Conceptual Model-Based Systems Biology: Mapping Knowledge and Discovering Gaps in the mRNA Transcription Cycle

We propose a Conceptual Model-based Systems Biology framework for qualitative modeling, executing, and eliciting knowledge gaps in molecular biology systems. The framework is an adaptation of Object-Process Methodology (OPM), a graphical and textual executable modeling language. OPM enables concurrent representation of the system's structure—the objects that comprise the system, and behavior—how processes transform objects over time. Applying a top-down approach of recursively zooming into processes, we model a case in point—the mRNA transcription cycle. Starting with this high level cell function, we model increasingly detailed processes along with participating objects. Our modeling approach is capable of modeling molecular processes such as complex formation, localization and trafficking, molecular binding, enzymatic stimulation, and environmental intervention. At the lowest level, similar to the Gene Ontology, all biological processes boil down to three basic molecular functions: catalysis, binding/dissociation, and transporting. During modeling and execution of the mRNA transcription model, we discovered knowledge gaps, which we present and classify into various types. We also show how model execution enhances a coherent model construction. Identification and pinpointing knowledge gaps is an important feature of the framework, as it suggests where research should focus and whether conjectures about uncertain mechanisms fit into the already verified model

Conceptual Modeling of mRNA Decay Provokes New Hypotheses

Biologists are required to integrate large amounts of data to construct a working model of the system under investigation. This model is often informal and stored mentally or textually, making it prone to contain undetected inconsistencies, inaccuracies, or even contradictions, not much less than a representation in free natural language. Using Object-Process Methodology (OPM), a formal yet visual and humanly accessible conceptual modeling language, we have created an executable working model of the mRNA decay process in Saccharomyces cerevisiae, as well as the import of its components to the nucleus following mRNA decay. We show how our model, which incorporates knowledge from 43 articles, can reproduce outcomes that match the experimental findings, evaluate hypotheses, and predict new possible outcomes. Moreover, we were able to analyze the effects of the mRNA decay model perturbations related to gene and interaction deletions, and predict the nuclear import of certain decay factors, which we then verified experimentally. In particular, we verified experimentally the hypothesis that Rpb4p, Lsm1p, and Pan2p remain bound to the RNA 3′-untralslated region during the entire process of the 5′ to 3′ degradation of the RNA open reading frame. The model has also highlighted erroneous hypotheses that indeed were not in line with the experimental outcomes. Beyond the scientific value of these specific findings, this work demonstrates the value of the conceptual model as an in silico vehicle for hypotheses generation and testing, which can reinforce, and often even replace, risky, costlier wet lab experiments

A Software System Development Life Cycle Model for Improved Stakeholders’ Communication and Collaboration

Software vendors and entrepreneurs, who try to introduce an innovative software product to a specific organization or an entire market, enter a long and tedious process. During this process, the market and various organizations evaluate the product from different perspectives, such as software robustness, manufacturer reliability, and corporate need for the product. The vendors and entrepreneurs engaged in this process encounter decision crossroads for which no relevant guidance exists in the literature. The research closely monitored the processes associated with the introduction and assimilation of an innovative off-the-shelf (OTS) software product into five different organizations in different vertical market segments. Observations were carried out to assess organizational and marketing processes and to document and analyze what the software product undergoes before it is accepted for acquisition or full implementation within the organization. The research outcomes offer a unified, collaborative multi-tier System Development Life Cycle (SDLC) framework and methodology for packaged OTS software products that greatly improves communication and collaboration among the stakeholders. Each tier addresses a different force or stakeholder involved in the software market: vendor, customer, consultants and integrators. All stakeholders refer to the same time-line thus; tasks of various stakeholders are streamlined. Adherence to the unified time-line brings about an increased amount of stakeholder interaction, communication and collaboration. Newly found tasks that improve communication and collaboration among stakeholders include (1) offering of the OTS software product together with personnel as a bundle, (2) an improvisation-intensive iterative task of weaving potential customers’ requirements into the prototype, and (3) a third sale milestone, representing the successful diffusion of the product. The significance of this interdisciplinary research stems from its unique position at a crossroad between software engineering, marketing, and business administration, which has not yet been sufficiently explored or cultivated

Search-based system architecture development using a holistic modeling approach

This dissertation presents an innovative approach to system architecting where search algorithms are used to explore design trade space for good architecture alternatives. Such an approach is achieved by integrating certain model construction, alternative generation, simulation, and assessment processes into a coherent and automated framework. This framework is facilitated by a holistic modeling approach that combines the capabilities of Object Process Methodology (OPM), Colored Petri Net (CPN), and feature model. The resultant holistic model can not only capture the structural, behavioral, and dynamic aspects of a system, allowing simulation and strong analysis methods to be applied, it can also specify the architectural design space. Both object-oriented analysis and design (OOA/D) and domain engineering were exploited to capture design variables and their domains and define architecture generation operations. A fully realized framework (with genetic algorithms as the search algorithm) was developed. Both the proposed framework and its suggested implementation, including the proposed holistic modeling approach and architecture alternative generation operations, are generic. They are targeted at systems that can be specified using object-oriented or process-oriented paradigm. The broad applicability of the proposed approach is demonstrated on two examples. One is the configuration of reconfigurable manufacturing systems (RMSs) under multi-objective optimization and the other is the architecture design of a manned lunar landing system for the Apollo program. The test results show that the proposed approach can cover a huge number of architecture alternatives and support the assessment of several performance measures. A set of quality results was obtained after running the optimization algorithm following the proposed framework --Abstract, page iii

Enterprise modeling using the foundation concepts of the RM-ODP ISO/ITU standard

Enterprise architecture (EA) projects require analyzing and designing across the whole enterprise and its environment. Enterprise architects, therefore, frequently develop enterprise models that span from the markets in which the organization operates down to the implementation of the IT systems that support its operations. In this paper, we present SEAM for EA: a method for defining an enterprise model in which all the systems are systematically represented with the same modeling ontology. We base our modeling ontology on the foundation modeling concepts defined in Part 2 of ISO/ITU Standard "Reference Model of Open Distributed Processing” (RM-ODP). This work has two contributions to enterprise architecture: the SEAM for EA method itself and the use of Part 2 of the RM-ODP standard as a modeling ontolog

Multi-level System Modeling Using the Foundation Concepts of RM-ODP

A specification in Enterprise Architecture (EA) requires the modeling of an enterprise across multiple levels, from the markets in which it operates down to the implementation of the IT systems that support its operations. Our goal is the development of a method and of a CAD tool that support such modeling. To achieve our goal, we need an ontology to represent systematically all the systems at the multiple levels identified in an enterprise. We base our ontology on the foundation modeling concepts defined in Part 2 of ISO/ITU Standard "Reference Model of Open Distributed Processing" (RM-ODP). In this paper, we present how multi-level systems can be represented using directly the concepts defined in Part 2 of the RM-ODP. Our modeling approach differs from that defined in Part 3 of the RM-ODP, which focuses on the specification of IT systems in terms of viewpoint models representing the IT system environment and its construction. The benefit of our approach is the capability to model systematically and consistently the multiple systems represented in a company

System level risk analysis of electromagnetic environmental effects and lightning effects in aircraft -- steady state and transient

2017 Summer.Includes bibliographical references.This dissertation is an investigation of the system level risk of electromagnetic and lightning effects in aircraft. It begins with an analysis to define a system, and a discussion of emergence as a characteristic of a system. Against this backdrop, risk is defined as an undesirable emergent property of a system. A procedure to translate the system level non-functional attributes to lower level functional requirements is developed. With this foundation, a model for risk analysis, resolution and management is developed by employing the standard risk model. The developed risk model is applied to evaluation of electromagnetic environmental effects and lightning effects in aircraft. Examples are shown to demonstrate the validity of the model. Object Process Methodology and systems thinking principles are used extensively throughout this work. The dissertation concludes with a summary and suggestions for additional work

A Method of Functional Alignment Verification in Hierarchical Enterprise Models

Enterprise modeling involves multiple domains of expertise: requirements engineering, business process modeling, IT development etc. Our experience has shown that hierarchical enterprise models, made of an assembly of system models, are effective. In these models, two hierarchies exist: an organizational level hierarchy (describing systems' construction) and a functional level hierarchy (describing systems' functionality). Using a uniform hierarchical modeling language, system models at different hierarchical levels can be aligned in the context of the enterprise model. Using an operational semantics, each system model can be translated into executable code for model simulation and testing. The possibility to simulate and test models leads to the alignment verification for all system models across both hierarchies. In this paper we propose a method and tool for functional alignment verification. We use the Abstract State Machine (ASM) and the ASM language (AsmL) to formalize our graphical models for simulation and testing. We illustrate this approach with an example

SeamCAD: a hierarchy-oriented modeling language and a computer-aided tool for entreprise architecture

Modeling Enterprise Architecture requires representing multiple diagrams of an enterprise, which typically shows the multiples business entities, IT systems, even software components and the services they offer. This could be done by a team of stakeholders having different backgrounds. One way to do this is to structure the model into hierarchical levels each of which can be of interest of just some, not all, stakeholders. Due to the differences in their background, stakeholders – the modelers may not want to use a single modeling approach, even a widely-recognized one, to build the enterprise model, which can be shared by the whole team. Developing a modeling framework that can be applied uniformly throughout the entire enterprise model and that can be used by all stakeholders is challenging. First, the framework should have a uniform approach to specifying the services offered by business entities, IT systems and software components and to describing their implementation across hierarchical levels. Second, the framework should allow the stakeholders to represent the service specification and the service implementation of multiple business entities and IT systems, even within the same hierarchical level. Third, the services offered by those entities and systems should be represented at different levels of granularity. Last but not least, the modeling framework should maintain the well-formedness of the enterprise model and the consistency between different diagrams opened by different stakeholders of the team. Today, there exist a few modeling methods or development processes in the field of Enterprise Architecture, as well as in software and system modeling that can address these issues to some extent. Among them, Adora, KobrA and OPM best meet the aforementioned four criteria, although they were not initially developed for modeling Enterprise Architecture. As a study on the state of the art, we analyzed these methods with respect to the four aforementioned modeling challenges. In this thesis, we define a modeling language and present a computer-aided tool for modeling Enterprise Architecture hierarchically. This modeling language allows the modeler to structure an enterprise into hierarchical levels, in terms of both organization and services. The computer-aided modeling tool helps the modeler visually build her model across levels and brings all levels together to make a coherent, well-formed model. Enterprise models can be visually built and represented in a notation that is based on the Unified Modeling Language using this tool. The modeling language is formally defined in Alloy – a lightweight declarative language based on first order logic and set theory. The data manipulated in the tool is verified against the Alloy code that formalizes the language. The modeling language and the computer-aided modeling tool constitute a hierarchy-oriented framework called SeamCAD that specifically address the four aforementioned issues. This framework has been applied several projects, both in industry and academic settings. We evaluated it by inviting external practitioners, researchers and master's students in our university to use it and to give their feedback

Integration of model-based systems engineering and virtual engineering tools for detailed design

Design and development of a system can be viewed as a process of transferring and transforming data using a set of tools that form the system\u27s development environment. Conversion of the systems engineering data into useful information is one of the prime objectives of the tools used in the process. With complex systems, the objective is further augmented with a need to represent the information in an accessible and comprehensible manner. The importance of representation is easily understood in light of the fact that the stakeholder\u27s ability to make prompt and appropriate decisions is directly related to his understanding of the available information. Systems Modeling Language (SysML), a graphical modeling language developed by Object Management Group is one such tool used to capture and convey information about a system under development. This work proposes a methodology for integrating the models developed using SysML with virtual engineering software to create an executable, interactive, and user-centered platform for engineering systems. The framework provides an opportunity to combine the benefits offered by both model-based systems engineering and virtual engineering for detail design. This research demonstrates how this framework can be implemented using a biotech fermentor to illustrate the coupling of information between SysML and virtual engineering --Abstract, page iii