Simulation and database software for computational systems biology : PySCes and JWS Online

Thesis (PhD)--Stellenbosch University, 2005.ENGLISH ABSTRACT: Since their inception, biology and biochemistry have been spectacularly successful in characterising the living cell and its components. As the volume of information about cellular components continues to increase, we need to ask how we should use this information to understand the functioning of the living cell? Computational systems biology uses an integrative approach that combines theoretical exploration, computer modelling and experimental research to answer this question. Central to this approach is the development of computational models, new modelling strategies and computational tools. Against this background, this study aims to: (i) develop a new modelling package: PySCeS, (ii) use PySCeS to study discontinuous behaviour in a metabolic pathway in a way that was very difficult, if not impossible, with existing software, (iii) develop an interactive, web-based repository (JWS Online) of cellular system models. Three principles that, in our opinion, should form the basis of any new modelling software were laid down: accessibility (there should be as few barriers as possible to PySCeS use and distribution), flexibility (pySCeS should be extendable by the user, not only the developers) and usability (PySCeS should provide the tools we needed for our research). After evaluating various alternatives we decided to base PySCeS on the freely available programming language, Python, which, in combination with the large collection of science and engineering algorithms in the SciPy libraries, would give us a powerful modern, interactive development environment.AFRIKAANSE OPSOMMING: Sedert hul totstandkoming was biologie en, meer spesifiek, biochemie uiters suksesvol in die karakterisering van die lewende sel se komponente. Steeds groei die hoeveelheid informasie oor die molekulêre bestanddele van die sel daagliks; ons moet onself dus afvra hoe ons hierdie informasie kan integreer tot 'n verstaanbare beskrywing van die lewende sel se werking. Om dié vraag te beantwoord gebruik rekenaarmatige sisteembiologie 'n geïntegreerde benadering wat teorie, rekenaarmatige modellering en eksperimenteeIe navorsing kombineer. Sentraal tot die benadering is die ontwikkeling van nuwe modelle, strategieë vir modellering, en sagteware. Teen hierdie agtergrond is die hoofdoelstelling van hierdie projek: (i) die ontwikkeling van 'n nuwe modelleringspakket, PySCeS (ii) die benutting van PySCeS om diskontinue gedrag in n metaboliese sisteem te bestudeer (iets wat met die huidiglik beskikbare sagteware redelik moeilik is), (en iii) die ontwikkeling vann interaktiewe, internet-gebaseerde databasis van sellulêre sisteem modelle, JWS Online. Ons is van mening dat nuwe sagteware op drie belangrike beginsels gebaseer behoort te wees: toeganklikheid (die sagteware moet maklik bekombaar en bruikbaar wees), buigsaamheid (die gebruiker moet self PySCeS kan verander en ontwikkel) en bruikbaarheid (al die funksionalitiet wat ons vir ons navorsing nodig moet in PySCeS ingebou wees). Ons het verskeie opsies oorweeg en besluit om die vrylik verkrygbare programmeringstaal, Python, in samehang die groot kolleksie wetenskaplike algoritmes, SciPy, te gebruik. Hierdie kombinasie verskaf n kragtige, interaktiewe ontwikkelings- en gebruikersomgewing. PySCeS is ontwikkel om onder beide die Windows en Linux bedryfstelsels te werk en, meer spesifiek, om gebruik te maak van 'n 'command line interface'. Dit beteken dat PySCeS op enige interaktiewe rekenaar-terminaal Python ondersteun sal werk. Hierdie eienskap maak ook moontlik die gebruik van PySCeS as 'n modelleringskomponent in 'n groter sagteware pakket onder enige bedryfstelsel wat Python ondersteun. PySCeS is op 'n modulere ontwerp gebaseer, wat dit moontlik vir die eindgebruiker maak om die sagteware se bronkode verder te ontwikkel. As 'n toepassing is PySCeS gebruik om die oorsaak van histeretiese gedrag van 'n lineêre, eindproduk-geïnhibeerde metaboliese pad te ondersoek. Ons het hierdie interessante gedrag in 'n vorige studie ontdek, maar kon nie, met die sagteware wat op daardie tydstip tot ons beskikking was, hierdie studie voortsit nie. Met PySCeS se ingeboude vermoë om parameter kontinuering te doen, kon ons die oorsake van hierdie diskontinuë gedrag volledig karakteriseer. Verder het ons 'n nuwe metode ontwikkel om hierdie gedrag te visualiseer as 'n interaksie tussen die volledige sisteem se subkomponente. Tydens PySCeS se ontwikkeling het ons opgemerk dat dit baie moeilik was om metaboliese modelle wat in die literature gepubliseer is te herbou en te bestudeer. Hierdie situasie is grotendeels die gevolg van die feit dat nêrens 'n sentrale databasis vir metaboliese modelle bestaan nie (soos dit wel bestaan vir genomiese data of proteïen strukture). Die JWS Online databasis is spesifiek ontwikkel om hierdie leemte te vul. JWS Online maak dit vir die gebruiker moontlik om, via die internet en sonder die installasie van enige gespesialiseerde modellerings sagteware, gepubliseerde modelle te bestudeer en ook af te laai vir gebruik met ander modelleringspakkette soos bv. PySCeS. JWS Online het alreeds 'n onmisbare hulpbron vir sisteembiologiese navorsing en onderwys geword

PhysioSim – A Full Hard- And Software Physiological Simulation Environment Applying A Hybrid Approach Based On Hierarchical Modeling Using Algebraic And Differential Systems and Dynamic Bayesian Networks

A system for physiological modeling and simulation is presented. The architecture is considering hardware and software support for real-time physiological simulators, which are very important for medical education and risk management. In contrary to other modeling methods, in this work the focus is to provide maximal modeling flexibility and extensibility. This is provided on the one hand by a hierarchical modeling notation in XML and on other hand by extending current methods by dynamic stochastic system modeling. Dynamic Bayesian Networks as well as deterministic system modeling by systems of algebraic and differential equations lead towards a sophisticated environment for medical simulation. Specific simulations of haemodynamics and physiological based pharmacokinetics and pharmacodynamics are performed by the proposed methods, demonstrating the applicability of the approaches. In contrary to physiological modeling and analysis tools, for an educational simulator, the models have to be computed in real-time, which requires extensive design of the hardware and software architecture. For this purpose generic and extensible frameworks have been suggested and realized. All the components together lead to a novel physiological simulator environment, including a dummy, which emulates ECG, SaO2 and IBP vital signals in addition to software signal simulation. The modeling approaches with DBN are furthermore analyzed in the domains of psychological and physiological reasoning, which should be integrated into a common basis for medical consideration. Furthermore the system is used to show new concepts for dependable medical data monitoring, which are strongly related to physiological and psychological simulations

Design automation in synthetic biology : a dual evolutionary strategy

PhD ThesisSynthetic biology o ers a new horizon in designing complex systems. However, unprecedented complexity hinders the development of biological systems to its full potential. Mitigating complexity via adopting design principles from engineering and computer science elds has resulted in some success. For example, modularisation to foster reuse of design elements, and using computer assisted design tools have helped contain complexity to an extent. Nevertheless, these design practices are still limited, due to their heavy dependence on rational decision making by human designers. The issue with rational design approaches here arises from the challenging nature of dealing with highly complex biological systems of which we currently do not have complete understanding. Systematic processes that can algorithmically nd design solutions would be better able to cope with uncertainties posed by high levels of design complexity. A new framework for enabling design automation in synthetic biology was investigated. The framework works by projecting design problems into search problems, and by searching for design solutions based on the dual-evolutionary approach to combine the respective power of design domains in vivo and in silico. Proof-of-concept ideas, software, and hardware were developed to exemplify key technologies necessary in realising the dual evolutionary approach. Some of the areas investigated as part of this research included single-cell-level micro uidics, programmatic data collection, processing and analysis, molecular devices supporting solution search in vivo, and mathematical modelling. These somewhat eclectic collection of research themes were shown to work together to provide necessary means with which to design and characterise biological systems in a systematic fashion

Emerging model spedies driven by transciptomics

This work is focused on 'emerging model species', i.e. question-driven model species which have sufficient molecular resources to investigate a specific phenomenon in molecular biology, developmental biology, molecular ecology and evolution or related molecular fields. This thesis shows how transcriptomic data can be generated, analyzed, and used to investigate such phenomena of interest even in species lacking a reference genome. The initial ButterflyBase resource has proven to be useful to researchers of species without a reference genome but is limited to the Lepidoptera and supports only the older Sanger sequencing technologies. Thanks to Next Generation Sequencing, transcriptome sequencing is more cost effective but the bottleneck of transcriptomic projects is now the bioinformatic analysis and data mining/dissemination. Therefore, this work continues with presenting novel and innovative approaches which effectively overcome this bottleneck. The est2assembly software produces deeply annotated reference transcriptomes stored in the Chado database. The Drupal Bioinformatic Server Framework and genes4all provide species-neutral and an innovative approach in building standardized online databases and associated web services. All public insect mRNA data were analyzed with est2assembly and genes4all to produce the InsectaCentral. With InsectaCentral, a powerful resource is now available to assist molecular biology in any question-driven model insect species. The software presented here was developed according to specifications of the General Model Organism Database (GMOD) community. All software specifications are species-neutral and can be seamlessly deployed to assist any research community. Further through a case studies chapter, it becomes apparent that the transcriptomic approach is more cost-effective than a genomic approach and therefore sequence-driven evolutionary biology will benefit faster with this field

The influence of website design features and consumer characteristics on internet banking adoption in Saudi Arabia

Recent years have seen rapid growth of Internet technology and its incorporation into many areas, including banking. Despite the potential advantages offered, however, adoption of Internet Banking (IB) has been relatively low. This thesis aims to enhance understanding of customers' adoption of IB, with particular reference to commercial banks in the Kingdom of Saudi Arabia (KSA). It investigates the rationale for and current status of IB in the KSA. Then, taking as a framework the Decomposed Theory of Planned Behaviour (DTPB), with the additional construct of website features, it investigates what factors may influence Saudi customers' adoption of IB, including the potential impact of website features at different stages of the customer's decision-making process (DMP). The research targeted policy makers, IB managers and clients in all 11 commercial banks operating in KSA. Data were collected in two phases, each containing qualitative and quantitative elements. In phase one, focused on the bank perspective, interviews were held with 11 bank officials, to explore the thinking behind their IB provision and website design. Then, content analysis was used to investigate the features of 22 websites – 1 corporate and 1 individual site for each bank. In phase two, semi-structured interviews (N = 40) were used to explore bank clients' perceptions of IB, and their responses used to inform a survey, delivered online and through bank branches, of IB users' (N = 651) and non-users' (N = 409) attitudes and behaviours in relation to IB. Results showed that bank managers attempted to attract and support clients throughout the DMP, and this was reflected in website content. However, support was constrained by some erroneous assumptions about clients, and the regulatory environment. Obstacles to IB use included psychological, marketing, educational, technical, cultural and linguistic barriers. IB non-users' intention to try IB was influenced by Trust and Subjective Norms, while users' intention to continue was influenced by perceived Relative Advantage and Compatibility, Ease of Use, Self-Efficacy, Resource Facilitating Conditions and Website Characteristics. Attitudes to IB also differed by clients' gender, age, income, education and Internet experience. Implications are drawn for technology adoption and e-marketing theory, and recommendations are made to government, the central bank and commercial banks to enhance the functionality and attractiveness of IB

The influence of website design features and consumer characteristics on internet banking adoption in Saudi Arabia

Recent years have seen rapid growth of Internet technology and its incorporation into many areas, including banking. Despite the potential advantages offered, however, adoption of Internet Banking (IB) has been relatively low. This thesis aims to enhance understanding of customers' adoption of IB, with particular reference to commercial banks in the Kingdom of Saudi Arabia (KSA). It investigates the rationale for and current status of IB in the KSA. Then, taking as a framework the Decomposed Theory of Planned Behaviour (DTPB), with the additional construct of website features, it investigates what factors may influence Saudi customers' adoption of IB, including the potential impact of website features at different stages of the customer's decision-making process (DMP).The research targeted policy makers, IB managers and clients in all 11 commercial banks operating in KSA. Data were collected in two phases, each containing qualitative and quantitative elements. In phase one, focused on the bank perspective, interviews were held with 11 bank officials, to explore the thinking behind their IB provision and website design. Then, content analysis was used to investigate the features of 22 websites – 1 corporate and 1 individual site for each bank. In phase two, semi-structured interviews (N = 40) were used to explore bank clients' perceptions of IB, and their responses used to inform a survey, delivered online and through bank branches, of IB users' (N = 651) and non-users' (N = 409) attitudes and behaviours in relation to IB.Results showed that bank managers attempted to attract and support clients throughout the DMP, and this was reflected in website content. However, support was constrained by some erroneous assumptions about clients, and the regulatory environment. Obstacles to IB use included psychological, marketing, educational, technical, cultural and linguistic barriers. IB non-users' intention to try IB was influenced by Trust and Subjective Norms, while users' intention to continue was influenced by perceived Relative Advantage and Compatibility, Ease of Use, Self-Efficacy, Resource Facilitating Conditions and Website Characteristics. Attitudes to IB also differed by clients' gender, age, income, education and Internet experience.Implications are drawn for technology adoption and e-marketing theory, and recommendations are made to government, the central bank and commercial banks to enhance the functionality and attractiveness of IB

Modern meat: the next generation of meat from cells

Modern Meat is the first textbook on cultivated meat, with contributions from over 100 experts within the cultivated meat community. The Sections of Modern Meat comprise 5 broad categories of cultivated meat: Context, Impact, Science, Society, and World. The 19 chapters of Modern Meat, spread across these 5 sections, provide detailed entries on cultivated meat. They extensively tour a range of topics including the impact of cultivated meat on humans and animals, the bioprocess of cultivated meat production, how cultivated meat may become a food option in Space and on Mars, and how cultivated meat may impact the economy, culture, and tradition of Asia

A profile of today's SBML-compatible software

Computational systems biologists today have a healthy selection of software resources to help them do research. Many software packages, especially those concerned with computational modeling, have adopted SBML (the Systems Biology Markup Language) as a machine-readable format to permit users to exchange models. Our group has a keen interest in understanding the landscape of SBML support. To help us ascertain the state of modern SBML-compatible software, in mid-2011 we initiated a survey of software packages that support SBML. Here we report the preliminary survey results. Based on 81 packages for which we have data so far, we summarize the trends in six areas: (1) What are the major types of functionality offered by the software systems? (2) What mathematical frameworks do they support? (3) What are their SBML-specific capabilities? (4) What other standards do they support besides SBML? (5) What are their characteristics with respect to run-time environments? And finally, (6) what are the availability and licensing terms

Collected Papers (on Physics, Artificial Intelligence, Health Issues, Decision Making, Economics, Statistics), Volume XI

This eleventh volume of Collected Papers includes 90 papers comprising 988 pages on Physics, Artificial Intelligence, Health Issues, Decision Making, Economics, Statistics, written between 2001-2022 by the author alone or in collaboration with the following 84 co-authors (alphabetically ordered) from 19 countries: Abhijit Saha, Abu Sufian, Jack Allen, Shahbaz Ali, Ali Safaa Sadiq, Aliya Fahmi, Atiqa Fakhar, Atiqa Firdous, Sukanto Bhattacharya, Robert N. Boyd, Victor Chang, Victor Christianto, V. Christy, Dao The Son, Debjit Dutta, Azeddine Elhassouny, Fazal Ghani, Fazli Amin, Anirudha Ghosha, Nasruddin Hassan, Hoang Viet Long, Jhulaneswar Baidya, Jin Kim, Jun Ye, Darjan Karabašević, Vasilios N. Katsikis, Ieva Meidutė-Kavaliauskienė, F. Kaymarm, Nour Eldeen M. Khalifa, Madad Khan, Qaisar Khan, M. Khoshnevisan, Kifayat Ullah,, Volodymyr Krasnoholovets, Mukesh Kumar, Le Hoang Son, Luong Thi Hong Lan, Tahir Mahmood, Mahmoud Ismail, Mohamed Abdel-Basset, Siti Nurul Fitriah Mohamad, Mohamed Loey, Mai Mohamed, K. Mohana, Kalyan Mondal, Muhammad Gulfam, Muhammad Khalid Mahmood, Muhammad Jamil, Muhammad Yaqub Khan, Muhammad Riaz, Nguyen Dinh Hoa, Cu Nguyen Giap, Nguyen Tho Thong, Peide Liu, Pham Huy Thong, Gabrijela Popović‬‬‬‬‬‬‬‬‬‬, Surapati Pramanik, Dmitri Rabounski, Roslan Hasni, Rumi Roy, Tapan Kumar Roy, Said Broumi, Saleem Abdullah, Muzafer Saračević, Ganeshsree Selvachandran, Shariful Alam, Shyamal Dalapati, Housila P. Singh, R. Singh, Rajesh Singh, Predrag S. Stanimirović, Kasan Susilo, Dragiša Stanujkić, Alexandra Şandru, Ovidiu Ilie Şandru, Zenonas Turskis, Yunita Umniyati, Alptekin Ulutaș, Maikel Yelandi Leyva Vázquez, Binyamin Yusoff, Edmundas Kazimieras Zavadskas, Zhao Loon Wang.‬‬‬