Scientific Workflows for Metabolic Flux Analysis

Metabolic engineering is a highly interdisciplinary research domain that interfaces biology, mathematics, computer science, and engineering. Metabolic flux analysis with carbon tracer experiments (13 C-MFA) is a particularly challenging metabolic engineering application that consists of several tightly interwoven building blocks such as modeling, simulation, and experimental design. While several general-purpose workflow solutions have emerged in recent years to support the realization of complex scientific applications, the transferability of these approaches are only partially applicable to 13C-MFA workflows. While problems in other research fields (e.g., bioinformatics) are primarily centered around scientific data processing, 13C-MFA workflows have more in common with business workflows. For instance, many bioinformatics workflows are designed to identify, compare, and annotate genomic sequences by "pipelining" them through standard tools like BLAST. Typically, the next workflow task in the pipeline can be automatically determined by the outcome of the previous step. Five computational challenges have been identified in the endeavor of conducting 13 C-MFA studies: organization of heterogeneous data, standardization of processes and the unification of tools and data, interactive workflow steering, distributed computing, and service orientation. The outcome of this thesis is a scientific workflow framework (SWF) that is custom-tailored for the specific requirements of 13 C-MFA applications. The proposed approach – namely, designing the SWF as a collection of loosely-coupled modules that are glued together with web services – alleviates the realization of 13C-MFA workflows by offering several features. By design, existing tools are integrated into the SWF using web service interfaces and foreign programming language bindings (e.g., Java or Python). Although the attributes "easy-to-use" and "general-purpose" are rarely associated with distributed computing software, the presented use cases show that the proposed Hadoop MapReduce framework eases the deployment of computationally demanding simulations on cloud and cluster computing resources. An important building block for allowing interactive researcher-driven workflows is the ability to track all data that is needed to understand and reproduce a workflow. The standardization of 13 C-MFA studies using a folder structure template and the corresponding services and web interfaces improves the exchange of information for a group of researchers. Finally, several auxiliary tools are developed in the course of this work to complement the SWF modules, i.e., ranging from simple helper scripts to visualization or data conversion programs. This solution distinguishes itself from other scientific workflow approaches by offering a system of loosely-coupled components that are flexibly arranged to match the typical requirements in the metabolic engineering domain. Being a modern and service-oriented software framework, new applications are easily composed by reusing existing components

Distributed Particle Filters for Data Assimilation in Simulation of Large Scale Spatial Temporal Systems

Assimilating real time sensor into a running simulation model can improve simulation results for simulating large-scale spatial temporal systems such as wildfire, road traffic and flood. Particle filters are important methods to support data assimilation. While particle filters can work effectively with sophisticated simulation models, they have high computation cost due to the large number of particles needed in order to converge to the true system state. This is especially true for large-scale spatial temporal simulation systems that have high dimensional state space and high computation cost by themselves. To address the performance issue of particle filter-based data assimilation, this dissertation developed distributed particle filters and applied them to large-scale spatial temporal systems. We first implemented a particle filter-based data assimilation framework and carried out data assimilation to estimate system state and model parameters based on an application of wildfire spread simulation. We then developed advanced particle routing methods in distributed particle filters to route particles among the Processing Units (PUs) after resampling in effective and efficient manners. In particular, for distributed particle filters with centralized resampling, we developed two routing policies named minimal transfer particle routing policy and maximal balance particle routing policy. For distributed PF with decentralized resampling, we developed a hybrid particle routing approach that combines the global routing with the local routing to take advantage of both. The developed routing policies are evaluated from the aspects of communication cost and data assimilation accuracy based on the application of data assimilation for large-scale wildfire spread simulations. Moreover, as cloud computing is gaining more and more popularity; we developed a parallel and distributed particle filter based on Hadoop & MapReduce to support large-scale data assimilation

Runtime Adaptation of Scientific Service Workflows

Software landscapes are rather subject to change than being complete after having been built. Changes may be caused by a modified customer behavior, the shift to new hardware resources, or otherwise changed requirements. In such situations, several challenges arise. New architectural models have to be designed and implemented, existing software has to be integrated, and, finally, the new software has to be deployed, monitored, and, where appropriate, optimized during runtime under realistic usage scenarios. All of these situations often demand manual intervention, which causes them to be error-prone. This thesis addresses these types of runtime adaptation. Based on service-oriented architectures, an environment is developed that enables the integration of existing software (i.e., the wrapping of legacy software as web services). A workflow modeling tool that aims at an easy-to-use approach by separating the role of the workflow expert and the role of the domain expert. After the development of workflows, tools that observe the executing infrastructure and perform automatic scale-in and scale-out operations are presented. Infrastructure-as-a-Service providers are used to scale the infrastructure in a transparent and cost-efficient way. The deployment of necessary middleware tools is automatically done. The use of a distributed infrastructure can lead to communication problems. In order to keep workflows robust, these exceptional cases need to treated. But, in this way, the process logic of a workflow gets mixed up and bloated with infrastructural details, which yields an increase in its complexity. In this work, a module is presented that can deal automatically with infrastructural faults and that thereby allows to keep the separation of these two layers. When services or their components are hosted in a distributed environment, some requirements need to be addressed at each service separately. Although techniques as object-oriented programming or the usage of design patterns like the interceptor pattern ease the adaptation of service behavior or structures. Still, these methods require to modify the configuration or the implementation of each individual service. On the other side, aspect-oriented programming allows to weave functionality into existing code even without having its source. Since the functionality needs to be woven into the code, it depends on the specific implementation. In a service-oriented architecture, where the implementation of a service is unknown, this approach clearly has its limitations. The request/response aspects presented in this thesis overcome this obstacle and provide a SOA-compliant and new methods to weave functionality into the communication layer of web services. The main contributions of this thesis are the following: Shifting towards a service-oriented architecture: The generic and extensible Legacy Code Description Language and the corresponding framework allow to wrap existing software, e.g., as web services, which afterwards can be composed into a workflow by SimpleBPEL without overburdening the domain expert with technical details that are indeed handled by a workflow expert. Runtime adaption: Based on the standardized Business Process Execution Language an automatic scheduling approach is presented that monitors all used resources and is able to automatically provision new machines in case a scale-out becomes necessary. If the resource's load drops, e.g., because of less workflow executions, a scale-in is also automatically performed. The scheduling algorithm takes the data transfer between the services into account in order to prevent scheduling allocations that eventually increase the workflow's makespan due to unnecessary or disadvantageous data transfers. Furthermore, a multi-objective scheduling algorithm that is based on a genetic algorithm is able to additionally consider cost, in a way that a user can define her own preferences rising from optimized execution times of a workflow and minimized costs. Possible communication errors are automatically detected and, according to certain constraints, corrected. Adaptation of communication: The presented request/response aspects allow to weave functionality into the communication of web services. By defining a pointcut language that only relies on the exchanged documents, the implementation of services must neither be known nor be available. The weaving process itself is modeled using web services. In this way, the concept of request/response aspects is naturally embedded into a service-oriented architecture

High-Performance Modelling and Simulation for Big Data Applications

This open access book was prepared as a Final Publication of the COST Action IC1406 “High-Performance Modelling and Simulation for Big Data Applications (cHiPSet)“ project. Long considered important pillars of the scientific method, Modelling and Simulation have evolved from traditional discrete numerical methods to complex data-intensive continuous analytical optimisations. Resolution, scale, and accuracy have become essential to predict and analyse natural and complex systems in science and engineering. When their level of abstraction raises to have a better discernment of the domain at hand, their representation gets increasingly demanding for computational and data resources. On the other hand, High Performance Computing typically entails the effective use of parallel and distributed processing units coupled with efficient storage, communication and visualisation systems to underpin complex data-intensive applications in distinct scientific and technical domains. It is then arguably required to have a seamless interaction of High Performance Computing with Modelling and Simulation in order to store, compute, analyse, and visualise large data sets in science and engineering. Funded by the European Commission, cHiPSet has provided a dynamic trans-European forum for their members and distinguished guests to openly discuss novel perspectives and topics of interests for these two communities. This cHiPSet compendium presents a set of selected case studies related to healthcare, biological data, computational advertising, multimedia, finance, bioinformatics, and telecommunications

High-Performance Modelling and Simulation for Big Data Applications

This open access book was prepared as a Final Publication of the COST Action IC1406 “High-Performance Modelling and Simulation for Big Data Applications (cHiPSet)“ project. Long considered important pillars of the scientific method, Modelling and Simulation have evolved from traditional discrete numerical methods to complex data-intensive continuous analytical optimisations. Resolution, scale, and accuracy have become essential to predict and analyse natural and complex systems in science and engineering. When their level of abstraction raises to have a better discernment of the domain at hand, their representation gets increasingly demanding for computational and data resources. On the other hand, High Performance Computing typically entails the effective use of parallel and distributed processing units coupled with efficient storage, communication and visualisation systems to underpin complex data-intensive applications in distinct scientific and technical domains. It is then arguably required to have a seamless interaction of High Performance Computing with Modelling and Simulation in order to store, compute, analyse, and visualise large data sets in science and engineering. Funded by the European Commission, cHiPSet has provided a dynamic trans-European forum for their members and distinguished guests to openly discuss novel perspectives and topics of interests for these two communities. This cHiPSet compendium presents a set of selected case studies related to healthcare, biological data, computational advertising, multimedia, finance, bioinformatics, and telecommunications

Comprehensive review of models and methods for inferences in bio-chemical reaction networks

The key processes in biological and chemical systems are described by networks of chemical reactions. From molecular biology to biotechnology applications, computational models of reaction networks are used extensively to elucidate their non-linear dynamics. The model dynamics are crucially dependent on the parameter values which are often estimated from observations. Over the past decade, the interest in parameter and state estimation in models of (bio-) chemical reaction networks (BRNs) grew considerably. The related inference problems are also encountered in many other tasks including model calibration, discrimination, identifiability, and checking, and optimum experiment design, sensitivity analysis, and bifurcation analysis. The aim of this review paper is to examine the developments in literature to understand what BRN models are commonly used, and for what inference tasks and inference methods. The initial collection of about 700 documents concerning estimation problems in BRNs excluding books and textbooks in computational biology and chemistry were screened to select over 270 research papers and 20 graduate research theses. The paper selection was facilitated by text mining scripts to automate the search for relevant keywords and terms. The outcomes are presented in tables revealing the levels of interest in different inference tasks and methods for given models in the literature as well as the research trends are uncovered. Our findings indicate that many combinations of models, tasks and methods are still relatively unexplored, and there are many new research opportunities to explore combinations that have not been considered—perhaps for good reasons. The most common models of BRNs in literature involve differential equations, Markov processes, mass action kinetics, and state space representations whereas the most common tasks are the parameter inference and model identification. The most common methods in literature are Bayesian analysis, Monte Carlo sampling strategies, and model fitting to data using evolutionary algorithms. The new research problems which cannot be directly deduced from the text mining data are also discussed

Novel approaches for modelling changes in phytoplankton diversity and lake ecosystem function

Ecosystem function represents the collective outcome of many different processes. Function may be interrupted by events that originate from outside a system, influencing biological diversity dynamics. Difficulties in expressing how a system is functioning originate firstly from being able to define a normative status for a dynamic system and secondly from the accuracy of common metrics of biodiversity changes. In this thesis, I used a numerical model and high-frequency ecological observations to express functioning of a system. Chapter 2 used biogeochemical parameter perturbations in a lake ecological model to identify seasonal parameter sensitivity variabilities. A set of internal process parameters of calibrated shallow eutrophic Lake Waahi DYRESM-CAEDYM ecological model was used to apply Monte-Carlo perturbation. Analysis was conducted by examining the collective results variability, a “spread” of the ensemble results from the iteration. The results showed that the spreads were small when lake inflows had high discharge, suggesting that lake internal dynamics had lesser effect on water quality and inflows dominated the system dynamics. Due to the simplicity of the methods, regular use of perturbation methods is suggested to assess model uncertainty and to better understand the model. Chapter 3 used interdisciplinary methods to identify changes in dissolved oxygen (DO) observations caused by biological processes. DO in lakes is a key indicator of ecosystem function. Methods used in this chapter included expert panel decision making, Symbolic Aggregate approXimation (SAX) analysis, and text classification. The use of an expert panel was motivated by the common practice of DO data visual assessment. Variability in experts’ boundaries for data quality were observed by data survey, reinforcing the necessity of robust and reproducible methods for unbiased analysis. Surface DO sensor data from 18 global lakes were used to create day-long data segments. The modelling framework successfully simulated the expert panel decisions on these segments, automatically labelling data to indicate when the signal is likely dominated by biological activities. In Chapter 4, species-neutral biological assemblage metrics were developed to account for phytoplankton changes associated with changes in species abundance. Every species’ population changes were converted into binary metrics (i.e., increases or decreases) to identify the “constituents” of species richness, to allow robust assessments of population dynamics. Four lakes (Lakes Annie, Feeagh, Esthwaite and Mendota) from different regions were analysed. The results showed several previously undocumented features. Species recruitment was proportional to the number of species that were increasing. The number of species that were decreasing did not immediately increase the number of species that went extinct. The rate of increase was logarithmically distributed from the fastest to the slowest growing species, with the distribution shape being strongly influenced by number of species that were increasing. Such species-neutral community metrics, along with abundance distribution and diversity, are helpful to assess mechanistic community ecology models. This thesis provides toolsets useful for future studies to understand relationships between forcing and functioning of ecosystems and changes in biodiversity, by providing means to assess ecosystem function and demonstrating examples of species-neutral community structural changes

Supporting Quality of Service in Scientific Workflows

While workflow management systems have been utilized in enterprises to support businesses for almost two decades, the use of workflows in scientific environments was fairly uncommon until recently. Nowadays, scientists use workflow systems to conduct scientific experiments, simulations, and distributed computations. However, most scientific workflow management systems have not been built using existing workflow technology; rather they have been designed and developed from scratch. Due to the lack of generality of early scientific workflow systems, many domain-specific workflow systems have been developed. Generally speaking, those domain-specific approaches lack common acceptance and tool support and offer lower robustness compared to business workflow systems. In this thesis, the use of the industry standard BPEL, a workflow language for modeling business processes, is proposed for the modeling and the execution of scientific workflows. Due to the widespread use of BPEL in enterprises, a number of stable and mature software products exist. The language is expressive (Turingcomplete) and not restricted to specific applications. BPEL is well suited for the modeling of scientific workflows, but existing implementations of the standard lack important features that are necessary for the execution of scientific workflows. This work presents components that extend an existing implementation of the BPEL standard and eliminate the identified weaknesses. The components thus provide the technical basis for use of BPEL in academia. The particular focus is on so-called non-functional (Quality of Service) requirements. These requirements include scalability, reliability (fault tolerance), data security, and cost (of executing a workflow). From a technical perspective, the workflow system must be able to interface with the middleware systems that are commonly used by the scientific workflow community to allow access to heterogeneous, distributed resources (especially Grid and Cloud resources). The major components cover exactly these requirements: Cloud Resource Provisioner Scalability of the workflow system is achieved by automatically adding additional (Cloud) resources to the workflow system’s resource pool when the workflow system is heavily loaded. Fault Tolerance Module High reliability is achieved via continuous monitoring of workflow execution and corrective interventions, such as re-execution of a failed workflow step or replacement of the faulty resource. Cost Aware Data Flow Aware Scheduler The majority of scientific workflow systems only take the performance and utilization of resources for the execution of workflow steps into account when making scheduling decisions. The presented workflow system goes beyond that. By defining preference values for the weighting of costs and the anticipated workflow execution time, workflow users may influence the resource selection process. The developed multiobjective scheduling algorithm respects the defined weighting and makes both efficient and advantageous decisions using a heuristic approach. Security Extensions Because it supports various encryption, signature and authentication mechanisms (e.g., Grid Security Infrastructure), the workflow system guarantees data security in the transfer of workflow data. Furthermore, this work identifies the need to equip workflow developers with workflow modeling tools that can be used intuitively. This dissertation presents two modeling tools that support users with different needs. The first tool, DAVO (domain-adaptable, Visual BPEL Orchestrator), operates at a low level of abstraction and allows users with knowledge of BPEL to use the full extent of the language. DAVO is a software that offers extensibility and customizability for different application domains. These features are used in the implementation of the second tool, SimpleBPEL Composer. SimpleBPEL is aimed at users with little or no background in computer science and allows for quick and intuitive development of BPEL workflows based on predefined components

Using MapReduce Streaming for Distributed Life Simulation on the Cloud

Distributed software simulations are indispensable in the study of large-scale life models but often require the use of technically complex lower-level distributed computing frameworks, such as MPI. We propose to overcome the complexity challenge by applying the emerging MapReduce (MR) model to distributed life simulations and by running such simulations on the cloud. Technically, we design optimized MR streaming algorithms for discrete and continuous versions of Conway’s life according to a general MR streaming pattern. We chose life because it is simple enough as a testbed for MR’s applicability to a-life simulations and general enough to make our results applicable to various lattice-based a-life models. We implement and empirically evaluate our algorithms’ performance on Amazon’s Elastic MR cloud. Our experiments demonstrate that a single MR optimization technique called strip partitioning can reduce the execution time of continuous life simulations by 64%. To the best of our knowledge, we are the first to propose and evaluate MR streaming algorithms for lattice-based simulations. Our algorithms can serve as prototypes in the development of novel MR simulation algorithms for large-scale lattice-based a-life models.https://digitalcommons.chapman.edu/scs_books/1014/thumbnail.jp