Modelling molecular networks: relationships between different formalisms and levels of details

This document is the deliverable 1.3 of French ANR CALAMAR. It presents a study of different formalisms used for modelling and analyzing large molecular regulation networks, their formal links, in terms of mutual encodings and of abstractions, and the corresponding levels of detail captured

In-silico-Systemanalyse von Biopathways

Chen M. In silico systems analysis of biopathways. Bielefeld (Germany): Bielefeld University; 2004.In the past decade with the advent of high-throughput technologies, biology has migrated from a descriptive science to a predictive one. A vast amount of information on the metabolism have been produced; a number of specific genetic/metabolic databases and computational systems have been developed, which makes it possible for biologists to perform in silico analysis of metabolism. With experimental data from laboratory, biologists wish to systematically conduct their analysis with an easy-to-use computational system. One major task is to implement molecular information systems that will allow to integrate different molecular database systems, and to design analysis tools (e.g. simulators of complex metabolic reactions). Three key problems are involved: 1) Modeling and simulation of biological processes; 2) Reconstruction of metabolic pathways, leading to predictions about the integrated function of the network; and 3) Comparison of metabolism, providing an important way to reveal the functional relationship between a set of metabolic pathways. This dissertation addresses these problems of in silico systems analysis of biopathways. We developed a software system to integrate the access to different databases, and exploited the Petri net methodology to model and simulate metabolic networks in cells. It develops a computer modeling and simulation technique based on Petri net methodology; investigates metabolic networks at a system level; proposes a markup language for biological data interchange among diverse biological simulators and Petri net tools; establishes a web-based information retrieval system for metabolic pathway prediction; presents an algorithm for metabolic pathway alignment; recommends a nomenclature of cellular signal transduction; and attempts to standardize the representation of biological pathways. Hybrid Petri net methodology is exploited to model metabolic networks. Kinetic modeling strategy and Petri net modeling algorithm are applied to perform the processes of elements functioning and model analysis. The proposed methodology can be used for all other metabolic networks or the virtual cell metabolism. Moreover, perspectives of Petri net modeling and simulation of metabolic networks are outlined. A proposal for the Biology Petri Net Markup Language (BioPNML) is presented. The concepts and terminology of the interchange format, as well as its syntax (which is based on XML) are introduced. BioPNML is designed to provide a starting point for the development of a standard interchange format for Bioinformatics and Petri nets. The language makes it possible to exchange biology Petri net diagrams between all supported hardware platforms and versions. It is also designed to associate Petri net models and other known metabolic simulators. A web-based metabolic information retrieval system, PathAligner, is developed in order to predict metabolic pathways from rudimentary elements of pathways. It extracts metabolic information from biological databases via the Internet, and builds metabolic pathways with data sources of genes, sequences, enzymes, metabolites, etc. The system also provides a navigation platform to investigate metabolic related information, and transforms the output data into XML files for further modeling and simulation of the reconstructed pathway. An alignment algorithm to compare the similarity between metabolic pathways is presented. A new definition of the metabolic pathway is proposed. The pathway defined as a linear event sequence is practical for our alignment algorithm. The algorithm is based on strip scoring the similarity of 4-hierarchical EC numbers involved in the pathways. The algorithm described has been implemented and is in current use in the context of the PathAligner system. Furthermore, new methods for the classification and nomenclature of cellular signal transductions are recommended. For each type of characterized signal transduction, a unique ST number is provided. The Signal Transduction Classification Database (STCDB), based on the proposed classification and nomenclature, has been established. By merging the ST numbers with EC numbers, alignments of biopathways are possible. Finally, a detailed model of urea cycle that includes gene regulatory networks, metabolic pathways and signal transduction is demonstrated by using our approaches. A system biological interpretation of the observed behavior of the urea cycle and its related transcriptomics information is proposed to provide new insights for metabolic engineering and medical care

IMPLEMENTATION AND UNIFORM MANAGEMENT OF MODELLING ENTITIES IN A MASSIVELY FEATURE-OBJECT ORIENTED ADVANCED CAD ENVIRONMENT

Today we are spectators of the transition process in computer aided design from traditional geometry based on design systems to advanced computer-based engineering systems. The key is the feature technology that allows both integrating and managing modelling entities in a coherent way. Feature technology is developing rapidly. New research topics and contexts are emerging from time to time. This paper introduces concept, design and technological feature-objects to support operational, structural and morphological modelling of mechanical products. First, the feature-centred approaches to conceptual design are summarized and evaluated. Then an implementation of concept feature-objects and the methodology for using them is presented. The strength of concept feature-objects is in their morphology inclusive nature. They appear as parametrized three-dimensional skeletons providing geometrical representations for the modelled engineering conceptions. A concept feature-object models the physical ports, contact surfaces related to ports, bones between ports, DOF of ports, relevant physical parameters, scientific and empirical descriptions of intentional transformations and environmental effects. Concept feature-objects are related to design feature-objects that, in turn, are constructed of a relevant set of technological feature-entities. Concept feature-objects refer to the configurable and parametrized design feature-objects through an indexing mechanism. The conceptions have been tested during the programming and further development of the authors' PRODES system

Computing multi-scale organizations built through assembly

The ability to generate and control assembling structures built over many orders of magnitude is an unsolved challenge of engineering and science. Many of the presumed transformational benefits of nanotechnology and robotics are based directly on this capability. There are still significant theoretical difficulties associated with building such systems, though technology is rapidly ensuring that the tools needed are becoming available in chemical, electronic, and robotic domains. In this thesis a simulated, general-purpose computational prototype is developed which is capable of unlimited assembly and controlled by external input, as well as an additional prototype which, in structures, can emulate any other computing device. These devices are entirely finite-state and distributed in operation. Because of these properties and the unique ability to form unlimited size structures of unlimited computational power, the prototypes represent a novel and useful blueprint on which to base scalable assembly in other domains. A new assembling model of Computational Organization and Regulation over Assembly Levels (CORAL) is also introduced, providing the necessary framework for this investigation. The strict constraints of the CORAL model allow only an assembling unit of a single type, distributed control, and ensure that units cannot be reprogrammed - all reprogramming is done via assembly. Multiple units are instead structured into aggregate computational devices using a procedural or developmental approach. Well-defined comparison of computational power between levels of organization is ensured by the structure of the model. By eliminating ambiguity, the CORAL model provides a pragmatic answer to open questions regarding a framework for hierarchical organization. Finally, a comparison between the designed prototypes and units evolved using evolutionary algorithms is presented as a platform for further research into novel scalable assembly. Evolved units are capable of recursive pairing ability under the control of a signal, a primitive form of unlimited assembly, and do so via symmetry-breaking operations at each step. Heuristic evidence for a required minimal threshold of complexity is provided by the results, and challenges and limitations of the approach are identified for future evolutionary studies

Scheduling and discrete event control of flexible manufacturing systems based on Petri nets

A flexible manufacturing system (FMS) is a computerized production system that can simultaneously manufacture multiple types of products using various resources such as robots and multi-purpose machines. The central problems associated with design of flexible manufacturing systems are related to process planning, scheduling, coordination control, and monitoring. Many methods exist for scheduling and control of flexible manufacturing systems, although very few methods have addressed the complexity of whole FMS operations. This thesis presents a Petri net based method for deadlock-free scheduling and discrete event control of flexible manufacturing systems. A significant advantage of Petri net based methods is their powerful modeling capability. Petri nets can explicitly and concisely model the concurrent and asynchronous activities, multi-layer resource sharing, routing flexibility, limited buffers and precedence constraints in FMSs. Petri nets can also provide an explicit way for considering deadlock situations in FMSs, and thus facilitate significantly the design of a deadlock-free scheduling and control system. The contributions of this work are multifold. First, it develops a methodology for discrete event controller synthesis for flexible manufacturing systems in a timed Petri net framework. The resulting Petri nets have the desired qualitative properties of liveness, boundedness (safeness), and reversibility, which imply freedom from deadlock, no capacity overflow, and cyclic behavior, respectively. This precludes the costly mathematical analysis for these properties and reduces on-line computation overhead to avoid deadlocks. The performance and sensitivity of resulting Petri nets, thus corresponding control systems, are evaluated. Second, it introduces a hybrid heuristic search algorithm based on Petri nets for deadlock-free scheduling of flexible manufacturing systems. The issues such as deadlock, routing flexibility, multiple lot size, limited buffer size and material handling (loading/unloading) are explored. Third, it proposes a way to employ fuzzy dispatching rules in a Petri net framework for multi-criterion scheduling. Finally, it shows the effectiveness of the developed methods through several manufacturing system examples compared with benchmark dispatching rules, integer programming and Lagrangian relaxation approaches

Symbolic planning for heterogeneous robots through composition of their motion description languages

This dissertation introduces a new formalism to define compositions of interacting heterogeneous systems, described by extended motion description languages (MDLes). The properties of the composition system are analyzed and an automatic process to generate sequential atom plan is introduced. The novelty of the formalism is in producing a composed system with a behavior that could be a superset of the union of the behaviors of its generators. As robotic systems perform increasingly complex tasks, people resort increasingly to switching or hybrid control algorithms. A need arises for a formalism to compose different robotic behaviors and meet a final target. The significant work produced to date on various aspects of robotics arguably has not yet effectively captured the interaction between systems. Another problem in motion control is automating the process of planning and it has been recognized that there is a gap between high level planning algorithms and low level motion control implementation. This dissertation is an attempt to address these problems. A new composition system is given and the properties are checked. We allow systems to have additional cooperative transitions and become active only when the systems are composed with other systems appropriately. We distinguish between events associated with transitions a push-down automaton representing an MDLe can take autonomously, and events that cannot initiate transitions. Among the latter, there can be events that when synchronized with some of another push-down automaton, become active and do initiate transitions. We identify MDLes as recursive systems in some basic process algebra (BPA) written in Greibach Normal Form. By identifying MDLes as a subclass of BPAs, we are able to borrow the syntax and semantics of the BPAs merge operator (instead of defining a new MDLe operator), and thus establish closeness and decidability properties for MDLe compositions. We introduce an instance of the sliding block puzzle as a multi-robot hybrid system. We automate the process of planning and dictate how the behaviors are sequentially synthesized into plans that drive the system into a desired state. The decidability result gives us hope to abstract the system to the point that some of the available model checkers can be used to construct motion plans. The new notion of system composition allows us to capture the interaction between systems and we realize that the whole system can do more than the sum of its parts. The framework can be used on groups of heterogeneous robotic systems to communicate and allocate tasks among themselves, and sort through possible solutions to find a plan of action without human intervention or guidance