and SoS requirements at high level, and analyse them using powerful toolsets coming from the formal verification area. At the high level, we use UPDM, the system model provided by the british army as well as a new type of contract based on behavioral patterns. At low level, we rely on a powerful simulation toolset combined with recent advances from the area of statistical model checking. The approach has been applied to a case study developed at EADS Innovation Works.Comment: In Proceedings AiSoS 2013, arXiv:1311.319

STL-based Analysis of TRAIL-induced Apoptosis Challenges the Notion of Type I/Type II Cell Line Classification

Extrinsic apoptosis is a programmed cell death triggered by external ligands, such as the TNF-related apoptosis inducing ligand (TRAIL). Depending on the cell line, the specific molecular mechanisms leading to cell death may significantly differ. Precise characterization of these differences is crucial for understanding and exploiting extrinsic apoptosis. Cells show distinct behaviors on several aspects of apoptosis, including (i) the relative order of caspases activation, (ii) the necessity of mitochondria outer membrane permeabilization (MOMP) for effector caspase activation, and (iii) the survival of cell lines overexpressing Bcl2. These differences are attributed to the activation of one of two pathways, leading to classification of cell lines into two groups: type I and type II. In this work we challenge this type I/type II cell line classification. We encode the three aforementioned distinguishing behaviors in a formal language, called signal temporal logic (STL), and use it to extensively test the validity of a previously-proposed model of TRAIL-induced apoptosis with respect to experimental observations made on different cell lines. After having solved a few inconsistencies using STL-guided parameter search, we show that these three criteria do not define consistent cell line classifications in type I or type II, and suggest mutants that are predicted to exhibit ambivalent behaviors. In particular, this finding sheds light on the role of a feedback loop between caspases, and reconciliates two apparently-conflicting views regarding the importance of either upstream or downstream processes for cell-type determination. More generally, our work suggests that these three distinguishing behaviors should be merely considered as type I/II features rather than cell-type defining criteria. On the methodological side, this work illustrates the biological relevance of STL-diagrams, STL population data, and STL-guided parameter search implemented in the tool Breach. Such tools are well-adapted to the ever-increasing availability of heterogeneous knowledge on complex signal transduction pathways

Measuring the World: Olfaction as a Process Model of Perception

How much does stimulus input shape perception? The common-sense view is that our perceptions are representations of objects and their features and that the stimulus structures the perceptual object. The problem for this view concerns perceptual biases as responsible for distortions and the subjectivity of perceptual experience. These biases are increasingly studied as constitutive factors of brain processes in recent neuroscience. In neural network models the brain is said to cope with the plethora of sensory information by predicting stimulus regularities on the basis of previous experiences. Drawing on this development, this chapter analyses perceptions as processes. Looking at olfaction as a model system, it argues for the need to abandon a stimulus-centred perspective, where smells are thought of as stable percepts, computationally linked to external objects such as odorous molecules. Perception here is presented as a measure of changing signal ratios in an environment informed by expectancy effects from top-down processes