WorldWideScience

Sample records for biological systems analysis

  1. Logical analysis of biological systems

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian

    2005-01-01

    R. Mardare, Logical analysis of biological systems. Fundamenta Informaticae, N 64:271-285, 2005.......R. Mardare, Logical analysis of biological systems. Fundamenta Informaticae, N 64:271-285, 2005....

  2. Static Analysis for Systems Biology

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nielson, Hanne Riis; Rosa, D. Schuch da

    2004-01-01

    This paper shows how static analysis techniques can help understanding biological systems. Based on a simple example we illustrate the outcome of performing three different analyses extracting information of increasing precision. We conclude by reporting on the potential impact and exploitation o...... of these techniques in systems biology....

  3. Dynamic sensitivity analysis of biological systems

    Directory of Open Access Journals (Sweden)

    Chang Maw

    2008-12-01

    Full Text Available Abstract Background A mathematical model to understand, predict, control, or even design a real biological system is a central theme in systems biology. A dynamic biological system is always modeled as a nonlinear ordinary differential equation (ODE system. How to simulate the dynamic behavior and dynamic parameter sensitivities of systems described by ODEs efficiently and accurately is a critical job. In many practical applications, e.g., the fed-batch fermentation systems, the system admissible input (corresponding to independent variables of the system can be time-dependent. The main difficulty for investigating the dynamic log gains of these systems is the infinite dimension due to the time-dependent input. The classical dynamic sensitivity analysis does not take into account this case for the dynamic log gains. Results We present an algorithm with an adaptive step size control that can be used for computing the solution and dynamic sensitivities of an autonomous ODE system simultaneously. Although our algorithm is one of the decouple direct methods in computing dynamic sensitivities of an ODE system, the step size determined by model equations can be used on the computations of the time profile and dynamic sensitivities with moderate accuracy even when sensitivity equations are more stiff than model equations. To show this algorithm can perform the dynamic sensitivity analysis on very stiff ODE systems with moderate accuracy, it is implemented and applied to two sets of chemical reactions: pyrolysis of ethane and oxidation of formaldehyde. The accuracy of this algorithm is demonstrated by comparing the dynamic parameter sensitivities obtained from this new algorithm and from the direct method with Rosenbrock stiff integrator based on the indirect method. The same dynamic sensitivity analysis was performed on an ethanol fed-batch fermentation system with a time-varying feed rate to evaluate the applicability of the algorithm to realistic

  4. Complexity, Analysis and Control of Singular Biological Systems

    CERN Document Server

    Zhang, Qingling; Zhang, Xue

    2012-01-01

    Complexity, Analysis and Control of Singular Biological Systems follows the control of real-world biological systems at both ecological and phyisological levels concentrating on the application of now-extensively-investigated singular system theory. Much effort has recently been dedicated to the modelling and analysis of developing bioeconomic systems and the text establishes singular examples of these, showing how proper control can help to maintain sustainable economic development of biological resources. The book begins from the essentials of singular systems theory and bifurcations before tackling  the use of various forms of control in singular biological systems using examples including predator-prey relationships and viral vaccination and quarantine control. Researchers and graduate students studying the control of complex biological systems are shown how a variety of methods can be brought to bear and practitioners working with the economics of biological systems and their control will also find the ...

  5. Computational Modeling, Formal Analysis, and Tools for Systems Biology.

    Science.gov (United States)

    Bartocci, Ezio; Lió, Pietro

    2016-01-01

    As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science.

  6. Continuum analysis of biological systems conserved quantities, fluxes and forces

    CERN Document Server

    Suraishkumar, G K

    2014-01-01

    This book addresses the analysis, in the continuum regime, of biological systems at various scales, from the cellular level to the industrial one. It presents both fundamental conservation principles (mass, charge, momentum and energy) and relevant fluxes resulting from appropriate driving forces, which are important for the analysis, design and operation of biological systems. It includes the concept of charge conservation, an important principle for biological systems that is not explicitly covered in any other book of this kind. The book is organized in five parts: mass conservation; charge conservation; momentum conservation; energy conservation; and multiple conservations simultaneously applied. All mathematical aspects are presented step by step, allowing any reader with a basic mathematical background (calculus, differential equations, linear algebra, etc.) to follow the text with ease. The book promotes an intuitive understanding of all the relevant principles and in so doing facilitates their applica...

  7. Integrated Network Analysis and Effective Tools in Plant Systems Biology

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima

    2014-11-01

    Full Text Available One of the ultimate goals in plant systems biology is to elucidate the genotype-phenotype relationship in plant cellular systems. Integrated network analysis that combines omics data with mathematical models has received particular attention. Here we focus on the latest cutting-edge computational advances that facilitate their combination. We highlight (1 network visualization tools, (2 pathway analyses, (3 genome-scale metabolic reconstruction, and (4 the integration of high-throughput experimental data and mathematical models. Multi-omics data that contain the genome, transcriptome, proteome, and metabolome and mathematical models are expected to integrate and expand our knowledge of complex plant metabolisms.

  8. Computational Proteomics: High-throughput Analysis for Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, William R.; Webb-Robertson, Bobbie-Jo M.

    2007-01-03

    High-throughput (HTP) proteomics is a rapidly developing field that offers the global profiling of proteins from a biological system. The HTP technological advances are fueling a revolution in biology, enabling analyses at the scales of entire systems (e.g., whole cells, tumors, or environmental communities). However, simply identifying the proteins in a cell is insufficient for understanding the underlying complexity and operating mechanisms of the overall system. Systems level investigations are relying more and more on computational analyses, especially in the field of proteomics generating large-scale global data.

  9. explorase: Multivariate Exploratory Analysis and Visualization for Systems Biology

    OpenAIRE

    2008-01-01

    The datasets being produced by high-throughput biological experiments, such as microarrays, have forced biologists to turn to sophisticated statistical analysis and visualization tools in order to understand their data. We address the particular need for an open-source exploratory data analysis tool that applies numerical methods in coordination with interactive graphics to the analysis of experimental data. The software package, known as explorase, provides a graphical user interface (GUI) ...

  10. explorase: Multivariate Exploratory Analysis and Visualization for Systems Biology

    Directory of Open Access Journals (Sweden)

    Michael Lawrence

    2008-03-01

    Full Text Available The datasets being produced by high-throughput biological experiments, such as microarrays, have forced biologists to turn to sophisticated statistical analysis and visualization tools in order to understand their data. We address the particular need for an open-source exploratory data analysis tool that applies numerical methods in coordination with interactive graphics to the analysis of experimental data. The software package, known as explorase, provides a graphical user interface (GUI on top of the R platform for statistical computing and the GGobi software for multivariate interactive graphics. The GUI is designed for use by biologists, many of whom are unfamiliar with the R language. It displays metadata about experimental design and biological entities in tables that are sortable and filterable. There are menu shortcuts to the analysis methods implemented in R, including graphical interfaces to linear modeling tools. The GUI is linked to data plots in GGobi through a brush tool that simultaneously colors rows in the entity information table and points in the GGobi plots.

  11. BioFNet: biological functional network database for analysis and synthesis of biological systems.

    Science.gov (United States)

    Kurata, Hiroyuki; Maeda, Kazuhiro; Onaka, Toshikazu; Takata, Takenori

    2014-09-01

    In synthetic biology and systems biology, a bottom-up approach can be used to construct a complex, modular, hierarchical structure of biological networks. To analyze or design such networks, it is critical to understand the relationship between network structure and function, the mechanism through which biological parts or biomolecules are assembled into building blocks or functional networks. A functional network is defined as a subnetwork of biomolecules that performs a particular function. Understanding the mechanism of building functional networks would help develop a methodology for analyzing the structure of large-scale networks and design a robust biological circuit to perform a target function. We propose a biological functional network database, named BioFNet, which can cover the whole cell at the level of molecular interactions. The BioFNet takes an advantage in implementing the simulation program for the mathematical models of the functional networks, visualizing the simulated results. It presents a sound basis for rational design of biochemical networks and for understanding how functional networks are assembled to create complex high-level functions, which would reveal design principles underlying molecular architectures.

  12. Fractal analysis in a systems biology approach to cancer.

    Science.gov (United States)

    Bizzarri, M; Giuliani, A; Cucina, A; D'Anselmi, F; Soto, A M; Sonnenschein, C

    2011-06-01

    Cancer is a highly complex disease due to the disruption of tissue architecture. Thus, tissues, and not individual cells, are the proper level of observation for the study of carcinogenesis. This paradigm shift from a reductionist approach to a systems biology approach is long overdue. Indeed, cell phenotypes are emergent modes arising through collective non-linear interactions among different cellular and microenvironmental components, generally described by "phase space diagrams", where stable states (attractors) are embedded into a landscape model. Within this framework, cell states and cell transitions are generally conceived as mainly specified by gene-regulatory networks. However, the system's dynamics is not reducible to the integrated functioning of the genome-proteome network alone; the epithelia-stroma interacting system must be taken into consideration in order to give a more comprehensive picture. Given that cell shape represents the spatial geometric configuration acquired as a result of the integrated set of cellular and environmental cues, we posit that fractal-shape parameters represent "omics" descriptors of the epithelium-stroma system. Within this framework, function appears to follow form, and not the other way around.

  13. mmnet: An R Package for Metagenomics Systems Biology Analysis

    Directory of Open Access Journals (Sweden)

    Yang Cao

    2015-01-01

    Full Text Available The human microbiome plays important roles in human health and disease. Previous microbiome studies focused mainly on single pure species function and overlooked the interactions in the complex communities on system-level. A metagenomic approach introduced recently integrates metagenomic data with community-level metabolic network modeling, but no comprehensive tool was available for such kind of approaches. To facilitate these kinds of studies, we developed an R package, mmnet, to implement community-level metabolic network reconstruction. The package also implements a set of functions for automatic analysis pipeline construction including functional annotation of metagenomic reads, abundance estimation of enzymatic genes, community-level metabolic network reconstruction, and integrated network analysis. The result can be represented in an intuitive way and sent to Cytoscape for further exploration. The package has substantial potentials in metagenomic studies that focus on identifying system-level variations of human microbiome associated with disease.

  14. mmnet: An R Package for Metagenomics Systems Biology Analysis.

    Science.gov (United States)

    Cao, Yang; Zheng, Xiaofei; Li, Fei; Bo, Xiaochen

    2015-01-01

    The human microbiome plays important roles in human health and disease. Previous microbiome studies focused mainly on single pure species function and overlooked the interactions in the complex communities on system-level. A metagenomic approach introduced recently integrates metagenomic data with community-level metabolic network modeling, but no comprehensive tool was available for such kind of approaches. To facilitate these kinds of studies, we developed an R package, mmnet, to implement community-level metabolic network reconstruction. The package also implements a set of functions for automatic analysis pipeline construction including functional annotation of metagenomic reads, abundance estimation of enzymatic genes, community-level metabolic network reconstruction, and integrated network analysis. The result can be represented in an intuitive way and sent to Cytoscape for further exploration. The package has substantial potentials in metagenomic studies that focus on identifying system-level variations of human microbiome associated with disease.

  15. Quantitative Analysis of the Trends Exhibited by the Three Interdisciplinary Biological Sciences: Biophysics, Bioinformatics, and Systems Biology.

    Science.gov (United States)

    Kang, Jonghoon; Park, Seyeon; Venkat, Aarya; Gopinath, Adarsh

    2015-12-01

    New interdisciplinary biological sciences like bioinformatics, biophysics, and systems biology have become increasingly relevant in modern science. Many papers have suggested the importance of adding these subjects, particularly bioinformatics, to an undergraduate curriculum; however, most of their assertions have relied on qualitative arguments. In this paper, we will show our metadata analysis of a scientific literature database (PubMed) that quantitatively describes the importance of the subjects of bioinformatics, systems biology, and biophysics as compared with a well-established interdisciplinary subject, biochemistry. Specifically, we found that the development of each subject assessed by its publication volume was well described by a set of simple nonlinear equations, allowing us to characterize them quantitatively. Bioinformatics, which had the highest ratio of publications produced, was predicted to grow between 77% and 93% by 2025 according to the model. Due to the large number of publications produced in bioinformatics, which nearly matches the number published in biochemistry, it can be inferred that bioinformatics is almost equal in significance to biochemistry. Based on our analysis, we suggest that bioinformatics be added to the standard biology undergraduate curriculum. Adding this course to an undergraduate curriculum will better prepare students for future research in biology.

  16. ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra

    CERN Document Server

    Hinkelmann, Franziska; Guang, Bonny; McNeill, Rustin; Blekherman, Grigoriy; Veliz-Cuba, Alan; Laubenbacher, Reinhard

    2010-01-01

    Motivation: Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, bounded Petri nets, and agent-based models. Simulation is a common practice for analyzing discrete models, but many systems are far too large to capture all the relevant dynamical features through simulation alone. Results: We convert discrete models into algebraic models and apply tools from computational algebra to analyze their dynamics. The key feature of biological systems that is exploited by our algorithms is their sparsity: while the number of nodes in a biological network may be quite large, each node is affected only by a small number of other nodes. In our experience with models arising in systems biology and random models, this structure leads to fast computations when using algebraic models, and thus efficient analysis. Availability: All algorithms and methods are available in our package Analysis of Dynamic Algebraic Models (ADAM), a user friendly web-interf...

  17. 7th Annual Systems Biology Symposium: Systems Biology and Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Galitski, Timothy P.

    2008-04-01

    Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology has been hosted by the Institute for Systems Biology in Seattle, Washington, since 2002. The annual two-day event gathers the most influential researchers transforming biology into an integrative discipline investingating complex systems. Engineering and application of new technology is a central element of systems biology. Genome-scale, or very small-scale, biological questions drive the enigneering of new technologies, which enable new modes of experimentation and computational analysis, leading to new biological insights and questions. Concepts and analytical methods in engineering are now finding direct applications in biology. Therefore, the 2008 Symposium, funded in partnership with the Department of Energy, featured global leaders in "Systems Biology and Engineering."

  18. Systems biology, emergence and antireductionism.

    Science.gov (United States)

    Kesić, Srdjan

    2016-09-01

    This study explores the conceptual history of systems biology and its impact on philosophical and scientific conceptions of reductionism, antireductionism and emergence. Development of systems biology at the beginning of 21st century transformed biological science. Systems biology is a new holistic approach or strategy how to research biological organisms, developed through three phases. The first phase was completed when molecular biology transformed into systems molecular biology. Prior to the second phase, convergence between applied general systems theory and nonlinear dynamics took place, hence allowing the formation of systems mathematical biology. The second phase happened when systems molecular biology and systems mathematical biology, together, were applied for analysis of biological data. Finally, after successful application in science, medicine and biotechnology, the process of the formation of modern systems biology was completed. Systems and molecular reductionist views on organisms were completely opposed to each other. Implications of systems and molecular biology on reductionist-antireductionist debate were quite different. The analysis of reductionism, antireductionism and emergence issues, in the era of systems biology, revealed the hierarchy between methodological, epistemological and ontological antireductionism. Primarily, methodological antireductionism followed from the systems biology. Only after, epistemological and ontological antireductionism could be supported.

  19. Systems cell biology.

    Science.gov (United States)

    Mast, Fred D; Ratushny, Alexander V; Aitchison, John D

    2014-09-15

    Systems cell biology melds high-throughput experimentation with quantitative analysis and modeling to understand many critical processes that contribute to cellular organization and dynamics. Recently, there have been several advances in technology and in the application of modeling approaches that enable the exploration of the dynamic properties of cells. Merging technology and computation offers an opportunity to objectively address unsolved cellular mechanisms, and has revealed emergent properties and helped to gain a more comprehensive and fundamental understanding of cell biology.

  20. Mathematical Analysis of a PDE System for Biological Network Formation

    KAUST Repository

    Haskovec, Jan

    2015-02-04

    Motivated by recent physics papers describing rules for natural network formation, we study an elliptic-parabolic system of partial differential equations proposed by Hu and Cai [13, 15]. The model describes the pressure field thanks to Darcy\\'s type equation and the dynamics of the conductance network under pressure force effects with a diffusion rate D >= 0 representing randomness in the material structure. We prove the existence of global weak solutions and of local mild solutions and study their long term behavior. It turns out that, by energy dissipation, steady states play a central role to understand the network formation capacity of the system. We show that for a large diffusion coefficient D, the zero steady state is stable, while network formation occurs for small values of D due to the instability of the zero steady state, and the borderline case D = 0 exhibits a large class of dynamically stable (in the linearized sense) steady states.

  1. Statistical analysis of highly correlated systems in biology and physics

    Science.gov (United States)

    Martin, Hector Garcia

    In this dissertation, I present my work on the statistical study of highly correlated systems in three fields of science: ecology, microbial ecology and physics. I propose an explanation for how the highly correlated distribution of species individuals, and an abundance distribution commonly observed in ecological systems, give rise to a power law dependence between a given area and the number of unique species it harbors. This is one of the oldest known ecological patterns: the power-law Species Area Rule. As a natural extension of my studies in ecology, I have undertaken both theoretical research and field work in the developing field of microbial ecology. In particular, I participated in a multidisciplinary study of the impact of microbes on the formation of macroscopic calcium carbonate terraces at Yellowstone National Park Hot Springs. I have used ecological techniques to characterize the biodiversity of our study site and developed a new bootstrap method for extracting abundance information from clone libraries. This has singled out the most abundant microorganisms and paved the way for future studies of the possible non-passive role of microorganisms in carbonate precipitation. The third part of my thesis uses statistical techniques to explore the correlations in rotating Bose-Einstein condensates. I have used finite difference techniques to solve the Gross-Pitaevskii equation in order to obtain the structure of a vortex in a lattice. Surprisingly, I have found that, in order to understand this structure, it is necessary to add a correction to the Gross-Pitaevskii equation which introduces a dependence on the particle scattering length. I have also used Path Integral Monte Carlo techniques to explore the limit of rapid rotations, where the Gross-Pitaevskii equation is no longer valid. Interestingly, the Gross-Pitaevskii equation seems to be valid for much higher densities than expected if properly renormalized. I show that, in accord with the prediction of

  2. A data integration approach for cell cycle analysis oriented to model simulation in systems biology

    Directory of Open Access Journals (Sweden)

    Mosca Ettore

    2007-08-01

    Full Text Available Abstract Background The cell cycle is one of the biological processes most frequently investigated in systems biology studies and it involves the knowledge of a large number of genes and networks of protein interactions. A deep knowledge of the molecular aspect of this biological process can contribute to making cancer research more accurate and innovative. In this context the mathematical modelling of the cell cycle has a relevant role to quantify the behaviour of each component of the systems. The mathematical modelling of a biological process such as the cell cycle allows a systemic description that helps to highlight some features such as emergent properties which could be hidden when the analysis is performed only from a reductionism point of view. Moreover, in modelling complex systems, a complete annotation of all the components is equally important to understand the interaction mechanism inside the network: for this reason data integration of the model components has high relevance in systems biology studies. Description In this work, we present a resource, the Cell Cycle Database, intended to support systems biology analysis on the Cell Cycle process, based on two organisms, yeast and mammalian. The database integrates information about genes and proteins involved in the cell cycle process, stores complete models of the interaction networks and allows the mathematical simulation over time of the quantitative behaviour of each component. To accomplish this task, we developed, a web interface for browsing information related to cell cycle genes, proteins and mathematical models. In this framework, we have implemented a pipeline which allows users to deal with the mathematical part of the models, in order to solve, using different variables, the ordinary differential equation systems that describe the biological process. Conclusion This integrated system is freely available in order to support systems biology research on the cell cycle and

  3. Protein microarrays for systems biology

    Institute of Scientific and Technical Information of China (English)

    Lina Yang; Shujuan Guo; Yang Li; Shumin Zhou; Shengce Tao

    2011-01-01

    Systems biology holds the key for understanding biological systems on a system level. It eventually holds the key for the treatment and cure of complex diseases such as cancer,diabetes, obesity, mental disorders, and many others. The '-omics' technologies, such as genomics, transcriptomics,proteomics, and metabonomics, are among the major driving forces of systems biology. Featured as highthroughput, miniaturized, and capable of parallel analysis,protein microarrays have already become an important technology platform for systems biology, In this review, we will focus on the system level or global analysis of biological systems using protein microarrays. Four major types of protein microarrays will be discussed: proteome microarrays, antibody microarrays, reverse-phase protein arrays,and lectin microarrays. We will also discuss the challenges and future directions of protein microarray technologies and their applications for systems biology. We strongly believe that protein microarrays will soon become an indispensable and invaluable tool for systems biology.

  4. Computational Systems Chemical Biology

    OpenAIRE

    Oprea, Tudor I.; Elebeoba E. May; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007).

  5. Systems genomics analysis centered on epigenetic inheritance supports development of a unified theory of biology.

    Science.gov (United States)

    Sharma, Abhay

    2015-11-01

    New discoveries are increasingly demanding integration of epigenetics, molecular biology, genomic networks and physiology with evolution. This article provides a proof of concept for evolutionary transgenerational systems biology, proposed recently in the context of epigenetic inheritance in mammals. Gene set enrichment analysis of available genome-level mammalian data presented here seem consistent with the concept that: (1) heritable information about environmental effects in somatic cells is communicated to the germline by circulating microRNAs (miRNAs) or other RNAs released in physiological fluids; (2) epigenetic factors including miRNA-like small RNAs, DNA methylation and histone modifications are propagated across generations via gene networks; and (3) inherited epigenetic variations in the form of methylated cytosines are fixed in the population as thymines over the evolutionary time course. The analysis supports integration of physiology and epigenetics with inheritance and evolution. This may catalyze efforts to develop a unified theory of biology.

  6. A Real-Time and Dynamic Biological Information Retrieval and Analysis System (BIRAS)

    Institute of Scientific and Technical Information of China (English)

    Qi Zhou; Hong Zhang; Meiying Geng; Chenggang Zhang

    2003-01-01

    The aim of this study is to design a biological information retrieval and analysis system (BIRAS) based on the Internet. Using the specific network protocol, BIRAS system could send and receive information from the Entrez search and retrieval system maintained by National Center for Biotechnology Information (NCBI) in USA. The literatures, nucleotide sequence, protein sequences, and other resources according to the user-defined term could then be retrieved and sent to the user by pop up message or by E-mail informing automatically using BIRAS system.All the information retrieving and analyzing processes are done in real-time. As a robust system for intelligently and dynamically retrieving and analyzing on the user-defined information, it is believed that BIRAS would be extensively used to retrieve specific information from large amount of biological databases in now days.The program is available on request from the corresponding author.

  7. Systems theoretic analysis of the central dogma of molecular biology: some recent results.

    Science.gov (United States)

    Gao, Rui; Yu, Juanyi; Zhang, Mingjun; Tarn, Tzyh-Jong; Li, Jr-Shin

    2010-03-01

    This paper extends our early study on a mathematical formulation of the central dogma of molecular biology, and focuses discussions on recent insights obtained by employing advanced systems theoretic analysis. The goal of this paper is to mathematically represent and interpret the genetic information flow at the molecular level, and explore the fundamental principle of molecular biology at the system level. Specifically, group theory was employed to interpret concepts and properties of gene mutation, and predict backbone torsion angle along the peptide chain. Finite state machine theory was extensively applied to interpret key concepts and analyze the processes related to DNA hybridization. Using the proposed model, we have transferred the character-based model in molecular biology to a sophisticated mathematical model for calculation and interpretation.

  8. Fostering synergy between cell biology and systems biology

    OpenAIRE

    2015-01-01

    In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules; predicting mechanisms and identifying generalizable themes; generating hypotheses...

  9. Tav4SB: integrating tools for analysis of kinetic models of biological systems

    Directory of Open Access Journals (Sweden)

    Rybiński Mikołaj

    2012-04-01

    Full Text Available Abstract Background Progress in the modeling of biological systems strongly relies on the availability of specialized computer-aided tools. To that end, the Taverna Workbench eases integration of software tools for life science research and provides a common workflow-based framework for computational experiments in Biology. Results The Taverna services for Systems Biology (Tav4SB project provides a set of new Web service operations, which extend the functionality of the Taverna Workbench in a domain of systems biology. Tav4SB operations allow you to perform numerical simulations or model checking of, respectively, deterministic or stochastic semantics of biological models. On top of this functionality, Tav4SB enables the construction of high-level experiments. As an illustration of possibilities offered by our project we apply the multi-parameter sensitivity analysis. To visualize the results of model analysis a flexible plotting operation is provided as well. Tav4SB operations are executed in a simple grid environment, integrating heterogeneous software such as Mathematica, PRISM and SBML ODE Solver. The user guide, contact information, full documentation of available Web service operations, workflows and other additional resources can be found at the Tav4SB project’s Web page: http://bioputer.mimuw.edu.pl/tav4sb/. Conclusions The Tav4SB Web service provides a set of integrated tools in the domain for which Web-based applications are still not as widely available as for other areas of computational biology. Moreover, we extend the dedicated hardware base for computationally expensive task of simulating cellular models. Finally, we promote the standardization of models and experiments as well as accessibility and usability of remote services.

  10. ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra

    Directory of Open Access Journals (Sweden)

    Blekherman Grigoriy

    2011-07-01

    Full Text Available Abstract Background Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. Results We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM, which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Conclusions Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides

  11. Biological conversion system

    Science.gov (United States)

    Scott, C.D.

    A system for bioconversion of organic material comprises a primary bioreactor column wherein a biological active agent (zymomonas mobilis) converts the organic material (sugar) to a product (alcohol), a rejuvenator column wherein the biological activity of said biological active agent is enhanced, and means for circulating said biological active agent between said primary bioreactor column and said rejuvenator column.

  12. Computational systems chemical biology.

    Science.gov (United States)

    Oprea, Tudor I; May, Elebeoba E; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology (SCB) (Nat Chem Biol 3: 447-450, 2007).The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules, and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology/systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology, and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology.

  13. ZBIT Bioinformatics Toolbox: A Web-Platform for Systems Biology and Expression Data Analysis.

    Science.gov (United States)

    Römer, Michael; Eichner, Johannes; Dräger, Andreas; Wrzodek, Clemens; Wrzodek, Finja; Zell, Andreas

    2016-01-01

    Bioinformatics analysis has become an integral part of research in biology. However, installation and use of scientific software can be difficult and often requires technical expert knowledge. Reasons are dependencies on certain operating systems or required third-party libraries, missing graphical user interfaces and documentation, or nonstandard input and output formats. In order to make bioinformatics software easily accessible to researchers, we here present a web-based platform. The Center for Bioinformatics Tuebingen (ZBIT) Bioinformatics Toolbox provides web-based access to a collection of bioinformatics tools developed for systems biology, protein sequence annotation, and expression data analysis. Currently, the collection encompasses software for conversion and processing of community standards SBML and BioPAX, transcription factor analysis, and analysis of microarray data from transcriptomics and proteomics studies. All tools are hosted on a customized Galaxy instance and run on a dedicated computation cluster. Users only need a web browser and an active internet connection in order to benefit from this service. The web platform is designed to facilitate the usage of the bioinformatics tools for researchers without advanced technical background. Users can combine tools for complex analyses or use predefined, customizable workflows. All results are stored persistently and reproducible. For each tool, we provide documentation, tutorials, and example data to maximize usability. The ZBIT Bioinformatics Toolbox is freely available at https://webservices.cs.uni-tuebingen.de/.

  14. Validation of systems biology models

    NARCIS (Netherlands)

    Hasdemir, D.

    2015-01-01

    The paradigm shift from qualitative to quantitative analysis of biological systems brought a substantial number of modeling approaches to the stage of molecular biology research. These include but certainly are not limited to nonlinear kinetic models, static network models and models obtained by the

  15. Introduction to systems biology

    NARCIS (Netherlands)

    Bruggeman, F.J.; Hornberg, J.J.; Boogerd, F.C.; Westerhoff, H.V.; Boogerd, F.C.; Bruggeman, F.J.; Hofmeyr, J.H.S.; Westerhoff, H.V.

    2007-01-01

    The developments in the molecular biosciences have made possible a shift to combined molecular and system-level approaches to biological research under the name of Systems Biology. It integrates many types of molecular knowledge, which can best be achieved by the synergistic use of models and experi

  16. Hopf Bifurcation Analysis of a Predator-Prey Biological Economic System with Nonselective Harvesting

    OpenAIRE

    Biwen Li; Zhenwei Li; Boshan Chen; Gan Wang

    2015-01-01

    A modified predator-prey biological economic system with nonselective harvesting is investigated. An important mathematical feature of the system is that the economic profit on the predator-prey system is investigated from an economic perspective. By using the local parameterization method and Hopf bifurcation theorem, we analyze the Hopf bifurcation of the proposed system. In addition, the modified model enriches the database for the predator-prey biological economic system. Finally, numeric...

  17. SYSTOMONAS — an integrated database for systems biology analysis of Pseudomonas

    OpenAIRE

    Choi, Claudia; Münch, Richard; Leupold, Stefan; Klein, Johannes; Siegel, Inga; Thielen, Bernhard; Benkert, Beatrice; Kucklick, Martin; Schobert, Max; Barthelmes, Jens; Ebeling, Christian; Haddad, Isam; Scheer, Maurice; Grote, Andreas; Hiller, Karsten

    2007-01-01

    To provide an integrated bioinformatics platform for a systems biology approach to the biology of pseudomonads in infection and biotechnology the database SYSTOMONAS (SYSTems biology of pseudOMONAS) was established. Besides our own experimental metabolome, proteome and transcriptome data, various additional predictions of cellular processes, such as gene-regulatory networks were stored. Reconstruction of metabolic networks in SYSTOMONAS was achieved via comparative genomics. Broad data integr...

  18. Analyzing the Biology on the System Level

    OpenAIRE

    Tong, Wei

    2016-01-01

    Although various genome projects have provided us enormous static sequence information, understanding of the sophisticated biology continues to require integrating the computational modeling, system analysis, technology development for experiments, and quantitative experiments all together to analyze the biology architecture on various levels, which is just the origin of systems biology subject. This review discusses the object, its characteristics, and research attentions in systems biology,...

  19. Industrial systems biology.

    Science.gov (United States)

    Otero, José Manuel; Nielsen, Jens

    2010-02-15

    The chemical industry is currently undergoing a dramatic change driven by demand for developing more sustainable processes for the production of fuels, chemicals, and materials. In biotechnological processes different microorganisms can be exploited, and the large diversity of metabolic reactions represents a rich repository for the design of chemical conversion processes that lead to efficient production of desirable products. However, often microorganisms that produce a desirable product, either naturally or because they have been engineered through insertion of heterologous pathways, have low yields and productivities, and in order to establish an economically viable process it is necessary to improve the performance of the microorganism. Here metabolic engineering is the enabling technology. Through metabolic engineering the metabolic landscape of the microorganism is engineered such that there is an efficient conversion of the raw material, typically glucose, to the product of interest. This process may involve both insertion of new enzymes activities, deletion of existing enzyme activities, but often also deregulation of existing regulatory structures operating in the cell. In order to rapidly identify the optimal metabolic engineering strategy the industry is to an increasing extent looking into the use of tools from systems biology. This involves both x-ome technologies such as transcriptome, proteome, metabolome, and fluxome analysis, and advanced mathematical modeling tools such as genome-scale metabolic modeling. Here we look into the history of these different techniques and review how they find application in industrial biotechnology, which will lead to what we here define as industrial systems biology.

  20. [Systems biology of cancer].

    Science.gov (United States)

    Barillot, Emmanuel; Calzone, Laurence; Zinovyev, Andrei

    2009-01-01

    Cancer Systems Biology is now accepted and recognized as a promising field both in biological and clinical research. It relies on a rigorous formalization of regulation networks into precise and unambiguous languages. It provides both detailed and modular views of the complex biological system of interest (which in cancer research is typically an interaction network governing essential cellular events such as proliferation, differentiation, cell death...) in order to facilitate the interpretation of molecular profiles of tumors. The translation of these networks into mathematical models allows prediction of the evolution of the system in time and under certain perturbations. As a result, it can not only propose specific target points for pharmaceutical purposes, but also anticipate the evolution of tumors as well as their classifications. These characteristics emphasize the important role of Systems Biology of Cancer in the future of biomedical research.

  1. Nutritional Systems Biology

    DEFF Research Database (Denmark)

    Jensen, Kasper

    sites of diet on the disease pathway. We propose a framework for interrogating the critical targets in colon cancer process and identifying plant-based dietary interventions as important modifiers using a systems chemical biology approach. The fifth chapter of the thesis is on discovering of novel anti...... number of thoroughly selected targets. Our need for fundamental understanding of the building blocks of the complex biological systems had been the main reason for the reductionist approach that was mainly applied in the past to elucidate these systems. Nowadays, it is widely recognized that systems...... components with biological systems and their connection to health and disease. The database will be enriched with predicted interactions between food components and protein targets, based on their structural and pharmacophore similarity with known small molecule ligands. Further to this, the associations...

  2. Biometrics Analysis and Evaluation on Korean Makgeolli Using Brainwaves and Taste Biological Sensor System

    Directory of Open Access Journals (Sweden)

    Yong-Sung Kim

    2015-01-01

    Full Text Available There are several methods available in measuring food taste. The sensory evaluation, for instance, is a typical method for panels to test of taste and recognize smell with their nose by measuring the degree of taste characteristic, intensity, and pleasure. There are many issues entailed in the traditional sensory evaluation method such as forming a panel and evaluation cost; moreover, it is only localized in particular areas. Accordingly, this paper aimed to select food in one particular area, and compare and review the content between sensory evaluations using a taste biological sensor, as well as presenting an analysis of brainwaves using EEG and finally a proposal of a new method for sensory evaluation. In this paper, the researchers have conducted a sensory evaluation whereas a maximum of nine points were accumulated by purchasing eight types of rice wine. These eight types of Makgeolli were generalized by generating multidimensional data with the use of TS-5000z, thus learning mapping points and scaling them. The contribution of this paper, therefore, is to overcome the disadvantages of the sensory evaluation with the usage of the suggested taste biological sensor system.

  3. Biometrics Analysis and Evaluation on Korean Makgeolli Using Brainwaves and Taste Biological Sensor System.

    Science.gov (United States)

    Kim, Yong-Sung; Kim, Yong-Suk

    2015-01-01

    There are several methods available in measuring food taste. The sensory evaluation, for instance, is a typical method for panels to test of taste and recognize smell with their nose by measuring the degree of taste characteristic, intensity, and pleasure. There are many issues entailed in the traditional sensory evaluation method such as forming a panel and evaluation cost; moreover, it is only localized in particular areas. Accordingly, this paper aimed to select food in one particular area, and compare and review the content between sensory evaluations using a taste biological sensor, as well as presenting an analysis of brainwaves using EEG and finally a proposal of a new method for sensory evaluation. In this paper, the researchers have conducted a sensory evaluation whereas a maximum of nine points were accumulated by purchasing eight types of rice wine. These eight types of Makgeolli were generalized by generating multidimensional data with the use of TS-5000z, thus learning mapping points and scaling them. The contribution of this paper, therefore, is to overcome the disadvantages of the sensory evaluation with the usage of the suggested taste biological sensor system.

  4. Systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-10-11

    Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

  5. Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

    Directory of Open Access Journals (Sweden)

    Bor-Sen Chen

    2013-10-01

    Full Text Available Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

  6. Analyzing the Biology on the System Level

    Institute of Scientific and Technical Information of China (English)

    Wei Tong

    2004-01-01

    Although various genome projects have provided us enormous static sequence information, understanding of the sophisticated biology continues to require integrating the computational modeling, system analysis, technology development for experiments, and quantitative experiments all together to analyze the biology architecture on various levels, which is just the origin of systems biology subject. This review discusses the object, its characteristics, and research attentions in systems biology, and summarizes the analysis methods, experimental technologies, research developments, and so on in the four key fields of systems biology-systemic structures, dynamics, control methods, and design principles.

  7. Plant Systems Biology (editorial)

    Science.gov (United States)

    In June 2003, Plant Physiology published an Arabidopsis special issue devoted to plant systems biology. The intention of Natasha Raikhel and Gloria Coruzzi, the two editors of this first-of-its-kind issue, was ‘‘to help nucleate this new effort within the plant community’’ as they considered that ‘‘...

  8. BIOZON: a system for unification, management and analysis of heterogeneous biological data

    Directory of Open Access Journals (Sweden)

    Yona Golan

    2006-02-01

    Full Text Available Abstract Background Integration of heterogeneous data types is a challenging problem, especially in biology, where the number of databases and data types increase rapidly. Amongst the problems that one has to face are integrity, consistency, redundancy, connectivity, expressiveness and updatability. Description Here we present a system (Biozon that addresses these problems, and offers biologists a new knowledge resource to navigate through and explore. Biozon unifies multiple biological databases consisting of a variety of data types (such as DNA sequences, proteins, interactions and cellular pathways. It is fundamentally different from previous efforts as it uses a single extensive and tightly connected graph schema wrapped with hierarchical ontology of documents and relations. Beyond warehousing existing data, Biozon computes and stores novel derived data, such as similarity relationships and functional predictions. The integration of similarity data allows propagation of knowledge through inference and fuzzy searches. Sophisticated methods of query that span multiple data types were implemented and first-of-a-kind biological ranking systems were explored and integrated. Conclusion The Biozon system is an extensive knowledge resource of heterogeneous biological data. Currently, it holds more than 100 million biological documents and 6.5 billion relations between them. The database is accessible through an advanced web interface that supports complex queries, "fuzzy" searches, data materialization and more, online at http://biozon.org.

  9. Building multivariate systems biology models

    NARCIS (Netherlands)

    Kirwan, G.M.; Johansson, E.; Kleemann, R.; Verheij, E.R.; Wheelock, A.M.; Goto, S.; Trygg, J.; Wheelock, C.E.

    2012-01-01

    Systems biology methods using large-scale "omics" data sets face unique challenges: integrating and analyzing near limitless data space, while recognizing and removing systematic variation or noise. Herein we propose a complementary multivariate analysis workflow to both integrate "omics" data from

  10. A Systems Biology Analysis Unfolds the Molecular Pathways and Networks of Two Proteobacteria in Spaceflight and Simulated Microgravity Conditions

    Science.gov (United States)

    Roy, Raktim; Phani Shilpa, P.; Bagh, Sangram

    2016-09-01

    Bacteria are important organisms for space missions due to their increased pathogenesis in microgravity that poses risks to the health of astronauts and for projected synthetic biology applications at the space station. We understand little about the effect, at the molecular systems level, of microgravity on bacteria, despite their significant incidence. In this study, we proposed a systems biology pipeline and performed an analysis on published gene expression data sets from multiple seminal studies on Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium under spaceflight and simulated microgravity conditions. By applying gene set enrichment analysis on the global gene expression data, we directly identified a large number of new, statistically significant cellular and metabolic pathways involved in response to microgravity. Alteration of metabolic pathways in microgravity has rarely been reported before, whereas in this analysis metabolic pathways are prevalent. Several of those pathways were found to be common across studies and species, indicating a common cellular response in microgravity. We clustered genes based on their expression patterns using consensus non-negative matrix factorization. The genes from different mathematically stable clusters showed protein-protein association networks with distinct biological functions, suggesting the plausible functional or regulatory network motifs in response to microgravity. The newly identified pathways and networks showed connection with increased survival of pathogens within macrophages, virulence, and antibiotic resistance in microgravity. Our work establishes a systems biology pipeline and provides an integrated insight into the effect of microgravity at the molecular systems level.

  11. Systems biology of industrial microorganisms.

    Science.gov (United States)

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

    2010-01-01

    The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

  12. Systems Biology of Industrial Microorganisms

    Science.gov (United States)

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

    The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

  13. Systems biology in animal sciences

    NARCIS (Netherlands)

    Woelders, H.; Pas, te M.F.W.; Bannink, A.; Veerkamp, R.F.; Smits, M.A.

    2011-01-01

    Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes an

  14. Systems biology: experimental design.

    Science.gov (United States)

    Kreutz, Clemens; Timmer, Jens

    2009-02-01

    Experimental design has a long tradition in statistics, engineering and life sciences, dating back to the beginning of the last century when optimal designs for industrial and agricultural trials were considered. In cell biology, the use of mathematical modeling approaches raises new demands on experimental planning. A maximum informative investigation of the dynamic behavior of cellular systems is achieved by an optimal combination of stimulations and observations over time. In this minireview, the existing approaches concerning this optimization for parameter estimation and model discrimination are summarized. Furthermore, the relevant classical aspects of experimental design, such as randomization, replication and confounding, are reviewed.

  15. ECO-BIOLOGICAL SYSTEM MODELING

    Directory of Open Access Journals (Sweden)

    T. I. Burak

    2015-01-01

    Full Text Available The methodology for computer modeling of complex eco-biological models is presented in this paper. It is based on system approach of J. Forrester. Developed methodology is universal for complex ecological and biological systems. Modeling algorithm considers specialties of eco-biological systems and shows adequate and accurate results in practice. 

  16. Biological signals classification and analysis

    CERN Document Server

    Kiasaleh, Kamran

    2015-01-01

    This authored monograph presents key aspects of signal processing analysis in the biomedical arena. Unlike wireless communication systems, biological entities produce signals with underlying nonlinear, chaotic nature that elude classification using the standard signal processing techniques, which have been developed over the past several decades for dealing primarily with standard communication systems. This book separates what is random from that which appears to be random, and yet is truly deterministic with random appearance. At its core, this work gives the reader a perspective on biomedical signals and the means to classify and process such signals. In particular, a review of random processes along with means to assess the behavior of random signals is also provided. The book also includes a general discussion of biological signals in order to demonstrate the inefficacy of the well-known techniques to correctly extract meaningful information from such signals. Finally, a thorough discussion of recently ...

  17. Systems biology: a biologist's viewpoint.

    Science.gov (United States)

    Bose, Biplab

    2013-12-01

    The debate over reductionism and antireductionism in biology is very old. Even the systems approach in biology is more than five decades old. However, mainstream biology, particularly experimental biology, has broadly sidestepped those debates and ideas. Post-genome data explosion and development of high-throughput techniques led to resurfacing of those ideas and debates as a new incarnation called Systems Biology. Though experimental biologists have co-opted systems biology and hailed it as a paradigm shift, it is practiced in different shades and understood with divergent meanings. Biology has certain questions linked with organization of multiple components and processes. Often such questions involve multilevel systems. Here in this essay we argue that systems theory provides required framework and abstractions to explore those questions. We argue that systems biology should follow the logical and mathematical approach of systems theory and transmogrification of systems biology to mere collection of higher dimensional data must be avoided. Therefore, the questions that we ask and the priority of those questions should also change. Systems biology should focus on system-level properties and investigate complexity without shying away from it.

  18. Fostering synergy between cell biology and systems biology.

    Science.gov (United States)

    Eddy, James A; Funk, Cory C; Price, Nathan D

    2015-08-01

    In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules, predicting mechanisms and identifying generalizable themes, generating hypotheses and guiding experimental design, and highlighting knowledge gaps and refining understanding. In turn, incorporating domain expertise and experimental data is crucial for building towards whole cell models. An iterative cycle of interaction between cell and systems biologists advances the goals of both fields and establishes a framework for mechanistic understanding of the genome-to-phenome relationship.

  19. Network systems biology for targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Zhou

    2012-01-01

    The era of targeted cancer therapies has arrived.However,due to the complexity of biological systems,the current progress is far from enough.From biological network modeling to structural/dynamic network analysis,network systems biology provides unique insight into the potential mechanisms underlying the growth and progression of cancer cells.It has also introduced great changes into the research paradigm of cancer-associated drug discovery and drug resistance.

  20. Use of a similarity index based on microbial fatty acid (MFA) analysis to monitor biological wastewater treatment systems.

    Science.gov (United States)

    Son, K S; Hall, E R

    2003-09-01

    Estimating the stability of microbial community structures may be useful in advanced biological wastewater treatment system design and operation. In this research, a monitoring method using fatty acid profiles was evaluated for detecting changes in microbial community structures. For the evaluation, the operating parameters such as pH, organic loading, and chlorine addition were varied in two identical laboratory scale conventional activated sludge systems. A similarity index based on microbial fatty acid analysis was used to express the stability of microbial community structures in the systems. Experiments using a model microbial community showed that microbial compositions changed daily even under constant operating conditions and that the rate of change increased under dynamic operating conditions. Substrate changes brought about a relatively large change in a microbial community structure, eventually resulting in a very different microbial community. After only 7 days following a substrate change in a lab-scale bioreactor, the biomass exhibited only 45% similarity to the original structure. The analysis of microbial fatty acids conveys additional information, in that it could be used for the calculation of biomass concentrations in a wastewater treatment system if microbial fatty acid analyses are executed on a routine basis as a monitoring tool for biological wastewater treatment systems. The total fatty acid concentrations were about 0.61% of the biomass concentration as mixed liquor volatile suspended solid concentrations in this research.

  1. In silico cell biology and biochemistry: a systems biology approach

    OpenAIRE

    Camacho, Diogo Mayo

    2007-01-01

    In the post-"omic" era the analysis of high-throughput data is regarded as one of the major challenges faced by researchers. One focus of this data analysis is uncovering biological network topologies and dynamics. It is believed that this kind of research will allow the development of new mathematical models of biological systems as well as aid in the improvement of already existing ones. The work that is presented in this dissertation addresses the problem of the analysis of highly complex ...

  2. Network dynamics and systems biology

    Science.gov (United States)

    Norrell, Johannes A.

    The physics of complex systems has grown considerably as a field in recent decades, largely due to improved computational technology and increased availability of systems level data. One area in which physics is of growing relevance is molecular biology. A new field, systems biology, investigates features of biological systems as a whole, a strategy of particular importance for understanding emergent properties that result from a complex network of interactions. Due to the complicated nature of the systems under study, the physics of complex systems has a significant role to play in elucidating the collective behavior. In this dissertation, we explore three problems in the physics of complex systems, motivated in part by systems biology. The first of these concerns the applicability of Boolean models as an approximation of continuous systems. Studies of gene regulatory networks have employed both continuous and Boolean models to analyze the system dynamics, and the two have been found produce similar results in the cases analyzed. We ask whether or not Boolean models can generically reproduce the qualitative attractor dynamics of networks of continuously valued elements. Using a combination of analytical techniques and numerical simulations, we find that continuous networks exhibit two effects---an asymmetry between on and off states, and a decaying memory of events in each element's inputs---that are absent from synchronously updated Boolean models. We show that in simple loops these effects produce exactly the attractors that one would predict with an analysis of the stability of Boolean attractors, but in slightly more complicated topologies, they can destabilize solutions that are stable in the Boolean approximation, and can stabilize new attractors. Second, we investigate ensembles of large, random networks. Of particular interest is the transition between ordered and disordered dynamics, which is well characterized in Boolean systems. Networks at the

  3. Mapping biological systems to network systems

    CERN Document Server

    Rathore, Heena

    2016-01-01

    The book presents the challenges inherent in the paradigm shift of network systems from static to highly dynamic distributed systems – it proposes solutions that the symbiotic nature of biological systems can provide into altering networking systems to adapt to these changes. The author discuss how biological systems – which have the inherent capabilities of evolving, self-organizing, self-repairing and flourishing with time – are inspiring researchers to take opportunities from the biology domain and map them with the problems faced in network domain. The book revolves around the central idea of bio-inspired systems -- it begins by exploring why biology and computer network research are such a natural match. This is followed by presenting a broad overview of biologically inspired research in network systems -- it is classified by the biological field that inspired each topic and by the area of networking in which that topic lies. Each case elucidates how biological concepts have been most successfully ...

  4. Success and failure of biological treatment in systemic lupus erythematosus: A critical analysis.

    Science.gov (United States)

    Gatto, Mariele; Saccon, Francesca; Zen, Margherita; Bettio, Silvano; Iaccarino, Luca; Punzi, Leonardo; Doria, Andrea

    2016-11-01

    Patients affected with systemic lupus erythematosus (SLE) still display increased mortality and decreased quality of life in respect to general population. The major determinant of poor long term prognosis is organ damage, which is predictive of more damage and death. Damage is in turn triggered by uncontrolled disease activity and especially by the long-standing corticosteroid use which often accompanies SLE patients over their disease course, owing both to the need of reaching disease remission and to the habit of keeping patients on a small steroid dose for an indefinite period of time. Hence, the need for new drugs and therapeutic strategies aiming at minimizing damage accrual through a better control of disease activity and a steroid-sparing potential is paramount. So far, however, the therapeutic strategy in SLE requires a multitarget approach which is not devoid of widespread immunesuppression. In fact, several studies have been carried out in recent years targeting both the adaptive and the innate immune system, the majority of which did not achieve their primary endpoint, being often divergent from successful clinical experience and thereby committing physician to off-label use of targeted therapies in face of refractory SLE manifestations. The study designs and the chosen endpoints were often blamed for inadequacy, being at least in part responsible for study failures. In this review, we go over major clinical trials conducted in SLE by analyzing any critical aspects related to study design, predefined endpoints and biological activity of novel compounds that may have hampered study outcome, despite the great effort of providing less toxic drugs within a targeted, pathogenic-based approach.

  5. Micro-separation toward systems biology.

    Science.gov (United States)

    Liu, Bi-Feng; Xu, Bo; Zhang, Guisen; Du, Wei; Luo, Qingming

    2006-02-17

    Current biology is experiencing transformation in logic or philosophy that forces us to reevaluate the concept of cell, tissue or entire organism as a collection of individual components. Systems biology that aims at understanding biological system at the systems level is an emerging research area, which involves interdisciplinary collaborations of life sciences, computational and mathematical sciences, systems engineering, and analytical technology, etc. For analytical chemistry, developing innovative methods to meet the requirement of systems biology represents new challenges as also opportunities and responsibility. In this review, systems biology-oriented micro-separation technologies are introduced for comprehensive profiling of genome, proteome and metabolome, characterization of biomolecules interaction and single cell analysis such as capillary electrophoresis, ultra-thin layer gel electrophoresis, micro-column liquid chromatography, and their multidimensional combinations, parallel integrations, microfabricated formats, and nano technology involvement. Future challenges and directions are also suggested.

  6. Telemetry System of Biological Parameters

    Directory of Open Access Journals (Sweden)

    Jan Spisak

    2005-01-01

    Full Text Available The mobile telemetry system of biological parameters serves for reading and wireless data transfer of measured values of selected biological parameters to an outlying computer. It concerns basically long time monitoring of vital function of car pilot.The goal of this projects is to propose mobile telemetry system for reading, wireless transfer and processing of biological parameters of car pilot during physical and psychical stress. It has to be made with respect to minimal consumption, weight and maximal device mobility. This system has to eliminate signal noise, which is created by biological artifacts and disturbances during the data transfer.

  7. Computer algebra in systems biology

    CERN Document Server

    Laubenbacher, Reinhard

    2007-01-01

    Systems biology focuses on the study of entire biological systems rather than on their individual components. With the emergence of high-throughput data generation technologies for molecular biology and the development of advanced mathematical modeling techniques, this field promises to provide important new insights. At the same time, with the availability of increasingly powerful computers, computer algebra has developed into a useful tool for many applications. This article illustrates the use of computer algebra in systems biology by way of a well-known gene regulatory network, the Lac Operon in the bacterium E. coli.

  8. Systems Chemo-Biology and Transcriptomic Meta-Analysis Reveal the Molecular Roles of Bioactive Lipids in Cardiomyocyte Differentiation.

    Science.gov (United States)

    de Faria Poloni, Joice; Bonatto, Diego

    2015-09-01

    Lipids, which are essential constituents of biological membranes, play structural and functional roles in the cell. In recent years, certain lipids have been identified as regulatory signaling molecules and have been termed "bioactive lipids". Subsequently, the importance of bioactive lipids in stem cell differentiation and cardiogenesis has gained increasing recognition. Therefore, the aim of this study was to identify the biological processes underlying murine cardiac differentiation and the mechanisms by which bioactive lipids affect these processes. For this purpose, a transcriptomic meta-analysis of microarray and RNA-seq data from murine stem cells undergoing cardiogenic differentiation was performed. The differentially expressed genes identified via this meta-analysis, as well as bioactive lipids, were evaluated using systems chemo-biology tools. These data indicated that bioactive lipids are associated with the regulation of cell motility, cell adhesion, cytoskeletal rearrangement, and gene expression. Moreover, bioactive lipids integrate the signaling pathways involved in cell migration, the secretion and remodeling of extracellular matrix components, and the establishment of the cardiac phenotype. In conclusion, this study provides new insights into the contribution of bioactive lipids to the induction of cellular responses to various stimuli, which may originate from the extracellular environment and morphogens, and the manner in which this contribution directly affects murine heart morphogenesis.

  9. Hierarchical structure of biological systems

    Science.gov (United States)

    Alcocer-Cuarón, Carlos; Rivera, Ana L; Castaño, Victor M

    2014-01-01

    A general theory of biological systems, based on few fundamental propositions, allows a generalization of both Wierner and Berthalanffy approaches to theoretical biology. Here, a biological system is defined as a set of self-organized, differentiated elements that interact pair-wise through various networks and media, isolated from other sets by boundaries. Their relation to other systems can be described as a closed loop in a steady-state, which leads to a hierarchical structure and functioning of the biological system. Our thermodynamical approach of hierarchical character can be applied to biological systems of varying sizes through some general principles, based on the exchange of energy information and/or mass from and within the systems. PMID:24145961

  10. Accuracy and repeatability of an optical motion analysis system for measuring small deformations of biological tissues.

    Science.gov (United States)

    Liu, Helen; Holt, Cathy; Evans, Sam

    2007-01-01

    Optical motion analysis techniques have been widely used in biomechanics for measuring large-scale motions such as gait, but have not yet been significantly explored for measuring smaller movements such as the tooth displacements under load. In principle, very accurate measurements could be possible and this could provide a valuable tool in many engineering applications. The aim of this study was to evaluate accuracy and repeatability of the Qualisys ProReflex-MCU120 system when measuring small displacements, as a step towards measuring tooth displacements to characterise the properties of the periodontal ligament. Accuracy and repeatability of the system was evaluated using a wedge comparator with a resolution of 0.25 microm to provide measured marker displacements in three orthogonal directions. The marker was moved in ten steps in each direction, for each of seven step sizes (0.5, 1, 2, 3, 5, 10, and 20 microm), repeated five times. Spherical and diamond markers were tested. The system accuracy (i.e. percentage of maximum absolute error in range/measurement range), in the 20-200 microm ranges, was +/-1.17%, +/-1.67% and +/-1.31% for the diamond marker in x, y and z directions, while the system accuracy for the spherical marker was +/-1.81%, +/-2.37% and +/-1.39%. The system repeatability (i.e. maximum standard deviation in the measurement range) measured under the different days, light intensity and temperatures for five times, carried out step up and then step down measurements for the same step size, was +/-1.7, +/-2.3 and +/-1.9 microm for the diamond marker, and +/-2.6, +/-3.9 and +/-1.9 microm for the spherical marker in x, y and z directions, respectively. These results demonstrate that the system suffices accuracy for measuring tooth displacements and could potentially be useful in many other applications.

  11. Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems.

    Science.gov (United States)

    Watson, Andrew D

    2006-10-01

    Lipids are water-insoluble molecules that have a wide variety of functions within cells, including: 1) maintenance of electrochemical gradients; 2) subcellular partitioning; 3) first- and second-messenger cell signaling; 4) energy storage; and 5) protein trafficking and membrane anchoring. The physiological importance of lipids is illustrated by the numerous diseases to which lipid abnormalities contribute, including atherosclerosis, diabetes, obesity, and Alzheimer's disease. Lipidomics, a branch of metabolomics, is a systems-based study of all lipids, the molecules with which they interact, and their function within the cell. Recent advances in soft-ionization mass spectrometry, combined with established separation techniques, have allowed the rapid and sensitive detection of a variety of lipid species with minimal sample preparation. A "lipid profile" from a crude lipid extract is a mass spectrum of the composition and abundance of the lipids it contains, which can be used to monitor changes over time and in response to particular stimuli. Lipidomics, integrated with genomics, proteomics, and metabolomics, will contribute toward understanding how lipids function in a biological system and will provide a powerful tool for elucidating the mechanism of lipid-based disease, for biomarker screening, and for monitoring pharmacologic therapy.

  12. Atlas of Cancer Signalling Network: a systems biology resource for integrative analysis of cancer data with Google Maps.

    Science.gov (United States)

    Kuperstein, I; Bonnet, E; Nguyen, H-A; Cohen, D; Viara, E; Grieco, L; Fourquet, S; Calzone, L; Russo, C; Kondratova, M; Dutreix, M; Barillot, E; Zinovyev, A

    2015-01-01

    Cancerogenesis is driven by mutations leading to aberrant functioning of a complex network of molecular interactions and simultaneously affecting multiple cellular functions. Therefore, the successful application of bioinformatics and systems biology methods for analysis of high-throughput data in cancer research heavily depends on availability of global and detailed reconstructions of signalling networks amenable for computational analysis. We present here the Atlas of Cancer Signalling Network (ACSN), an interactive and comprehensive map of molecular mechanisms implicated in cancer. The resource includes tools for map navigation, visualization and analysis of molecular data in the context of signalling network maps. Constructing and updating ACSN involves careful manual curation of molecular biology literature and participation of experts in the corresponding fields. The cancer-oriented content of ACSN is completely original and covers major mechanisms involved in cancer progression, including DNA repair, cell survival, apoptosis, cell cycle, EMT and cell motility. Cell signalling mechanisms are depicted in detail, together creating a seamless 'geographic-like' map of molecular interactions frequently deregulated in cancer. The map is browsable using NaviCell web interface using the Google Maps engine and semantic zooming principle. The associated web-blog provides a forum for commenting and curating the ACSN content. ACSN allows uploading heterogeneous omics data from users on top of the maps for visualization and performing functional analyses. We suggest several scenarios for ACSN application in cancer research, particularly for visualizing high-throughput data, starting from small interfering RNA-based screening results or mutation frequencies to innovative ways of exploring transcriptomes and phosphoproteomes. Integration and analysis of these data in the context of ACSN may help interpret their biological significance and formulate mechanistic hypotheses

  13. Comparative Systems Biology Analysis To Study the Mode of Action of the Isothiocyanate Compound Iberin on Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Tan, Sean Yang-Yi; Liu, Yang; Chua, Song Lin;

    2014-01-01

    Pseudomonas aeruginosa. In this study, we used a comparative systems biology approach to unravel the molecular mechanisms of the effects of iberin on QS and virulence factor expression of P. aeruginosa. Our study shows that the two systems biology methods used (i.e., RNA sequencing and proteomics) complement...

  14. Quantum Effects in Biological Systems

    CERN Document Server

    2016-01-01

    Since the last decade the study of quantum mechanical phenomena in biological systems has become a vibrant field of research. Initially sparked by evidence of quantum effects in energy transport that is instrumental for photosynthesis, quantum biology asks the question of how methods and models from quantum theory can help us to understand fundamental mechanisms in living organisms. This approach entails a paradigm change challenging the related disciplines: The successful framework of quantum theory is taken out of its low-temperature, microscopic regimes and applied to hot and dense macroscopic environments, thereby extending the toolbox of biology and biochemistry at the same time. The Quantum Effects in Biological Systems conference is a platform for researchers from biology, chemistry and physics to present and discuss the latest developments in the field of quantum biology. After meetings in Lisbon (2009), Harvard (2010), Ulm (2011), Berkeley (2012), Vienna (2013), Singapore (2014) and Florence (2015),...

  15. Biological sequence analysis

    DEFF Research Database (Denmark)

    Durbin, Richard; Eddy, Sean; Krogh, Anders Stærmose

    This book provides an up-to-date and tutorial-level overview of sequence analysis methods, with particular emphasis on probabilistic modelling. Discussed methods include pairwise alignment, hidden Markov models, multiple alignment, profile searches, RNA secondary structure analysis, and phylogene......This book provides an up-to-date and tutorial-level overview of sequence analysis methods, with particular emphasis on probabilistic modelling. Discussed methods include pairwise alignment, hidden Markov models, multiple alignment, profile searches, RNA secondary structure analysis...

  16. Systems biology of fungal infection

    Directory of Open Access Journals (Sweden)

    Fabian eHorn

    2012-04-01

    Full Text Available Elucidation of pathogenicity mechanisms of the most important human pathogenic fungi, Aspergillus fumigatus and Candida albicans, has gained great interest in the light of the steadily increasing number of cases of invasive fungal infections.A key feature of these infections is the interaction of the different fungal morphotypes with epithelial and immune effector cells in the human host. Because of the high level of complexity, it is necessary to describe and understand invasive fungal infection by taking a systems biological approach, i.e., by a comprehensive quantitative analysis of the non-linear and selective interactions of a large number of functionally diverse, and frequently multifunctional, sets of elements, e.g., genes, proteins, metabolites, which produce coherent and emergent behaviours in time and space. The recent advances in systems biology will now make it possible to uncover the structure and dynamics of molecular and cellular cause-effect relationships within these pathogenic interactions.We review current efforts to integrate omics and image-based data of host-pathogen interactions into network and spatio-temporal models. The modelling will help to elucidate pathogenicity mechanisms and to identify diagnostic biomarkers and potential drug targets for therapy and could thus pave the way for novel intervention strategies based on novel antifungal drugs and cell therapy.

  17. Developmental systems biology flourishing on new technologies

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Organism development is a systems level process. It has benefited greatly from the recent technological advances in the field of systems biology. DNA microarray, phenome, interactome and transcriptome mapping, the new generation of deep sequencing technologies,and faster and better computational and modeling approaches have opened new frontiers for both systems biologists and developmental biologists to reexamine the old developmental biology questions, such as pattern formation, and to tackle new problems, such as stem cell reprogramming. As showcased in the International Developmental Systems Biology Symposium organized by Chinese Academy of Sciences, developmental systems biology is flourishing in many perspectives, from the evolution of developmental systems, to the underlying genetic and molecular pathways and networks, to the genomic, epigenomic and noncoding levels, to the computational analysis and modeling. We believe that the field will continue to reap rewards into the future with these new approaches.

  18. Systems and synthetic biology as emerging technosciences

    Directory of Open Access Journals (Sweden)

    Karen Kastenhofer

    2016-12-01

    Full Text Available Systems and synthetic biology can be understood as emerging technosciences. Both are characteristically shaped by promises and visions, a certain logic and function of labelling, specific forms of social organisation, an embedding in specific regimes of funding and innovation as well as a characteristic matrix of orientations within research practice. This characteristic constitution of systems and synthetic biology has fundamental consequences for scientific practice, its analysis and its governance.

  19. Systems biology of human atherosclerosis.

    Science.gov (United States)

    Shalhoub, Joseph; Sikkel, Markus B; Davies, Kerry J; Vorkas, Panagiotis A; Want, Elizabeth J; Davies, Alun H

    2014-01-01

    Systems biology describes a holistic and integrative approach to understand physiology and pathology. The "omic" disciplines include genomics, transcriptomics, proteomics, and metabolic profiling (metabonomics and metabolomics). By adopting a stance, which is opposing (yet complimentary) to conventional research techniques, systems biology offers an overview by assessing the "net" biological effect imposed by a disease or nondisease state. There are a number of different organizational levels to be understood, from DNA to protein, metabolites, cells, organs and organisms, even beyond this to an organism's context. Systems biology relies on the existence of "nodes" and "edges." Nodes are the constituent part of the system being studied (eg, proteins in the proteome), while the edges are the way these constituents interact. In future, it will be increasingly important to collaborate, collating data from multiple studies to improve data sets, making them freely available and undertaking integrative analyses.

  20. Aging and computational systems biology.

    Science.gov (United States)

    Mooney, Kathleen M; Morgan, Amy E; Mc Auley, Mark T

    2016-01-01

    Aging research is undergoing a paradigm shift, which has led to new and innovative methods of exploring this complex phenomenon. The systems biology approach endeavors to understand biological systems in a holistic manner, by taking account of intrinsic interactions, while also attempting to account for the impact of external inputs, such as diet. A key technique employed in systems biology is computational modeling, which involves mathematically describing and simulating the dynamics of biological systems. Although a large number of computational models have been developed in recent years, these models have focused on various discrete components of the aging process, and to date no model has succeeded in completely representing the full scope of aging. Combining existing models or developing new models may help to address this need and in so doing could help achieve an improved understanding of the intrinsic mechanisms which underpin aging.

  1. Text mining for systems biology.

    Science.gov (United States)

    Fluck, Juliane; Hofmann-Apitius, Martin

    2014-02-01

    Scientific communication in biomedicine is, by and large, still text based. Text mining technologies for the automated extraction of useful biomedical information from unstructured text that can be directly used for systems biology modelling have been substantially improved over the past few years. In this review, we underline the importance of named entity recognition and relationship extraction as fundamental approaches that are relevant to systems biology. Furthermore, we emphasize the role of publicly organized scientific benchmarking challenges that reflect the current status of text-mining technology and are important in moving the entire field forward. Given further interdisciplinary development of systems biology-orientated ontologies and training corpora, we expect a steadily increasing impact of text-mining technology on systems biology in the future.

  2. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

    to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as 'systems biology' by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many......In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist...

  3. Informing biological design by integration of systems and synthetic biology.

    Science.gov (United States)

    Smolke, Christina D; Silver, Pamela A

    2011-03-18

    Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields.

  4. Systems biology: Functional analysis of natural microbial consortia using community proteomics.

    Science.gov (United States)

    VerBerkmoes, Nathan C; Denef, Vincent J; Hettich, Robert L; Banfield, Jillian F

    2009-03-01

    We know very little about the metabolic functioning and evolutionary dynamics of microbial communities. Recent advances in comprehensive, sequencing-based methods, however, are laying a molecular foundation for new insights into how microbial communities shape the Earth's biosphere. Here we explore the convergence of microbial ecology, genomics, biological mass spectrometry and informatics that form the new field of microbial community proteogenomics. We discuss the first applications of proteogenomics and its potential for studying the physiology, ecology and evolution of microbial populations and communities.

  5. Fetal alcohol syndrome, chemo-biology and OMICS: ethanol effects on vitamin metabolism during neurodevelopment as measured by systems biology analysis.

    Science.gov (United States)

    Feltes, Bruno César; de Faria Poloni, Joice; Nunes, Itamar José Guimarães; Bonatto, Diego

    2014-06-01

    Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the interplay between ethanol metabolism and vitamins during mouse neurodevelopment. For this purpose, we designed interactomes and employed transcriptomic data analysis approaches to study the neural tissue of Mus musculus exposed to ethanol prenatally and postnatally, simulating conditions that could lead to FAS development at different life stages. Our results showed that FAS can promote early changes in neurotransmitter release and glutamate equilibrium, as well as an abnormal calcium influx that can lead to neuroinflammation and impaired neurodifferentiation, both extensively connected with vitamin action and metabolism. Genes related to retinoic acid, niacin, vitamin D, and folate metabolism were underexpressed during neurodevelopment and appear to contribute to neuroinflammation progression and impaired synapsis. Our results also indicate that genes coding for tubulin, tubulin-associated proteins, synapse plasticity proteins, and proteins related to neurodifferentiation are extensively affected by ethanol exposure. Finally, we developed a molecular model of how ethanol can affect vitamin metabolism and impair neurodevelopment.

  6. Fetal Alcohol Syndrome, Chemo-Biology and OMICS: Ethanol Effects on Vitamin Metabolism During Neurodevelopment as Measured by Systems Biology Analysis

    Science.gov (United States)

    Feltes, Bruno César; de Faria Poloni, Joice; Nunes, Itamar José Guimarães

    2014-01-01

    Abstract Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the interplay between ethanol metabolism and vitamins during mouse neurodevelopment. For this purpose, we designed interactomes and employed transcriptomic data analysis approaches to study the neural tissue of Mus musculus exposed to ethanol prenatally and postnatally, simulating conditions that could lead to FAS development at different life stages. Our results showed that FAS can promote early changes in neurotransmitter release and glutamate equilibrium, as well as an abnormal calcium influx that can lead to neuroinflammation and impaired neurodifferentiation, both extensively connected with vitamin action and metabolism. Genes related to retinoic acid, niacin, vitamin D, and folate metabolism were underexpressed during neurodevelopment and appear to contribute to neuroinflammation progression and impaired synapsis. Our results also indicate that genes coding for tubulin, tubulin-associated proteins, synapse plasticity proteins, and proteins related to neurodifferentiation are extensively affected by ethanol exposure. Finally, we developed a molecular model of how ethanol can affect vitamin metabolism and impair neurodevelopment. PMID:24816220

  7. Kinetic Modeling of Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

    Resat, Haluk; Petzold, Linda; Pettigrew, Michel F.

    2009-04-21

    The dynamics of how its constituent components interact define the spatio-temporal response of a natural system to stimuli. Modeling the kinetics of the processes that represent a biophysical system has long been pursued with the aim of improving our understanding of the studied system. Due to the unique properties of biological systems, in addition to the usual difficulties faced in modeling the dynamics of physical or chemical systems, biological simulations encounter difficulties that result from intrinsic multiscale and stochastic nature of the biological processes. This chapter discusses the implications for simulation of models involving interacting species with very low copy numbers, which often occur in biological systems and give rise to significant relative fluctuations. The conditions necessitating the use of stochastic kinetic simulation methods and the mathematical foundations of the stochastic simulation algorithms are presented. How the well-organized structural hierarchies often seen in biological systems can lead to multiscale problems, and possible ways to address the encountered computational difficulties are discussed. We present the details of the existing kinetic simulation methods, and discuss their strengths and shortcomings. A list of the publicly available kinetic simulation tools and our reflections for future prospects are also provided.

  8. Circadian systems biology in Metazoa.

    Science.gov (United States)

    Lin, Li-Ling; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2015-11-01

    Systems biology, which can be defined as integrative biology, comprises multistage processes that can be used to understand components of complex biological systems of living organisms and provides hierarchical information to decoding life. Using systems biology approaches such as genomics, transcriptomics and proteomics, it is now possible to delineate more complicated interactions between circadian control systems and diseases. The circadian rhythm is a multiscale phenomenon existing within the body that influences numerous physiological activities such as changes in gene expression, protein turnover, metabolism and human behavior. In this review, we describe the relationships between the circadian control system and its related genes or proteins, and circadian rhythm disorders in systems biology studies. To maintain and modulate circadian oscillation, cells possess elaborative feedback loops composed of circadian core proteins that regulate the expression of other genes through their transcriptional activities. The disruption of these rhythms has been reported to be associated with diseases such as arrhythmia, obesity, insulin resistance, carcinogenesis and disruptions in natural oscillations in the control of cell growth. This review demonstrates that lifestyle is considered as a fundamental factor that modifies circadian rhythm, and the development of dysfunctions and diseases could be regulated by an underlying expression network with multiple circadian-associated signals.

  9. Network Analyses in Systems Biology: New Strategies for Dealing with Biological Complexity

    DEFF Research Database (Denmark)

    Green, Sara; Serban, Maria; Scholl, Raphael;

    2017-01-01

    The increasing application of network models to interpret biological systems raises a number of important methodological and epistemological questions. What novel insights can network analysis provide in biology? Are network approaches an extension of or in conflict with mechanistic research...

  10. Nanoscale technology in biological systems

    CERN Document Server

    Greco, Ralph S; Smith, R Lane

    2004-01-01

    Reviewing recent accomplishments in the field of nanobiology Nanoscale Technology in Biological Systems introduces the application of nanoscale matrices to human biology. It focuses on the applications of nanotechnology fabrication to biomedical devices and discusses new physical methods for cell isolation and manipulation and intracellular communication at the molecular level. It also explores the application of nanobiology to cardiovascular diseases, oncology, transplantation, and a range of related disciplines. This book build a strong background in nanotechnology and nanobiology ideal for

  11. Biological and environmental efficiency of high producing dairy systems through application of life cycle analysis

    OpenAIRE

    Ross, Stephen Alexander

    2014-01-01

    Dairy production systems are an important global contributor to anthropogenic greenhouse gas (GHG) emissions including methane (CH4), nitrous oxide (N2O) and carbon dioxide (CO2). Due to the role GHG play in climate change, it is important to investigate ways to minimise their global warming potential (GWP) and to maximise the efficiency of dairy production systems. Finding a balance between improving productivity and suppressing the range and quantity of GHG produced in dairy ...

  12. [Medical applications of systems biology].

    Science.gov (United States)

    Demongeot, Jacques

    2009-01-01

    We illustrate in this review some applications of systems biology in the medical and biological areas. After a brief summary of time scales experienced by medical -observations and of the general scheme of dynamic systems, we describe how some techniques underlying the complex systems theory can be applied to model medical issues in immunology, medical genetics, developmental morphogenesis, biochemistry, epidemiology, telemedecine and multiple platforms of expertise. In concluding, we will discuss the issue of "clinomics" coupling clinical and -omics data in a unique patient-specific file.

  13. Systems biology and cardiac arrhythmias.

    Science.gov (United States)

    Grace, Andrew A; Roden, Dan M

    2012-10-27

    During the past few years, the development of effective, empirical technologies for treatment of cardiac arrhythmias has exceeded the pace at which detailed knowledge of the underlying biology has accumulated. As a result, although some clinical arrhythmias can be cured with techniques such as catheter ablation, drug treatment and prediction of the risk of sudden death remain fairly primitive. The identification of key candidate genes for monogenic arrhythmia syndromes shows that to bring basic biology to the clinic is a powerful approach. Increasingly sophisticated experimental models and methods of measurement, including stem cell-based models of human cardiac arrhythmias, are being deployed to study how perturbations in several biologic pathways can result in an arrhythmia-prone heart. The biology of arrhythmia is largely quantifiable, which allows for systematic analysis that could transform treatment strategies that are often still empirical into management based on molecular evidence.

  14. Equilibrating errors: reliable estimation of information transmission rates in biological systems with spectral analysis-based methods.

    Science.gov (United States)

    Ignatova, Irina; French, Andrew S; Immonen, Esa-Ville; Frolov, Roman; Weckström, Matti

    2014-06-01

    Shannon's seminal approach to estimating information capacity is widely used to quantify information processing by biological systems. However, the Shannon information theory, which is based on power spectrum estimation, necessarily contains two sources of error: time delay bias error and random error. These errors are particularly important for systems with relatively large time delay values and for responses of limited duration, as is often the case in experimental work. The window function type and size chosen, as well as the values of inherent delays cause changes in both the delay bias and random errors, with possibly strong effect on the estimates of system properties. Here, we investigated the properties of these errors using white-noise simulations and analysis of experimental photoreceptor responses to naturalistic and white-noise light contrasts. Photoreceptors were used from several insect species, each characterized by different visual performance, behavior, and ecology. We show that the effect of random error on the spectral estimates of photoreceptor performance (gain, coherence, signal-to-noise ratio, Shannon information rate) is opposite to that of the time delay bias error: the former overestimates information rate, while the latter underestimates it. We propose a new algorithm for reducing the impact of time delay bias error and random error, based on discovering, and then using that size of window, at which the absolute values of these errors are equal and opposite, thus cancelling each other, allowing minimally biased measurement of neural coding.

  15. Systems biology analysis unravels the complementary action of combined rosuvastatin and ezetimibe therapy

    NARCIS (Netherlands)

    Verschuren, L.; Radonjic, M.; Wielinga, P.Y.; Kelder, T.; Kooistra, T.; Ommen, B. van; Kleemann, R.

    2012-01-01

    AIMS: Combination-drug therapy takes advantage of the complementary action of their individual components, thereby potentiating its therapeutic effect. Potential disadvantages include side effects that are not foreseen on basis of the data available from drug monotherapy. Here, we used a systems bio

  16. Fetal Alcohol Syndrome, Chemo-Biology and OMICS: Ethanol Effects on Vitamin Metabolism During Neurodevelopment as Measured by Systems Biology Analysis

    OpenAIRE

    Feltes, Bruno César; de Faria Poloni, Joice; Nunes, Itamar José Guimarães; Bonatto, Diego

    2014-01-01

    Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the...

  17. Systems biology in molecular psychiatry.

    Science.gov (United States)

    Gebicke-Haerter, P J

    2008-09-01

    The last ten to fifteen years have seen a remarkable shift of research strategies from hypothesis-driven, reductionistic to data driven, hypothesis-free approaches. This tendency has become evident after completion of the sequencing of the human genome, when publications under the label systems biology have been skyrocketing. This shift marks a gradual revision of scientific understanding of biological systems. Whilst the former has been component-oriented, precluding elements that do not belong to the hypothesis, the latter try to extract information from the whole system in the first place. Only with this information at hand, data driven strategies develop hypotheses. Data driven strategies unearth the immense complexity of biological systems and, hence, necessitate computer-aided support. Mathematical tools derived from chaos theory appear to be applicable in biological systems, but require significant improvements. The combination of high throughput data collection with in silico modelling of molecular or higher order systems can markedly extend our understanding of onset and progression of diseases. Undoubtedly, systems thinking in brain research is the greatest challenge for the years to come.

  18. Innovative analytical methods for Central Nervous System Drug analysis in biological fluids

    OpenAIRE

    Musenga, Alessandro

    2009-01-01

    During recent years a consistent number of central nervous system (CNS) drugs have been approved and introduced on the market for the treatment of many psychiatric and neurological disorders, including psychosis, depression, Parkinson disease and epilepsy. Despite the great advancements obtained in the treatment of CNS diseases/disorders, partial response to therapy or treatment failure are frequent, at least in part due to poor compliance, but also genetic variability in the metabolism of ps...

  19. Boolean network model for GPR142 against Type 2 diabetes and relative dynamic change ratio analysis using systems and biological circuits approach.

    Science.gov (United States)

    Kaushik, Aman Chandra; Sahi, Shakti

    2015-06-01

    Systems biology addresses challenges in the analysis of genomics data, especially for complex genes and protein interactions using Meta data approach on various signaling pathways. In this paper, we report systems biology and biological circuits approach to construct pathway and identify early gene and protein interactions for predicting GPR142 responses in Type 2 diabetes. The information regarding genes, proteins and other molecules involved in Type 2 diabetes were retrieved from literature and kinetic simulation of GPR142 was carried out in order to determine the dynamic interactions. The major objective of this work was to design a GPR142 biochemical pathway using both systems biology as well as biological circuits synthetically. The term 'synthetically' refers to building biological circuits for cell signaling pathway especially for hormonal pathway disease. The focus of the paper is on logical components and logical circuits whereby using these applications users can create complex virtual circuits. Logic gates process represents only true or false and investigates whether biological regulatory circuits are active or inactive. The basic gates used are AND, NAND, OR, XOR and NOT gates and Integrated circuit composition of many such basic gates and some derived gates. Biological circuits may have a futuristic application in biomedical sciences which may involve placing a micro chip in human cells to modulate the down or up regulation of hormonal disease.

  20. Systems biology approach to bioremediation

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Romy; Wu, Cindy H.; Hazen, Terry C.

    2012-06-01

    Bioremediation has historically been approached as a ‘black box’ in terms of our fundamental understanding. Thus it succeeds and fails, seldom without a complete understanding of why. Systems biology is an integrated research approach to study complex biological systems, by investigating interactions and networks at the molecular, cellular, community, and ecosystem level. The knowledge of these interactions within individual components is fundamental to understanding the dynamics of the ecosystem under investigation. Finally, understanding and modeling functional microbial community structure and stress responses in environments at all levels have tremendous implications for our fundamental understanding of hydrobiogeochemical processes and the potential for making bioremediation breakthroughs and illuminating the ‘black box’.

  1. The response of Chlamydomonas reinhardtii to nitrogen deprivation: a systems biology analysis.

    Science.gov (United States)

    Park, Jeong-Jin; Wang, Hongxia; Gargouri, Mahmoud; Deshpande, Rahul R; Skepper, Jeremy N; Holguin, F Omar; Juergens, Matthew T; Shachar-Hill, Yair; Hicks, Leslie M; Gang, David R

    2015-02-01

    Drastic alteration in macronutrients causes large changes in gene expression in the photosynthetic unicellular alga Chlamydomonas reinhardtii. Preliminary data suggested that cells follow a biphasic response to this change hinging on the initiation of lipid accumulation, and we hypothesized that drastic repatterning of metabolism also followed this biphasic modality. To test this hypothesis, transcriptomic, proteomic, and metabolite changes that occur under nitrogen (N) deprivation were analyzed. Eight sampling times were selected covering the progressive slowing of growth and induction of oil synthesis between 4 and 6 h after N deprivation. Results of the combined, systems-level investigation indicated that C. reinhardtii cells sense and respond on a large scale within 30 min to a switch to N-deprived conditions turning on a largely gluconeogenic metabolic state, which then transitions to a glycolytic stage between 4 and 6 h after N depletion. This nitrogen-sensing system is transduced to carbon- and nitrogen-responsive pathways, leading to down-regulation of carbon assimilation and chlorophyll biosynthesis, and an increase in nitrogen metabolism and lipid biosynthesis. For example, the expression of nearly all the enzymes for assimilating nitrogen from ammonium, nitrate, nitrite, urea, formamide/acetamide, purines, pyrimidines, polyamines, amino acids and proteins increased significantly. Although arginine biosynthesis enzymes were also rapidly up-regulated, arginine pool size changes and isotopic labeling results indicated no increased flux through this pathway.

  2. Theoretical aspects of Systems Biology.

    Science.gov (United States)

    Bizzarri, Mariano; Palombo, Alessandro; Cucina, Alessandra

    2013-05-01

    The natural world consists of hierarchical levels of complexity that range from subatomic particles and molecules to ecosystems and beyond. This implies that, in order to explain the features and behavior of a whole system, a theory might be required that would operate at the corresponding hierarchical level, i.e. where self-organization processes take place. In the past, biological research has focused on questions that could be answered by a reductionist program of genetics. The organism (and its development) was considered an epiphenomenona of its genes. However, a profound rethinking of the biological paradigm is now underway and it is likely that such a process will lead to a conceptual revolution emerging from the ashes of reductionism. This revolution implies the search for general principles on which a cogent theory of biology might rely. Because much of the logic of living systems is located at higher levels, it is imperative to focus on them. Indeed, both evolution and physiology work on these levels. Thus, by no means Systems Biology could be considered a 'simple' 'gradual' extension of Molecular Biology.

  3. Systems biology: the reincarnation of systems theory applied in biology?

    Science.gov (United States)

    Wolkenhauer, O

    2001-09-01

    With the availability of quantitative data on the transcriptome and proteome level, there is an increasing interest in formal mathematical models of gene expression and regulation. International conferences, research institutes and research groups concerned with systems biology have appeared in recent years and systems theory, the study of organisation and behaviour per se, is indeed a natural conceptual framework for such a task. This is, however, not the first time that systems theory has been applied in modelling cellular processes. Notably in the 1960s systems theory and biology enjoyed considerable interest among eminent scientists, mathematicians and engineers. Why did these early attempts vanish from research agendas? Here we shall review the domain of systems theory, its application to biology and the lessons that can be learned from the work of Robert Rosen. Rosen emerged from the early developments in the 1960s as a main critic but also developed a new alternative perspective to living systems, a concept that deserves a fresh look in the post-genome era of bioinformatics.

  4. Systems biology analysis of drivers underlying hallmarks of cancer cell metabolism

    Science.gov (United States)

    Zielinski, Daniel C.; Jamshidi, Neema; Corbett, Austin J.; Bordbar, Aarash; Thomas, Alex; Palsson, Bernhard O.

    2017-01-01

    Malignant transformation is often accompanied by significant metabolic changes. To identify drivers underlying these changes, we calculated metabolic flux states for the NCI60 cell line collection and correlated the variance between metabolic states of these lines with their other properties. The analysis revealed a remarkably consistent structure underlying high flux metabolism. The three primary uptake pathways, glucose, glutamine and serine, are each characterized by three features: (1) metabolite uptake sufficient for the stoichiometric requirement to sustain observed growth, (2) overflow metabolism, which scales with excess nutrient uptake over the basal growth requirement, and (3) redox production, which also scales with nutrient uptake but greatly exceeds the requirement for growth. We discovered that resistance to chemotherapeutic drugs in these lines broadly correlates with the amount of glucose uptake. These results support an interpretation of the Warburg effect and glutamine addiction as features of a growth state that provides resistance to metabolic stress through excess redox and energy production. Furthermore, overflow metabolism observed may indicate that mitochondrial catabolic capacity is a key constraint setting an upper limit on the rate of cofactor production possible. These results provide a greater context within which the metabolic alterations in cancer can be understood.

  5. Systems biology. Conditional density-based analysis of T cell signaling in single-cell data.

    Science.gov (United States)

    Krishnaswamy, Smita; Spitzer, Matthew H; Mingueneau, Michael; Bendall, Sean C; Litvin, Oren; Stone, Erica; Pe'er, Dana; Nolan, Garry P

    2014-11-28

    Cellular circuits sense the environment, process signals, and compute decisions using networks of interacting proteins. To model such a system, the abundance of each activated protein species can be described as a stochastic function of the abundance of other proteins. High-dimensional single-cell technologies, such as mass cytometry, offer an opportunity to characterize signaling circuit-wide. However, the challenge of developing and applying computational approaches to interpret such complex data remains. Here, we developed computational methods, based on established statistical concepts, to characterize signaling network relationships by quantifying the strengths of network edges and deriving signaling response functions. In comparing signaling between naïve and antigen-exposed CD4(+) T lymphocytes, we find that although these two cell subtypes had similarly wired networks, naïve cells transmitted more information along a key signaling cascade than did antigen-exposed cells. We validated our characterization on mice lacking the extracellular-regulated mitogen-activated protein kinase (MAPK) ERK2, which showed stronger influence of pERK on pS6 (phosphorylated-ribosomal protein S6), in naïve cells as compared with antigen-exposed cells, as predicted. We demonstrate that by using cell-to-cell variation inherent in single-cell data, we can derive response functions underlying molecular circuits and drive the understanding of how cells process signals.

  6. Analysis of undergraduate students' conceptual models of a complex biological system across a diverse body of learners

    Science.gov (United States)

    Dirnbeck, Matthew R.

    Biological systems pose a challenge both for learners and teachers because they are complex systems mediated by feedback loops; networks of cause-effect relationships; and non-linear, hierarchical, and emergent properties. Teachers and scientists routinely use models to communicate ideas about complex systems. Model-based pedagogies engage students in model construction as a means of practicing higher-order reasoning skills. One such modeling paradigm describes systems in terms of their structures, behaviors, and functions (SBF). The SBF framework is a simple modeling language that has been used to teach about complex biological systems. Here, we used student-generated SBF models to assess students' causal reasoning in the context of a novel biological problem on an exam. We compared students' performance on the modeling problem, their performance on a set of knowledge/comprehension questions, and their performance on a set of scientific reasoning questions. We found that students who performed well on knowledge and understanding questions also constructed more networked, higher quality models. Previous studies have shown that learners' mental maps increase in complexity with increased expertise. We wanted to investigate if biology students with varying levels of training in biology showed a similar pattern when constructing system models. In a pilot study, we administered the same modeling problem to two additional groups of students: 1) an animal physiology course for students pursuing a major in biology (n=37) and 2) an exercise physiology course for non-majors (n=27). We found that there was no significant difference in model organization across the three student populations, but there was a significant difference in the ability to represent function between the three populations. Between the three groups the non-majors had the lowest function scores, the introductory majors had the middle function scores, and the upper division majors had the highest function

  7. Stochastic simulation in systems biology.

    Science.gov (United States)

    Székely, Tamás; Burrage, Kevin

    2014-11-01

    Natural systems are, almost by definition, heterogeneous: this can be either a boon or an obstacle to be overcome, depending on the situation. Traditionally, when constructing mathematical models of these systems, heterogeneity has typically been ignored, despite its critical role. However, in recent years, stochastic computational methods have become commonplace in science. They are able to appropriately account for heterogeneity; indeed, they are based around the premise that systems inherently contain at least one source of heterogeneity (namely, intrinsic heterogeneity). In this mini-review, we give a brief introduction to theoretical modelling and simulation in systems biology and discuss the three different sources of heterogeneity in natural systems. Our main topic is an overview of stochastic simulation methods in systems biology. There are many different types of stochastic methods. We focus on one group that has become especially popular in systems biology, biochemistry, chemistry and physics. These discrete-state stochastic methods do not follow individuals over time; rather they track only total populations. They also assume that the volume of interest is spatially homogeneous. We give an overview of these methods, with a discussion of the advantages and disadvantages of each, and suggest when each is more appropriate to use. We also include references to software implementations of them, so that beginners can quickly start using stochastic methods for practical problems of interest.

  8. Using a Classroom Response System for Real-Time Data Display and Analysis in Introductory Biology Labs

    Science.gov (United States)

    Hunter, Allison; Rulfs, Jill; Caron, Jessica Marie; Buckholt, Michael Allan

    2010-01-01

    Clickers were used for real-time data collection in two introductory biology laboratory courses so that students could perform statistical analysis on large data sets. Student attitudes toward this use of clickers were surveyed and students were administered a pre- and posttest on statistical content. Capture of large data sets allowed instructors…

  9. [Research progress of cardiac systems biology].

    Science.gov (United States)

    Wang, Juan; Shang, Tong

    2009-04-01

    Systems Biology is one of the most widely discussed fields among emerging post-genomic disciplines. Medical systems biology is an important component of systems biology. The goals of medical systems biology are gaining a complete understanding of human body in normal and disease states. Driven by the great importance of cardiovascular diseases, cardiac systems biology is improving rapidly. This review provides an overview of major themes in the developing field of cardiac systems biology, including some of the high-throughput experiments and strategies used to integrate the datasets, various types of computational approaches used for developing useful quantitative models, and successful examples, future directions of cardiac systems biology.

  10. Systems Biology Toolbox for MATLAB: a computational platform for research in systems biology.

    Science.gov (United States)

    Schmidt, Henning; Jirstrand, Mats

    2006-02-15

    We present a Systems Biology Toolbox for the widely used general purpose mathematical software MATLAB. The toolbox offers systems biologists an open and extensible environment, in which to explore ideas, prototype and share new algorithms, and build applications for the analysis and simulation of biological and biochemical systems. Additionally it is well suited for educational purposes. The toolbox supports the Systems Biology Markup Language (SBML) by providing an interface for import and export of SBML models. In this way the toolbox connects nicely to other SBML-enabled modelling packages. Models are represented in an internal model format and can be described either by entering ordinary differential equations or, more intuitively, by entering biochemical reaction equations. The toolbox contains a large number of analysis methods, such as deterministic and stochastic simulation, parameter estimation, network identification, parameter sensitivity analysis and bifurcation analysis.

  11. Aspergilli: Systems biology and industrial applications

    DEFF Research Database (Denmark)

    Knuf, Christoph; Nielsen, Jens

    2012-01-01

    possible to implement systems biology tools to advance metabolic engineering. These tools include genome-wide transcription analysis and genome-scale metabolic models. Herein, we review achievements in the field and highlight the impact of Aspergillus systems biology on industrial biotechnology....... genetic modifications has enabled the use of metabolic engineering strategies. Genome sequencing of Aspergilli was originally trailing behind developments in the field of bacteria and yeasts, but with the recent availability of genome sequences for several industrially relevant Aspergilli, it has become...

  12. Bridging the gap between systems biology and synthetic biology.

    Science.gov (United States)

    Liu, Di; Hoynes-O'Connor, Allison; Zhang, Fuzhong

    2013-01-01

    Systems biology is an inter-disciplinary science that studies the complex interactions and the collective behavior of a cell or an organism. Synthetic biology, as a technological subject, combines biological science and engineering, allowing the design and manipulation of a system for certain applications. Both systems and synthetic biology have played important roles in the recent development of microbial platforms for energy, materials, and environmental applications. More importantly, systems biology provides the knowledge necessary for the development of synthetic biology tools, which in turn facilitates the manipulation and understanding of complex biological systems. Thus, the combination of systems and synthetic biology has huge potential for studying and engineering microbes, especially to perform advanced tasks, such as producing biofuels. Although there have been very few studies in integrating systems and synthetic biology, existing examples have demonstrated great power in extending microbiological capabilities. This review focuses on recent efforts in microbiological genomics, transcriptomics, proteomics, and metabolomics, aiming to fill the gap between systems and synthetic biology.

  13. Integrative Biological Analysis of the APOE*3-Leiden Transgenic Mouse

    NARCIS (Netherlands)

    Clish, C.B.; Davidov, E.; Oresic, M.; Plasterer, T.N.; Lavine, G.; Londo, T.; Meys, M.; Snell, P.; Stochaj, W.; Adourian, A.; Zhang, X.; Morel, N.; Neumann, E.; Verheij, E.; Vogels, J.T.W.E.; Havekes, L.M.; Afeyan, N.; Regnier, F.; Greef, J. van der; Naylor, S.

    2004-01-01

    Integrative (or systems biology) is a new approach to analyzing biological entities as integrated systems of genetic, genomic, protein, metabolite, cellular, and pathway events that are in flux and interdependent. Here, we demonstrate the application of intregrative biological analysis to a mammalia

  14. System biology of gene regulation.

    Science.gov (United States)

    Baitaluk, Michael

    2009-01-01

    ) questions of biological relevance. Thus systems biology could be treated as such a socioscientific phenomenon and a new approach to both experiments and theory that is defined by the strategy of pursuing integration of complex data about the interactions in biological systems from diverse experimental sources using interdisciplinary tools and personnel.

  15. A systems biology approach to the analysis of subset-specific responses to lipopolysaccharide in dendritic cells.

    Directory of Open Access Journals (Sweden)

    David G Hancock

    Full Text Available Dendritic cells (DCs are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 commitment, generating inducible Tregs, and mediating tolerance. It is believed that distinct DC subsets have evolved to control these different immune outcomes. However, how DC subsets mount different responses to inflammatory and/or tolerogenic signals in order to accomplish their divergent functions remains unclear. Lipopolysaccharide (LPS provides an excellent model for investigating responses in closely related splenic DC subsets, as all subsets express the LPS receptor TLR4 and respond to LPS in vitro. However, previous studies of the LPS-induced DC transcriptome have been performed only on mixed DC populations. Moreover, comparisons of the in vivo response of two closely related DC subsets to LPS stimulation have not been reported in the literature to date. We compared the transcriptomes of murine splenic CD8 and CD11b DC subsets after in vivo LPS stimulation, using RNA-Seq and systems biology approaches. We identified subset-specific gene signatures, which included multiple functional immune mediators unique to each subset. To explain the observed subset-specific differences, we used a network analysis approach. While both DC subsets used a conserved set of transcription factors and major signalling pathways, the subsets showed differential regulation of sets of genes that 'fine-tune' the network Hubs expressed in common. We propose a model in which signalling through common pathway components is 'fine-tuned' by transcriptional control of subset-specific modulators, thus allowing for distinct functional outcomes in closely related DC subsets. We extend this analysis to comparable datasets from the literature and confirm that our model can account for cell subset-specific responses to LPS stimulation in multiple subpopulations in mouse and man.

  16. Carbon nanomaterials in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Pu Chun Ke [Laboratory of Single-Molecule Biophysics and Polymer Physics, Department of Physics and Astronomy, Clemson University, Clemson, SC 29634 (United States); Qiao Rui [Department of Mechanical Engineering, Clemson University, Clemson, SC 29634 (United States)

    2007-09-19

    This paper intends to reflect, from the biophysical viewpoint, our current understanding on interfacing nanomaterials, such as carbon nanotubes and fullerenes, with biological systems. Strategies for improving the solubility, and therefore, the bioavailability of nanomaterials in aqueous solutions are summarized. In particular, the underlining mechanisms of attaching biomacromolecules (DNA, RNA, proteins) and lysophospholipids onto carbon nanotubes and gallic acids onto fullerenes are analyzed. The diffusion and the cellular delivery of RNA-coated carbon nanotubes are characterized using fluorescence microscopy. The translocation of fullerenes across cell membranes is simulated using molecular dynamics to offer new insight into the complex issue of nanotoxicity. To assess the fate of nanomaterials in the environment, the biomodification of lipid-coated carbon nanotubes by the aquatic organism Daphnia magna is discussed. The aim of this paper is to illuminate the need for adopting multidisciplinary approaches in the field study of nanomaterials in biological systems and in the environment. (topical review)

  17. Anion binding in biological systems

    Science.gov (United States)

    Feiters, Martin C.; Meyer-Klaucke, Wolfram; Kostenko, Alexander V.; Soldatov, Alexander V.; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Küpper, Frithjof C.; Hollenstein, Kaspar; Locher, Kaspar P.; Bevers, Loes E.; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

    2009-11-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L3 (2p3/2) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  18. Anion binding in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Feiters, Martin C [Department of Organic Chemistry, Institute for Molecules and Materials, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Meyer-Klaucke, Wolfram [EMBL Hamburg Outstation at DESY, Notkestrasse 85, D-22607 Hamburg (Germany); Kostenko, Alexander V; Soldatov, Alexander V [Faculty of Physics, Southern Federal University, Sorge 5, Rostov-na-Donu, 344090 (Russian Federation); Leblanc, Catherine; Michel, Gurvan; Potin, Philippe [Centre National de la Recherche Scientifique and Universite Pierre et Marie Curie Paris-VI, Station Biologique de Roscoff, Place Georges Teissier, BP 74, F-29682 Roscoff cedex, Bretagne (France); Kuepper, Frithjof C [Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban, Argyll PA37 1QA, Scotland (United Kingdom); Hollenstein, Kaspar; Locher, Kaspar P [Institute of Molecular Biology and Biophysics, ETH Zuerich, Schafmattstrasse 20, Zuerich, 8093 (Switzerland); Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R, E-mail: m.feiters@science.ru.n [Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft (Netherlands)

    2009-11-15

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L{sub 3} (2p{sub 3/2}) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  19. Neutron scattering for the analysis of biological structures. Brookhaven symposia in biology. Number 27

    Energy Technology Data Exchange (ETDEWEB)

    Schoenborn, B P [ed.

    1976-01-01

    Sessions were included on neutron scattering and biological structure analysis, protein crystallography, neutron scattering from oriented systems, solution scattering, preparation of deuterated specimens, inelastic scattering, data analysis, experimental techniques, and instrumentation. Separate entries were made for the individual papers.

  20. Decavanadate effects in biological systems.

    Science.gov (United States)

    Aureliano, Manuel; Gândara, Ricardo M C

    2005-05-01

    Vanadium biological studies often disregarded the formation of decameric vanadate species known to interact, in vitro, with high-affinity with many proteins such as myosin and sarcoplasmic reticulum calcium pump and also to inhibit these biochemical systems involved in energy transduction. Moreover, very few in vivo animal studies involving vanadium consider the contribution of decavanadate to vanadium biological effects. Recently, it has been shown that an acute exposure to decavanadate but not to other vanadate oligomers induced oxidative stress and a different fate in vanadium intracellular accumulation. Several markers of oxidative stress analyzed on hepatic and cardiac tissue were monitored after in vivo effect of an acute exposure (12, 24 h and 7 days), to a sub-lethal concentration (5 mM; 1 mg/kg) of two vanadium solutions ("metavanadate" and "decavanadate"). It was observed that "decavanadate" promote different effects than other vanadate oligomers in catalase activity, glutathione content, lipid peroxidation, mitochondrial superoxide anion production and vanadium accumulation, whereas both solutions seem to equally depress reactive oxygen species (ROS) production as well as total intracellular reducing power. Vanadium is accumulated in mitochondria in particular when "decavanadate" is administered. These recent findings, that are now summarized, point out the decameric vanadate species contributions to in vivo and in vitro effects induced by vanadium in biological systems.

  1. Systems biology analysis of Brucella infected Peyer's patch reveals rapid invasion with modest transient perturbations of the host transcriptome.

    Directory of Open Access Journals (Sweden)

    Carlos A Rossetti

    Full Text Available Brucella melitensis causes the most severe and acute symptoms of all Brucella species in human beings and infects hosts primarily through the oral route. The epithelium covering domed villi of jejunal-ileal Peyer's patches is an important site of entry for several pathogens, including Brucella. Here, we use the calf ligated ileal loop model to study temporal in vivo Brucella-infected host molecular and morphological responses. Our results document Brucella bacteremia occurring within 30 min after intraluminal inoculation of the ileum without histopathologic traces of lesions. Based on a system biology Dynamic Bayesian Network modeling approach (DBN of microarray data, a very early transient perturbation of the host enteric transcriptome was associated with the initial host response to Brucella contact that is rapidly averted allowing invasion and dissemination. A detailed analysis revealed active expression of Syndecan 2, Integrin alpha L and Integrin beta 2 genes, which may favor initial Brucella adhesion. Also, two intestinal barrier-related pathways (Tight Junction and Trefoil Factors Initiated Mucosal Healing were significantly repressed in the early stage of infection, suggesting subversion of mucosal epithelial barrier function to facilitate Brucella transepithelial migration. Simultaneously, the strong activation of the innate immune response pathways would suggest that the host mounts an appropriate protective immune response; however, the expression of the two key genes that encode innate immunity anti-Brucella cytokines such as TNF-α and IL12p40 were not significantly changed throughout the study. Furthermore, the defective expression of Toll-Like Receptor Signaling pathways may partially explain the lack of proinflammatory cytokine production and consequently the absence of morphologically detectable inflammation at the site of infection. Cumulatively, our results indicate that the in vivo pathogenesis of the early infectious process

  2. Nonlinear dynamics in biological systems

    CERN Document Server

    Carballido-Landeira, Jorge

    2016-01-01

    This book presents recent research results relating to applications of nonlinear dynamics, focusing specifically on four topics of wide interest: heart dynamics, DNA/RNA, cell mobility, and proteins. The book derives from the First BCAM Workshop on Nonlinear Dynamics in Biological Systems, held in June 2014 at the Basque Center of Applied Mathematics (BCAM). At this international meeting, researchers from different but complementary backgrounds, including molecular dynamics, physical chemistry, bio-informatics and biophysics, presented their most recent results and discussed the future direction of their studies using theoretical, mathematical modeling and experimental approaches. Such was the level of interest stimulated that the decision was taken to produce this publication, with the organizers of the event acting as editors. All of the contributing authors are researchers working on diverse biological problems that can be approached using nonlinear dynamics. The book will appeal especially to applied math...

  3. An Automated Biological Dosimetry System

    Science.gov (United States)

    Lorch, T.; Bille, J.; Frieben, M.; Stephan, G.

    1986-04-01

    The scoring of structural chromosome aberrations in peripheral human blood lymphocytes can be used in biological dosimetry to estimate the radiation dose which an individual has received. Especially the dicentric chromosome is a rather specific indicator for an exposure to ionizing radiation. For statistical reasons, in the low dose range a great number of cells must be analysed, which is a very tedious task. The resulting high cost of a biological dose estimation limits the application of this method to cases of suspected irradiation for which physical dosimetry is not possible or not sufficient. Therefore an automated system has been designed to do the major part of the routine work. It uses a standard light microscope with motorized scanning stage, a Plumbicon TV-camera, a real-time hardware preprocessor, a binary and a grey level image buffer system. All computations are performed by a very powerful multi-microprocessor-system (POLYP) based on a MIMD-architecture. The task of the automated system can be split in finding the metaphases (see Figure 1) at low microscope magnification and scoring dicentrics at high magnification. The metaphase finding part has been completed and is now in routine use giving good results. The dicentric scoring part is still under development.

  4. Small RNA biology is systems biology.

    Science.gov (United States)

    Jost, Daniel; Nowojewski, Andrzej; Levine, Erel

    2011-01-01

    During the last decade small regulatory RNA (srRNA) emerged as central players in the regulation of gene expression in all kingdoms of life. Multiple pathways for srRNA biogenesis and diverse mechanisms of gene regulation may indicate that srRNA regulation evolved independently multiple times. However, small RNA pathways share numerous properties, including the ability of a single srRNA to regulate multiple targets. Some of the mechanisms of gene regulation by srRNAs have significant effect on the abundance of free srRNAs that are ready to interact with new targets. This results in indirect interactions among seemingly unrelated genes, as well as in a crosstalk between different srRNA pathways. Here we briefly review and compare the major srRNA pathways, and argue that the impact of srRNA is always at the system level. We demonstrate how a simple mathematical model can ease the discussion of governing principles. To demonstrate these points we review a few examples from bacteria and animals.

  5. [Network structures in biological systems].

    Science.gov (United States)

    Oleskin, A V

    2013-01-01

    Network structures (networks) that have been extensively studied in the humanities are characterized by cohesion, a lack of a central control unit, and predominantly fractal properties. They are contrasted with structures that contain a single centre (hierarchies) as well as with those whose elements predominantly compete with one another (market-type structures). As far as biological systems are concerned, their network structures can be subdivided into a number of types involving different organizational mechanisms. Network organization is characteristic of various structural levels of biological systems ranging from single cells to integrated societies. These networks can be classified into two main subgroups: (i) flat (leaderless) network structures typical of systems that are composed of uniform elements and represent modular organisms or at least possess manifest integral properties and (ii) three-dimensional, partly hierarchical structures characterized by significant individual and/or intergroup (intercaste) differences between their elements. All network structures include an element that performs structural, protective, and communication-promoting functions. By analogy to cell structures, this element is denoted as the matrix of a network structure. The matrix includes a material and an immaterial component. The material component comprises various structures that belong to the whole structure and not to any of its elements per se. The immaterial (ideal) component of the matrix includes social norms and rules regulating network elements' behavior. These behavioral rules can be described in terms of algorithms. Algorithmization enables modeling the behavior of various network structures, particularly of neuron networks and their artificial analogs.

  6. Tunable promoters in systems biology

    DEFF Research Database (Denmark)

    Mijakovic, Ivan; Petranovic, Dina; Jensen, Peter Ruhdal

    2005-01-01

    The construction of synthetic promoter libraries has represented a major breakthrough in systems biology, enabling the subtle tuning of enzyme activities. A number of tools are now available that allow the modulation of gene expression and the detection of changes in expression patterns. But, how...... does one choose the correct promoter and what are the appropriate methods for reading promoter strength? Furthermore, how fine should the tuning of gene expression be for some specific applications and how can the simultaneous and individual tuning of multiple genes be achieved? Some recent studies...

  7. Systems biology of Microbial Communities

    Energy Technology Data Exchange (ETDEWEB)

    Navid, A; Ghim, C; Fenley, A; Yoon, S; Lee, S; Almaas, E

    2008-04-11

    Microbes exist naturally in a wide range of environments, spanning the extremes of high acidity and high temperature to soil and the ocean, in communities where their interactions are significant. We present a practical discussion of three different approaches for modeling microbial communities: rate equations, individual-based modeling, and population dynamics. We illustrate the approaches with detailed examples. Each approach is best fit to different levels of system representation, and they have different needs for detailed biological input. Thus, this set of approaches is able to address the operation and function of microbial communities on a wide range of organizational levels.

  8. Systems biology of cancer biomarker detection.

    Science.gov (United States)

    Mitra, Sanga; Das, Smarajit; Chakrabarti, Jayprokas

    2013-01-01

    Cancer systems-biology is an ever-growing area of research due to explosion of data; how to mine these data and extract useful information is the problem. To have an insight on carcinogenesis one need to systematically mine several resources, such as databases, microarray and next-generation sequences. This review encompasses management and analysis of cancer data, databases construction and data deposition, whole transcriptome and genome comparison, analysing results from high throughput experiments to uncover cellular pathways and molecular interactions, and the design of effective algorithms to identify potential biomarkers. Recent technical advances such as ChIP-on-chip, ChIP-seq and RNA-seq can be applied to get epigenetic information transformed into a high-throughput endeavour to which systems biology and bioinformatics are making significant inroads. The data from ENCODE and GENCODE projects available through UCSC genome browser can be considered as benchmark for comparison and meta-analysis. A pipeline for integrating next generation sequencing data, microarray data, and putting them together with the existing database is discussed. The understanding of cancer genomics is changing the way we approach cancer diagnosis and treatment. To give a better understanding of utilizing available resources' we have chosen oral cancer to show how and what kind of analysis can be done. This review is a computational genomic primer that provides a bird's eye view of computational and bioinformatics' tools currently available to perform integrated genomic and system biology analyses of several carcinoma.

  9. Systems biology characterization of engineered tissues.

    Science.gov (United States)

    Rajagopalan, Padmavathy; Kasif, Simon; Murali, T M

    2013-01-01

    Tissue engineering and molecular systems biology are inherently interdisciplinary fields that have been developed independently so far. In this review, we first provide a brief introduction to tissue engineering and to molecular systems biology. Next, we highlight some prominent applications of systems biology techniques in tissue engineering. Finally, we outline research directions that can successfully blend these two fields. Through these examples, we propose that experimental and computational advances in molecular systems biology can lead to predictive models of bioengineered tissues that enhance our understanding of bioengineered systems. In turn, the unique challenges posed by tissue engineering will usher in new experimental techniques and computational advances in systems biology.

  10. SysBioCube: A Data Warehouse and Integrative Data Analysis Platform Facilitating Systems Biology Studies of Disorders of Military Relevance.

    Science.gov (United States)

    Chowbina, Sudhir; Hammamieh, Rasha; Kumar, Raina; Chakraborty, Nabarun; Yang, Ruoting; Mudunuri, Uma; Jett, Marti; Palma, Joseph M; Stephens, Robert

    2013-01-01

    SysBioCube is an integrated data warehouse and analysis platform for experimental data relating to diseases of military relevance developed for the US Army Medical Research and Materiel Command Systems Biology Enterprise (SBE). It brings together, under a single database environment, pathophysio-, psychological, molecular and biochemical data from mouse models of post-traumatic stress disorder and (pre-) clinical data from human PTSD patients.. SysBioCube will organize, centralize and normalize this data and provide an access portal for subsequent analysis to the SBE. It provides new or expanded browsing, querying and visualization to provide better understanding of the systems biology of PTSD, all brought about through the integrated environment. We employ Oracle database technology to store the data using an integrated hierarchical database schema design. The web interface provides researchers with systematic information and option to interrogate the profiles of pan-omics component across different data types, experimental designs and other covariates.

  11. A lab-on-a-chip device for analysis of amlodipine in biological fluids using peroxyoxalate chemiluminescence system.

    Science.gov (United States)

    Al Lawati, Haider A J; Al-Nadabi, Mira M; Varma, Gouri B; Suliman, Fakhr Eldin O; Al-Abri, Hasnaa

    2014-12-01

    A highly sensitive, rapid and economical method for the determination of amlodipine (AM) in biological fluids was developed using a peroxyoxalate chemiluminescence (CL) system in a lab-on-a-chip device. Peroxyoxalate-CL is an indirect type of CL that allows the detection of native fluorophores or compounds derivatized with fluorescent labels. Here, fluorescamine was reacted with AM, and the derivatization product was used in a bis-(2,4,6-trichlorophenyl)oxalate-CL system. Fluorescamine reacts selectively with aliphatic primary amine at neutral or basic pH. As most of the calcium channel blocker and many cardiovascular drugs do not contain primary amine, the developed method is highly selective. The parameters that influenced the CL signal intensity were studied carefully. These included the chip geometry, pH, concentration of reagents used and flow rates. Moreover, we confirmed our previous observation about the effects of imidazole, which is commonly used in the bis-(2,4,6-trichlorophenyl)oxalate-CL system as a catalyst, and found that the signal was significantly improved when imidazole was absent. Under optimized conditions, a calibration curve was obtained with a linear range (10-100 µg/L). The limit of detection was 3 µg/L, while the limit of quantification was 10 µg/L. Finally the method was applied for the determination of AM in biological fluids successfully.

  12. Gradient Matching Methods for Computational Inference in Mechanistic Models for Systems Biology: A Review and Comparative Analysis.

    Science.gov (United States)

    Macdonald, Benn; Husmeier, Dirk

    2015-01-01

    Parameter inference in mathematical models of biological pathways, expressed as coupled ordinary differential equations (ODEs), is a challenging problem in contemporary systems biology. Conventional methods involve repeatedly solving the ODEs by numerical integration, which is computationally onerous and does not scale up to complex systems. Aimed at reducing the computational costs, new concepts based on gradient matching have recently been proposed in the computational statistics and machine learning literature. In a preliminary smoothing step, the time series data are interpolated; then, in a second step, the parameters of the ODEs are optimized, so as to minimize some metric measuring the difference between the slopes of the tangents to the interpolants, and the time derivatives from the ODEs. In this way, the ODEs never have to be solved explicitly. This review provides a concise methodological overview of the current state-of-the-art methods for gradient matching in ODEs, followed by an empirical comparative evaluation based on a set of widely used and representative benchmark data.

  13. Quantum Effects in Biological Systems

    Science.gov (United States)

    Roy, Sisir

    2014-07-01

    The debates about the trivial and non-trivial effects in biological systems have drawn much attention during the last decade or so. What might these non-trivial sorts of quantum effects be? There is no consensus so far among the physicists and biologists regarding the meaning of "non-trivial quantum effects". However, there is no doubt about the implications of the challenging research into quantum effects relevant to biology such as coherent excitations of biomolecules and photosynthesis, quantum tunneling of protons, van der Waals forces, ultrafast dynamics through conical intersections, and phonon-assisted electron tunneling as the basis for our sense of smell, environment assisted transport of ions and entanglement in ion channels, role of quantum vacuum in consciousness. Several authors have discussed the non-trivial quantum effects and classified them into four broad categories: (a) Quantum life principle; (b) Quantum computing in the brain; (c) Quantum computing in genetics; and (d) Quantum consciousness. First, I will review the above developments. I will then discuss in detail the ion transport in the ion channel and the relevance of quantum theory in brain function. The ion transport in the ion channel plays a key role in information processing by the brain.

  14. Integrating systems biology models and biomedical ontologies

    Directory of Open Access Journals (Sweden)

    de Bono Bernard

    2011-08-01

    Full Text Available Abstract Background Systems biology is an approach to biology that emphasizes the structure and dynamic behavior of biological systems and the interactions that occur within them. To succeed, systems biology crucially depends on the accessibility and integration of data across domains and levels of granularity. Biomedical ontologies were developed to facilitate such an integration of data and are often used to annotate biosimulation models in systems biology. Results We provide a framework to integrate representations of in silico systems biology with those of in vivo biology as described by biomedical ontologies and demonstrate this framework using the Systems Biology Markup Language. We developed the SBML Harvester software that automatically converts annotated SBML models into OWL and we apply our software to those biosimulation models that are contained in the BioModels Database. We utilize the resulting knowledge base for complex biological queries that can bridge levels of granularity, verify models based on the biological phenomenon they represent and provide a means to establish a basic qualitative layer on which to express the semantics of biosimulation models. Conclusions We establish an information flow between biomedical ontologies and biosimulation models and we demonstrate that the integration of annotated biosimulation models and biomedical ontologies enables the verification of models as well as expressive queries. Establishing a bi-directional information flow between systems biology and biomedical ontologies has the potential to enable large-scale analyses of biological systems that span levels of granularity from molecules to organisms.

  15. Analysis and prediction of pathways in HeLa cells by integrating biological levels of organization with systems-biology approaches.

    Directory of Open Access Journals (Sweden)

    Juan Carlos Higareda-Almaraz

    Full Text Available It has recently begun to be considered that cancer is a systemic disease and that it must be studied at every level of complexity using many of the currently available approaches, including high-throughput technologies and bioinformatics. To achieve such understanding in cervical cancer, we collected information on gene, protein and phosphoprotein expression of the HeLa cell line and performed a comprehensive analysis of the different signaling pathways, transcription networks and metabolic events in which they participate. A total expression analysis by RNA-Seq of the HeLa cell line showed that 19,974 genes were transcribed. Of these, 3,360 were over-expressed, and 2,129 under-expressed when compared to the NHEK cell line. A protein-protein interaction network was derived from the over-expressed genes and used to identify central elements and, together with the analysis of over-represented transcription factor motifs, to predict active signaling and regulatory pathways. This was further validated by Metal-Oxide Affinity Chromatography (MOAC and Tandem Mass Spectrometry (MS/MS assays which retrieved phosphorylated proteins. The 14-3-3 family members emerge as important regulators in carcinogenesis and as possible clinical targets. We observed that the different over- and under-regulated pathways in cervical cancer could be interrelated through elements that participate in crosstalks, therefore belong to what we term "meta-pathways". Additionally, we highlighted the relations of each one of the differentially represented pathways to one or more of the ten hallmarks of cancer. These features could be maintained in many other types of cancer, regardless of mutations or genomic rearrangements, and favor their robustness, adaptations and the evasion of tissue control. Probably, this could explain why cancer cells are not eliminated by selective pressure and why therapy trials directed against molecular targets are not as effective as expected.

  16. Towards Systems Biology of Mycotoxin Regulation

    OpenAIRE

    Christof Rampitsch; Rajagopal Subramaniam

    2013-01-01

    Systems biology is a scientific approach that integrates many scientific disciplines to develop a comprehensive understanding of biological phenomena, thus allowing the prediction and accurate simulation of complex biological behaviors. It may be presumptuous to write about toxin regulation at the level of systems biology, but the last decade of research is leading us closer than ever to this approach. Past research has delineated multiple levels of regulation in the pathways leading to the b...

  17. Peroxisystem: harnessing systems cell biology to study peroxisomes.

    Science.gov (United States)

    Schuldiner, Maya; Zalckvar, Einat

    2015-04-01

    In recent years, high-throughput experimentation with quantitative analysis and modelling of cells, recently dubbed systems cell biology, has been harnessed to study the organisation and dynamics of simple biological systems. Here, we suggest that the peroxisome, a fascinating dynamic organelle, can be used as a good candidate for studying a complete biological system. We discuss several aspects of peroxisomes that can be studied using high-throughput systematic approaches and be integrated into a predictive model. Such approaches can be used in the future to study and understand how a more complex biological system, like a cell and maybe even ultimately a whole organism, works.

  18. Co-design in synthetic biology: a system-level analysis of the development of an environmental sensing device.

    Science.gov (United States)

    Ball, David A; Lux, Matthew W; Graef, Russell R; Peterson, Matthew W; Valenti, Jane D; Dileo, John; Peccoud, Jean

    2010-01-01

    The concept of co-design is common in engineering, where it is necessary, for example, to determine the optimal partitioning between hardware and software of the implementation of a system features. Here we propose to adapt co-design methodologies for synthetic biology. As a test case, we have designed an environmental sensing device that detects the presence of three chemicals, and returns an output only if at least two of the three chemicals are present. We show that the logical operations can be implemented in three different design domains: (1) the transcriptional domain using synthetically designed hybrid promoters, (2) the protein domain using bi-molecular fluorescence complementation, and (3) the fluorescence domain using spectral unmixing and relying on electronic processing. We discuss how these heterogeneous design strategies could be formalized to develop co-design algorithms capable of identifying optimal designs meeting user specifications.

  19. Systems biology in the context of big data and networks.

    Science.gov (United States)

    Altaf-Ul-Amin, Md; Afendi, Farit Mochamad; Kiboi, Samuel Kuria; Kanaya, Shigehiko

    2014-01-01

    Science is going through two rapidly changing phenomena: one is the increasing capabilities of the computers and software tools from terabytes to petabytes and beyond, and the other is the advancement in high-throughput molecular biology producing piles of data related to genomes, transcriptomes, proteomes, metabolomes, interactomes, and so on. Biology has become a data intensive science and as a consequence biology and computer science have become complementary to each other bridged by other branches of science such as statistics, mathematics, physics, and chemistry. The combination of versatile knowledge has caused the advent of big-data biology, network biology, and other new branches of biology. Network biology for instance facilitates the system-level understanding of the cell or cellular components and subprocesses. It is often also referred to as systems biology. The purpose of this field is to understand organisms or cells as a whole at various levels of functions and mechanisms. Systems biology is now facing the challenges of analyzing big molecular biological data and huge biological networks. This review gives an overview of the progress in big-data biology, and data handling and also introduces some applications of networks and multivariate analysis in systems biology.

  20. Biologically inspired autonomouse system; Seibutsugata jiritsu system

    Energy Technology Data Exchange (ETDEWEB)

    Yuta, S. [Tsukuba Univ., Ibaraki (Japan)

    1996-04-10

    The intelligence robot was begun to try to make up a machine to imitate the human intelligent actions as a model of human thoughts. However, robots created with the results of traditional artificial intelligence based on the logical knowledge impression and logic judgement have been found to be unable to realize the usual actions conducted by humans and animals even though having superior brains or remembrances. Research on `The biological inspired autonomous robots` in the intelligence robots, aims to peruse a method to realize on a machine not for high class intelligence capable to execute logical thoughts down by human but for intelligence corresponding to ability response to environment autonomously and to live in a given environment which is had even by animals except human being. Here is examined on the non-human biological type robot and its intelligence under a center of research on the biological inspired autonomous system in the intelligence robots, and is outlined on their research field. 2 refs., 1 fig.

  1. Robust design of biological circuits: evolutionary systems biology approach.

    Science.gov (United States)

    Chen, Bor-Sen; Hsu, Chih-Yuan; Liou, Jing-Jia

    2011-01-01

    Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter fluctuations and environmental molecular noise from the cellular context in the host cell. Based on evolutionary systems biology algorithm, the design parameters of target gene circuits can evolve to specific values in order to robustly track a desired biologic function in spite of intrinsic and environmental noise. The fitness function is selected to be inversely proportional to the tracking error so that the evolutionary biological circuit can achieve the optimal tracking mimicking the evolutionary process of a gene circuit. Finally, several design examples are given in silico with the Monte Carlo simulation to illustrate the design procedure and to confirm the robust performance of the proposed design method. The result shows that the designed gene circuits can robustly track desired behaviors with minimal errors even with nontrivial intrinsic and external noise.

  2. Adaptable data management for systems biology investigations

    Directory of Open Access Journals (Sweden)

    Burdick David

    2009-03-01

    Full Text Available Abstract Background Within research each experiment is different, the focus changes and the data is generated from a continually evolving barrage of technologies. There is a continual introduction of new techniques whose usage ranges from in-house protocols through to high-throughput instrumentation. To support these requirements data management systems are needed that can be rapidly built and readily adapted for new usage. Results The adaptable data management system discussed is designed to support the seamless mining and analysis of biological experiment data that is commonly used in systems biology (e.g. ChIP-chip, gene expression, proteomics, imaging, flow cytometry. We use different content graphs to represent different views upon the data. These views are designed for different roles: equipment specific views are used to gather instrumentation information; data processing oriented views are provided to enable the rapid development of analysis applications; and research project specific views are used to organize information for individual research experiments. This management system allows for both the rapid introduction of new types of information and the evolution of the knowledge it represents. Conclusion Data management is an important aspect of any research enterprise. It is the foundation on which most applications are built, and must be easily extended to serve new functionality for new scientific areas. We have found that adopting a three-tier architecture for data management, built around distributed standardized content repositories, allows us to rapidly develop new applications to support a diverse user community.

  3. Spatial Aspects in Biological System Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Resat, Haluk; Costa, Michelle N.; Shankaran, Harish

    2011-01-30

    Mathematical models of the dynamical properties of biological systems aim to improve our understanding of the studied system with the ultimate goal of being able to predict system responses in the absence of experimentation. Despite the enormous advances that have been made in biological modeling and simulation, the inherently multiscale character of biological systems and the stochasticity of biological processes continue to present significant computational and conceptual challenges. Biological systems often consist of well-organized structural hierarchies, which inevitably lead to multiscale problems. This chapter introduces and discusses the advantages and shortcomings of several simulation methods that are being used by the scientific community to investigate the spatio-temporal properties of model biological systems. We first describe the foundations of the methods and then describe their relevance and possible application areas with illustrative examples from our own research. Possible ways to address the encountered computational difficulties are also discussed.

  4. Applicability of Computational Systems Biology in Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning; Hadrup, Niels; Audouze, Karine Marie Laure

    2014-01-01

    Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources...... and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search...... be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method...

  5. Set membership experimental design for biological systems

    Directory of Open Access Journals (Sweden)

    Marvel Skylar W

    2012-03-01

    Full Text Available Abstract Background Experimental design approaches for biological systems are needed to help conserve the limited resources that are allocated for performing experiments. The assumptions used when assigning probability density functions to characterize uncertainty in biological systems are unwarranted when only a small number of measurements can be obtained. In these situations, the uncertainty in biological systems is more appropriately characterized in a bounded-error context. Additionally, effort must be made to improve the connection between modelers and experimentalists by relating design metrics to biologically relevant information. Bounded-error experimental design approaches that can assess the impact of additional measurements on model uncertainty are needed to identify the most appropriate balance between the collection of data and the availability of resources. Results In this work we develop a bounded-error experimental design framework for nonlinear continuous-time systems when few data measurements are available. This approach leverages many of the recent advances in bounded-error parameter and state estimation methods that use interval analysis to generate parameter sets and state bounds consistent with uncertain data measurements. We devise a novel approach using set-based uncertainty propagation to estimate measurement ranges at candidate time points. We then use these estimated measurements at the candidate time points to evaluate which candidate measurements furthest reduce model uncertainty. A method for quickly combining multiple candidate time points is presented and allows for determining the effect of adding multiple measurements. Biologically relevant metrics are developed and used to predict when new data measurements should be acquired, which system components should be measured and how many additional measurements should be obtained. Conclusions The practicability of our approach is illustrated with a case study. This

  6. Set membership experimental design for biological systems

    Science.gov (United States)

    2012-01-01

    Background Experimental design approaches for biological systems are needed to help conserve the limited resources that are allocated for performing experiments. The assumptions used when assigning probability density functions to characterize uncertainty in biological systems are unwarranted when only a small number of measurements can be obtained. In these situations, the uncertainty in biological systems is more appropriately characterized in a bounded-error context. Additionally, effort must be made to improve the connection between modelers and experimentalists by relating design metrics to biologically relevant information. Bounded-error experimental design approaches that can assess the impact of additional measurements on model uncertainty are needed to identify the most appropriate balance between the collection of data and the availability of resources. Results In this work we develop a bounded-error experimental design framework for nonlinear continuous-time systems when few data measurements are available. This approach leverages many of the recent advances in bounded-error parameter and state estimation methods that use interval analysis to generate parameter sets and state bounds consistent with uncertain data measurements. We devise a novel approach using set-based uncertainty propagation to estimate measurement ranges at candidate time points. We then use these estimated measurements at the candidate time points to evaluate which candidate measurements furthest reduce model uncertainty. A method for quickly combining multiple candidate time points is presented and allows for determining the effect of adding multiple measurements. Biologically relevant metrics are developed and used to predict when new data measurements should be acquired, which system components should be measured and how many additional measurements should be obtained. Conclusions The practicability of our approach is illustrated with a case study. This study shows that our

  7. Introducing systems biology for nursing science.

    Science.gov (United States)

    Founds, Sandra A

    2009-07-01

    Systems biology expands on general systems theory as the "omics'' era rapidly progresses. Although systems biology has been institutionalized as an interdisciplinary framework in the biosciences, it is not yet apparent in nursing. This article introduces systems biology for nursing science by presenting an overview of the theory. This framework for the study of organisms from molecular to environmental levels includes iterations of computational modeling, experimentation, and theory building. Synthesis of complex biological processes as whole systems rather than isolated parts is emphasized. Pros and cons of systems biology are discussed, and relevance of systems biology to nursing is described. Nursing research involving molecular, physiological, or biobehavioral questions may be guided by and contribute to the developing science of systems biology. Nurse scientists can proactively incorporate systems biology into their investigations as a framework for advancing the interdisciplinary science of human health care. Systems biology has the potential to advance the research and practice goals of the National Institute for Nursing Research in the National Institutes of Health Roadmap initiative.

  8. Metabolic Reconstruction of Setaria italica: A Systems Biology Approach for Integrating Tissue-Specific Omics and Pathway Analysis of Bioenergy Grasses.

    Science.gov (United States)

    de Oliveira Dal'Molin, Cristiana G; Orellana, Camila; Gebbie, Leigh; Steen, Jennifer; Hodson, Mark P; Chrysanthopoulos, Panagiotis; Plan, Manuel R; McQualter, Richard; Palfreyman, Robin W; Nielsen, Lars K

    2016-01-01

    The urgent need for major gains in industrial crops productivity and in biofuel production from bioenergy grasses have reinforced attention on understanding C4 photosynthesis. Systems biology studies of C4 model plants may reveal important features of C4 metabolism. Here we chose foxtail millet (Setaria italica), as a C4 model plant and developed protocols to perform systems biology studies. As part of the systems approach, we have developed and used a genome-scale metabolic reconstruction in combination with the use of multi-omics technologies to gain more insights into the metabolism of S. italica. mRNA, protein, and metabolite abundances, were measured in mature and immature stem/leaf phytomers, and the multi-omics data were integrated into the metabolic reconstruction framework to capture key metabolic features in different developmental stages of the plant. RNA-Seq reads were mapped to the S. italica resulting for 83% coverage of the protein coding genes of S. italica. Besides revealing similarities and differences in central metabolism of mature and immature tissues, transcriptome analysis indicates significant gene expression of two malic enzyme isoforms (NADP- ME and NAD-ME). Although much greater expression levels of NADP-ME genes are observed and confirmed by the correspondent protein abundances in the samples, the expression of multiple genes combined to the significant abundance of metabolites that participates in C4 metabolism of NAD-ME and NADP-ME subtypes suggest that S. italica may use mixed decarboxylation modes of C4 photosynthetic pathways under different plant developmental stages. The overall analysis also indicates different levels of regulation in mature and immature tissues in carbon fixation, glycolysis, TCA cycle, amino acids, fatty acids, lignin, and cellulose syntheses. Altogether, the multi-omics analysis reveals different biological entities and their interrelation and regulation over plant development. With this study, we demonstrated

  9. Metabolic Reconstruction of Setaria italica: A Systems Biology Approach for Integrating Tissue-Specific Omics and Pathway Analysis of Bioenergy Grasses

    Science.gov (United States)

    de Oliveira Dal'Molin, Cristiana G.; Orellana, Camila; Gebbie, Leigh; Steen, Jennifer; Hodson, Mark P.; Chrysanthopoulos, Panagiotis; Plan, Manuel R.; McQualter, Richard; Palfreyman, Robin W.; Nielsen, Lars K.

    2016-01-01

    The urgent need for major gains in industrial crops productivity and in biofuel production from bioenergy grasses have reinforced attention on understanding C4 photosynthesis. Systems biology studies of C4 model plants may reveal important features of C4 metabolism. Here we chose foxtail millet (Setaria italica), as a C4 model plant and developed protocols to perform systems biology studies. As part of the systems approach, we have developed and used a genome-scale metabolic reconstruction in combination with the use of multi-omics technologies to gain more insights into the metabolism of S. italica. mRNA, protein, and metabolite abundances, were measured in mature and immature stem/leaf phytomers, and the multi-omics data were integrated into the metabolic reconstruction framework to capture key metabolic features in different developmental stages of the plant. RNA-Seq reads were mapped to the S. italica resulting for 83% coverage of the protein coding genes of S. italica. Besides revealing similarities and differences in central metabolism of mature and immature tissues, transcriptome analysis indicates significant gene expression of two malic enzyme isoforms (NADP- ME and NAD-ME). Although much greater expression levels of NADP-ME genes are observed and confirmed by the correspondent protein abundances in the samples, the expression of multiple genes combined to the significant abundance of metabolites that participates in C4 metabolism of NAD-ME and NADP-ME subtypes suggest that S. italica may use mixed decarboxylation modes of C4 photosynthetic pathways under different plant developmental stages. The overall analysis also indicates different levels of regulation in mature and immature tissues in carbon fixation, glycolysis, TCA cycle, amino acids, fatty acids, lignin, and cellulose syntheses. Altogether, the multi-omics analysis reveals different biological entities and their interrelation and regulation over plant development. With this study, we demonstrated

  10. Language Based Techniques for Systems Biology

    DEFF Research Database (Denmark)

    Pilegaard, Henrik

    calculi have similarly been used for the study of bio-chemical reactive systems. In this dissertation it is argued that techniques rooted in the theory and practice of programming languages, language based techniques if you will, constitute a strong basis for the investigation of models of biological.......g., the effects of receptor defects or drug delivery mechanisms. The property of sequential realisability. which is closely related to the function of biochemical pathways, is addressed by a variant of traditional Data Flow Analysis (DFA). This so-called ‘Pathway Analysis’ computes safe approximations to the set...

  11. Information theory applications for biological sequence analysis.

    Science.gov (United States)

    Vinga, Susana

    2014-05-01

    Information theory (IT) addresses the analysis of communication systems and has been widely applied in molecular biology. In particular, alignment-free sequence analysis and comparison greatly benefited from concepts derived from IT, such as entropy and mutual information. This review covers several aspects of IT applications, ranging from genome global analysis and comparison, including block-entropy estimation and resolution-free metrics based on iterative maps, to local analysis, comprising the classification of motifs, prediction of transcription factor binding sites and sequence characterization based on linguistic complexity and entropic profiles. IT has also been applied to high-level correlations that combine DNA, RNA or protein features with sequence-independent properties, such as gene mapping and phenotype analysis, and has also provided models based on communication systems theory to describe information transmission channels at the cell level and also during evolutionary processes. While not exhaustive, this review attempts to categorize existing methods and to indicate their relation with broader transversal topics such as genomic signatures, data compression and complexity, time series analysis and phylogenetic classification, providing a resource for future developments in this promising area.

  12. Morphogenesis and pattern formation in biological systems experiments and models

    CERN Document Server

    Noji, Sumihare; Ueno, Naoto; Maini, Philip

    2003-01-01

    A central goal of current biology is to decode the mechanisms that underlie the processes of morphogenesis and pattern formation. Concerned with the analysis of those phenomena, this book covers a broad range of research fields, including developmental biology, molecular biology, plant morphogenesis, ecology, epidemiology, medicine, paleontology, evolutionary biology, mathematical biology, and computational biology. In Morphogenesis and Pattern Formation in Biological Systems: Experiments and Models, experimental and theoretical aspects of biology are integrated for the construction and investigation of models of complex processes. This collection of articles on the latest advances by leading researchers not only brings together work from a wide spectrum of disciplines, but also provides a stepping-stone to the creation of new areas of discovery.

  13. Using the Unified Modelling Language (UML) to guide the systemic description of biological processes and systems.

    Science.gov (United States)

    Roux-Rouquié, Magali; Caritey, Nicolas; Gaubert, Laurent; Rosenthal-Sabroux, Camille

    2004-07-01

    One of the main issues in Systems Biology is to deal with semantic data integration. Previously, we examined the requirements for a reference conceptual model to guide semantic integration based on the systemic principles. In the present paper, we examine the usefulness of the Unified Modelling Language (UML) to describe and specify biological systems and processes. This makes unambiguous representations of biological systems, which would be suitable for translation into mathematical and computational formalisms, enabling analysis, simulation and prediction of these systems behaviours.

  14. Marine biological data and information management system

    Digital Repository Service at National Institute of Oceanography (India)

    Sarupria, J.S.

    Indian National Oceanographic Data Centre (INODC) is engaged in developing a marine biological data and information management system (BIODIMS). This system will contain the information on zooplankton in the water column, zoobenthic biomass...

  15. Biosensors for antioxidant evaluation in biological systems.

    Science.gov (United States)

    Mello, Lucilene Dornelles; Kisner, Alexandre; Goulart, Marilia Oliveira Fonseca; Kubota, Lauro Tatsuo

    2013-02-01

    The prevention of oxidative reactions in a biological medium as well as the role of reactive oxygen species (ROS) in chronic degenerative diseases are questions that continue to be investigated. Electrochemical biosensors have shown attractive features to evaluate the oxidative stress condition at a level comparable to chromatographic and spectroscopic techniques. The biosensors developed so far are based on direct analysis of specific indicators such as biomarkers of oxidative stress on the monitoring of reactive oxygen species the free radicals in cells or tissues, aiming to obtain a correlation between the index obtained from these indicators with the oxidative stress levels in cells. In this review we will provide an overview of the development of electrochemical biosensors to evaluate the content of antioxidants and reactive oxygen species in physiological systems. Some discussion regarding the analysis of antioxidant capacity at the single cell level is also presented.

  16. Genomes, Phylogeny, and Evolutionary Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Medina, Monica

    2005-03-25

    With the completion of the human genome and the growing number of diverse genomes being sequenced, a new age of evolutionary research is currently taking shape. The myriad of technological breakthroughs in biology that are leading to the unification of broad scientific fields such as molecular biology, biochemistry, physics, mathematics and computer science are now known as systems biology. Here I present an overview, with an emphasis on eukaryotes, of how the postgenomics era is adopting comparative approaches that go beyond comparisons among model organisms to shape the nascent field of evolutionary systems biology.

  17. HTML帮助系统在生物统计分析平台中的应用%Application of HTML help system in biological statistic analysis platform

    Institute of Scientific and Technical Information of China (English)

    吴延熊

    2001-01-01

    This paper discusses characteristics of the new help system basedon HTML,and puts forward unit file“CallHHelp” which can be used to call HTML help by Delphi that is developing tool of biological statistic analysis platform.The core method of this unit file is to map HTML help commands to corresponding Win help commands.Finally,the biological statistic analysis platform can correctly call HTML help system by the unit file.%论述了基于HTML的新型帮助系统的特点,提出一个可以在生物统计分析平台的开发工具Delphi中调用HTML帮助系统的单元文件CallHHelp。该调用单元的核心思想是将HTML帮助命令映射到对应的WinHelp命令上,从而实现生物统计分析平台对HTML帮助系统的正确响应。图1参3

  18. Integrative Systems Biology: Elucidating Complex Traits

    DEFF Research Database (Denmark)

    Pers, Tune Hannes

    product itself. My doctoral studies have been focused on the development of integrative approaches to identify systemic risk-modifying and disease-causing patterns. ey have been rooted in the hypothesis that data integration of complementary data sets may yield additional etiologic insights compared...... traits and disease. e esis is structured as follows. Chapter  presents a few introductory remarks to integrative systems biology, and Chapter  gives a brief description of human genetic variation and GWA analysis. Chapters - present the main topics in the esis (integrative methodologies...... to analyses conducted within a single type of data. e first line of research presented here outlines two integrative methodologies designed to identify etiological pathways and susceptibility genes. In Paper I, my coworkers and I present an integrative approach that interrogates protein complexes...

  19. Nonlinear analysis of biological sequences

    Energy Technology Data Exchange (ETDEWEB)

    Torney, D.C.; Bruno, W.; Detours, V. [and others

    1998-11-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The main objectives of this project involved deriving new capabilities for analyzing biological sequences. The authors focused on tabulating the statistical properties exhibited by Human coding DNA sequences and on techniques of inferring the phylogenetic relationships among protein sequences related by descent.

  20. Applicability of computational systems biology in toxicology.

    Science.gov (United States)

    Kongsbak, Kristine; Hadrup, Niels; Audouze, Karine; Vinggaard, Anne Marie

    2014-07-01

    Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search. However, computational systems biology offers more advantages than providing a high-throughput literature search; it may form the basis for establishment of hypotheses on potential links between environmental chemicals and human diseases, which would be very difficult to establish experimentally. This is possible due to the existence of comprehensive databases containing information on networks of human protein-protein interactions and protein-disease associations. Experimentally determined targets of the specific chemical of interest can be fed into these networks to obtain additional information that can be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method in the hypothesis-generating phase of toxicological research.

  1. Stochastic transport processes in discrete biological systems

    CERN Document Server

    Frehland, Eckart

    1982-01-01

    These notes are in part based on a course for advanced students in the applications of stochastic processes held in 1978 at the University of Konstanz. These notes contain the results of re­ cent studies on the stochastic description of ion transport through biological membranes. In particular, they serve as an introduction to an unified theory of fluctuations in complex biological transport systems. We emphasize that the subject of this volume is not to introduce the mathematics of stochastic processes but to present a field of theoretical biophysics in which stochastic methods are important. In the last years the study of membrane noise has become an important method in biophysics. Valuable information on the ion transport mechanisms in membranes can be obtained from noise analysis. A number of different processes such as the opening and closing of ion channels have been shown to be sources of the measured current or voltage fluctuations. Bio­ logical 'transport systems can be complex. For example, the tr...

  2. Bioinformatics resource manager v2.3: an integrated software environment for systems biology with microRNA and cross-species analysis tools

    Directory of Open Access Journals (Sweden)

    Tilton Susan C

    2012-11-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are noncoding RNAs that direct post-transcriptional regulation of protein coding genes. Recent studies have shown miRNAs are important for controlling many biological processes, including nervous system development, and are highly conserved across species. Given their importance, computational tools are necessary for analysis, interpretation and integration of high-throughput (HTP miRNA data in an increasing number of model species. The Bioinformatics Resource Manager (BRM v2.3 is a software environment for data management, mining, integration and functional annotation of HTP biological data. In this study, we report recent updates to BRM for miRNA data analysis and cross-species comparisons across datasets. Results BRM v2.3 has the capability to query predicted miRNA targets from multiple databases, retrieve potential regulatory miRNAs for known genes, integrate experimentally derived miRNA and mRNA datasets, perform ortholog mapping across species, and retrieve annotation and cross-reference identifiers for an expanded number of species. Here we use BRM to show that developmental exposure of zebrafish to 30 uM nicotine from 6–48 hours post fertilization (hpf results in behavioral hyperactivity in larval zebrafish and alteration of putative miRNA gene targets in whole embryos at developmental stages that encompass early neurogenesis. We show typical workflows for using BRM to integrate experimental zebrafish miRNA and mRNA microarray datasets with example retrievals for zebrafish, including pathway annotation and mapping to human ortholog. Functional analysis of differentially regulated (p Conclusions BRM provides the ability to mine complex data for identification of candidate miRNAs or pathways that drive phenotypic outcome and, therefore, is a useful hypothesis generation tool for systems biology. The miRNA workflow in BRM allows for efficient processing of multiple miRNA and mRNA datasets in a single

  3. Carbon Nanotubes – Interactions with Biological Systems

    OpenAIRE

    Reis, Joana; Capela-Silva, Fernando; Potes, José; Fonseca, Alexandra; Oliveira, Mónica; Kanagaraj, Subramani; Marques, António Torres

    2011-01-01

    his book chapter discusses the prospective biomedical applications of carbon nanotubes based materials, the impact of carbon nanotubes properties in the interaction with biological systems. Protein adsorption, impact on cell viability and cytokine production are explored. Potential respiratory and dermal toxicity are reviewed, as the difficulties on studying the biological response. In face of recent studies, special attention is drawn upon promising orthopaedic use.

  4. Biological Systems, Energy Sources, and Biology Teaching. Biology and Human Welfare.

    Science.gov (United States)

    Tribe, Michael; Pritchard, Alan J.

    This five-chapter document (part of a series on biology and human welfare) focuses on biological systems as energy sources and on the teaching of this subject area. Chapter 1 discusses various topics related to energy and ecology, including biomass, photosynthesis and world energy balances, energy flow through ecosystems, and others. Chapter 2…

  5. Topological data analysis of biological aggregation models.

    Science.gov (United States)

    Topaz, Chad M; Ziegelmeier, Lori; Halverson, Tom

    2015-01-01

    We apply tools from topological data analysis to two mathematical models inspired by biological aggregations such as bird flocks, fish schools, and insect swarms. Our data consists of numerical simulation output from the models of Vicsek and D'Orsogna. These models are dynamical systems describing the movement of agents who interact via alignment, attraction, and/or repulsion. Each simulation time frame is a point cloud in position-velocity space. We analyze the topological structure of these point clouds, interpreting the persistent homology by calculating the first few Betti numbers. These Betti numbers count connected components, topological circles, and trapped volumes present in the data. To interpret our results, we introduce a visualization that displays Betti numbers over simulation time and topological persistence scale. We compare our topological results to order parameters typically used to quantify the global behavior of aggregations, such as polarization and angular momentum. The topological calculations reveal events and structure not captured by the order parameters.

  6. Biological Sabatier reaction with CFD analysis

    Science.gov (United States)

    Leonzio, Grazia

    2016-12-01

    The biological Sabatier reaction is a suitable option for the future energy storage. In this research a computational fluid dynamics analysis is carried out to study the mixing inside the anaerobic digester, to evaluate the gas to liquid mass transfer and the efficiency of the reaction. A detailed modeling about the hydrodynamics and mixing is developed: the standard k-ɛ mixture turbulence model and the Eulerian-Eulerian approach are used to simulate the flow inside the anaerobic digestion. The system mixing uses external sludge re-circulating pumps. Results of simulations show that with higher liquid velocity there are higher mass to transfer from gas to liquid and turbulent dissipation rate. The future construction of the anaerobic digester will provide the obtained results.

  7. Modeling and Simulation Tools: From Systems Biology to Systems Medicine.

    Science.gov (United States)

    Olivier, Brett G; Swat, Maciej J; Moné, Martijn J

    2016-01-01

    Modeling is an integral component of modern biology. In this chapter we look into the role of the model, as it pertains to Systems Medicine, and the software that is required to instantiate and run it. We do this by comparing the development, implementation, and characteristics of tools that have been developed to work with two divergent methodologies: Systems Biology and Pharmacometrics. From the Systems Biology perspective we consider the concept of "Software as a Medical Device" and what this may imply for the migration of research-oriented, simulation software into the domain of human health.In our second perspective, we see how in practice hundreds of computational tools already accompany drug discovery and development at every stage of the process. Standardized exchange formats are required to streamline the model exchange between tools, which would minimize translation errors and reduce the required time. With the emergence, almost 15 years ago, of the SBML standard, a large part of the domain of interest is already covered and models can be shared and passed from software to software without recoding them. Until recently the last stage of the process, the pharmacometric analysis used in clinical studies carried out on subject populations, lacked such an exchange medium. We describe a new emerging exchange format in Pharmacometrics which covers the non-linear mixed effects models, the standard statistical model type used in this area. By interfacing these two formats the entire domain can be covered by complementary standards and subsequently the according tools.

  8. Stress and toxicity of biologically important transition metals (Co, Ni, Cu and Zn) on phytoplankton in a tropical freshwater system: An investigation with pigment analysis by HPLC

    Digital Repository Service at National Institute of Oceanography (India)

    Chakraborty, P.; Babu, P.V.R.; Acharyya, T.; Bandyopadhyay, D.

    Stress and toxicity of four biologically important transition metals (Co, Ni, Cu and Zn) on phytoplankton in Godavari River (a tropical freshwater system) were studied to understand the fate of phytoplankton of freshwater if it receives metal...

  9. Integrated systems biology analysis of transcriptomes reveals candidate genes for acidity control in developing fruits of sweet orange (Citrus sinensis L. Osbeck

    Directory of Open Access Journals (Sweden)

    Dingquan eHuang

    2016-04-01

    Full Text Available Organic acids, such as citrate and malate, are important contributors for the sensory traits of fleshy fruits. Although their biosynthesis has been illustrated, regulatory mechanisms of acid accumulation remain to be dissected. To provide transcriptional architecture and identify candidate genes for citrate accumulation in fruits, we have selected for transcriptome analysis four varieties of sweet orange (Citrus sinensis L. Osbeck with varying fruit acidity, Succari (acidless, Bingtang (low acid, and Newhall and Xinhui (normal acid. Fruits of these varieties at 45 days post anthesis (DPA, which corresponds to Stage I (cell division, had similar acidity, but they displayed differential acid accumulation at 142 DPA (Stage II, cell expansion. Transcriptomes of fruits at 45 and 142 DPA were profiled using RNA sequencing and analyzed with three different algorithms (Pearson correlation, gene coexpression network and surrogate variable analysis. Our network analysis shows that the acid-correlated genes belong to three distinct network modules. Several of these candidate fruit acidity genes encode regulatory proteins involved in transport (such as AH10, degradation (such as APD2 and transcription (such as AIL6 and act as hubs in the citrate accumulation gene networks. Taken together, our integrated systems biology analysis has provided new insights into the fruit citrate accumulation gene network and led to the identification of candidate genes likely associated with the fruit acidity control.

  10. Mathematical aspects of pattern formation in biological systems

    CERN Document Server

    Wei, Juncheng

    2013-01-01

    This monograph is concerned with the mathematical analysis of patterns which are encountered in biological systems. It summarises, expands and relates results obtained in the field during the last fifteen years. It also links the results to biological applications and highlights their relevance to phenomena in nature. Of particular concern are large-amplitude patterns far from equilibrium in biologically relevant models.The approach adopted in the monograph is based on the following paradigms:• Examine the existence of spiky steady states in reaction-diffusion systems and select as observabl

  11. Role of SPI-1 secreted effectors in acute bovine response to Salmonella enterica Serovar Typhimurium: a systems biology analysis approach.

    Directory of Open Access Journals (Sweden)

    Sara D Lawhon

    Full Text Available Salmonella enterica Serovar Typhimurium (S. Typhimurium causes enterocolitis with diarrhea and polymorphonuclear cell (PMN influx into the intestinal mucosa in humans and calves. The Salmonella Type III Secretion System (T3SS encoded at Pathogenicity Island I translocates Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into epithelial cells and is required for induction of diarrhea. These effector proteins act together to induce intestinal fluid secretion and transcription of C-X-C chemokines, recruiting PMNs to the infection site. While individual molecular interactions of the effectors with cultured host cells have been characterized, their combined role in intestinal fluid secretion and inflammation is less understood. We hypothesized that comparison of the bovine intestinal mucosal response to wild type Salmonella and a SipA, SopABDE2 effector mutant relative to uninfected bovine ileum would reveal heretofore unidentified diarrhea-associated host cellular pathways. To determine the coordinated effects of these virulence factors, a bovine ligated ileal loop model was used to measure responses to wild type S. Typhimurium (WT and a ΔsipA, sopABDE2 mutant (MUT across 12 hours of infection using a bovine microarray. Data were analyzed using standard microarray analysis and a dynamic bayesian network modeling approach (DBN. Both analytical methods confirmed increased expression of immune response genes to Salmonella infection and novel gene expression. Gene expression changes mapped to 219 molecular interaction pathways and 1620 gene ontology groups. Bayesian network modeling identified effects of infection on several interrelated signaling pathways including MAPK, Phosphatidylinositol, mTOR, Calcium, Toll-like Receptor, CCR3, Wnt, TGF-β, and Regulation of Actin Cytoskeleton and Apoptosis that were used to model of host-pathogen interactions. Comparison of WT and MUT demonstrated significantly different patterns of host response

  12. Micro and nanoplatforms for biological cell analysis

    DEFF Research Database (Denmark)

    Svendsen, Winnie Edith; Castillo, Jaime; Moresco, Jacob Lange

    2010-01-01

    In this paper some of the technological platforms developed in our group for biological cell analysis will be highlighted. The paper first presents a short introduction pinpointing the advantages of using micro and nano technology in cellular studies. The issues of requiring transient analysis...

  13. Carbon-13 NMR spectroscopy of biological systems

    CERN Document Server

    Beckmann, Nicolau

    1995-01-01

    This book is intended to provide an in-depth understanding of 13C NMR as a tool in biological research. 13C NMR has provided unique information concerning complex biological systems, from proteins and nucleic acids to animals and humans. The subjects addressed include multidimensional heteronuclear techniques for structural studies of molecules in the liquid and solid states, the investigation of interactions in model membranes, the elucidation of metabolic pathwaysin vitro and in vivo on animals, and noninvasive metabolic studies performed on humans. The book is a unique mix of NMR methods and biological applications which makes it a convenient reference for those interested in research in this interdisciplinary area of physics, chemistry, biology, and medicine.Key Features* An interdisciplinary text with emphasis on both 13C NMR methodology and the relevant biological and biomedical issues* State-of-the-art 13C NMR techniques are described; Whenever possible, their advantages over other approaches are empha...

  14. Systems biology: leading the revolution in ecotoxicology.

    Science.gov (United States)

    Garcia-Reyero, Natàlia; Perkins, Edward J

    2011-02-01

    The rapid development of new technologies such as transcriptomics, proteomics, and metabolomics (Omics) are changing the way ecotoxicology is practiced. The data deluge has begun with genomes of over 65 different aquatic species that are currently being sequenced, and many times that number with at least some level of transcriptome sequencing. Integrating these top-down methodologies is an essential task in the field of systems biology. Systems biology is a biology-based interdisciplinary field that focuses on complex interactions in biological systems, with the intent to model and discover emergent properties of the system. Recent studies demonstrate that Omics technologies provide valuable insight into ecotoxicity, both in laboratory exposures with model organisms and with animals exposed in the field. However, these approaches require a context of the whole animal and population to be relevant. Powerful approaches using reverse engineering to determine interacting networks of genes, proteins, or biochemical reactions are uncovering unique responses to toxicants. Modeling efforts in aquatic animals are evolving to interrelate the interacting networks of a system and the flow of information linking these elements. Just as is happening in medicine, systems biology approaches that allow the integration of many different scales of interaction and information are already driving a revolution in understanding the impacts of pollutants on aquatic systems.

  15. Software for systems biology: from tools to integrated platforms.

    Science.gov (United States)

    Ghosh, Samik; Matsuoka, Yukiko; Asai, Yoshiyuki; Hsin, Kun-Yi; Kitano, Hiroaki

    2011-11-03

    Understanding complex biological systems requires extensive support from software tools. Such tools are needed at each step of a systems biology computational workflow, which typically consists of data handling, network inference, deep curation, dynamical simulation and model analysis. In addition, there are now efforts to develop integrated software platforms, so that tools that are used at different stages of the workflow and by different researchers can easily be used together. This Review describes the types of software tools that are required at different stages of systems biology research and the current options that are available for systems biology researchers. We also discuss the challenges and prospects for modelling the effects of genetic changes on physiology and the concept of an integrated platform.

  16. Geostatistics and spatial analysis in biological anthropology.

    Science.gov (United States)

    Relethford, John H

    2008-05-01

    A variety of methods have been used to make evolutionary inferences based on the spatial distribution of biological data, including reconstructing population history and detection of the geographic pattern of natural selection. This article provides an examination of geostatistical analysis, a method used widely in geology but which has not often been applied in biological anthropology. Geostatistical analysis begins with the examination of a variogram, a plot showing the relationship between a biological distance measure and the geographic distance between data points and which provides information on the extent and pattern of spatial correlation. The results of variogram analysis are used for interpolating values of unknown data points in order to construct a contour map, a process known as kriging. The methods of geostatistical analysis and discussion of potential problems are applied to a large data set of anthropometric measures for 197 populations in Ireland. The geostatistical analysis reveals two major sources of spatial variation. One pattern, seen for overall body and craniofacial size, shows an east-west cline most likely reflecting the combined effects of past population dispersal and settlement. The second pattern is seen for craniofacial height and shows an isolation by distance pattern reflecting rapid spatial changes in the midlands region of Ireland, perhaps attributable to the genetic impact of the Vikings. The correspondence of these results with other analyses of these data and the additional insights generated from variogram analysis and kriging illustrate the potential utility of geostatistical analysis in biological anthropology.

  17. Biological Robustness: Paradigms, Mechanisms, and Systems Principles

    Directory of Open Access Journals (Sweden)

    James Michael Whitacre

    2012-05-01

    Full Text Available Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g. mutational, environmental are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior.

  18. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

    Mashayekhi, Kaveh; Hall, Vanessa; Freude, Kristine

    2016-01-01

    Recent breakthroughs in stem cell biology have accelerated research in the area of regenerative medicine. Over the past years, it has become possible to derive patient-specific stem cells which can be used to generate different cell populations for potential cell therapy. Systems biological...... modeling of stem cell pluripotency and differentiation have largely been based on prior knowledge of signaling pathways, gene regulatory networks, and epigenetic factors. However, there is a great need to extend the complexity of the modeling and to integrate different types of data, which would further...... improve systems biology and its uses in the field. In this chapter, we first give a general background on stem cell biology and regenerative medicine. Stem cell potency is introduced together with the hierarchy of stem cells ranging from pluripotent embryonic stem cells (ESCs) and induced pluripotent stem...

  19. Natural production of biological optical systems

    Science.gov (United States)

    Choi, Seung Ho; Kim, Young L.

    2015-03-01

    Synthesis and production in nature often provide ideas to design and fabricate advanced biomimetic photonic materials and structures, leading to excellent physical properties and enhanced performance. In addition, the recognition and utilization of natural or biological substances have been typical routes to develop biocompatible and biodegradable materials for medical applications. In this respect, biological lasers utilizing such biomaterials and biostructures have been received considerable attention, given a variety of implications and potentials for bioimaging, biosensing, implantation, and therapy. However, without relying on industrial facilities, eco-friendly massive production of such optical components or systems has not yet been investigated. We show examples of bioproduction of biological lasers using agriculture and fisheries. We anticipate that such approaches will open new possibilities for scalable eco-friendly `green' production of biological photonics components and systems.

  20. Computational Methods for Quality Check, Preprocessing and Normalization of RNA-Seq Data for Systems Biology and Analysis

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Kadarmideen, Haja N.

    2016-01-01

    is the complexity of the RNA-Seq data analysis. Furthermore, numerous biases can arise from RNA-Seq technology, and these biases have to be identified and removed properly in order to obtain accurate results. Nowadays, many tools have been developed which allow to perform each step without high-level programming...

  1. Computer Simulation and Computabiblity of Biological Systems

    CERN Document Server

    Baianu, I C

    2004-01-01

    The ability to simulate a biological organism by employing a computer is related to the ability of the computer to calculate the behavior of such a dynamical system, or the "computability" of the system. However, the two questions of computability and simulation are not equivalent. Since the question of computability can be given a precise answer in terms of recursive functions, automata theory and dynamical systems, it will be appropriate to consider it first. The more elusive question of adequate simulation of biological systems by a computer will be then addressed and a possible connection between the two answers given will be considered as follows. A symbolic, algebraic-topological "quantum computer" (as introduced in Baianu, 1971b) is here suggested to provide one such potential means for adequate biological simulations based on QMV Quantum Logic and meta-Categorical Modeling as for example in a QMV-based, Quantum-Topos (Baianu and Glazebrook,2004.

  2. Computational systems biology in cancer brain metastasis.

    Science.gov (United States)

    Peng, Huiming; Tan, Hua; Zhao, Weiling; Jin, Guangxu; Sharma, Sambad; Xing, Fei; Watabe, Kounosuke; Zhou, Xiaobo

    2016-01-01

    Brain metastases occur in 20-40% of patients with advanced malignancies. A better understanding of the mechanism of this disease will help us to identify novel therapeutic strategies. In this review, we will discuss the systems biology approaches used in this area, including bioinformatics and mathematical modeling. Bioinformatics has been used for identifying the molecular mechanisms driving brain metastasis and mathematical modeling methods for analyzing dynamics of a system and predicting optimal therapeutic strategies. We will illustrate the strategies, procedures, and computational techniques used for studying systems biology in cancer brain metastases. We will give examples on how to use a systems biology approach to analyze a complex disease. Some of the approaches used to identify relevant networks, pathways, and possibly biomarkers in metastasis will be reviewed into details. Finally, certain challenges and possible future directions in this area will also be discussed.

  3. Tunable promoters in synthetic and systems biology

    DEFF Research Database (Denmark)

    Dehli, Tore; Solem, Christian; Jensen, Peter Ruhdal

    2012-01-01

    in synthetic biology. A number of tools exist to manipulate the steps in between gene sequence and functional protein in living cells, but out of these the most straight-forward approach is to alter the gene expression level by manipulating the promoter sequence. Some of the promoter tuning tools available......Synthetic and systems biologists need standardized, modular and orthogonal tools yielding predictable functions in vivo. In systems biology such tools are needed to quantitatively analyze the behavior of biological systems while the efficient engineering of artificial gene networks is central...... for accomplishing such altered gene expression levels are discussed here along with examples of their use, and ideas for new tools are described. The road ahead looks very promising for synthetic and systems biologists as tools to achieve just about anything in terms of tuning and timing multiple gene expression...

  4. Ins and outs of systems biology vis-à-vis molecular biology: continuation or clear cut?

    Science.gov (United States)

    De Backer, Philippe; De Waele, Danny; Van Speybroeck, Linda

    2010-03-01

    The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology 'revolutionizes' molecular biology and 'transcends' its assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology's use of modelling and bioinformatics, and by its scale enlargement.

  5. Conditional robustness analysis for fragility discovery and target identification in biochemical networks and in cancer systems biology

    OpenAIRE

    Bianconi, Fortunato; Baldelli, Elisa; Luovini, Vienna; Petricoin, Emanuel F.; Crinò, Lucio; Valigi, Paolo

    2015-01-01

    Background The study of cancer therapy is a key issue in the field of oncology research and the development of target therapies is one of the main problems currently under investigation. This is particularly relevant in different types of tumor where traditional chemotherapy approaches often fail, such as lung cancer. Results We started from the general definition of robustness introduced by Kitano and applied it to the analysis of dynamical biochemical networks, proposing a new algorithm bas...

  6. Pancreatic Beta Cell G-Protein Coupled Receptors and Second Messenger Interactions: A Systems Biology Computational Analysis.

    Science.gov (United States)

    Fridlyand, Leonid E; Philipson, Louis H

    2016-01-01

    Insulin secretory in pancreatic beta-cells responses to nutrient stimuli and hormonal modulators include multiple messengers and signaling pathways with complex interdependencies. Here we present a computational model that incorporates recent data on glucose metabolism, plasma membrane potential, G-protein-coupled-receptors (GPCR), cytoplasmic and endoplasmic reticulum calcium dynamics, cAMP and phospholipase C pathways that regulate interactions between second messengers in pancreatic beta-cells. The values of key model parameters were inferred from published experimental data. The model gives a reasonable fit to important aspects of experimentally measured metabolic and second messenger concentrations and provides a framework for analyzing the role of metabolic, hormones and neurotransmitters changes on insulin secretion. Our analysis of the dynamic data provides support for the hypothesis that activation of Ca2+-dependent adenylyl cyclases play a critical role in modulating the effects of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and catecholamines. The regulatory properties of adenylyl cyclase isoforms determine fluctuations in cytoplasmic cAMP concentration and reveal a synergistic action of glucose, GLP-1 and GIP on insulin secretion. On the other hand, the regulatory properties of phospholipase C isoforms determine the interaction of glucose, acetylcholine and free fatty acids (FFA) (that act through the FFA receptors) on insulin secretion. We found that a combination of GPCR agonists activating different messenger pathways can stimulate insulin secretion more effectively than a combination of GPCR agonists for a single pathway. This analysis also suggests that the activators of GLP-1, GIP and FFA receptors may have a relatively low risk of hypoglycemia in fasting conditions whereas an activator of muscarinic receptors can increase this risk. This computational analysis demonstrates that study of second messenger

  7. System biology analysis of long-term effect and mechanism of Bufei Yishen on COPD revealed by system pharmacology and 3-omics profiling

    Science.gov (United States)

    Li, Jiansheng; Zhao, Peng; Yang, Liping; Li, Ya; Tian, Yange; Li, Suyun

    2016-01-01

    System pharmacology identified 195 potential targets of Bufei Yishen formula (BYF), and BYF was proven to have a short-term therapeutic effect on chronic obstructive pulmonary disease (COPD) rats previously. However, the long-term effect and mechanism of BYF on COPD is still unclear. Herein, we explored its long-term effect and underlying mechanism at system level. We administered BYF to COPD rats from week 9 to 20, and found that BYF could prevent COPD by inhibiting the inflammatory cytokines expression, protease-antiprotease imbalance and collagen deposition on week 32. Then, using transcriptomics, proteomics and metabolomics analysis, we identified significant regulated genes, proteins and metabolites in lung tissues of COPD and BYF-treated rats, which could be mainly attributed to oxidoreductase-antioxidant activity, focal adhesion, tight junction or lipid metabolism. Finally, based on the comprehensive analysis of system pharmacology target, transcript, protein and metabolite data sets, we found a number of genes, proteins, metabolites regulated in BYF-treated rats and the target proteins of BYF were involved in lipid metabolism, inflammatory response, oxidative stress and focal adhension. In conclusion, BYF exerts long-term therapeutic action on COPD probably through modulating the lipid metabolism, oxidative stress, cell junction and inflammatory response pathways at system level. PMID:27146975

  8. Nanoscale analysis of unstained biological specimens in water without radiation damage using high-resolution frequency transmission electric-field system based on FE-SEM.

    Science.gov (United States)

    Ogura, Toshihiko

    2015-04-10

    Scanning electron microscopy (SEM) has been widely used to examine biological specimens of bacteria, viruses and proteins. Until now, atmospheric and/or wet biological specimens have been examined using various atmospheric holders or special equipment involving SEM. Unfortunately, they undergo heavy radiation damage by the direct electron beam. In addition, images of unstained biological samples in water yield poor contrast. We recently developed a new analytical technology involving a frequency transmission electric-field (FTE) method based on thermionic SEM. This method is suitable for high-contrast imaging of unstained biological specimens. Our aim was to optimise the method. Here we describe a high-resolution FTE system based on field-emission SEM; it allows for imaging and nanoscale examination of various biological specimens in water without radiation damage. The spatial resolution is 8 nm, which is higher than 41 nm of the existing FTE system. Our new method can be easily utilised for examination of unstained biological specimens including bacteria, viruses and protein complexes. Furthermore, our high-resolution FTE system can be used for diverse liquid samples across a broad range of scientific fields, e.g. nanoparticles, nanotubes and organic and catalytic materials.

  9. The development of synthetic biology: a patent analysis.

    Science.gov (United States)

    van Doren, Davy; Koenigstein, Stefan; Reiss, Thomas

    2013-12-01

    In the past decades, synthetic biology has gained interest regarding research and development efforts within the biotechnology domain. However, it is unclear to what extent synthetic biology has matured already into being commercially exploitable. By means of a patent analysis, this study shows that there is an increasing trend regarding synthetic biology related patent applications. The majority of retrieved patents relates to innovations facilitating the realisation of synthetic biology through improved understanding of biological systems. In addition, there is increased activity concerning the development of synthetic biology based applications. When looking at potential application areas, the majority of synthetic biology patents seems most relevant for the medical, energy and industrial sector. Furthermore, the analysis shows that most activity has been carried out by the USA, with Japan and a number of European countries considerably trailing behind. In addition, both universities and companies are major patent applicant actor types. The results presented here form a starting point for follow-up studies concerning the identification of drivers explaining the observed patent application trends in synthetic biology.

  10. Leaving out control groups: an internal contrast analysis of gene expression profiles in atrial fibrillation patients--a systems biology approach to clinical categorization.

    Science.gov (United States)

    Vanhoutte, Kurt; de Asmundis, Carlo; Francesconi, Anna; Figysl, Jurgen; Steurs, Griet; Boussy, Tim; Roos, Markus; Mueller, Andreas; Massimo, Lucio; Paparella, Gaetano; Van Caelenberg, Kristien; Chierchia, Gian Battista; Sarkozy, Andrea; Terradellas, Pedro Brugada Y; Zizi, Martin

    2009-01-01

    Atrial fibrillation (AF) is a frequent chronic dysrythmia with an incidence that increases with age (>40). Because of its medical and socio-economic impacts it is expected to become an increasing burden on most health care systems. AF is a multi-factorial disease for which the identification of subtypes is warranted. Novel approaches based on the broad concepts of systems biology may overcome the blurred notion of normal and pathological phenotype, which is inherent to high throughput molecular arrays analysis. Here we apply an internal contrast algorithm on AF patient data with an analytical focus on potential entry pathways into the disease. We used a RMA (Robust Multichip Average) normalized Affymetrix micro-array data set from 10 AF patients (geo_accession #GSE2240). Four series of probes were selected based on physiopathogenic links with AF entryways: apoptosis (remodeling), MAP kinase (cell remodeling), OXPHOS (ability to sustain hemodynamic workload) and glycolysis (ischemia). Annotated probe lists were polled with Bioconductor packages in R (version 2.7.1). Genetic profile contrasts were analysed with hierarchical clustering and principal component analysis. The analysis revealed distinct patient groups for all probe sets. A substantial part (54% till 67%) of the variance is explained in the first 2 principal components. Genes in PC1/2 with high discriminatory value were selected and analyzed in detail. We aim for reliable molecular stratification of AF. We show that stratification is possible based on physiologically relevant gene sets. Genes with high contrast value are likely to give pathophysiological insight into permanent AF subtypes.

  11. Systems biology: confronting the complexity of cancer.

    Science.gov (United States)

    Gentles, Andrew J; Gallahan, Daniel

    2011-09-15

    The AACR-NCI Conference "Systems Biology: Confronting the Complexity of Cancer" took place from February 27 to March 2, 2011, in San Diego, CA. Several themes resonated during the meeting, notably (i) the need for better methods to distill insights from large-scale networks, (ii) the importance of integrating multiple data types in constructing more realistic models, (iii) challenges in translating insights about tumorigenic mechanisms into therapeutic interventions, and (iv) the role of the tumor microenvironment, at the physical, cellular, and molecular levels. The meeting highlighted concrete applications of systems biology to cancer, and the value of collaboration between interdisciplinary researchers in attacking formidable problems.

  12. Stochastic Physics, Complex Systems and Biology

    CERN Document Server

    Qian, Hong

    2012-01-01

    In complex systems, the interplay between nonlinear and stochastic dynamics gives rise to an evolution process in Darwinian sense with punctuated equilibrium, random "mutations" and "adaptations". The emergent discrete states in such a system, i.e., attractors, have natural robustness against both internal and external perturbations. Epigenetic states of a biological cell, a mesoscopic nonlinear stochastic open biochemical system, could be understood through such a framework.

  13. Fractal analysis as a complementary approach to predict the stability of drug delivery nano systems in aqueous and biological media: a regulatory proposal or a dream?

    Science.gov (United States)

    Demetzos, Costas; Pippa, Natassa

    2014-10-01

    The morphology of drug nanocarriers correlates with their functionality, which is mainly shuttled on their surface where most of the interactions and interfacial phenomena occur. The quantification of their morphological fingerprint requires an analytical tool that should be established based on experimental data and can be correlated with their stability. The morphological quantification picture of the advanced Drug Delivery nano Systems (aDDnSs) could be achieved via fractal analysis and by introducing a novel proposed parameter, defined as ωD. This parameter is based on mathematical limits determined experimentally and on already existing theories on the colloidal fractal aggregation process which can correlate the morphological characteristics of aDDnSs with their physicochemical stability in aqueous and biological media. This review article proposes the fractal analysis and the ωD as an analytical tool and prediction parameter, respectively, which are able to promote an attractive and alternative path for studying drug delivery nanocarriers. Moreover, these approaches could facilitate the scale up process of pharmaceutical industry, and could shed more light in the quantification of drug delivery nanosystems.

  14. A Rapid Method for the Extraction and Analysis of Carotenoids and Other Hydrophobic Substances Suitable for Systems Biology Studies with Photosynthetic Bacteria

    Directory of Open Access Journals (Sweden)

    Oliver Sawodny

    2013-10-01

    Full Text Available A simple, rapid, and inexpensive extraction method for carotenoids and other non-polar compounds present in phototrophic bacteria has been developed. The method, which has been extensively tested on the phototrophic purple non-sulphur bacterium Rhodospirillum rubrum, is suitable for extracting large numbers of samples, which is common in systems biology studies, and yields material suitable for subsequent analysis using HPLC and mass spectroscopy. The procedure is particularly suitable for carotenoids and other terpenoids, including quinones, bacteriochlorophyll a and bacteriopheophytin a, and is also useful for the analysis of polar phospholipids. The extraction procedure requires only a single step extraction with a hexane/methanol/water mixture, followed by HPLC using a Spherisorb C18 column, with a mobile phase consisting of acetone-water and a non-linear gradient of 50%–100% acetone. The method was employed for examining the carotenoid composition observed during microaerophilic growth of R. rubrum strains, and was able to determine 18 carotenoids, 4 isoprenoid-quinones, bacteriochlorophyll a and bacteriopheophytin a as well as four different phosphatidylglycerol species of different acyl chain compositions. The analytical procedure was used to examine the dynamics of carotenoid biosynthesis in the major and minor pathways operating simultaneously in a carotenoid biosynthesis mutant of R. rubrum.

  15. Magellan: A Web Based System for the Integrated Analysis of Heterogeneous Biological Data and Annotations; Application to DNA Copy Number and Expression Data in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Chris B. Kingsley

    2006-01-01

    Full Text Available Recent advances in high throughput biological methods allow researchers to generate enormous amounts of data from a single experiment. In order to extract meaningful conclusions from this tidal wave of data, it will be necessary to develop analytical methods of sufficient power and utility. It is particularly important that biologists themselves be able to perform many of these analyses, such that their background knowledge of the experimental system under study can be used to interpret results and direct further inquiries. We have developed a web-based system, Magellan, which allows the upload, storage, and analysis of multivariate data and textual or numerical annotations. Data and annotations are treated as abstract entities, to maximize the different types of information the system can store and analyze. Annotations can be used in analyses/visualizations, as a means of subsetting data to reduce dimensionality, or as a means of projecting variables from one data type or data set to another. Analytical methods are deployed within Magellan such that new functionalities can be added in a straightforward fashion. Using Magellan, we performed an integrated analysis of genome-wide comparative genomic hybridization (CGH, mRNA expression, and clinical data from ovarian tumors. Analyses included the use of permutation-based methods to identify genes whose mRNA expression levels correlated with patient survival, a nearest neighbor classifier to predict patient survival from CGH data, and curated annotations such as genomic position and derived annotations such as statistical computations to explore the quantitative relationship between CGH and mRNA expression data.

  16. Magellan: a web based system for the integrated analysis of heterogeneous biological data and annotations; application to DNA copy number and expression data in ovarian cancer.

    Science.gov (United States)

    Kingsley, Chris B; Kuo, Wen-Lin; Polikoff, Daniel; Berchuck, Andy; Gray, Joe W; Jain, Ajay N

    2007-02-05

    Recent advances in high throughput biological methods allow researchers to generate enormous amounts of data from a single experiment. In order to extract meaningful conclusions from this tidal wave of data, it will be necessary to develop analytical methods of sufficient power and utility. It is particularly important that biologists themselves be able to perform many of these analyses, such that their background knowledge of the experimental system under study can be used to interpret results and direct further inquiries. We have developed a web-based system, Magellan, which allows the upload, storage, and analysis of multivariate data and textual or numerical annotations. Data and annotations are treated as abstract entities, to maximize the different types of information the system can store and analyze. Annotations can be used in analyses/visualizations, as a means of subsetting data to reduce dimensionality, or as a means of projecting variables from one data type or data set to another. Analytical methods are deployed within Magellan such that new functionalities can be added in a straightforward fashion. Using Magellan, we performed an integrated analysis of genome-wide comparative genomic hybridization (CGH), mRNA expression, and clinical data from ovarian tumors. Analyses included the use of permutation-based methods to identify genes whose mRNA expression levels correlated with patient survival, a nearest neighbor classifier to predict patient survival from CGH data, and curated annotations such as genomic position and derived annotations such as statistical computations to explore the quantitative relationship between CGH and mRNA expression data.

  17. Catabolite regulation analysis of Escherichia coli for acetate overflow mechanism and co-consumption of multiple sugars based on systems biology approach using computer simulation.

    Science.gov (United States)

    Matsuoka, Yu; Shimizu, Kazuyuki

    2013-10-20

    It is quite important to understand the basic principle embedded in the main metabolism for the interpretation of the fermentation data. For this, it may be useful to understand the regulation mechanism based on systems biology approach. In the present study, we considered the perturbation analysis together with computer simulation based on the models which include the effects of global regulators on the pathway activation for the main metabolism of Escherichia coli. Main focus is the acetate overflow metabolism and the co-fermentation of multiple carbon sources. The perturbation analysis was first made to understand the nature of the feed-forward loop formed by the activation of Pyk by FDP (F1,6BP), and the feed-back loop formed by the inhibition of Pfk by PEP in the glycolysis. Those together with the effect of transcription factor Cra caused by FDP level affected the glycolysis activity. The PTS (phosphotransferase system) acts as the feed-back system by repressing the glucose uptake rate for the increase in the glucose uptake rate. It was also shown that the increased PTS flux (or glucose consumption rate) causes PEP/PYR ratio to be decreased, and EIIA-P, Cya, cAMP-Crp decreased, where cAMP-Crp in turn repressed TCA cycle and more acetate is formed. This was further verified by the detailed computer simulation. In the case of multiple carbon sources such as glucose and xylose, it was shown that the sequential utilization of carbon sources was observed for wild type, while the co-consumption of multiple carbon sources with slow consumption rates were observed for the ptsG mutant by computer simulation, and this was verified by experiments. Moreover, the effect of a specific gene knockout such as Δpyk on the metabolic characteristics was also investigated based on the computer simulation.

  18. Systems Biology — the Broader Perspective

    Directory of Open Access Journals (Sweden)

    Jonathan Bard

    2013-06-01

    Full Text Available Systems biology has two general aims: a narrow one, which is to discover how complex networks of proteins work, and a broader one, which is to integrate the molecular and network data with the generation and function of organism phenotypes. Doing all this involves complex methodologies, but underpinning the subject are more general conceptual problems about upwards and downwards causality, complexity and information storage, and their solutions provide the constraints within which these methodologies can be used. This essay considers these general aspects and the particular role of protein networks; their functional outputs are often the processes driving phenotypic change and physiological function—networks are, in a sense, the units of systems biology much as proteins are for molecular biology. It goes on to argue that the natural language for systems-biological descriptions of biological phenomena is the mathematical graph (a set of connected facts of the general form [process] (e.g., [activates] . Such graphs not only integrate events at different levels but emphasize the distributed nature of control as well as displaying a great deal of data. The implications and successes of these ideas for physiology, pharmacology, development and evolution are briefly considered. The paper concludes with some challenges for the future.

  19. Semantic annotation for biological information retrieval system.

    Science.gov (United States)

    Oshaiba, Mohamed Marouf Z; El Houby, Enas M F; Salah, Akram

    2015-01-01

    Online literatures are increasing in a tremendous rate. Biological domain is one of the fast growing domains. Biological researchers face a problem finding what they are searching for effectively and efficiently. The aim of this research is to find documents that contain any combination of biological process and/or molecular function and/or cellular component. This research proposes a framework that helps researchers to retrieve meaningful documents related to their asserted terms based on gene ontology (GO). The system utilizes GO by semantically decomposing it into three subontologies (cellular component, biological process, and molecular function). Researcher has the flexibility to choose searching terms from any combination of the three subontologies. Document annotation is taking a place in this research to create an index of biological terms in documents to speed the searching process. Query expansion is used to infer semantically related terms to asserted terms. It increases the search meaningful results using the term synonyms and term relationships. The system uses a ranking method to order the retrieved documents based on the ranking weights. The proposed system achieves researchers' needs to find documents that fit the asserted terms semantically.

  20. Introduction to focus issue: dynamics in systems biology.

    Science.gov (United States)

    Brackley, Chris A; Ebenhöh, Oliver; Grebogi, Celso; Kurths, Jürgen; de Moura, Alessandro; Romano, M Carmen; Thiel, Marco

    2010-12-01

    The methods of nonlinear systems form an extensive toolbox for the study of biology, and systems biology provides a rich source of motivation for the development of new mathematical techniques and the furthering of understanding of dynamical systems. This Focus Issue collects together a large variety of work which highlights the complementary nature of these two fields, showing what each has to offer the other. While a wide range of subjects is covered, the papers often have common themes such as "rhythms and oscillations," "networks and graph theory," and "switches and decision making." There is a particular emphasis on the links between experimental data and modeling and mathematical analysis.

  1. Synthetic biology: advancing biological frontiers by building synthetic systems

    OpenAIRE

    Chen, Yvonne Yu-Hsuan; Galloway, Kate E; Smolke, Christina D.

    2012-01-01

    Advances in synthetic biology are contributing to diverse research areas, from basic biology to biomanufacturing and disease therapy. We discuss the theoretical foundation, applications, and potential of this emerging field.

  2. Systems biology analysis of gene expression during in vivo Mycobacterium avium paratuberculosis enteric colonization reveals role for immune tolerance.

    Directory of Open Access Journals (Sweden)

    Sangeeta Khare

    Full Text Available Survival and persistence of Mycobacterium avium subsp. paratuberculosis (MAP in the intestinal mucosa is associated with host immune tolerance. However, the initial events during MAP interaction with its host that lead to pathogen survival, granulomatous inflammation, and clinical disease progression are poorly defined. We hypothesize that immune tolerance is initiated upon initial contact of MAP with the intestinal Peyer's patch. To test our hypothesis, ligated ileal loops in neonatal calves were infected with MAP. Intestinal tissue RNAs were collected (0.5, 1, 2, 4, 8 and 12 hrs post-infection, processed, and hybridized to bovine gene expression microarrays. By comparing the gene transcription responses of calves infected with the MAP, informative complex patterns of expression were clearly visible. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis, and genes were grouped into the specific pathways and gene ontology categories to create a holistic model. This model revealed three different phases of responses: i early (30 min and 1 hr post-infection, ii intermediate (2, 4 and 8 hrs post-infection, and iii late (12 hrs post-infection. We describe here the data that include expression profiles for perturbed pathways, as well as, mechanistic genes (genes predicted to have regulatory influence that are associated with immune tolerance. In the Early Phase of MAP infection, multiple pathways were initiated in response to MAP invasion via receptor mediated endocytosis and changes in intestinal permeability. During the Intermediate Phase, perturbed pathways involved the inflammatory responses, cytokine-cytokine receptor interaction, and cell-cell signaling. During the Late Phase of infection, gene responses associated with immune tolerance were initiated at the level of T-cell signaling. Our study provides evidence that MAP infection resulted in differentially regulated genes, perturbed

  3. Nanoscale analysis of unstained biological specimens in water without radiation damage using high-resolution frequency transmission electric-field system based on FE-SEM

    Energy Technology Data Exchange (ETDEWEB)

    Ogura, Toshihiko, E-mail: t-ogura@aist.go.jp

    2015-04-10

    Scanning electron microscopy (SEM) has been widely used to examine biological specimens of bacteria, viruses and proteins. Until now, atmospheric and/or wet biological specimens have been examined using various atmospheric holders or special equipment involving SEM. Unfortunately, they undergo heavy radiation damage by the direct electron beam. In addition, images of unstained biological samples in water yield poor contrast. We recently developed a new analytical technology involving a frequency transmission electric-field (FTE) method based on thermionic SEM. This method is suitable for high-contrast imaging of unstained biological specimens. Our aim was to optimise the method. Here we describe a high-resolution FTE system based on field-emission SEM; it allows for imaging and nanoscale examination of various biological specimens in water without radiation damage. The spatial resolution is 8 nm, which is higher than 41 nm of the existing FTE system. Our new method can be easily utilised for examination of unstained biological specimens including bacteria, viruses and protein complexes. Furthermore, our high-resolution FTE system can be used for diverse liquid samples across a broad range of scientific fields, e.g. nanoparticles, nanotubes and organic and catalytic materials. - Highlights: • We developed a high-resolution frequency transmission electric-field (FTE) system. • High-resolution FTE system is introduced in the field-emission SEM. • The spatial resolution of high-resolution FTE method is 8 nm. • High-resolution FTE system enables observation of the intact IgM particles in water.

  4. Systems Biology for Organotypic Cell Cultures

    Energy Technology Data Exchange (ETDEWEB)

    Grego, Sonia [RTI International, Research Triangle Park, NC (United States); Dougherty, Edward R. [Texas A & M Univ., College Station, TX (United States); Alexander, Francis J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Auerbach, Scott S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Berridge, Brian R. [GlaxoSmithKline, Research Triangle Park, NC (United States); Bittner, Michael L. [Translational Genomics Research Inst., Phoenix, AZ (United States); Casey, Warren [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Cooley, Philip C. [RTI International, Research Triangle Park, NC (United States); Dash, Ajit [HemoShear Therapeutics, Charlottesville, VA (United States); Ferguson, Stephen S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Fennell, Timothy R. [RTI International, Research Triangle Park, NC (United States); Hawkins, Brian T. [RTI International, Research Triangle Park, NC (United States); Hickey, Anthony J. [RTI International, Research Triangle Park, NC (United States); Kleensang, Andre [Johns Hopkins Univ., Baltimore, MD (United States). Center for Alternatives to Animal Testing; Liebman, Michael N. [IPQ Analytics, Kennett Square, PA (United States); Martin, Florian [Phillip Morris International, Neuchatel (Switzerland); Maull, Elizabeth A. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Paragas, Jason [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Qiao, Guilin [Defense Threat Reduction Agency, Ft. Belvoir, VA (United States); Ramaiahgari, Sreenivasa [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Sumner, Susan J. [RTI International, Research Triangle Park, NC (United States); Yoon, Miyoung [The Hamner Inst. for Health Sciences, Research Triangle Park, NC (United States); ScitoVation, Research Triangle Park, NC (United States)

    2016-08-04

    Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, “organotypic” cell cultures, which mimic functional responses of living tissue. However, there remains a knowledge gap regarding interactions across different biological scales, complicating accurate prediction of health outcomes from molecular/genomic data and tissue responses. Systems biology aims at mathematical modeling of complex, non-linear biological systems. We propose to apply a systems biology approach to achieve a computational representation of tissue-level physiological responses by integrating empirical data derived from organotypic culture systems with computational models of intracellular pathways to better predict human responses. Successful implementation of this integrated approach will provide a powerful tool for faster, more accurate and cost-effective screening of potential toxicants and therapeutics. On September 11, 2015, an interdisciplinary group of scientists, engineers, and clinicians gathered for a workshop in Research Triangle Park, North Carolina, to discuss this ambitious goal. Participants represented laboratory-based and computational modeling approaches to pharmacology and toxicology, as well as the pharmaceutical industry, government, non-profits, and academia. Discussions focused on identifying critical system perturbations to model, the computational tools required, and the experimental approaches best suited to generating key data. This consensus report summarizes the discussions held.

  5. Systems Biology of Metabolism: A Driver for Developing Personalized and Precision Medicine

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2017-01-01

    Systems biology uses mathematical models to analyze large datasets and simulate system behavior. It enables integrative analysis of different types of data and can thereby provide new insight into complex biological systems. Here will be discussed the challenges of using systems medicine for adva......Systems biology uses mathematical models to analyze large datasets and simulate system behavior. It enables integrative analysis of different types of data and can thereby provide new insight into complex biological systems. Here will be discussed the challenges of using systems medicine...

  6. Systems biology solutions for biochemical production challenges

    DEFF Research Database (Denmark)

    Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus

    2017-01-01

    There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics character......There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics...... characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity...... compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains...

  7. Nutritional Systems Biology: Definitions and Approaches

    DEFF Research Database (Denmark)

    Panagiotou, Gianni; Nielsen, Jens

    2009-01-01

    waiting for a predictive knowledge of genetic variation. It is widely recognized that systems and network biology has the potential to increase our understanding of how nutrition influences metabolic pathways and homeostasis, how this regulation is disturbed in a diet-related disease, and to what extent...

  8. Identification of Biocontrol Bacteria against Soybean Root Rot with Biolog Automatic Microbiology Analysis System%拮抗大豆根腐病细菌的Biolog鉴定

    Institute of Scientific and Technical Information of China (English)

    许艳丽; 刘海龙; 李春杰; 潘凤娟; 李淑娴; 刘新晶

    2012-01-01

    In order to identify the systematic position of taxonomy of two biocontrol bacteria against soybean root rot. Traditional morphological identification and BIOLOG automatic microbiology analysis system were used to identify strain B021a and B04b. The results showed that similarity value of strain B021a with Vibrio tubiashii was 0. 634, possibility to 86% and genetic distance to 4.00,and similarity value of strain B04b with Pasteurella trehalosi was 0. 610,probability to 75% and genetic distance to 2. 77. Strain B021a was identified as Vibrio tubiashii and strain B04b as Pasteurella trehalosi by colony morphological propertie and BIOLOC analysis system.%为明确2株生防细菌的分类地位,采用传统形态学方法结合Biolog微生物自动分析系统,鉴定了大豆根腐病的2株生防细菌.结果表明,菌株B021a与塔式弧菌相似度值为0.634,可能性是86%,遗传距离为4.00.菌株B04b与海藻巴斯德菌相似度值为0.610,可能性是75%,遗传距离为2.77.综合形态学和Biolog鉴定结果,认为菌株B021a是塔式弧菌,菌株B04b是海藻巴斯德菌.

  9. GPU-powered Simulation Methodologies for Biological Systems

    Directory of Open Access Journals (Sweden)

    Dario Pescini

    2013-09-01

    Full Text Available The study of biological systems witnessed a pervasive cross-fertilization between experimental investigation and computational methods. This gave rise to the development of new methodologies, able to tackle the complexity of biological systems in a quantitative manner. Computer algorithms allow to faithfully reproduce the dynamics of the corresponding biological system, and, at the price of a large number of simulations, it is possible to extensively investigate the system functioning across a wide spectrum of natural conditions. To enable multiple analysis in parallel, using cheap, diffused and highly efficient multi-core devices we developed GPU-powered simulation algorithms for stochastic, deterministic and hybrid modeling approaches, so that also users with no knowledge of GPUs hardware and programming can easily access the computing power of graphics engines.

  10. Integrative Systems Biology Applied to Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning

    associated with combined exposure to multiple chemicals. Testing all possible combinations of the tens of thousands environmental chemicals is impractical. This PhD project was launched to apply existing computational systems biology methods to toxicological research. In this thesis, I present in three...... of a system thereby suggesting new ways of thinking specific toxicological endpoints. Furthermore, computational methods can serve as valuable input for the hypothesis generating phase of the preparations of a research project....

  11. Biological Indicator Systems in Floodplains - a Review

    Science.gov (United States)

    Dziock, Frank; Henle, Klaus; Foeckler, Francis; Follner, Klaus; Scholz, Mathias

    2006-08-01

    Based on a literature review, the different approaches to biological indicator systems in floodplains are summarised. Four general categories of bioindication are defined and proposed here: 1. Classification indicators, 2.1 Environmental indicators, 2.2 Biodiversity indicators, 3. Valuation indicators. Furthermore, existing approaches in floodplains are classified according to the four categories. Relevant and widely used approaches in floodplains are explained in more detail. The results of the RIVA project are put into the context of these indication approaches. It is concluded that especially functional assessment approaches using biological traits of the species can be seen as very promising and deserve more attention by conservation biologists and floodplain ecologists.

  12. Application of the principles of systems biology and Wiener's cybernetics for analysis of regulation of energy fluxes in muscle cells in vivo.

    Science.gov (United States)

    Guzun, Rita; Saks, Valdur

    2010-03-08

    The mechanisms of regulation of respiration and energy fluxes in the cells are analyzed based on the concepts of systems biology, non-equilibrium steady state kinetics and applications of Wiener's cybernetic principles of feedback regulation. Under physiological conditions cardiac function is governed by the Frank-Starling law and the main metabolic characteristic of cardiac muscle cells is metabolic homeostasis, when both workload and respiration rate can be changed manifold at constant intracellular level of phosphocreatine and ATP in the cells. This is not observed in skeletal muscles. Controversies in theoretical explanations of these observations are analyzed. Experimental studies of permeabilized fibers from human skeletal muscle vastus lateralis and adult rat cardiomyocytes showed that the respiration rate is always an apparent hyperbolic but not a sigmoid function of ADP concentration. It is our conclusion that realistic explanations of regulation of energy fluxes in muscle cells require systemic approaches including application of the feedback theory of Wiener's cybernetics in combination with detailed experimental research. Such an analysis reveals the importance of limited permeability of mitochondrial outer membrane for ADP due to interactions of mitochondria with cytoskeleton resulting in quasi-linear dependence of respiration rate on amplitude of cyclic changes in cytoplasmic ADP concentrations. The system of compartmentalized creatine kinase (CK) isoenzymes functionally coupled to ANT and ATPases, and mitochondrial-cytoskeletal interactions separate energy fluxes (mass and energy transfer) from signalling (information transfer) within dissipative metabolic structures - intracellular energetic units (ICEU). Due to the non-equilibrium state of CK reactions, intracellular ATP utilization and mitochondrial ATP regeneration are interconnected by the PCr flux from mitochondria. The feedback regulation of respiration occurring via cyclic fluctuations of

  13. Computational systems biology for aging research.

    Science.gov (United States)

    Mc Auley, Mark T; Mooney, Kathleen M

    2015-01-01

    Computational modelling is a key component of systems biology and integrates with the other techniques discussed thus far in this book by utilizing a myriad of data that are being generated to quantitatively represent and simulate biological systems. This chapter will describe what computational modelling involves; the rationale for using it, and the appropriateness of modelling for investigating the aging process. How a model is assembled and the different theoretical frameworks that can be used to build a model are also discussed. In addition, the chapter will describe several models which demonstrate the effectiveness of each computational approach for investigating the constituents of a healthy aging trajectory. Specifically, a number of models will be showcased which focus on the complex age-related disorders associated with unhealthy aging. To conclude, we discuss the future applications of computational systems modelling to aging research.

  14. Measuring cell identity in noisy biological systems

    OpenAIRE

    Kenneth D Birnbaum; Kussell, Edo

    2011-01-01

    Global gene expression measurements are increasingly obtained as a function of cell type, spatial position within a tissue and other biologically meaningful coordinates. Such data should enable quantitative analysis of the cell-type specificity of gene expression, but such analyses can often be confounded by the presence of noise. We introduce a specificity measure Spec that quantifies the information in a gene's complete expression profile regarding any given cell type, and an uncertainty me...

  15. KPFM and PFM of Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, Brian [University College, Dublin; Kalinin, Sergei V [ORNL

    2011-01-01

    Surface potentials and electrostatic interactions in biological systems are a key element of cellular regulation and interaction. Examples include cardiac and muscular activity, voltage-gated ion channels, protein folding and assembly, and electroactive cells and electrotransduction. The coupling between electrical, mechanical, and chemical signals and responses in cellular systems necessitates the development of tools capable of measuring the distribution of charged species, surface potentials, and mechanical responses to applied electrical stimuli and vice versa, ultimately under physiological conditions. In this chapter, applications of voltage-modulated atomic force microscopy (AFM) methods including Kelvin probe force microscopy (KPFM) and piezoresponse force microscopy (PFM) to biological systems are discussed. KPFM is a force-sensitive non-contact or intermittent-contact mode AFM technique that allows electrostatic interactions and surface potentials to be addressed. Beyond long-range electrostatic interactions, the application of bias can lead to a mechanical response, e.g., due to linear piezoelectric coupling in polar biopolymers or via more complex electrotransduction and redox pathways in other biosystems. The use and development of PFM, based on direct electromechanical detection, to biological systems will also be addressed. The similarities and limitations of measuring surface potentials and electromechanical coupling in solution will be outlined.

  16. A Converter from the Systems Biology Markup Language to the Synthetic Biology Open Language.

    Science.gov (United States)

    Nguyen, Tramy; Roehner, Nicholas; Zundel, Zach; Myers, Chris J

    2016-06-17

    Standards are important to synthetic biology because they enable exchange and reproducibility of genetic designs. This paper describes a procedure for converting between two standards: the Systems Biology Markup Language (SBML) and the Synthetic Biology Open Language (SBOL). SBML is a standard for behavioral models of biological systems at the molecular level. SBOL describes structural and basic qualitative behavioral aspects of a biological design. Converting SBML to SBOL enables a consistent connection between behavioral and structural information for a biological design. The conversion process described in this paper leverages Systems Biology Ontology (SBO) annotations to enable inference of a designs qualitative function.

  17. A Systems Biology Starter Kit for Arenaviruses

    Directory of Open Access Journals (Sweden)

    Magali E. Droniou-Bonzom

    2012-12-01

    Full Text Available Systems biology approaches in virology aim to integrate viral and host biological networks, and thus model the infection process. The growing availability of high-throughput “-omics” techniques and datasets, as well as the ever-increasing sophistication of in silico modeling tools, has resulted in a corresponding rise in the complexity of the analyses that can be performed. The present study seeks to review and organize published evidence regarding virus-host interactions for the arenaviruses, from alterations in the host proteome during infection, to reported protein-protein interactions. In this way, we hope to provide an overview of the interplay between arenaviruses and the host cell, and lay the foundations for complementing current arenavirus research with a systems-level approach.

  18. A systems biology starter kit for arenaviruses.

    Science.gov (United States)

    Droniou-Bonzom, Magali E; Cannon, Paula M

    2012-12-01

    Systems biology approaches in virology aim to integrate viral and host biological networks, and thus model the infection process. The growing availability of high-throughput “-omics” techniques and datasets, as well as the ever-increasing sophistication of in silico modeling tools, has resulted in a corresponding rise in the complexity of the analyses that can be performed. The present study seeks to review and organize published evidence regarding virus-host interactions for the arenaviruses, from alterations in the host proteome during infection, to reported protein-protein interactions. In this way, we hope to provide an overview of the interplay between arenaviruses and the host cell, and lay the foundations for complementing current arenavirus research with a systems-level approach.

  19. Network news: innovations in 21st century systems biology.

    Science.gov (United States)

    Arkin, Adam P; Schaffer, David V

    2011-03-18

    A decade ago, seminal perspectives and papers set a strong vision for the field of systems biology, and a number of these themes have flourished. Here, we describe key technologies and insights that have elucidated the evolution, architecture, and function of cellular networks, ultimately leading to the first predictive genome-scale regulatory and metabolic models of organisms. Can systems approaches bridge the gap between correlative analysis and mechanistic insights?

  20. Systems Biology Approaches to a Rational Drug Discovery Paradigm.

    Science.gov (United States)

    Prathipati, Philip; Mizuguchi, Kenji

    2016-01-01

    Ligand- and structure-based drug design approaches complement phenotypic and target screens, respectively, and are the two major frameworks for guiding early-stage drug discovery efforts. Since the beginning of this century, the advent of the genomic era has presented researchers with a myriad of high throughput biological data (parts lists and their interaction networks) to address efficacy and toxicity, augmenting the traditional ligand- and structure-based approaches. This data rich era has also presented us with challenges related to integrating and analyzing these multi-platform and multi-dimensional datasets and translating them into viable hypotheses. Hence in the present paper, we review these existing approaches to drug discovery research and argue the case for a new systems biology based approach. We present the basic principles and the foundational arguments/underlying assumptions of the systems biology based approaches to drug design. Also discussed are systems biology data types (key entities, their attributes and their relationships with each other, and data models/representations), software and tools used for both retrospective and prospective analysis, and the hypotheses that can be inferred. In addition, we summarize some of the existing resources for a systems biology based drug discovery paradigm (open TG-GATEs, DrugMatrix, CMap and LINCs) in terms of their strengths and limitations.

  1. Method for photo-altering a biological system to improve biological effect

    Science.gov (United States)

    Hill, Richard A.; Doiron, Daniel R.; Crean, David H.

    2000-08-01

    Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

  2. A Systems Biology-Based Approach to Uncovering the Molecular Mechanisms Underlying the Effects of Dragon's Blood Tablet in Colitis, Involving the Integration of Chemical Analysis, ADME Prediction, and Network Pharmacology

    OpenAIRE

    Haiyu Xu; Yanqiong Zhang; Yun Lei; Xiumei Gao; Huaqiang Zhai; Na Lin; Shihuan Tang; Rixin Liang; Yan Ma; Defeng Li; Yi Zhang; Guangrong Zhu; Hongjun Yang; Luqi Huang

    2014-01-01

    Traditional Chinese medicine (TCM) is one of the oldest East Asian medical systems. The present study adopted a systems biology-based approach to provide new insights relating to the active constituents and molecular mechanisms underlying the effects of dragon's blood (DB) tablets for the treatment of colitis. This study integrated chemical analysis, prediction of absorption, distribution, metabolism, and excretion (ADME), and network pharmacology. Firstly, a rapid, reliable, and accurate ult...

  3. Complex biological and bio-inspired systems

    Energy Technology Data Exchange (ETDEWEB)

    Ecke, Robert E [Los Alamos National Laboratory

    2009-01-01

    The understanding and characterization ofthe fundamental processes of the function of biological systems underpins many of the important challenges facing American society, from the pathology of infectious disease and the efficacy ofvaccines, to the development of materials that mimic biological functionality and deliver exceptional and novel structural and dynamic properties. These problems are fundamentally complex, involving many interacting components and poorly understood bio-chemical kinetics. We use the basic science of statistical physics, kinetic theory, cellular bio-chemistry, soft-matter physics, and information science to develop cell level models and explore the use ofbiomimetic materials. This project seeks to determine how cell level processes, such as response to mechanical stresses, chemical constituents and related gradients, and other cell signaling mechanisms, integrate and combine to create a functioning organism. The research focuses on the basic physical processes that take place at different levels ofthe biological organism: the basic role of molecular and chemical interactions are investigated, the dynamics of the DNA-molecule and its phylogenetic role are examined and the regulatory networks of complex biochemical processes are modeled. These efforts may lead to early warning algorithms ofpathogen outbreaks, new bio-sensors to detect hazards from pathomic viruses to chemical contaminants. Other potential applications include the development of efficient bio-fuel alternative-energy processes and the exploration ofnovel materials for energy usages. Finally, we use the notion of 'coarse-graining,' which is a method for averaging over less important degrees of freedom to develop computational models to predict cell function and systems-level response to disease, chemical stress, or biological pathomic agents. This project supports Energy Security, Threat Reduction, and the missions of the DOE Office of Science through its efforts to

  4. [Systems theory in medicine and biology].

    Science.gov (United States)

    Feigl, W; Bonet, E M

    1989-03-15

    We try to determinate, that systems theory has to be introduced into modern medicine. The biological roots as well as the cybernetic ones are outlined. Among various concepts about systems theory the evaluation by Riedl seems to be the most efficient to explain medical procedures. His basic informations refer to von Bertalanffy, the additional introduction of a 4-cause-principle, Aristoteles, permits the explanation of complex relations. The examples of tumor and inflammation are used to demonstrate the basic idea of the formal cause as well as the final cause. The latter should also become an important fact in the solution of other medical problems.

  5. Life: An Introduction to Complex Systems Biology

    CERN Document Server

    Kaneko, Kunihiko

    2006-01-01

    What is life? Has molecular biology given us a satisfactory answer to this question? And if not, why, and how to carry on from there? This book examines life not from the reductionist point of view, but rather asks the question: what are the universal properties of living systems and how can one construct from there a phenomenological theory of life that leads naturally to complex processes such as reproductive cellular systems, evolution and differentiation? The presentation has been deliberately kept fairly non-technical so as to address a broad spectrum of students and researchers from the natural sciences and informatics.

  6. Systems biology: A tool for charting the antiviral landscape.

    Science.gov (United States)

    Bowen, James R; Ferris, Martin T; Suthar, Mehul S

    2016-06-15

    The host antiviral programs that are initiated following viral infection form a dynamic and complex web of responses that we have collectively termed as "the antiviral landscape". Conventional approaches to studying antiviral responses have primarily used reductionist systems to assess the function of a single or a limited subset of molecules. Systems biology is a holistic approach that considers the entire system as a whole, rather than individual components or molecules. Systems biology based approaches facilitate an unbiased and comprehensive analysis of the antiviral landscape, while allowing for the discovery of emergent properties that are missed by conventional approaches. The antiviral landscape can be viewed as a hierarchy of complexity, beginning at the whole organism level and progressing downward to isolated tissues, populations of cells, and single cells. In this review, we will discuss how systems biology has been applied to better understand the antiviral landscape at each of these layers. At the organismal level, the Collaborative Cross is an invaluable genetic resource for assessing how genetic diversity influences the antiviral response. Whole tissue and isolated bulk cell transcriptomics serves as a critical tool for the comprehensive analysis of antiviral responses at both the tissue and cellular levels of complexity. Finally, new techniques in single cell analysis are emerging tools that will revolutionize our understanding of how individual cells within a bulk infected cell population contribute to the overall antiviral landscape.

  7. SBEToolbox: A Matlab Toolbox for Biological Network Analysis.

    Science.gov (United States)

    Konganti, Kranti; Wang, Gang; Yang, Ence; Cai, James J

    2013-01-01

    We present SBEToolbox (Systems Biology and Evolution Toolbox), an open-source Matlab toolbox for biological network analysis. It takes a network file as input, calculates a variety of centralities and topological metrics, clusters nodes into modules, and displays the network using different graph layout algorithms. Straightforward implementation and the inclusion of high-level functions allow the functionality to be easily extended or tailored through developing custom plugins. SBEGUI, a menu-driven graphical user interface (GUI) of SBEToolbox, enables easy access to various network and graph algorithms for programmers and non-programmers alike. All source code and sample data are freely available at https://github.com/biocoder/SBEToolbox/releases.

  8. Standards, Data Exchange and Intellectual Property Rights in Systems Biology

    DEFF Research Database (Denmark)

    van Zimmeren, Esther; Rutz, Berthold; Minssen, Timo

    2016-01-01

    we provided a number of recommendations for a variety of stakeholders. The current article offers some deeper reflections about the interface between IPRs, standards and data exchange in Systems Biology resulting from an Expert Meeting funded by another ERA-Net, ERASysAPP. The meeting brought...... assets to be formatted and described in standard ways to enable exchange and reuse of high quality data. This allows a more effective utilisation of the enormous potential that rests in “big data” analysis. Finally, SysBio is often closely linked to or provides the foundation for Synthetic Biology (Syn...

  9. Engineering biological systems toward a sustainable bioeconomy.

    Science.gov (United States)

    Lopes, Mateus Schreiner Garcez

    2015-06-01

    The nature of our major global risks calls for sustainable innovations to decouple economic growth from greenhouse gases emission. The development of sustainable technologies has been negatively impacted by several factors including sugar production costs, production scale, economic crises, hydraulic fracking development and the market inability to capture externality costs. However, advances in engineering of biological systems allow bridging the gap between exponential growth of knowledge about biology and the creation of sustainable value chains for a broad range of economic sectors. Additionally, industrial symbiosis of different biobased technologies can increase competitiveness and sustainability, leading to the development of eco-industrial parks. Reliable policies for carbon pricing and revenue reinvestments in disruptive technologies and in the deployment of eco-industrial parks could boost the welfare while addressing our major global risks toward the transition from a fossil to a biobased economy.

  10. Biological Therapy in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Mariana Postal

    2012-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototypic inflammatory autoimmune disorder characterized by multisystem involvement and fluctuating disease activity. Symptoms range from rather mild manifestations such as rash or arthritis to life-threatening end-organ manifestations. Despite new and improved therapy having positively impacted the prognosis of SLE, a subgroup of patients do not respond to conventional therapy. Moreover, the risk of fatal outcomes and the damaging side effects of immunosuppressive therapies in SLE call for an improvement in the current therapeutic management. New therapeutic approaches are focused on B-cell targets, T-cell downregulation and costimulatory blockade, cytokine inhibition, and the modulation of complement. Several biological agents have been developed, but this encouraging news is associated with several disappointments in trials and provide a timely moment to reflect on biologic therapy in SLE.

  11. The Feasibility of Systems Thinking in Biology Education

    Science.gov (United States)

    Boersma, Kerst; Waarlo, Arend Jan; Klaassen, Kees

    2011-01-01

    Systems thinking in biology education is an up and coming research topic, as yet with contrasting feasibility claims. In biology education systems thinking can be understood as thinking backward and forward between concrete biological objects and processes and systems models representing systems theoretical characteristics. Some studies claim that…

  12. Systems Biology: Impressions from a Newcomer Graduate Student in 2016

    Science.gov (United States)

    Simpson, Melanie Rae

    2016-01-01

    As a newcomer, the philosophical basis of systems biology seems intuitive and appealing, the underlying philosophy being that the whole of a living system cannot be completely understood by the study of its individual parts. Yet answers to the questions "What is systems biology?" and "What constitutes a systems biology approach in…

  13. Controlled biological and biomimetic systems for landmine detection.

    Science.gov (United States)

    Habib, Maki K

    2007-08-30

    Humanitarian demining requires to accurately detect, locate and deactivate every single landmine and other buried mine-like objects as safely and as quickly as possible, and in the most non-invasive manner. The quality of landmine detection affects directly the efficiency and safety of this process. Most of the available methods to detect explosives and landmines are limited by their sensitivity and/or operational complexities. All landmines leak with time small amounts of their explosives that can be found on surrounding ground and plant life. Hence, explosive signatures represent the robust primary indicator of landmines. Accordingly, developing innovative technologies and efficient techniques to identify in real-time explosives residue in mined areas represents an attractive and promising approach. Biological and biologically inspired detection technology has the potential to compete with or be used in conjunction with other artificial technology to complement performance strengths. Biological systems are sensitive to many different scents concurrently, a property that has proven difficult to replicate artificially. Understanding biological systems presents unique opportunities for developing new capabilities through direct use of trained bio-systems, integration of living and non-living components, or inspiring new design by mimicking biological capabilities. It is expected that controlled bio-systems, biotechnology and microbial techniques will contribute to the advancement of mine detection and other application domains. This paper provides directions, evaluation and analysis on the progress of controlled biological and biomimetic systems for landmine detection. It introduces and discusses different approaches developed, underlining their relative advantages and limitations, and highlighting trends, safety and ecology concern, and possible future directions.

  14. Biological systems in high magnetic field

    Science.gov (United States)

    Yamagishi, A.

    1990-12-01

    Diamagnetic orientation of biological systems have been investigated theoretically and experimentally. Fibrinogen, one of blood proteins, were polymerized in static high magnetic fields up to 8 T. Clotted gels composed of oriented fibrin fibers were obtained even in a field as low as 1 T. Red blood cells (RBC) show full orientation with their plane parallel to the applied field of 4 T. It is confirmed experimentally that the magnetic orientation of RBC is caused by diamagnetic anisotropy. Full orientation is also obtained with blood platelet in a field of 3 T.

  15. Dielectric relaxation in biological systems physical principles, methods, and applications

    CERN Document Server

    Feldman, Yuri

    2015-01-01

    This title covers the theoretical basis and practical aspects of the study of dielectric properties of biological systems, such as water, electrolyte and polyelectrolytes, solutions of biological macromolecules, cells suspensions and cellular systems.

  16. Analysis of complex networks from biology to linguistics

    CERN Document Server

    Dehmer, Matthias

    2009-01-01

    Mathematical problems such as graph theory problems are of increasing importance for the analysis of modelling data in biomedical research such as in systems biology, neuronal network modelling etc. This book follows a new approach of including graph theory from a mathematical perspective with specific applications of graph theory in biomedical and computational sciences. The book is written by renowned experts in the field and offers valuable background information for a wide audience.

  17. Model checking biological systems described using ambient calculus

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian; Priami, Corrado; Qualia, Paola;

    2005-01-01

    Model checking biological systems described using ambient calculus. In Proc. of the second International Workshop on Computational Methods in Systems Biology (CMSB04), Lecture Notes in Bioinformatics 3082:85-103, Springer, 2005.......Model checking biological systems described using ambient calculus. In Proc. of the second International Workshop on Computational Methods in Systems Biology (CMSB04), Lecture Notes in Bioinformatics 3082:85-103, Springer, 2005....

  18. BiDMAP - A Biological Data Management and Analysis Platform

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    With the rapid development of biotechnology, more and more genomic and associated functional data are available. It is necessary and possible for biologists and bioinformaticians to integrate various databases in order to mine biological knowledge.Moreover, the complexity of huge amount of biological data and their complicated structure need an advanced management system which can store and manage data efficiently, and provide subject-oriented analysis tools for further study. BiDMAP is a platform designed to meet these needs. The core of BiDMAP is based on an Object Relational Database Management System (ORDBMS) which makes it possible not only to store and manage biological data but also to implement analysis tools on a single platform. The goal of BiDMAP is to integrate different datasets on specific subjects into one platform and provides a unified, easy-to-learn, easy to-use interface to access those data. Complicated data structures are viewed as objects, stored in the database and manipulated viastandard SQL. BiDMAP presents an intuitive approach for biologists with little computational skills and leaves the flexibility for further development. This paper gives an overview of the design and implementation of BiDMAP and gives a simple analysis example - finding interleukin candidates with implemented analysis tool of pattern scan.

  19. From globally coupled maps to complex-systems biology

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Kunihiko, E-mail: kaneko@complex.c.u-tokyo.ac.jp [Research Center for Complex Systems Biology, Graduate School of Arts and Sciences, The University of Tokyo 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902 (Japan)

    2015-09-15

    Studies of globally coupled maps, introduced as a network of chaotic dynamics, are briefly reviewed with an emphasis on novel concepts therein, which are universal in high-dimensional dynamical systems. They include clustering of synchronized oscillations, hierarchical clustering, chimera of synchronization and desynchronization, partition complexity, prevalence of Milnor attractors, chaotic itinerancy, and collective chaos. The degrees of freedom necessary for high dimensionality are proposed to equal the number in which the combinatorial exceeds the exponential. Future analysis of high-dimensional dynamical systems with regard to complex-systems biology is briefly discussed.

  20. Neuroscience in the era of functional genomics and systems biology.

    Science.gov (United States)

    Geschwind, Daniel H; Konopka, Genevieve

    2009-10-15

    Advances in genetics and genomics have fuelled a revolution in discovery-based, or hypothesis-generating, research that provides a powerful complement to the more directly hypothesis-driven molecular, cellular and systems neuroscience. Genetic and functional genomic studies have already yielded important insights into neuronal diversity and function, as well as disease. One of the most exciting and challenging frontiers in neuroscience involves harnessing the power of large-scale genetic, genomic and phenotypic data sets, and the development of tools for data integration and mining. Methods for network analysis and systems biology offer the promise of integrating these multiple levels of data, connecting molecular pathways to nervous system function.

  1. Systems biology approaches and pathway tools for investigating cardiovascular disease

    NARCIS (Netherlands)

    Wheelock, C.E.; Wheelock, A.M.; Kawashima, S.; Diez, D.; Kanehisa, M.; Erk, M. van; Kleemann, R.; Haeggström, J.Z.; Goto, S.

    2009-01-01

    Systems biology aims to understand the nonlinear interactions of multiple biomolecular components that characterize a living organism. One important aspect of systems biology approaches is to identify the biological pathways or networks that connect the differing elements of a system, and examine ho

  2. Systems Biology and Synthetic Biology: A New Epoch for Toxicology Research

    OpenAIRE

    Mark T. Mc Auley; Hyunok Choi; Kathleen Mooney; Emily Paul; Miller, Veronica M.

    2015-01-01

    Systems biology and synthetic biology are emerging disciplines which are becoming increasingly utilised in several areas of bioscience. Toxicology is beginning to benefit from systems biology and we suggest in the future that is will also benefit from synthetic biology. Thus, a new era is on the horizon. This review illustrates how a suite of innovative techniques and tools can be applied to understanding complex health and toxicology issues. We review limitations confronted by the traditiona...

  3. Systems biology of ageing and longevity.

    Science.gov (United States)

    Kirkwood, Thomas B L

    2011-01-12

    Ageing is intrinsically complex, being driven by multiple causal mechanisms. Each mechanism tends to be partially supported by data indicating that it has a role in the overall cellular and molecular pathways underlying the ageing process. However, the magnitude of this role is usually modest. The systems biology approach combines (i) data-driven modelling, often using the large volumes of data generated by functional genomics technologies, and (ii) hypothesis-driven experimental studies to investigate causal pathways and identify their parameter values in an unusually quantitative manner, which enables the contributions of individual mechanisms and their interactions to be better understood, and allows for the design of experiments explicitly to test the complex predictions arising from such models. A clear example of the success of the systems biology approach in unravelling the complexity of ageing can be seen in recent studies on cell replicative senescence, revealing interactions between mitochondrial dysfunction, telomere erosion and DNA damage. An important challenge also exists in connecting the network of (random) damage-driven proximate mechanisms of ageing with the higher level (genetically specified) signalling pathways that influence longevity. This connection is informed by actions of natural selection on the determinants of ageing and longevity.

  4. Complex fluids in biological systems experiment, theory, and computation

    CERN Document Server

    2015-01-01

    This book serves as an introduction to the continuum mechanics and mathematical modeling of complex fluids in living systems. The form and function of living systems are intimately tied to the nature of surrounding fluid environments, which commonly exhibit nonlinear and history dependent responses to forces and displacements. With ever-increasing capabilities in the visualization and manipulation of biological systems, research on the fundamental phenomena, models, measurements, and analysis of complex fluids has taken a number of exciting directions. In this book, many of the world’s foremost experts explore key topics such as: Macro- and micro-rheological techniques for measuring the material properties of complex biofluids and the subtleties of data interpretation Experimental observations and rheology of complex biological materials, including mucus, cell membranes, the cytoskeleton, and blood The motility of microorganisms in complex fluids and the dynamics of active suspensions Challenges and solut...

  5. Biological Systems for Hydrogen Photoproduction (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Ghirardi, M. L.

    2012-05-01

    This presentation summarizes NREL biological systems for hydrogen photoproduction work for the DOE Hydrogen and Fuel Cells Program Annual Merit Review and Peer Evaluation Meeting, May 14-18, 2012. General goal is develop photobiological systems for large-scale, low cost and efficient H{sub 2} production from water (barriers AH, AI and AJ). Specific tasks are: (1) Address the O{sub 2} sensitivity of hydrogenases that prevent continuity of H{sub 2} photoproduction under aerobic, high solar-to-hydrogen (STH) light conversion efficiency conditions; and (2) Utilize a limited STH H{sub 2}-producing method (sulfur deprivation) as a platform to address or test other factors limiting commercial algal H{sub 2} photoproduction, including low rates due to biochemical and engineering mechanisms.

  6. Modeling delayed processes in biological systems

    Science.gov (United States)

    Feng, Jingchen; Sevier, Stuart A.; Huang, Bin; Jia, Dongya; Levine, Herbert

    2016-09-01

    Delayed processes are ubiquitous in biological systems and are often characterized by delay differential equations (DDEs) and their extension to include stochastic effects. DDEs do not explicitly incorporate intermediate states associated with a delayed process but instead use an estimated average delay time. In an effort to examine the validity of this approach, we study systems with significant delays by explicitly incorporating intermediate steps. We show that such explicit models often yield significantly different equilibrium distributions and transition times as compared to DDEs with deterministic delay values. Additionally, different explicit models with qualitatively different dynamics can give rise to the same DDEs revealing important ambiguities. We also show that DDE-based predictions of oscillatory behavior may fail for the corresponding explicit model.

  7. Software that goes with the flow in systems biology

    Directory of Open Access Journals (Sweden)

    Le Novère Nicolas

    2010-11-01

    Full Text Available Abstract A recent article in BMC Bioinformatics describes new advances in workflow systems for computational modeling in systems biology. Such systems can accelerate, and improve the consistency of, modeling through automation not only at the simulation and results-production stages, but also at the model-generation stage. Their work is a harbinger of the next generation of more powerful software for systems biologists. See research article: http://www.biomedcentral.com/1471-2105/11/582/abstract/ Ever since the rise of systems biology at the end of the last century, mathematical representations of biological systems and their activities have flourished. They are being used to describe everything from biomolecular networks, such as gene regulation, metabolic processes and signaling pathways, at the lowest biological scales, to tissue growth and differentiation, drug effects, environmental interactions, and more. A very active area in the field has been the development of techniques that facilitate the construction, analysis and dissemination of computational models. The heterogeneous, distributed nature of most data resources today has increased not only the opportunities for, but also the difficulties of, developing software systems to support these tasks. The work by Li et al. 1 published in BMC Bioinformatics represents a promising evolutionary step forward in this area. They describe a workflow system - a visual software environment enabling a user to create a connected set of operations to be performed sequentially using seperate tools and resources. Their system uses third-party data resources accessible over the Internet to elaborate and parametrize (that is, assign parameter values to computational models in a semi-automated manner. In Li et al.'s work, the authors point towards a promising future for computational modeling and simultaneously highlight some of the difficulties that need to be overcome before we get there.

  8. Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases

    Directory of Open Access Journals (Sweden)

    George E. Louridas

    2017-02-01

    Full Text Available Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction and emergence (upward biological direction could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

  9. Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases.

    Science.gov (United States)

    Louridas, George E; Lourida, Katerina G

    2017-02-21

    Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

  10. Predicting biological system objectives de novo from internal state measurements

    Directory of Open Access Journals (Sweden)

    Maranas Costas D

    2008-01-01

    Full Text Available Abstract Background Optimization theory has been applied to complex biological systems to interrogate network properties and develop and refine metabolic engineering strategies. For example, methods are emerging to engineer cells to optimally produce byproducts of commercial value, such as bioethanol, as well as molecular compounds for disease therapy. Flux balance analysis (FBA is an optimization framework that aids in this interrogation by generating predictions of optimal flux distributions in cellular networks. Critical features of FBA are the definition of a biologically relevant objective function (e.g., maximizing the rate of synthesis of biomass, a unit of measurement of cellular growth and the subsequent application of linear programming (LP to identify fluxes through a reaction network. Despite the success of FBA, a central remaining challenge is the definition of a network objective with biological meaning. Results We present a novel method called Biological Objective Solution Search (BOSS for the inference of an objective function of a biological system from its underlying network stoichiometry as well as experimentally-measured state variables. Specifically, BOSS identifies a system objective by defining a putative stoichiometric "objective reaction," adding this reaction to the existing set of stoichiometric constraints arising from known interactions within a network, and maximizing the putative objective reaction via LP, all the while minimizing the difference between the resultant in silico flux distribution and available experimental (e.g., isotopomer flux data. This new approach allows for discovery of objectives with previously unknown stoichiometry, thus extending the biological relevance from earlier methods. We verify our approach on the well-characterized central metabolic network of Saccharomyces cerevisiae. Conclusion We illustrate how BOSS offers insight into the functional organization of biochemical networks

  11. Arrays in biological and chemical analysis

    DEFF Research Database (Denmark)

    Christensen, Claus Bo Vöge

    2002-01-01

    Recently a dramatic change has happened for biological and biochemical analysis. Originally developed as an academic massive parallel screening tool, industry has caught the idea as well of performing all kinds of assays in the new format of microarrays. From food manufacturers over water supply...... plants to the omnipresent pharmaceutical industry, the buzz-word is bioarrays, attracting scientific funding and investor capital. Although only few commercial products are currently out in the research laboratorium, hospital clinic or at the local doctor, there are high expectations for arrays screening...... predispositions and following therapy, monitoring the amount of bacteria in food stuff, measuring the small signs from cardiac arrest before it happens, analysing the toxin level in a water sample (preferentially on-line) or deciphering the identity of an infecting bug. (C) 2002 Elsevier Science B.V. All rights...

  12. Computational Modeling of Biological Systems From Molecules to Pathways

    CERN Document Server

    2012-01-01

    Computational modeling is emerging as a powerful new approach for studying and manipulating biological systems. Many diverse methods have been developed to model, visualize, and rationally alter these systems at various length scales, from atomic resolution to the level of cellular pathways. Processes taking place at larger time and length scales, such as molecular evolution, have also greatly benefited from new breeds of computational approaches. Computational Modeling of Biological Systems: From Molecules to Pathways provides an overview of established computational methods for the modeling of biologically and medically relevant systems. It is suitable for researchers and professionals working in the fields of biophysics, computational biology, systems biology, and molecular medicine.

  13. A systems biology approach reveals common metastatic pathways in osteosarcoma

    Directory of Open Access Journals (Sweden)

    Flores Ricardo J

    2012-05-01

    Full Text Available Abstract Background Osteosarcoma (OS is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest-path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic profiles but remained hidden from the direct analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified significant common pathways, including “Cytoskeleton remodeling/TGF/WNT”, “Cytoskeleton remodeling/Cytoskeleton remodeling”, and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the genomic and proteomic profiles in the two metastatic models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the Sa

  14. The start of systems biology in Ukraine

    Directory of Open Access Journals (Sweden)

    Obolenskaya M. Yu.

    2014-01-01

    Full Text Available The first laboratory of Systems Biology in Ukraine (IMBIG NASU represents a track record of its scientific results. They include the pioneered development of a web-based tool for genome-wide surveys of eukaryotic promoters for the presence of transcription factors binding sites (COTRASIF; the deciphered mechanisms of the fine-tuned and balanced response of primary hepatocytes to interferon alpha levels recorded after partial hepatectomy; the elaboration of a novel method of gene regulatory network inference compatible with GRID environment and the development of a stoichiometric model of folate-related one carbon unit metabolism in human placenta and its application for the characteristics of the system’s behavior as a whole at different human pathologies.

  15. Quantum integrable systems. Quantitative methods in biology

    CERN Document Server

    Feverati, Giovanni

    2011-01-01

    Quantum integrable systems have very strong mathematical properties that allow an exact description of their energetic spectrum. From the Bethe equations, I formulate the Baxter "T-Q" relation, that is the starting point of two complementary approaches based on nonlinear integral equations. The first one is known as thermodynamic Bethe ansatz, the second one as Kl\\"umper-Batchelor-Pearce-Destri- de Vega. I show the steps toward the derivation of the equations for some of the models concerned. I study the infrared and ultraviolet limits and discuss the numerical approach. Higher rank integrals of motion can be obtained, so gaining some control on the eigenvectors. After, I discuss the Hubbard model in relation to the N = 4 supersymmetric gauge theory. The Hubbard model describes hopping electrons on a lattice. In the second part, I present an evolutionary model based on Turing machines. The goal is to describe aspects of the real biological evolution, or Darwinism, by letting evolve populations of algorithms. ...

  16. Systems Biology and Ecology of Streamlined Bacterioplankton

    Science.gov (United States)

    Giovannoni, S. J.

    2014-12-01

    complex questions hinge on translating gene frequencies into trait based ecological models that reflect the systems biology of cells.

  17. Web API for biology with a workflow navigation system.

    Science.gov (United States)

    Kwon, Yeondae; Shigemoto, Yasumasa; Kuwana, Yoshikazu; Sugawara, Hideaki

    2009-07-01

    DNA Data Bank of Japan (DDBJ) provides Web-based systems for biological analysis, called Web APIs for biology (WABI). So far, we have developed over 20 SOAP services and several workflows that consist of a series of method invocations. In this article, we present newly developed services of WABI, that is, REST-based Web services, additional workflows and a workflow navigation system. Each Web service and workflow can be used as a complete service or a building block for programmers to construct more complex information processing systems. The workflow navigation system aims to help non-programming biologists perform analysis tasks by providing next applicable services on Web browsers according to the output of a previously selected service. With this function, users can apply multiple services consecutively only by following links without any programming or manual copy-and-paste operations on Web browsers. The listed services are determined automatically by the system referring to the dictionaries of service categories, the input/output types of services and HTML tags. WABI and the workflow navigation system are freely accessible at http://www.xml.nig.ac.jp/index.html and http://cyclamen.ddbj.nig.ac.jp/, respectively.

  18. Algebraic Systems Biology: A Case Study for the Wnt Pathway.

    Science.gov (United States)

    Gross, Elizabeth; Harrington, Heather A; Rosen, Zvi; Sturmfels, Bernd

    2016-01-01

    Steady-state analysis of dynamical systems for biological networks gives rise to algebraic varieties in high-dimensional spaces whose study is of interest in their own right. We demonstrate this for the shuttle model of the Wnt signaling pathway. Here, the variety is described by a polynomial system in 19 unknowns and 36 parameters. It has degree 9 over the parameter space. This case study explores multistationarity, model comparison, dynamics within regions of the state space, identifiability, and parameter estimation, from a geometric point of view. We employ current methods from computational algebraic geometry, polyhedral geometry, and combinatorics.

  19. A SYSTEMIC VISION OF BIOLOGY: OVERCOMING LINEARITY

    Directory of Open Access Journals (Sweden)

    M. Mayer

    2005-07-01

    Full Text Available Many  authors have proposed  that contextualization of reality  is necessary  to teach  Biology, empha- sizing students´ social and  economic realities.   However, contextualization means  more than  this;  it is related  to working with  different kinds of phenomena  and/or objects  which enable  the  expression of scientific concepts.  Thus,  contextualization allows the integration of different contents.  Under this perspective,  the  objectives  of this  work were to articulate different  biology concepts  in order  to de- velop a systemic vision of biology; to establish  relationships with other areas of knowledge and to make concrete the  cell molecular  structure and organization as well as their  implications  on living beings´ environment, using  contextualization.  The  methodology  adopted  in this  work  was based  on three aspects:  interdisciplinarity, contextualization and development of competences,  using energy:  its flux and transformations as a thematic axis and  an approach  which allowed the  interconnection between different situations involving  these  concepts.   The  activities developed  were:  1.   dialectic exercise, involving a movement around  micro and macroscopic aspects,  by using questions  and activities,  sup- ported  by the use of alternative material  (as springs, candles on the energy, its forms, transformations and  implications  in the  biological way (microscopic  concepts;  2, Construction of molecular  models, approaching the concepts of atom,  chemical bonds and bond energy in molecules; 3. Observations de- veloped in Manguezal¨(mangrove swamp  ecosystem (Itapissuma, PE  were used to work macroscopic concepts  (as  diversity  and  classification  of plants  and  animals,  concerning  to  energy  flow through food chains and webs. A photograph register of all activities  along the course plus texts

  20. A systems biology perspective of wine fermentations.

    Science.gov (United States)

    Pizarro, Francisco; Vargas, Felipe A; Agosin, Eduardo

    2007-11-01

    The yeast Saccharomyces cerevisiae is an important industrial microorganism. Nowadays, it is being used as a cell factory for the production of pharmaceuticals such as insulin, although this yeast has long been utilized in the bakery to raise dough, and in the production of alcoholic beverages, fermenting the sugars derived from rice, wheat, barley, corn and grape juice. S. cerevisiae has also been extensively used as a model eukaryotic system. In the last decade, genomic techniques have revealed important features of its molecular biology. For example, DNA array technologies are routinely used for determining gene expression levels in cells under different physiological conditions or environmental stimuli. Laboratory strains of S. cerevisiae are different from wine strains. For instance, laboratory yeasts are unable to completely transform all the sugar in the grape must into ethanol under winemaking conditions. In fact, standard culture conditions are usually very different from winemaking conditions, where multiple stresses occur simultaneously and sequentially throughout the fermentation. The response of wine yeasts to these stimuli differs in some aspects from laboratory strains, as suggested by the increasing number of studies in functional genomics being conducted on wine strains. In this paper we review the most recent applications of post-genomic techniques to understand yeast physiology in the wine industry. We also report recent advances in wine yeast strain improvement and propose a reference framework for integration of genomic information, bioinformatic tools and molecular biology techniques for cellular and metabolic engineering. Finally, we discuss the current state and future perspectives for using 'modern' biotechnology in the wine industry.

  1. Dynamical Systems and Control Theory Inspired by Molecular Biology

    Science.gov (United States)

    2014-10-02

    in both bacterial and eukaryotic signaling pathways. A common theme in the systems biology literature is that certain systems whose output variables...AFRL-OSR-VA-TR-2014-0282 DYNAMICAL SYSTEMS AND CONTROL THEORY INSPIRED BY MOLECULAR BIOLOGY Eduardo Sontag RUTGERS THE STATE UNIVERSITY OF NEW JERSEY...Standard Form 298 (Re . 8-98) v Prescribed by ANSI Std. Z39.18 DYNAMICAL SYSTEMS AND CONTROL THEORY INSPIRED BY MOLECULAR BIOLOGY AFOSR FA9550-11-1-0247

  2. Exoproteomics: exploring the world around biological systems.

    Science.gov (United States)

    Armengaud, Jean; Christie-Oleza, Joseph A; Clair, Gérémy; Malard, Véronique; Duport, Catherine

    2012-10-01

    The term 'exoproteome' describes the protein content that can be found in the extracellular proximity of a given biological system. These proteins arise from cellular secretion, other protein export mechanisms or cell lysis, but only the most stable proteins in this environment will remain in abundance. It has been shown that these proteins reflect the physiological state of the cells in a given condition and are indicators of how living systems interact with their environments. High-throughput proteomic approaches based on a shotgun strategy, and high-resolution mass spectrometers, have modified the authors' view of exoproteomes. In the present review, the authors describe how these new approaches should be exploited to obtain the maximum useful information from a sample, whatever its origin. The methodologies used for studying secretion from model cell lines derived from eukaryotic, multicellular organisms, virulence determinants of pathogens and environmental bacteria and their relationships with their habitats are illustrated with several examples. The implication of such data, in terms of proteogenomics and the discovery of novel protein functions, is discussed.

  3. Programmable temperature control system for biological materials

    Science.gov (United States)

    Anselmo, V. J.; Harrison, R. G.; Rinfret, A. P.

    1982-01-01

    A system was constructed which allows programmable temperature-time control for a 5 cu cm sample volume of arbitrary biological material. The system also measures the parameters necessary for the determination of the sample volume specific heat and thermal conductivity as a function of temperature, and provides a detailed measurement of the temperature during phase change and a means of calculating the heat of the phase change. Steady-state and dynamic temperature control is obtained by supplying heat to the sample volume through resistive elements constructed as an integral part of the sample container. For cooling purposes, this container is totally immersed into a cold heat sink. Using a mixture of dry ice and alcohol at 79 C, the sample volume can be controlled from +40 to -60 C at rates from steady state to + or - 65 C/min. Steady-state temperature precision is better than 0.2 C, while the dynamic capability depends on the temperature rate of change as well as the mass of both the sample and the container.

  4. Quantifying electron transfer reactions in biological systems

    DEFF Research Database (Denmark)

    Sjulstok, Emil Sjulstok; Olsen, Jógvan Magnus Haugaard; Solov'yov, Ilia A

    2015-01-01

    Various biological processes involve the conversion of energy into forms that are usable for chemical transformations and are quantum mechanical in nature. Such processes involve light absorption, excited electronic states formation, excitation energy transfer, electrons and protons tunnelling...... which for example occur in photosynthesis, cellular respiration, DNA repair, and possibly magnetic field sensing. Quantum biology uses computation to model biological interactions in light of quantum mechanical effects and has primarily developed over the past decade as a result of convergence between...... quantum physics and biology. In this paper we consider electron transfer in biological processes, from a theoretical view-point; namely in terms of quantum mechanical and semi-classical models. We systematically characterize the interactions between the moving electron and its biological environment...

  5. Systems biology of microbial exopolysaccharides production

    Directory of Open Access Journals (Sweden)

    Ozlem eAtes

    2015-12-01

    Full Text Available Exopolysaccharides (EPS produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture and medicine. EPSs are mainly associated with high-value applications and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore a systems-based approach constitutes an important step towards understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan and dextran.

  6. Designing the Cloud-based DOE Systems Biology Knowledgebase

    Energy Technology Data Exchange (ETDEWEB)

    Lansing, Carina S.; Liu, Yan; Yin, Jian; Corrigan, Abigail L.; Guillen, Zoe C.; Kleese van Dam, Kerstin; Gorton, Ian

    2011-09-01

    Systems Biology research, even more than many other scientific domains, is becoming increasingly data-intensive. Not only have advances in experimental and computational technologies lead to an exponential increase in scientific data volumes and their complexity, but increasingly such databases themselves are providing the basis for new scientific discoveries. To engage effectively with these community resources, integrated analyses, synthesis and simulation software is needed, regularly supported by scientific workflows. In order to provide a more collaborative, community driven research environment for this heterogeneous setting, the Department of Energy (DOE) has decided to develop a federated, cloud based cyber infrastructure - the Systems Biology Knowledgebase (Kbase). Pacific Northwest National Laboratory (PNNL) with its long tradition in data intensive science lead two of the five initial pilot projects, these two focusing on defining and testing the basic federated cloud-based system architecture and develop a prototype implementation. Hereby the community wide accessibility of biological data and the capability to integrate and analyze this data within its changing research context were seen as key technical functionalities the Kbase needed to enable. In this paper we describe the results of our investigations into the design of a cloud based federated infrastructure for: (1) Semantics driven data discovery, access and integration; (2) Data annotation, publication and sharing; (3) Workflow enabled data analysis; and (4) Project based collaborative working. We describe our approach, exemplary use cases and our prototype implementation that demonstrates the feasibility of this approach.

  7. Systems Biology for Mapping Genotype-Phenotype Relations in Yeast

    KAUST Repository

    Nielsen, Jens

    2016-01-25

    The yeast Saccharomyces cerevisiae is widely used for production of fuels, chemicals, pharmaceuticals and materials. Through metabolic engineering of this yeast a number of novel new industrial processes have been developed over the last 10 years. Besides its wide industrial use, S. cerevisiae serves as an eukaryal model organism, and many systems biology tools have therefore been developed for this organism. Among these genome-scale metabolic models have shown to be most successful as they easy integrate with omics data and at the same time have been shown to have excellent predictive power. Despite our extensive knowledge of yeast metabolism and its regulation we are still facing challenges when we want to engineer complex traits, such as improved tolerance to toxic metabolites like butanol and elevated temperatures or when we want to engineer the highly complex protein secretory pathway. In this presentation it will be demonstrated how we can combine directed evolution with systems biology analysis to identify novel targets for rational design-build-test of yeast strains that have improved phenotypic properties. In this lecture an overview of systems biology of yeast will be presented together with examples of how genome-scale metabolic modeling can be used for prediction of cellular growth at different conditions. Examples will also be given on how adaptive laboratory evolution can be used for identifying targets for improving tolerance towards butanol, increased temperature and low pH and for improving secretion of heterologous proteins.

  8. Exploring Synthetic and Systems Biology at the University of Edinburgh.

    Science.gov (United States)

    Fletcher, Liz; Rosser, Susan; Elfick, Alistair

    2016-06-15

    The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme.

  9. [Biological material sampling for atomic absorption analysis].

    Science.gov (United States)

    Makarenko, N P; Ganebnykh, E V

    2007-01-01

    The optimum conditions have been chosen for mineralization of biological material for the atomic absorption determination of toxic metals, by using a [Russian characters: see text]-01 laboratory furnace (Gefest) upon exposure to high temperature, pressure, and microwave field. The completeness of dissection of biological material by microwave mineralization is shown under the optimal conditions.

  10. Hierarchical structure of biological systems: A bioengineering approach

    OpenAIRE

    Alcocer-Cuarón, Carlos; Rivera, Ana L; Castaño, Victor M.

    2013-01-01

    A general theory of biological systems, based on few fundamental propositions, allows a generalization of both Wierner and Berthalanffy approaches to theoretical biology. Here, a biological system is defined as a set of self-organized, differentiated elements that interact pair-wise through various networks and media, isolated from other sets by boundaries. Their relation to other systems can be described as a closed loop in a steady-state, which leads to a hierarchical structure and function...

  11. Radionuclide Imaging Technologies for Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

    Howell, Calvin R. [Duke Univ., Durham, NC (United States); Reid, Chantal D. [Duke Univ., Durham, NC (United States); Weisenberger, Andrew G. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States)

    2014-05-14

    The main objective of this project is to develop technologies and experimental techniques for studying the dynamics of physiological responses of plants to changes in their interface with the local environment and to educate a new generation of scientists in an interdisciplinary environment of biology, physics and engineering. Also an important goal is to perform measurements to demonstrate the new data that can be produced and made available to the plant-biology community using the imaging technologies and experimental techniques developed in this project. The study of the plant-environment interface includes a wide range of topics in plant physiology, e.g., the root-soil interface, resource availability, impact of herbivores, influence of microbes on root surface, and responses to toxins in the air and soil. The initial scientific motivation for our work is to improve understanding of the mechanisms for physiological responses to abrupt changes in the local environment, in particular, the responses that result in short-term adjustments in resource (e.g., sugars, nutrients and water) allocations. Data of time-dependent responses of plants to environmental changes are essential in developing mechanistic models for substance intake and resource allocation. Our approach is to use radioisotope tracing techniques to study whole-plant and plant organ (e.g., leaves, stems, roots) dynamical responses to abrupt changes in environmental conditions such as concentration of CO2 in the atmosphere, nutrient availability and lighting. To this aim we are collaborating with the Radiation Detector and Imaging Group at the Thomas Jefferson National Laboratory Facility (JLab) to develop gamma-ray and beta particle imaging systems optimized for plant studies. The radioisotope tracing measurements are conducted at the Phytotron facility at Duke University. The Phytotron is a controlled environment plant research facility with a variety of plant growth chambers. One chamber

  12. Cell-Based Systems Biology Analysis of Human AS03-Adjuvanted H5N1 Avian Influenza Vaccine Responses: A Phase I Randomized Controlled Trial

    Science.gov (United States)

    Samir, Parimal; Galassie, Allison; Allos, Tara M.; Niu, Xinnan; Gordy, Laura E.; Creech, C. Buddy; Prasad, Nripesh; Jensen, Travis L.; Hill, Heather; Levy, Shawn E.; Joyce, Sebastian; Link, Andrew J.; Edwards, Kathryn M.

    2017-01-01

    Background Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. Objective and Methods We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18–49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination. Results Both vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination. Conclusions Using this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed. Trial Registration ClinicalTrials.gov NCT

  13. Toward metabolic engineering in the context of system biology and synthetic biology: advances and prospects.

    Science.gov (United States)

    Liu, Yanfeng; Shin, Hyun-dong; Li, Jianghua; Liu, Long

    2015-02-01

    Metabolic engineering facilitates the rational development of recombinant bacterial strains for metabolite overproduction. Building on enormous advances in system biology and synthetic biology, novel strategies have been established for multivariate optimization of metabolic networks in ensemble, spatial, and dynamic manners such as modular pathway engineering, compartmentalization metabolic engineering, and metabolic engineering guided by genome-scale metabolic models, in vitro reconstitution, and systems and synthetic biology. Herein, we summarize recent advances in novel metabolic engineering strategies. Combined with advancing kinetic models and synthetic biology tools, more efficient new strategies for improving cellular properties can be established and applied for industrially important biochemical production.

  14. A guide to numerical modelling in systems biology

    CERN Document Server

    Deuflhard, Peter

    2015-01-01

    This book is intended for students of computational systems biology with only a limited background in mathematics. Typical books on systems biology merely mention algorithmic approaches, but without offering a deeper understanding. On the other hand, mathematical books are typically unreadable for computational biologists. The authors of the present book have worked hard to fill this gap. The result is not a book on systems biology, but on computational methods in systems biology. This book originated from courses taught by the authors at Freie Universität Berlin. The guiding idea of the courses was to convey those mathematical insights that are indispensable for systems biology, teaching the necessary mathematical prerequisites by means of many illustrative examples and without any theorems. The three chapters cover the mathematical modelling of biochemical and physiological processes, numerical simulation of the dynamics of biological networks, and identification of model parameters by means of comparisons...

  15. Pattern recognition software and techniques for biological image analysis.

    Directory of Open Access Journals (Sweden)

    Lior Shamir

    Full Text Available The increasing prevalence of automated image acquisition systems is enabling new types of microscopy experiments that generate large image datasets. However, there is a perceived lack of robust image analysis systems required to process these diverse datasets. Most automated image analysis systems are tailored for specific types of microscopy, contrast methods, probes, and even cell types. This imposes significant constraints on experimental design, limiting their application to the narrow set of imaging methods for which they were designed. One of the approaches to address these limitations is pattern recognition, which was originally developed for remote sensing, and is increasingly being applied to the biology domain. This approach relies on training a computer to recognize patterns in images rather than developing algorithms or tuning parameters for specific image processing tasks. The generality of this approach promises to enable data mining in extensive image repositories, and provide objective and quantitative imaging assays for routine use. Here, we provide a brief overview of the technologies behind pattern recognition and its use in computer vision for biological and biomedical imaging. We list available software tools that can be used by biologists and suggest practical experimental considerations to make the best use of pattern recognition techniques for imaging assays.

  16. Pattern recognition software and techniques for biological image analysis.

    Science.gov (United States)

    Shamir, Lior; Delaney, John D; Orlov, Nikita; Eckley, D Mark; Goldberg, Ilya G

    2010-11-24

    The increasing prevalence of automated image acquisition systems is enabling new types of microscopy experiments that generate large image datasets. However, there is a perceived lack of robust image analysis systems required to process these diverse datasets. Most automated image analysis systems are tailored for specific types of microscopy, contrast methods, probes, and even cell types. This imposes significant constraints on experimental design, limiting their application to the narrow set of imaging methods for which they were designed. One of the approaches to address these limitations is pattern recognition, which was originally developed for remote sensing, and is increasingly being applied to the biology domain. This approach relies on training a computer to recognize patterns in images rather than developing algorithms or tuning parameters for specific image processing tasks. The generality of this approach promises to enable data mining in extensive image repositories, and provide objective and quantitative imaging assays for routine use. Here, we provide a brief overview of the technologies behind pattern recognition and its use in computer vision for biological and biomedical imaging. We list available software tools that can be used by biologists and suggest practical experimental considerations to make the best use of pattern recognition techniques for imaging assays.

  17. Controlled ecological life support system - biological problems

    Science.gov (United States)

    Moore, B., III (Editor); Macelroy, R. D. (Editor)

    1982-01-01

    The general processes and controls associated with two distinct experimental paradigms are examined. Specific areas for research related to biotic production (food production) and biotic decomposition (waste management) are explored. The workshop discussions were directed toward Elemental cycles and the biological factors that affect the transformations of nutrients into food, of food material into waste, and of waste into nutrients were discussed. To focus on biological issues, the discussion assumed that (1) food production would be by biological means (thus excluding chemical synthesis), (2) energy would not be a limiting factor, and (3) engineering capacity for composition and leak rate would be adequate.

  18. Analysis of biological processes and diseases using text mining approaches.

    Science.gov (United States)

    Krallinger, Martin; Leitner, Florian; Valencia, Alfonso

    2010-01-01

    A number of biomedical text mining systems have been developed to extract biologically relevant information directly from the literature, complementing bioinformatics methods in the analysis of experimentally generated data. We provide a short overview of the general characteristics of natural language data, existing biomedical literature databases, and lexical resources relevant in the context of biomedical text mining. A selected number of practically useful systems are introduced together with the type of user queries supported and the results they generate. The extraction of biological relationships, such as protein-protein interactions as well as metabolic and signaling pathways using information extraction systems, will be discussed through example cases of cancer-relevant proteins. Basic strategies for detecting associations of genes to diseases together with literature mining of mutations, SNPs, and epigenetic information (methylation) are described. We provide an overview of disease-centric and gene-centric literature mining methods for linking genes to phenotypic and genotypic aspects. Moreover, we discuss recent efforts for finding biomarkers through text mining and for gene list analysis and prioritization. Some relevant issues for implementing a customized biomedical text mining system will be pointed out. To demonstrate the usefulness of literature mining for the molecular oncology domain, we implemented two cancer-related applications. The first tool consists of a literature mining system for retrieving human mutations together with supporting articles. Specific gene mutations are linked to a set of predefined cancer types. The second application consists of a text categorization system supporting breast cancer-specific literature search and document-based breast cancer gene ranking. Future trends in text mining emphasize the importance of community efforts such as the BioCreative challenge for the development and integration of multiple systems into

  19. Industrial systems biology and its impact on synthetic biology of yeast cell factories

    DEFF Research Database (Denmark)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-01-01

    Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools......, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex...... regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal...

  20. Industrial systems biology and its impact on synthetic biology of yeast cell factories.

    Science.gov (United States)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-06-01

    Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal of developing improved yeast cell factories. Biotechnol. Bioeng. 2016;113: 1164-1170. © 2015 Wiley Periodicals, Inc.

  1. How do precision medicine and system biology response to human body's complex adaptability?

    Science.gov (United States)

    Yuan, Bing

    2016-12-01

    In the field of life sciences, although system biology and "precision medicine" introduce some complex scientifific methods and techniques, it is still based on the "analysis-reconstruction" of reductionist theory as a whole. Adaptability of complex system increase system behaviour uncertainty as well as the difficulties of precise identifification and control. It also put systems biology research into trouble. To grasp the behaviour and characteristics of organism fundamentally, systems biology has to abandon the "analysis-reconstruction" concept. In accordance with the guidelines of complexity science, systems biology should build organism model from holistic level, just like the Chinese medicine did in dealing with human body and disease. When we study the living body from the holistic level, we will fifind the adaptability of complex system is not the obstacle that increases the diffificulty of problem solving. It is the "exceptional", "right-hand man" that helping us to deal with the complexity of life more effectively.

  2. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

    Directory of Open Access Journals (Sweden)

    Sudin eBhattacharya

    2012-12-01

    Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

  3. Systems biology studies of Aspergilli - from sequence to science

    DEFF Research Database (Denmark)

    Andersen, Mikael Rørdam

    2008-01-01

    The recent dawn of the new biological mindset called systems biology has put forth a new way of analyzing and understanding biology. Carried by the notion that no element of a cell is an island, systems biology takes a holistic approach, and attempts to understand life as systems that have co...... a few. The recent publication of the genome sequences of several filamentous fungi of the Aspergillus species (Aspergilli), has, along with the accumulation of years of reductionist studies, been a catalyst for the application of systems biology to this interesting group of fungi. Among the genome...... biology approach has been applied to a wide range of issues. These tools include the compilation of data from literature on A. niger enzymes to form a re-constructed metabolic network and model of metabolism, allowing assessment of the industrial production potential of metabolites from this fungus. Based...

  4. A review of imaging techniques for systems biology

    Directory of Open Access Journals (Sweden)

    Po Ming J

    2008-08-01

    Full Text Available Abstract This paper presents a review of imaging techniques and of their utility in system biology. During the last decade systems biology has matured into a distinct field and imaging has been increasingly used to enable the interplay of experimental and theoretical biology. In this review, we describe and compare the roles of microscopy, ultrasound, CT (Computed Tomography, MRI (Magnetic Resonance Imaging, PET (Positron Emission Tomography, and molecular probes such as quantum dots and nanoshells in systems biology. As a unified application area among these different imaging techniques, examples in cancer targeting are highlighted.

  5. Systems biology studies of Aspergilli - from sequence to science

    OpenAIRE

    Andersen, Mikael Rørdam; Nielsen, Jens; Nielsen, Michael Lynge

    2008-01-01

    The recent dawn of the new biological mindset called systems biology has put forth a new way of analyzing and understanding biology. Carried by the notion that no element of a cell is an island, systems biology takes a holistic approach, and attempts to understand life as systems that have co-evolved and not as a haphazardly compiled list of parts. This has been made possible by the socalled genomic revolution — the sequencing of the genomic DNA of a rapidly increasing number of organisms — a...

  6. A Magnetic Sensor System for Biological Detection

    KAUST Repository

    Li, Fuquan

    2015-05-01

    Magnetic biosensors detect biological targets through sensing the stray field of magnetic beads which label the targets. Commonly, magnetic biosensors employ the “sandwich” method to immobilize biological targets, i.e., the targets are sandwiched between a bio-functionalized sensor surface and bio-functionalized magnetic beads. This method has been used very successfully in different application, but its execution requires a rather elaborate procedure including several washing and incubation steps. This dissertation investigates a new magnetic biosensor concept, which enables a simple and effective detection of biological targets. The biosensor takes advantage of the size difference between bare magnetic beads and compounds of magnetic beads and biological targets. First, the detection of super-paramagnetic beads via magnetic tunnel junction (MTJ) sensors is implemented. Frequency modulation is used to enhance the signal-to-noise ratio, enabling the detection of a single magnetic bead. Second, the concept of the magnetic biosensor is investigated theoretically. The biosensor consists of an MTJ sensor, which detects the stray field of magnetic beads inside of a trap on top of the MTJ. A microwire between the trap and the MTJ is used to attract magnetic beads to the trapping well by applying a current to it. The MTJ sensor’s output depends on the number of beads inside the trap. If biological targets are in the sample solution, the beads will form bead compounds consisting of beads linked to the biological targets. Since bead compounds are larger than bare beads, the number of beads inside the trapping well will depend on the presence of biological targets. Hence, the output of the MTJ sensor will depend on the biological targets. The dependences of sensor signals on the sizes of the MTJ sensor, magnetic beads and biological targets are studied to find the optimum constellations for the detection of specific biological targets. The optimization is demonstrated

  7. Global sensitivity and identifiability implications in systems biology

    OpenAIRE

    Dobre, Simona; Bastogne, Thierry; Richard, Alain

    2010-01-01

    International audience; In systems biology, a common approach to model biological processes is to use large systems of differential equations.The associated parameter estimation problem requires to prior handle identifiability and sensitivity issues in a practical biological framework. The lack of method to assess global practical identifiability has leaded us to analyze and establish bridges between global sensitivity and identifiability measures. Specifically, we are interested in deriving ...

  8. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

    Science.gov (United States)

    He, Fei; Murabito, Ettore; Westerhoff, Hans V

    2016-04-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways.

  9. TissueCypher™: A systems biology approach to anatomic pathology

    Directory of Open Access Journals (Sweden)

    Jeffrey W Prichard

    2015-01-01

    Full Text Available Background: Current histologic methods for diagnosis are limited by intra- and inter-observer variability. Immunohistochemistry (IHC methods are frequently used to assess biomarkers to aid diagnoses, however, IHC staining is variable and nonlinear and the manual interpretation is subjective. Furthermore, the biomarkers assessed clinically are typically biomarkers of epithelial cell processes. Tumors and premalignant tissues are not composed only of epithelial cells but are interacting systems of multiple cell types, including various stromal cell types that are involved in cancer development. The complex network of the tissue system highlights the need for a systems biology approach to anatomic pathology, in which quantification of system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making. Aims: Here, we describe a quantitative, multiplexed biomarker imaging approach termed TissueCypher™ that applies systems biology to anatomic pathology. Applications of TissueCypher™ in understanding the tissue system of Barrett's esophagus (BE and the potential use as an adjunctive tool in the diagnosis of BE are described. Patients and Methods: The TissueCypher™ Image Analysis Platform was used to assess 14 epithelial and stromal biomarkers with known diagnostic significance in BE in a set of BE biopsies with nondysplastic BE with reactive atypia (RA, n = 22 and Barrett's with high-grade dysplasia (HGD, n = 17. Biomarker and morphology features were extracted and evaluated in the confirmed BE HGD cases versus the nondysplastic BE cases with RA. Results: Multiple image analysis features derived from epithelial and stromal biomarkers, including immune biomarkers and morphology, showed significant differences between HGD and RA. Conclusions: The assessment of epithelial cell abnormalities combined with an assessment of cellular changes in the lamina propria may serve as an adjunct to conventional

  10. A Comparative Nitrogen Balance and Productivity Analysis of Legume and Non-legume Supported Cropping Systems: The Potential Role of Biological Nitrogen Fixation

    Science.gov (United States)

    Iannetta, Pietro P. M.; Young, Mark; Bachinger, Johann; Bergkvist, Göran; Doltra, Jordi; Lopez-Bellido, Rafael J.; Monti, Michele; Pappa, Valentini A.; Reckling, Moritz; Topp, Cairistiona F. E.; Walker, Robin L.; Rees, Robert M.; Watson, Christine A.; James, Euan K.; Squire, Geoffrey R.; Begg, Graham S.

    2016-01-01

    The potential of biological nitrogen fixation (BNF) to provide sufficient N for production has encouraged re-appraisal of cropping systems that deploy legumes. It has been argued that legume-derived N can maintain productivity as an alternative to the application of mineral fertilizer, although few studies have systematically evaluated the effect of optimizing the balance between legumes and non N-fixing crops to optimize production. In addition, the shortage, or even absence in some regions, of measurements of BNF in crops and forages severely limits the ability to design and evaluate new legume–based agroecosystems. To provide an indication of the magnitude of BNF in European agriculture, a soil-surface N-balance approach was applied to historical data from 8 experimental cropping systems that compared legume and non-legume crop types (e.g., grains, forages and intercrops) across pedoclimatic regions of Europe. Mean BNF for different legume types ranged from 32 to 115 kg ha−1 annually. Output in terms of total biomass (grain, forage, etc.) was 30% greater in non-legumes, which used N to produce dry matter more efficiently than legumes, whereas output of N was greater from legumes. When examined over the crop sequence, the contribution of BNF to the N-balance increased to reach a maximum when the legume fraction was around 0.5 (legume crops were present in half the years). BNF was lower when the legume fraction increased to 0.6–0.8, not because of any feature of the legume, but because the cropping systems in this range were dominated by mixtures of legume and non-legume forages to which inorganic N as fertilizer was normally applied. Forage (e.g., grass and clover), as opposed to grain crops in this range maintained high outputs of biomass and N. In conclusion, BNF through grain and forage legumes has the potential to generate major benefit in terms of reducing or dispensing with the need for mineral N without loss of total output. PMID:27917178

  11. Effect of amino acid supplementation on titer and glycosylation distribution in hybridoma cell cultures-Systems biology-based interpretation using genome-scale metabolic flux balance model and multivariate data analysis.

    Science.gov (United States)

    Reimonn, Thomas M; Park, Seo-Young; Agarabi, Cyrus D; Brorson, Kurt A; Yoon, Seongkyu

    2016-09-01

    Genome-scale flux balance analysis (FBA) is a powerful systems biology tool to characterize intracellular reaction fluxes during cell cultures. FBA estimates intracellular reaction rates by optimizing an objective function, subject to the constraints of a metabolic model and media uptake/excretion rates. A dynamic extension to FBA, dynamic flux balance analysis (DFBA), can calculate intracellular reaction fluxes as they change during cell cultures. In a previous study by Read et al. (2013), a series of informed amino acid supplementation experiments were performed on twelve parallel murine hybridoma cell cultures, and this data was leveraged for further analysis (Read et al., Biotechnol Prog. 2013;29:745-753). In order to understand the effects of media changes on the model murine hybridoma cell line, a systems biology approach is applied in the current study. Dynamic flux balance analysis was performed using a genome-scale mouse metabolic model, and multivariate data analysis was used for interpretation. The calculated reaction fluxes were examined using partial least squares and partial least squares discriminant analysis. The results indicate media supplementation increases product yield because it raises nutrient levels extending the growth phase, and the increased cell density allows for greater culture performance. At the same time, the directed supplementation does not change the overall metabolism of the cells. This supports the conclusion that product quality, as measured by glycoform assays, remains unchanged because the metabolism remains in a similar state. Additionally, the DFBA shows that metabolic state varies more at the beginning of the culture but less by the middle of the growth phase, possibly due to stress on the cells during inoculation. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1163-1173, 2016.

  12. Systems biology of neutrophil differentiation and immune response

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

    2005-01-01

    Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies...

  13. Modeling of Biological Intelligence for SCM System Optimization

    OpenAIRE

    Shengyong Chen; Yujun Zheng; Carlo Cattani; Wanliang Wang

    2012-01-01

    This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM) systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing c...

  14. Analysis of undergraduate cell biology contents in Brazilian public universities.

    Science.gov (United States)

    Mermelstein, Claudia; Costa, Manoel Luis

    2017-04-01

    The enormous amount of information available in cell biology has created a challenge in selecting the core concepts we should be teaching our undergraduates. One way to define a set of essential core ideas in cell biology is to analyze what a specific cell biology community is teaching their students. Our main objective was to analyze the cell biology content currently being taught in Brazilian universities. We collected the syllabi of cell biology courses from public universities in Brazil and analyzed the frequency of cell biology topics in each course. We also compared the Brazilian data with the contents of a major cell biology textbook. Our analysis showed that while some cell biology topics such as plasma membrane and cytoskeleton was present in ∼100% of the Brazilian curricula analyzed others such as cell signaling and cell differentiation were present in only ∼35%. The average cell biology content taught in the Brazilian universities is quite different from what is presented in the textbook. We discuss several possible explanations for these observations. We also suggest a list with essential cell biology topics for any biological or biomedical undergraduate course. The comparative discussion of cell biology topics presented here could be valuable in other educational contexts.

  15. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  16. A basic analysis toolkit for biological sequences

    Directory of Open Access Journals (Sweden)

    Siragusa Enrico

    2007-09-01

    Full Text Available Abstract This paper presents a software library, nicknamed BATS, for some basic sequence analysis tasks. Namely, local alignments, via approximate string matching, and global alignments, via longest common subsequence and alignments with affine and concave gap cost functions. Moreover, it also supports filtering operations to select strings from a set and establish their statistical significance, via z-score computation. None of the algorithms is new, but although they are generally regarded as fundamental for sequence analysis, they have not been implemented in a single and consistent software package, as we do here. Therefore, our main contribution is to fill this gap between algorithmic theory and practice by providing an extensible and easy to use software library that includes algorithms for the mentioned string matching and alignment problems. The library consists of C/C++ library functions as well as Perl library functions. It can be interfaced with Bioperl and can also be used as a stand-alone system with a GUI. The software is available at http://www.math.unipa.it/~raffaele/BATS/ under the GNU GPL.

  17. The Current State and Perspectives of Systems Biology

    Institute of Scientific and Technical Information of China (English)

    Tielui Shi; Yixue Li

    2006-01-01

    Emerging as a new field in biology recently, Systems Biology provides a branch new way to study the biological activities in organisms. In order to decode the complexity of life systematically,systems biology integrates the "-omics" and uses the high throughput methods from transcriptomics,protomics and metabonomics to detect the dynamic activities in cell; and then, it incorporates bioinformatics methods to integrate and analyze those data, and simulate the biological processes based on the model built from those integrated data. In this paper, the current state, the research field and the methods for the Systems Biology are introduced briefly, and then, several ideas about future development in this field are also proposed.

  18. Strategies for structuring interdisciplinary education in Systems Biology

    DEFF Research Database (Denmark)

    Cvijovic, Marija; Höfer, Thomas; Aćimović, Jure

    2016-01-01

    and example curricula. As university education at the Bachelor’s level is traditionally built upon disciplinary degrees, we believe that the most effective way to implement education in Systems Biology would be at the Master’s level, as it offers a more flexible framework. Our team of experts and active......Systems Biology is an approach to biology and medicine that has the potential to lead to a better understanding of how biological properties emerge from the interaction of genes, proteins, molecules, cells and organisms. The approach aims at elucidating how these interactions govern biological...... function by employing experimental data, mathematical models and computational simulations. As Systems Biology is inherently multidisciplinary, education within this field meets numerous hurdles including departmental barriers, availability of all required expertise locally, appropriate teaching material...

  19. Bayesian networks: a powerful tool for systems biology study

    Institute of Scientific and Technical Information of China (English)

    Xiu-Jie WANG

    2010-01-01

    @@ Higher Education Press and Springer-Verlag Berlin Heidelberg 2010The wide application of omics research approaches caused a burst of biological data in the past decade, and also promoted the growth of systems biology, a research field that studies biological questions from a genome-wide point of view. One feature of systems biology study is to integrate and identify. Not only experiments are carried out at whole-genome scales, but also data from various resources, such as genomics, transcriptomics, proteomics,and metabolics data, need to be integrated to identify correlations among targeted entities. Therefore, plenty amounts of experimental data, robust statistical methods, and reliable network construction models are indispensable for systems biology study. Among the available network construction models, Bayesian network is considered as one of the most effective methods available so far for biological network predictions (Pe'er, 2005).

  20. Biological oceanography of the red oceanic system

    Science.gov (United States)

    Theil, Hjalmar; Weikert, Horst

    1. In 1977, 1979 and 1980-81, investigations were carried out which aimed at evaluating the potential risks from mining metalliferous muds precipating in the Atlantis II Deep of the central Red Sea. This environmental research was initiated by the Saudi Sudanese Red Sea Joint Commission in order to avoid any danger for the Red Sea ecosystem. The broad environmental research programme coherent studies in physical, chemical, biological, and geological oceanography as well as toxicological investigations in the oceanic and in reef zones. We summarise the results from our biological fiels studies in the open sea. 2. The biological investigations were concentrated on the area of the Atlantis II Deep. Benthos was sampled between 700-2000m. For comparison a few samples were also taken further north in the central Red Sea, and to east and west along the flanking deep terraces (500-1000m). Plankton studies covered the total water column above the Deep, and were extended along the axial through to north and south. 3. Benthos sampling was carried out using a heavy closing trawl, a large box grab (box size 50 × 50 cm), Van Veen grabs and traps; photographic surveys were made a phototrap and a photosled. Community respiration was measured with a ship-board method using grab subsamples. Nutrient concentrations, seston and phytoplankton standing stocks as well as in situ primary production were determined from hydrocast samples. Data on zooplankton and micronekton composition and standing stock were obtained from samples collected using different multiple opening-and-closing nets equipped with 100 μm, 300 μm, and 1000 μm mesh sizes. Daily and ontogenetical vertical migration patterns were studied by comparisons of data from midday and midnight tows. 4. Throughout the whole area the sediment is a pteropod ooze containing low contentrations of organic matter; measured organic carbon and nitrogen contents were 0.5 and 0.05% respectively, and chloroplastic pigment equivalents

  1. Tracing organizing principles: Learning from the history of systems biology

    DEFF Research Database (Denmark)

    Green, Sara; Wolkenhauer, Olaf

    2014-01-01

    With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to “reverse engineer” the functional organization of biological systems using methodologies from mathematics, engineering and computer science while...... taking advantage of data produced by new experimental techniques. While systems biology is a relatively new approach, the quest for general principles of biological organization dates back to systems theoretic approaches in early and mid-twentieth century. The aim of this paper is to draw...... on this historical background in order to increase the understanding of the motivation behind the search for general principles and to clarify different epistemic aims within systems biology. We pinpoint key aspects of earlier approaches that also underlie the current practice. These are i) the focus on relational...

  2. Growing trend of CE at the omics level: the frontier of systems biology--an update.

    Science.gov (United States)

    Ban, Eunmi; Park, Soo Hyun; Kang, Min-Jung; Lee, Hyun-Jung; Song, Eun Joo; Yoo, Young Sook

    2012-01-01

    Omics is the study of proteins, peptides, genes, and metabolites in living organisms. Systems biology aims to understand the system through the study of the relationship between elements such as genes and proteins in biological system. Recently, systems biology emerged as the result of the advanced development of high-throughput analysis technologies such as DNA sequencers, DNA arrays, and mass spectrometry for omics studies. Among a number of analytical tools and technologies, CE and CE coupled to MS are promising and relatively rapidly developing tools with the potential to provide qualitative and quantitative analyses of biological molecules. With an emphasis on CE for systems biology, this review summarizes the method developments and applications of CE for the genomic, transcriptomic, proteomic, and metabolomic studies focusing on the drug discovery and disease diagnosis and therapies since 2009.

  3. Biological exposure models for oil spill impact analysis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The oil spill impact analysis (OSIA) software system has been developed to supply a tool for comprehensive, quantitative environmental impact assessments resulting from oil spills. In the system, a biological component evaluates potential effects on exposed organisms based on results from a physico-chemieal fates component, including the extent and characteristics of the surface slick, and dissolved and total concentrations of hydrocarbons in the water column. The component includes a particle-based exposure model for migratory adult fish populations, a particle-based exposure model for spawning planktonic organisms (eggs and larvae), and an exposure model for wildlife species (sea birds or marine mammals). The exposure model for migratory adult fish populations simulates the migration behaviors of fish populations migrating to or staying in their feeding areas, over-wintering areas or spawning areas, and determines the acute effects (mortality) and chronic accumulation (body burdens) from the dissolved contaminant. The exposure model for spawning planktonic organisms simulates the release of eggs and larvae, also as particles, from specific spawning areas during the spawning period, and determines their potential exposure to contaminants in the water or sediment. The exposure model for wild species calculates the exposure to surrace oil of wildlife (bird and marine mammal ) categories inhabiting the contaminated area. Compared with the earlier models in which all kinds of organisms are assumed evenly and randomly distributed, the updated biological exposure models can more realistically estimate potential effects on marine ecological system from oil spill pollution events.

  4. Micro and nano-platforms for biological cell analysis

    DEFF Research Database (Denmark)

    Svendsen, Winnie Edith; Castillo, Jaime; Moresco, Jacob Lange;

    2011-01-01

    In this paper some technological platforms developed for biological cell analysis will be presented and compared to existing systems. In brief, we present a novel micro cell culture chamber based on diffusion feeding of cells, into which cells can be introduced and extracted after culturing using...... normal pipettes, thus making it readily usable for clinical laboratories. To enhance the functionality of such a chamber we have been investigating the use of active or passive 3D surface modifications. Active modifications involve miniature electrodes able to record electrical or electrochemical signals...... from the cells, while passive modifications involve the presence of a peptide nanotube based scaffold for the cell culturing that mimics the in vivo environment. Two applications involving fluorescent in situ hybridization (FISH) analysis and cancer cell sorting are presented, as examples of further...

  5. The Systems Biology Research Tool: evolvable open-source software

    Directory of Open Access Journals (Sweden)

    Wright Jeremiah

    2008-06-01

    Full Text Available Abstract Background Research in the field of systems biology requires software for a variety of purposes. Software must be used to store, retrieve, analyze, and sometimes even to collect the data obtained from system-level (often high-throughput experiments. Software must also be used to implement mathematical models and algorithms required for simulation and theoretical predictions on the system-level. Results We introduce a free, easy-to-use, open-source, integrated software platform called the Systems Biology Research Tool (SBRT to facilitate the computational aspects of systems biology. The SBRT currently performs 35 methods for analyzing stoichiometric networks and 16 methods from fields such as graph theory, geometry, algebra, and combinatorics. New computational techniques can be added to the SBRT via process plug-ins, providing a high degree of evolvability and a unifying framework for software development in systems biology. Conclusion The Systems Biology Research Tool represents a technological advance for systems biology. This software can be used to make sophisticated computational techniques accessible to everyone (including those with no programming ability, to facilitate cooperation among researchers, and to expedite progress in the field of systems biology.

  6. Data acquisition and analysis at the Structural Biology Center

    Energy Technology Data Exchange (ETDEWEB)

    Westbrook, M.L.; Coleman, T.A.; Daly, R.T. [Argonne National Lab., IL (United States); Pflugrath, J.W. [Molecular Structure Corp., The Woodlands, TX (United States)

    1996-12-31

    The Structural Biology Center (SBC), a national user facility for macromolecular crystallography located at Argonne National Laboratory`s Advanced Photon Source, is currently being built and commissioned. SBC facilities include a bending-magnet beamline, an insertion-device beamline, laboratory and office space adjacent to the beamlines, and associated instrumentation, experimental apparatus, and facilities. SBC technical facilities will support anomalous dispersion phasing experiments, data collection from microcrystals, data collection from crystals with large molecular structures and rapid data collection from multiple related crystal structures for protein engineering and drug design. The SBC Computing Systems and Software Engineering Group is tasked with developing the SBC Control System, which includes computing systems, network, and software. The emphasis of SBC Control System development has been to provide efficient and convenient beamline control, data acquisition, and data analysis for maximal facility and experimenter productivity. This paper describes the SBC Control System development, specifically data acquisition and analysis at the SBC, and the development methods used to meet this goal.

  7. Biological networks to the analysis of microarray data

    Institute of Scientific and Technical Information of China (English)

    FANG Zhuo; LUO Qingming; ZHANG Guoqing; LI Yixue

    2006-01-01

    Microarray technology, which permits rapid and large-scale screening for patterns of gene expressions, usually generates a large amount of data. How to mine the biological meanings under these data is one of the main challenges in bioinformatics. Compared to the pure mathematical techniques, those methods incorporated with some prior biological knowledge generally bring better interpretations.Recently, a new analysis, in which the knowledge of biological networks such as metabolic network and protein interaction network is introduced, is widely applied to microarray data analysis. The microarray data analysis based on biological networks contains two main research aspects: identification of active components in biological networks and assessment of gene sets significance. In this paper, we briefly review the progress of these two categories of analyses, especially some representative methods.

  8. Analysis of English language learner performance on the biology Massachusetts comprehensive assessment system: The impact of english proficiency, first language characteristics, and late-entry ELL status

    Science.gov (United States)

    Mitchell, Mary A.

    This study analyzed English language learner (ELL) performance on the June 2012 Biology MCAS, namely on item attributes of domain, cognitive skill, and linguistic complexity. It examined the impact of English proficiency, Latinate first language, first language orthography, and late-entry ELL status. The results indicated that English proficiency was a strong predictor of performance and that ELLs at higher levels of English proficiency overwhelmingly passed. The results further indicated that English proficiency introduced a construct-irrelevant variance on the Biology MCAS and raised validity issues for using this assessment at lower levels of English proficiency. This study also found that ELLs with a Latinate first language consistently had statistically significant lower performance. Late-entry ELL status did not predict Biology MCAS performance.

  9. Integrative systems biology for data-driven knowledge discovery.

    Science.gov (United States)

    Greene, Casey S; Troyanskaya, Olga G

    2010-09-01

    Integrative systems biology is an approach that brings together diverse high-throughput experiments and databases to gain new insights into biological processes or systems at molecular through physiological levels. These approaches rely on diverse high-throughput experimental techniques that generate heterogeneous data by assaying varying aspects of complex biological processes. Computational approaches are necessary to provide an integrative view of these experimental results and enable data-driven knowledge discovery. Hypotheses generated from these approaches can direct definitive molecular experiments in a cost-effective manner. By using integrative systems biology approaches, we can leverage existing biological knowledge and large-scale data to improve our understanding of as yet unknown components of a system of interest and how its malfunction leads to disease.

  10. International Conference on Recent Advances in Mathematical Biology, Analysis and Applications

    CERN Document Server

    Saleem, M; Srivastava, H; Khan, Mumtaz; Merajuddin, M

    2016-01-01

    The book contains recent developments and contemporary research in mathematical analysis and in its application to problems arising from the biological and physical sciences. The book is of interest to readers who wish to learn of new research in such topics as linear and nonlinear analysis, mathematical biology and ecology, dynamical systems, graph theory, variational analysis and inequalities, functional analysis, differential and difference equations, partial differential equations, approximation theory, and chaos. All papers were prepared by participants at the International Conference on Recent Advances in Mathematical Biology, Analysis and Applications (ICMBAA-2015) held during 4–6 June 2015 in Aligarh, India. A focal theme of the conference was the application of mathematics to the biological sciences and on current research in areas of theoretical mathematical analysis that can be used as sophisticated tools for the study of scientific problems. The conference provided researchers, academicians and ...

  11. Methods of information geometry in computational system biology (consistency between chemical and biological evolution).

    Science.gov (United States)

    Astakhov, Vadim

    2009-01-01

    Interest in simulation of large-scale metabolic networks, species development, and genesis of various diseases requires new simulation techniques to accommodate the high complexity of realistic biological networks. Information geometry and topological formalisms are proposed to analyze information processes. We analyze the complexity of large-scale biological networks as well as transition of the system functionality due to modification in the system architecture, system environment, and system components. The dynamic core model is developed. The term dynamic core is used to define a set of causally related network functions. Delocalization of dynamic core model provides a mathematical formalism to analyze migration of specific functions in biosystems which undergo structure transition induced by the environment. The term delocalization is used to describe these processes of migration. We constructed a holographic model with self-poetic dynamic cores which preserves functional properties under those transitions. Topological constraints such as Ricci flow and Pfaff dimension were found for statistical manifolds which represent biological networks. These constraints can provide insight on processes of degeneration and recovery which take place in large-scale networks. We would like to suggest that therapies which are able to effectively implement estimated constraints, will successfully adjust biological systems and recover altered functionality. Also, we mathematically formulate the hypothesis that there is a direct consistency between biological and chemical evolution. Any set of causal relations within a biological network has its dual reimplementation in the chemistry of the system environment.

  12. Analysis and enumeration algorithms for biological graphs

    CERN Document Server

    Marino, Andrea

    2015-01-01

    In this work we plan to revise the main techniques for enumeration algorithms and to show four examples of enumeration algorithms that can be applied to efficiently deal with some biological problems modelled by using biological networks: enumerating central and peripheral nodes of a network, enumerating stories, enumerating paths or cycles, and enumerating bubbles. Notice that the corresponding computational problems we define are of more general interest and our results hold in the case of arbitrary graphs. Enumerating all the most and less central vertices in a network according to their eccentricity is an example of an enumeration problem whose solutions are polynomial and can be listed in polynomial time, very often in linear or almost linear time in practice. Enumerating stories, i.e. all maximal directed acyclic subgraphs of a graph G whose sources and targets belong to a predefined subset of the vertices, is on the other hand an example of an enumeration problem with an exponential number of solutions...

  13. Characterization Techniques for Aggregated Nanomaterials in Biological and Environmental Systems

    Science.gov (United States)

    Jeon, Seongho

    Nanoparticles, which are defined as objects with characteristic lengths in the 10--9 -- 10--7 m (nanoscale) size range, are used with increasing frequency in a wide of applications, leading to increases in nanomaterial interactions with biological and environmental systems. There is therefore considerable interest in studying the influence nanomaterials can have when inside the human body or dispersed in the ambient environment. However, nanoparticles persist as homo aggregates or heterogeneous mixtures with organic matters, such as proteins, in biological and environmental systems. A large and growing body of research confirm that nanomaterial morphology as well as the degree of aggregation between nanomaterials influences nanomaterial interactions with their surroundings. Specifically, the structures/morphologies of nanoparticles determine their overall surface areas and corresponding surface reactivity (e.g. their catalytic activity). Nanoparticle transport properties (e.g. diffusion coefficient and extent of cellular uptake) are also determined by both their structures and surface properties. Unfortunately, techniques to characterize nanomaterial size and shape quantitatively, when nanomaterials have complex geometries or persist as aggregates, are lacking. Hydrodynamic sizes of nanoparticles and their aggregates can be inferred by dynamic light scattering (DLS) or nanoparticle tracking analysis (NTA). However, since these techniques are relied on the scattering light intensity properties, sizes of polydisperse sub 30 nm particles cannot be effectively measured in those techniques. For structure inference of aggregated nanomaterials, microscopy images have been used for qualitative visual analysis, but the quantitative morphology analysis technique is yet to be developed. Five studies in this dissertation are hence aimed to develop new techniques to provide improved morphology characterization of aggregated nanomaterials in various biological and environmental

  14. Adapting to Biology: Maintaining Container-Closure System Compatibility with the Therapeutic Biologic Revolution.

    Science.gov (United States)

    Degrazio, Dominick

    Many pharmaceutical companies are transitioning their research and development drug product pipeline from traditional small-molecule injectables to the dimension of evolving therapeutic biologics. Important concerns associated with this changeover are becoming forefront, as challenges develop of varying complexity uncommon with the synthesis and production of traditional drugs. Therefore, alternative measures must be established that aim to preserve the efficacy and functionality of a biologic that might not be implemented for small molecules. Conserving protein stability is relative to perpetuating a net equilibrium of both intrinsic and extrinsic factors. Key to sustaining this balance is the ability of container-closure systems to maintain their compatibility with the ever-changing dynamics of therapeutic biologics. Failure to recognize and adjust the material properties of packaging components to support compatibility with therapeutic biologics can compromise patient safety, drug productivity, and biological stability. This review will examine the differences between small-molecule drugs and therapeutic biologics, lay a basic foundation for understanding the stability of therapeutic biologics, and demonstrate potential sources of container-closure systems' incompatibilities with therapeutic biologics at a mechanistic level.

  15. Magnetic biosensor system to detect biological targets

    KAUST Repository

    Li, Fuquan

    2012-09-01

    Magneto-resistive sensors in combination with magnetic beads provide sensing platforms, which are small in size and highly sensitive. These platforms can be fully integrated with microchannels and electronics to enable devices capable of performing complex tasks. Commonly, a sandwich method is used that requires a specific coating of the sensor\\'s surface to immobilize magnetic beads and biological targets on top of the sensor. This paper concerns a micro device to detect biological targets using magnetic concentration, magnetic as well as mechanical trapping and magnetic sensing. Target detection is based on the size difference between bare magnetic beads and magnetic beads with targets attached. This method remedies the need for a coating layer and reduces the number of steps required to run an experiment. © 2012 IEEE.

  16. The influence of two reciprocating single-file and two rotary-file systems on the apical extrusion of debris and its biological relationship with symptomatic apical periodontitis. A systematic review and meta-analysis.

    Science.gov (United States)

    Caviedes-Bucheli, J; Castellanos, F; Vasquez, N; Ulate, E; Munoz, H R

    2016-03-01

    This systematic review and meta-analysis investigated the influence of the number of files (full-sequence rotary-file versus reciprocating single-file systems) used during root canal preparation on the apical extrusion of debris and its biological relationship with the occurrence of symptomatic apical periodontitis. An extensive literature research was carried out in the Medline, ISI Web of Science and Cochrane databases, for relevant articles with the keyword search strategy. Based on inclusion and exclusion criteria, two reviewers independently rated the quality of each study determining the level of evidence of the articles selected. The primary outcome for the meta-analysis was determined by the amount of debris extruded into the periapical tissue during root canal preparation with multiple- or single-file systems in four laboratory studies. Analysis of in vivo release of neuropeptides (SP and CGRP) after root canal preparation with single- or multiple-file systems was also carried out. Amongst the 128 articles initially found, 113 were excluded for being nonrelevant or not fulfilling the selection criteria. Another four articles were excluded after methodology evaluation. Finally, nine laboratory studies and two in vivo studies were included in the systematic review. Four of the laboratory studies were further included for meta-analysis that revealed greater debris extrusion after the use of single-file techniques when compared to multiple-file systems. Analysis of in vivo neuropeptide expression in the periodontal ligament suggests that the design of the instrument is more important than the number of files used. Both rotary and reciprocating single-file systems generate apical extrusion of debris in laboratory studies, or expression of neuropeptides in vivo. Available evidence is limited, but supports the fact that this inflammatory reaction is not influenced by the number of files but the type of movement and the instrument design.

  17. Complex systems in pulmonary medicine: a systems biology approach to lung disease.

    Science.gov (United States)

    Kaminsky, David A; Irvin, Charles G; Sterk, Peter J

    2011-06-01

    The lung is a highly complex organ that can only be understood by integrating the many aspects of its structure and function into a comprehensive view. Such a view is provided by a systems biology approach, whereby the many layers of complexity, from the molecular genetic, to the cellular, to the tissue, to the whole organ, and finally to the whole body, are synthesized into a working model of understanding. The systems biology approach therefore relies on the expertise of many disciplines, including genomics, proteomics, metabolomics, physiomics, and, ultimately, clinical medicine. The overall structure and functioning of the lung cannot be predicted from studying any one of these systems in isolation, and so this approach highlights the importance of emergence as the fundamental feature of systems biology. In this paper, we will provide an overview of a systems biology approach to lung disease by briefly reviewing the advances made at many of these levels, with special emphasis on recent work done in the realm of pulmonary physiology and the analysis of clinical phenotypes.

  18. Tracing organizing principles: learning from the history of systems biology.

    Science.gov (United States)

    Green, Sara; Wolkenhauer, Olaf

    2013-01-01

    With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to "reverse engineer" the functional organization of biological systems using methodologies from mathematics, engineering and computer science while taking advantage of data produced by new experimental techniques. While systems biology is a relatively new approach, the quest for general principles of biological organization dates back to systems theoretic approaches in early and mid-twentieth century. The aim of this paper is to draw on this historical background in order to increase the understanding of the motivation behind the search for general principles and to clarify different epistemic aims within systems biology. We pinpoint key aspects of earlier approaches that also underlie the current practice. These are i) the focus on relational and system-level properties, ii) the inherent critique of reductionism and fragmentation of knowledge resulting from overspecialization, and iii) the insight that the ideal of formulating abstract organizing principles is complementary to, rather than conflicting with, the aim of formulating detailed explanations of biological mechanisms. We argue that looking back not only helps us understand the current practice but also points to possible future directions for systems biology.

  19. Methods for analysis of fluoroquinolones in biological fluids

    Science.gov (United States)

    Methods for analysis of 10 selected fluoroquinolone antibiotics in biological fluids are reviewed. Approaches for sample preparation, detection methods, limits of detection and quantitation and recovery information are provided for both single analyte and multi-analyte fluoroquinolone methods....

  20. Multi-scale modelling and simulation in systems biology.

    Science.gov (United States)

    Dada, Joseph O; Mendes, Pedro

    2011-02-01

    The aim of systems biology is to describe and understand biology at a global scale where biological functions are recognised as a result of complex mechanisms that happen at several scales, from the molecular to the ecosystem. Modelling and simulation are computational tools that are invaluable for description, prediction and understanding these mechanisms in a quantitative and integrative way. Therefore the study of biological functions is greatly aided by multi-scale methods that enable the coupling and simulation of models spanning several spatial and temporal scales. Various methods have been developed for solving multi-scale problems in many scientific disciplines, and are applicable to continuum based modelling techniques, in which the relationship between system properties is expressed with continuous mathematical equations or discrete modelling techniques that are based on individual units to model the heterogeneous microscopic elements such as individuals or cells. In this review, we survey these multi-scale methods and explore their application in systems biology.

  1. Global gene expression and systems biology analysis of bovine monocyte-derived macrophages in response to in vitro challenge with Mycobacterium bovis.

    Directory of Open Access Journals (Sweden)

    David A Magee

    Full Text Available BACKGROUND: Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1. Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array. RESULTS: Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ≤ 0.05. Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1 the inflammatory response; (2 cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3 apoptosis. CONCLUSIONS: The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in

  2. Introductory biology and ecological literacy: A critical cultural analysis

    Science.gov (United States)

    Kellogg, Joseph Damian

    Despite the lack of accepted standards for the introductory biology course for students majoring in biology, the content and format of the first-year biology course is remarkably uniform in terms of both curriculum and pedagogy. This investigation is a critical cultural analysis of the purpose of, and practices within, undergraduate biology education in general, and the introductory biology course in particular. Drawing on a theoretical framework that combines critical philosophical inquiry, ecological literacy, science studies, and cultural studies, I argue that the failure of biology educators within the university to acknowledge the diversity of their student body and to actively engage social and ecological issues has resulted in a curriculum that has almost no meaning for students, and that is socially and ecologically irresponsible. This work is a search for meaningful alternatives. Within this work, I attempt to provide biology educators, as well as would-be reformers, with a seldom-seen view of academic biology. This is done to unsettle the status quo, and to initiate processes of seeking out spaces for change. Through the discourses of critical pedagogy and ecological literacy I examine the laboratories, lecture halls, teaching practices, and course materials that students encounter as they experience "the study of life." Additionally, I place the genesis and evolution of the introductory biology course within the sociohistorical context of reform in science education and academic biology in an effort to explain the amazing and problematic stability of this course.

  3. Systems biology-based analysis implicates a novel role for vitamin D metabolism in the pathogenesis of age-related macular degeneration.

    Science.gov (United States)

    Morrison, Margaux A; Silveira, Alexandra C; Huynh, Nancy; Jun, Gyungah; Smith, Silvia E; Zacharaki, Fani; Sato, Hajime; Loomis, Stephanie; Andreoli, Michael T; Adams, Scott M; Radeke, Monte J; Jelcick, Austin S; Yuan, Yang; Tsiloulis, Aristoteles N; Chatzoulis, Dimitrios Z; Silvestri, Giuliana; Kotoula, Maria G; Tsironi, Evangelia E; Hollis, Bruce W; Chen, Rui; Haider, Neena B; Miller, Joan W; Farrer, Lindsay A; Hageman, Gregory S; Kim, Ivana K; Schaumberg, Debra A; DeAngelis, Margaret M

    2011-10-01

    validated and replicated in the extended family cohort, an unrelated case-control cohort from central Greece and a prospective nested case-control population from the Nurse's Health Study and Health Professionals Follow-Up Studies, which included patients with all subtypes of AMD for a total of 2,528 individuals. Single point variants in CYP24A1 (the gene encoding the catabolising enzyme of the vitamin D pathway) were demonstrated to influence AMD risk after controlling for smoking history, sex and age in all populations, both separately and, more importantly, in a meta-analysis. This is the first report demonstrating a genetic association between vitamin D metabolism and AMD risk. These findings were also supplemented with expression data from human donor eyes and human retinal cell lines. These data not only extend previous biological studies in the AMD field, but further emphasise common antecedents between several disorders with an inflammatory/immunogenic component such as cardiovascular disease, cancer and AMD.

  4. Systems biology-based analysis implicates a novel role for vitamin D metabolism in the pathogenesis of age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Morrison Margaux A

    2011-10-01

    findings were then validated and replicated in the extended family cohort, an unrelated case-control cohort from central Greece and a prospective nested case-control population from the Nurse's Health Study and Health Professionals Follow-Up Studies, which included patients with all subtypes of AMD for a total of 2,528 individuals. Single point variants in CYP24A1 (the gene encoding the catabolising enzyme of the vitamin D pathway were demonstrated to influence AMD risk after controlling for smoking history, sex and age in all populations, both separately and, more importantly, in a meta-analysis. This is the first report demonstrating a genetic association between vitamin D metabolism and AMD risk. These findings were also supplemented with expression data from human donor eyes and human retinal cell lines. These data not only extend previous biological studies in the AMD field, but further emphasise common antecedents between several disorders with an inflammatory/immunogenic component such as cardiovascular disease, cancer and AMD.

  5. Systems Biology: The elements and principles of Life

    NARCIS (Netherlands)

    Westerhoff, H.V.; Winder, C.; Messiha, H.; Simeonidis, E.; Adamczyk, M.; Verma, M.; Bruggeman, F.J.; Dunn, W.

    2009-01-01

    Systems Biology has a mission that puts it at odds with traditional paradigms of physics and molecular biology, such as the simplicity requested by Occam’s razor and minimum energy/maximal efficiency. By referring to biochemical experiments on control and regulation, and on flux balancing in yeast,

  6. Quantum dynamics of biological systems and dust plasma nanoparticles

    Science.gov (United States)

    Lasukov, V. V.; Lasukova, T. V.; Lasukova, O. V.

    2012-12-01

    A quantum solution of the Fisher-Kolmogorov-Petrovskii-Piskunov equation with convection and linear diffusion is obtained which can provide the basis for the quantum biology and quantum microphysics equation. On this basis, quantum emission of biological systems, separate microorganisms (cells or bacteria), and dust plasma particles is investigated.

  7. Interdisciplinary problem-solving: emerging modes in integrative systems biology

    NARCIS (Netherlands)

    MacLeod, Miles; Nersessian, Nancy J.

    2016-01-01

    Integrative systems biology is an emerging field that attempts to integrate computation, applied mathematics, engineering concepts and methods, and biological experimentation in order to model large-scale complex biochemical networks. The field is thus an important contemporary instance of an interd

  8. Systems biology applied to vaccine and immunotherapy development

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2011-09-01

    Full Text Available Abstract Immunotherapies, including vaccines, represent a potent tool to prevent or contain disease with high morbidity or mortality such as infections and cancer. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the induction of protective immune responses. Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules; among those is a growing appreciation for the role the innate immunity (i.e. pathogen recognition receptors - PRRs plays in determining the nature and duration (immune memory of adaptive T and B cell immunity. The complex network of interactions between immune manipulation of the host (immunotherapy on one side and innate and adaptive responses on the other might be fully understood only employing the global level of investigation provided by systems biology. In this framework, the advancement of high-throughput technologies, together with the extensive identification of new genes, proteins and other biomolecules in the "omics" era, facilitate large-scale biological measurements. Moreover, recent development of new computational tools enables the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time. Here, we review recent progress in using systems biology to study and evaluate immunotherapy and vaccine strategies for infectious and neoplastic diseases. Multi-parametric data provide novel and often unsuspected mechanistic insights while enabling the identification of common immune signatures relevant to human investigation such as the prediction of immune responsiveness that could lead to the improvement of the design of future immunotherapy trials. Thus, the paradigm switch from "empirical" to "knowledge-based" conduct of medicine and immunotherapy in particular, leading to patient-tailored treatment.

  9. Systems Biology and Synthetic Biology: A New Epoch for Toxicology Research

    Directory of Open Access Journals (Sweden)

    Mark T. Mc Auley

    2015-01-01

    Full Text Available Systems biology and synthetic biology are emerging disciplines which are becoming increasingly utilised in several areas of bioscience. Toxicology is beginning to benefit from systems biology and we suggest in the future that is will also benefit from synthetic biology. Thus, a new era is on the horizon. This review illustrates how a suite of innovative techniques and tools can be applied to understanding complex health and toxicology issues. We review limitations confronted by the traditional computational approaches to toxicology and epidemiology research, using polycyclic aromatic hydrocarbons (PAHs and their effects on adverse birth outcomes as an illustrative example. We introduce how systems toxicology (and their subdisciplines, genomic, proteomic, and metabolomic toxicology will help to overcome such limitations. In particular, we discuss the advantages and disadvantages of mathematical frameworks that computationally represent biological systems. Finally, we discuss the nascent discipline of synthetic biology and highlight relevant toxicological centred applications of this technique, including improvements in personalised medicine. We conclude this review by presenting a number of opportunities and challenges that could shape the future of these rapidly evolving disciplines.

  10. Search for organising principles: understanding in systems biology.

    Science.gov (United States)

    Mesarovic, M D; Sreenath, S N; Keene, J D

    2004-06-01

    Due in large measure to the explosive progress in molecular biology, biology has become arguably the most exciting scientific field. The first half of the 21st century is sometimes referred to as the 'era of biology', analogous to the first half of the 20th century, which was considered to be the 'era of physics'. Yet, biology is facing a crisis--or is it an opportunity--reminiscent of the state of biology in pre-double-helix time. The principal challenge facing systems biology is complexity. According to Hood, 'Systems biology defines and analyses the interrelationships of all of the elements in a functioning system in order to understand how the system works.' With 30000+ genes in the human genome the study of all relationships simultaneously becomes a formidably complex problem. Hanahan and Weinberg raised the question as to whether progress will consist of 'adding further layers of complexity to a scientific literature that is already complex almost beyond measure' or whether the progress will lead to a 'science with a conceptual structure and logical coherence that rivals that of chemistry or physics.' At the core of the challenge is the need for a new approach, a shift from reductionism to a holistic perspective. However, more than just a pronouncement of a new approach is needed. We suggest that what is needed is to provide a conceptual framework for systems biology research. We propose that the concept of a complex system, i.e. a system of systems as defined in mathematical general systems theory (MGST), is central to provide such a framework. We further argue that for a deeper understanding in systems biology investigations should go beyond building numerical mathematical or computer models--important as they are. Biological phenomena cannot be predicted with the level of numerical precision as in classical physics. Explanations in terms of how the categories of systems are organised to function in ever changing conditions are more revealing. Non

  11. Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites

    DEFF Research Database (Denmark)

    Kim, Hyun Uk; Charusanti, Pep; Lee, Sang Yup;

    2016-01-01

    for the optimal production of various prokaryotic secondary metabolites: native versus heterologous hosts (e.g., Escherichia coli) and rational versus random approaches. This comparative analysis is followed by discussions on systems biology tools deployed in optimizing the production of secondary metabolites....... The potential contributions of additional systems biology tools are also discussed in the context of current challenges encountered during optimization of secondary metabolite production....

  12. Advancing metabolic engineering through systems biology of industrial microorganisms

    DEFF Research Database (Denmark)

    Dai, Zongjie; Nielsen, Jens

    2015-01-01

    resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review...... the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further.......Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable...

  13. Yeast systems biology to unravel the network of life

    DEFF Research Database (Denmark)

    Mustacchi, Roberta; Hohmann, S; Nielsen, Jens

    2006-01-01

    Systems biology focuses on obtaining a quantitative description of complete biological systems, even complete cellular function. In this way, it will be possible to perform computer-guided design of novel drugs, advanced therapies for treatment of complex diseases, and to perform in silico design...... of advanced cell factories for production of fuels, chemicals, food ingredients and pharmaceuticals. The yeast Saccharomyces cerevisiae represents an excellent model system; the density of biological information available on this organism allows it to serve as a eukaryotic model for studying human diseases....... Furthermore, it serves as an industrial workhorse for production of a wide range of chemicals and pharmaceuticals. Systems biology involves the combination of novel experimental techniques from different disciplines as well as functional genomics, bioinformatics and mathematical modelling, and hence no single...

  14. Network benchmarking: a happy marriage between systems and synthetic biology.

    Science.gov (United States)

    Minty, Jeremy J; Varedi K, S Marjan; Nina Lin, Xiaoxia

    2009-03-27

    In their new Cell paper, Cantone et al. (2009) present exciting results on constructing and utilizing a small synthetic gene regulatory network in yeast that draws from two rapidly developing fields of systems and synthetic biology.

  15. Advancing metabolic engineering through systems biology of industrial microorganisms.

    Science.gov (United States)

    Dai, Zongjie; Nielsen, Jens

    2015-12-01

    Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further.

  16. Integrated physiology and systems biology of PPARα.

    Science.gov (United States)

    Kersten, Sander

    2014-07-01

    The Peroxisome Proliferator Activated Receptor alpha (PPARα) is a transcription factor that plays a major role in metabolic regulation. This review addresses the functional role of PPARα in intermediary metabolism and provides a detailed overview of metabolic genes targeted by PPARα, with a focus on liver. A distinction is made between the impact of PPARα on metabolism upon physiological, pharmacological, and nutritional activation. Low and high throughput gene expression analyses have allowed the creation of a comprehensive map illustrating the role of PPARα as master regulator of lipid metabolism via regulation of numerous genes. The map puts PPARα at the center of a regulatory hub impacting fatty acid uptake, fatty acid activation, intracellular fatty acid binding, mitochondrial and peroxisomal fatty acid oxidation, ketogenesis, triglyceride turnover, lipid droplet biology, gluconeogenesis, and bile synthesis/secretion. In addition, PPARα governs the expression of several secreted proteins that exert local and endocrine functions.

  17. Differential effects of drug interventions and dietary lifestyle in developing type 2 diabetes and complications: a systems biology analysis in LDLr-/- mice.

    Directory of Open Access Journals (Sweden)

    Marijana Radonjic

    Full Text Available Excess caloric intake leads to metabolic overload and is associated with development of type 2 diabetes (T2DM. Current disease management concentrates on risk factors of the disease such as blood glucose, however with limited success. We hypothesize that normalizing blood glucose levels by itself is insufficient to reduce the development of T2DM and complications, and that removal of the metabolic overload with dietary interventions may be more efficacious. We explored the efficacy and systems effects of pharmaceutical interventions versus dietary lifestyle intervention (DLI in developing T2DM and complications. To mimic the situation in humans, high fat diet (HFD-fed LDLr-/- mice with already established disease phenotype were treated with ten different drugs mixed into HFD or subjected to DLI (switch to low-fat chow, for 7 weeks. Interventions were compared to untreated reference mice kept on HFD or chow only. Although most of the drugs improved HFD-induced hyperglycemia, drugs only partially affected other risk factors and also had limited effect on disease progression towards microalbuminuria, hepatosteatosis and atherosclerosis. By contrast, DLI normalized T2DM risk factors, fully reversed hepatosteatosis and microalbuminuria, and tended to attenuate atherogenesis. The comprehensive beneficial effect of DLI was reflected by normalized metabolite profiles in plasma and liver. Analysis of disease pathways in liver confirmed reversion of the metabolic distortions with DLI. This study demonstrates that the pathogenesis of T2DM towards complications is reversible with DLI and highlights the differential effects of current pharmacotherapies and their limitation to resolve the disease.

  18. Systems Biology, Neuroimaging, Neuropsychology, Neuroconnectivity and Traumatic Brain Injury.

    Science.gov (United States)

    Bigler, Erin D

    2016-01-01

    The patient who sustains a traumatic brain injury (TBI) typically undergoes neuroimaging studies, usually in the form of computed tomography (CT) and magnetic resonance imaging (MRI). In most cases the neuroimaging findings are clinically assessed with descriptive statements that provide qualitative information about the presence/absence of visually identifiable abnormalities; though little if any of the potential information in a scan is analyzed in any quantitative manner, except in research settings. Fortunately, major advances have been made, especially during the last decade, in regards to image quantification techniques, especially those that involve automated image analysis methods. This review argues that a systems biology approach to understanding quantitative neuroimaging findings in TBI provides an appropriate framework for better utilizing the information derived from quantitative neuroimaging and its relation with neuropsychological outcome. Different image analysis methods are reviewed in an attempt to integrate quantitative neuroimaging methods with neuropsychological outcome measures and to illustrate how different neuroimaging techniques tap different aspects of TBI-related neuropathology. Likewise, how different neuropathologies may relate to neuropsychological outcome is explored by examining how damage influences brain connectivity and neural networks. Emphasis is placed on the dynamic changes that occur following TBI and how best to capture those pathologies via different neuroimaging methods. However, traditional clinical neuropsychological techniques are not well suited for interpretation based on contemporary and advanced neuroimaging methods and network analyses. Significant improvements need to be made in the cognitive and behavioral assessment of the brain injured individual to better interface with advances in neuroimaging-based network analyses. By viewing both neuroimaging and neuropsychological processes within a systems biology

  19. Input-output relations in biological systems: measurement, information and the Hill equation.

    Science.gov (United States)

    Frank, Steven A

    2013-01-01

    Biological systems produce outputs in response to variable inputs. Input-output relations tend to follow a few regular patterns. For example, many chemical processes follow the S-shaped Hill equation relation between input concentrations and output concentrations. That Hill equation pattern contradicts the fundamental Michaelis-Menten theory of enzyme kinetics. I use the discrepancy between the expected Michaelis-Menten process of enzyme kinetics and the widely observed Hill equation pattern of biological systems to explore the general properties of biological input-output relations. I start with the various processes that could explain the discrepancy between basic chemistry and biological pattern. I then expand the analysis to consider broader aspects that shape biological input-output relations. Key aspects include the input-output processing by component subsystems and how those components combine to determine the system's overall input-output relations. That aggregate structure often imposes strong regularity on underlying disorder. Aggregation imposes order by dissipating information as it flows through the components of a system. The dissipation of information may be evaluated by the analysis of measurement and precision, explaining why certain common scaling patterns arise so frequently in input-output relations. I discuss how aggregation, measurement and scale provide a framework for understanding the relations between pattern and process. The regularity imposed by those broader structural aspects sets the contours of variation in biology. Thus, biological design will also tend to follow those contours. Natural selection may act primarily to modulate system properties within those broad constraints.

  20. Compatibility analysis of 3D printer resin for biological applications

    KAUST Repository

    Sivashankar, Shilpa

    2016-08-30

    The salient features of microfluidics such as reduced cost, handling small sample and reagent volumes and less time required to fabricate the devices has inspired the present work. The incompatibility of three-dimensional printer resins in their native form and the method to improve their compatibility to many biological processes via surface modification are reported. The compatibility of the material to build microfluidic devices was evaluated in three different ways: (i) determining if the ultraviolet (UV) cured resin inhibits the polymerase chain reaction (PCR), i.e. testing devices for PCR compatibility; (ii) observing agglutination complex formed on the surface of the UV cured resin when anti-C-reactive protein (CRP) antibodies and CRP proteins were allowed to agglutinate; and (iii) by culturing human embryonic kidney cell line cells and testing for its attachment and viability. It is shown that only a few among four in its native form could be used for fabrication of microchannels and that had the least effect on biological molecules that could be used for PCR and protein interactions and cells, whereas the others were used after treating the surface. Importance in building lab-on-chip/micrototal analysis systems and organ-on-chip devices is found.

  1. Apparatus and methods for manipulation and optimization of biological systems

    Science.gov (United States)

    Ho, Chih-Ming (Inventor); Wong, Pak Kin (Inventor); Sun, Ren (Inventor); Yu, Fuqu (Inventor)

    2012-01-01

    The invention provides systems and methods for manipulating, e.g., optimizing and controlling, biological systems, e.g., for eliciting a more desired biological response of biological sample, such as a tissue, organ, and/or a cell. In one aspect, systems and methods of the invention operate by efficiently searching through a large parametric space of stimuli and system parameters to manipulate, control, and optimize the response of biological samples sustained in the system, e.g., a bioreactor. In alternative aspects, systems include a device for sustaining cells or tissue samples, one or more actuators for stimulating the samples via biochemical, electromagnetic, thermal, mechanical, and/or optical stimulation, one or more sensors for measuring a biological response signal of the samples resulting from the stimulation of the sample. In one aspect, the systems and methods of the invention use at least one optimization algorithm to modify the actuator's control inputs for stimulation, responsive to the sensor's output of response signals. The compositions and methods of the invention can be used, e.g., to for systems optimization of any biological manufacturing or experimental system, e.g., bioreactors for proteins, e.g., therapeutic proteins, polypeptides or peptides for vaccines, and the like, small molecules (e.g., antibiotics), polysaccharides, lipids, and the like. Another use of the apparatus and methods includes combination drug therapy, e.g. optimal drug cocktail, directed cell proliferations and differentiations, e.g. in tissue engineering, e.g. neural progenitor cells differentiation, and discovery of key parameters in complex biological systems.

  2. A Generic Language for Biological Systems based on Bigraphs

    DEFF Research Database (Denmark)

    Damgaard, Troels Christoffer; Krivine, Jean

    Several efforts have shown that process calculi developed for reasoning about concurrent and mobile systems may be employed for modelling biological systems at the molecular level. In this paper, we initiate investigation of the meta-language framework bigraphical reactive systems, due to Milner et...

  3. Integrated Design of Antibodies for Systems Biology Using Ab Designer.

    Science.gov (United States)

    Pisitkun, Trairak; Dummer, Patrick; Somparn, Poorichaya; Hirankarn, Nattiya; Kopp, Jeffrey B; Knepper, Mark A

    2014-03-24

    In the current era of large-scale biology, systems biology has evolved as a powerful approach to identify complex interactions within biological systems. In addition to high throughput identification and quantification techniques, methods based on high-quality mono-specific antibodies remain an essential element of the approach. To assist the large-scale design and production of peptide-directed antibodies for systems biology studies, we developed a fully integrated online application, AbDesigner (http://helixweb.nih.gov/AbDesigner/), to help researchers select optimal peptide immunogens for antibody generation against relatively disordered regions of target proteins. Here we describe AbDesigner in terms of its features, comparing it to other software tools, and use it to design three antibodies against kidney disease-related proteins in human, viz. nephrin, podocin, and apolipoprotein L1.

  4. Application of Bioinformatics and Systems Biology in Medicinal Plant Studies

    Institute of Scientific and Technical Information of China (English)

    DENG You-ping; AI Jun-mei; XIAO Pei-gen

    2010-01-01

    One important purpose to investigate medicinal plants is to understand genes and enzymes that govern the biological metabolic process to produce bioactive compounds.Genome wide high throughput technologies such as genomics,transcriptomics,proteomics and metabolomics can help reach that goal.Such technologies can produce a vast amount of data which desperately need bioinformatics and systems biology to process,manage,distribute and understand these data.By dealing with the"omics"data,bioinformatics and systems biology can also help improve the quality of traditional medicinal materials,develop new approaches for the classification and authentication of medicinal plants,identify new active compounds,and cultivate medicinal plant species that tolerate harsh environmental conditions.In this review,the application of bioinformatics and systems biology in medicinal plants is briefly introduced.

  5. Primary energy-transformations in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Lehninger, A.L.

    1980-10-01

    In this paper I shall review the main outlines of current research on the molecular aspects of the primary energy-coupling mechanisms in cells, those carried out by energy-transducing membranes. They include the capture of solar energy by the chloroplast membranes of green plants, used to generate carbohydrates and molecular oxygen from carbon dioxide and water, and the counterpart of photosynthesis, the process of respiration in heterotrophic organisms, in which reduced organic products generated by photosynthesis are oxidized at the expense of dioxygen to form carbon dioxide and water. Although the cycling of dioxygen, carbon dioxide, and organic matter between the plant and animal worlds is well known, it is not generally appreciated that the magnitude of biological energy flux in these cycles is huge compared to the total energy flux in man-made devices. A major consequence is that the concentration of carbon dioxide in the atmosphere has been increasing at a significant rate, at a time when there is also a decrease, at least in some parts of the world, in the counterbalancing utilization of CO/sub 2/ by green plants, due to deforestation. The greenhouse effect of increased atmospheric CO/sub 2/ may not only change the earth's climate, but also may influence the rate of photosynthesis. It is also not generally appreciated that energy flow in the biosphere leads to production of enormous amounts of organic matter potentially useful in furnishing man's energy requirements.

  6. System chemical biology studies of endocrine disruptors

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Oprea, Tudor I.

    Endocrine disrupting chemicals (EDCs) alter hormonal balance and other physiological systems through inappropriate developmental or adult exposure, perturbing the reproductive function of further generations. While disruption of key receptors (e.g., estrogen, androgen, and thyroid) at the ligand...

  7. From Coupled Dynamical Systems to Biological Irreversibility

    OpenAIRE

    Kaneko, Kunihiko

    2002-01-01

    In the first half of the paper, some recent advances in coupled dynamical systems, in particular, a globally coupled map are surveyed. First, dominance of Milnor attractors in partially ordered phase is demonstrated. Second, chaotic itinerancy in high-dimensional dynamical systems is briefly reviewed, with discussion on a possible connection with a Milnor attractor network. Third, infinite-dimensional collective dynamics is studied, in the thermodynamic limit of the globally coupled map, wher...

  8. Complexity and the reductionism-holism debate in systems biology.

    Science.gov (United States)

    Mazzocchi, Fulvio

    2012-01-01

    Reductionism has largely influenced the development of science, culminating in its application to molecular biology. An increasing number of novel research findings have, however, shattered this view, showing how the molecular-reductionist approach cannot entirely handle the complexity of biological systems. Within this framework, the advent of systems biology as a new and more integrative field of research is described, along with the form which has taken on the debate of reductionism versus holism. Such an issue occupies a central position in systems biology, and nonetheless it is not always clearly delineated. This partly occurs because different dimensions (ontological, epistemological, methodological) are involved, and yet the concerned ones often remain unspecified. Besides, within systems biology different streams can be distinguished depending on the degree of commitment to embrace genuine systemic principles. Some useful insights into the future development of this discipline might be gained from the tradition of complexity and self-organization. This is especially true with regards the idea of self-reference, which incorporated into the organizational scheme is able to generate autonomy as an emergent property of the biological whole.

  9. A comprehensive company database analysis of biological assay variability.

    Science.gov (United States)

    Kramer, Christian; Dahl, Göran; Tyrchan, Christian; Ulander, Johan

    2016-08-01

    Analysis of data from various compounds measured in diverse biological assays is a central part of drug discovery research projects. However, no systematic overview of the variability in biological assays has been published and judgments on assay quality and robustness of data are often based on personal belief and experience within the drug discovery community. To address this we performed a reproducibility analysis of all biological assays at AstraZeneca between 2005 and 2014. We found an average experimental uncertainty of less than a twofold difference and no technologies or assay types had higher variability than others. This work suggests that robust data can be obtained from the most commonly applied biological assays.

  10. Towards Engineering Biological Systems in a Broader Context.

    Science.gov (United States)

    Venturelli, Ophelia S; Egbert, Robert G; Arkin, Adam P

    2016-02-27

    Significant advances have been made in synthetic biology to program information processing capabilities in cells. While these designs can function predictably in controlled laboratory environments, the reliability of these devices in complex, temporally changing environments has not yet been characterized. As human society faces global challenges in agriculture, human health and energy, synthetic biology should develop predictive design principles for biological systems operating in complex environments. Natural biological systems have evolved mechanisms to overcome innumerable and diverse environmental challenges. Evolutionary design rules should be extracted and adapted to engineer stable and predictable ecological function. We highlight examples of natural biological responses spanning the cellular, population and microbial community levels that show promise in synthetic biology contexts. We argue that synthetic circuits embedded in host organisms or designed ecologies informed by suitable measurement of biotic and abiotic environmental parameters could be used as engineering substrates to achieve target functions in complex environments. Successful implementation of these methods will broaden the context in which synthetic biological systems can be applied to solve important problems.

  11. PathSys: integrating molecular interaction graphs for systems biology

    Directory of Open Access Journals (Sweden)

    Raval Alpan

    2006-02-01

    Full Text Available Abstract Background The goal of information integration in systems biology is to combine information from a number of databases and data sets, which are obtained from both high and low throughput experiments, under one data management scheme such that the cumulative information provides greater biological insight than is possible with individual information sources considered separately. Results Here we present PathSys, a graph-based system for creating a combined database of networks of interaction for generating integrated view of biological mechanisms. We used PathSys to integrate over 14 curated and publicly contributed data sources for the budding yeast (S. cerevisiae and Gene Ontology. A number of exploratory questions were formulated as a combination of relational and graph-based queries to the integrated database. Thus, PathSys is a general-purpose, scalable, graph-data warehouse of biological information, complete with a graph manipulation and a query language, a storage mechanism and a generic data-importing mechanism through schema-mapping. Conclusion Results from several test studies demonstrate the effectiveness of the approach in retrieving biologically interesting relations between genes and proteins, the networks connecting them, and of the utility of PathSys as a scalable graph-based warehouse for interaction-network integration and a hypothesis generator system. The PathSys's client software, named BiologicalNetworks, developed for navigation and analyses of molecular networks, is available as a Java Web Start application at http://brak.sdsc.edu/pub/BiologicalNetworks.

  12. Exploring lipids with nonlinear optical microscopy in multiple biological systems

    Science.gov (United States)

    Alfonso-Garcia, Alba

    Lipids are crucial biomolecules for the well being of humans. Altered lipid metabolism may give rise to a variety of diseases that affect organs from the cardiovascular to the central nervous system. A deeper understanding of lipid metabolic processes would spur medical research towards developing precise diagnostic tools, treatment methods, and preventive strategies for reducing the impact of lipid diseases. Lipid visualization remains a complex task because of the perturbative effect exerted by traditional biochemical assays and most fluorescence markers. Coherent Raman scattering (CRS) microscopy enables interrogation of biological samples with minimum disturbance, and is particularly well suited for label-free visualization of lipids, providing chemical specificity without compromising on spatial resolution. Hyperspectral imaging yields large datasets that benefit from tailored multivariate analysis. In this thesis, CRS microscopy was combined with Raman spectroscopy and other label-free nonlinear optical techniques to analyze lipid metabolism in multiple biological systems. We used nonlinear Raman techniques to characterize Meibum secretions in the progression of dry eye disease, where the lipid and protein contributions change in ratio and phase segregation. We employed similar tools to examine lipid droplets in mice livers aboard a spaceflight mission, which lose their retinol content contributing to the onset of nonalcoholic fatty-liver disease. We also focused on atherosclerosis, a disease that revolves around lipid-rich plaques in arterial walls. We examined the lipid content of macrophages, whose variable phenotype gives rise to contrasting healing and inflammatory activities. We also proposed new label-free markers, based on lifetime imaging, for macrophage phenotype, and to detect products of lipid oxidation. Cholesterol was also detected in hepatitis C virus infected cells, and in specific strains of age-related macular degeneration diseased cells by

  13. Construction of a Linux based chemical and biological information system.

    Science.gov (United States)

    Molnár, László; Vágó, István; Fehér, András

    2003-01-01

    A chemical and biological information system with a Web-based easy-to-use interface and corresponding databases has been developed. The constructed system incorporates all chemical, numerical and textual data related to the chemical compounds, including numerical biological screen results. Users can search the database by traditional textual/numerical and/or substructure or similarity queries through the web interface. To build our chemical database management system, we utilized existing IT components such as ORACLE or Tripos SYBYL for database management and Zope application server for the web interface. We chose Linux as the main platform, however, almost every component can be used under various operating systems.

  14. HISTCOMP : Bibliographic analysis and visualization of the "Biological Bulletin”

    OpenAIRE

    Wulff-Barreiro, Enrique

    2007-01-01

    A collection of citation data, the HistComp, is available from the Internet as a database of examples of real life citation networks. The purposes of this approach is the analysis of these citation networks on learned literature by presenting its typical steps and results. We have selected the bibliographic insights into the "The Biological Bulletin", the journal published since 1897 by the Woods Hole Marine Biological Laboratory. Since the bibliographic networks tend to be very scattered, th...

  15. Biologically-Inspired Water Propulsion System

    Institute of Scientific and Technical Information of China (English)

    Andrzej Sioma

    2013-01-01

    Most propulsion systems of vehicles travelling in the aquatic environment are equipped with propellers.Observations of nature,however,show that the absolute majority of organisms travel through water using wave motion,paddling or using water jet power.Inspired by these observations of nature,an innovative propulsion system working in aquatic environment was developed.This paper presents the design of the water propulsion system.Particular attention was paid to the use of paddling techniques and water jet power.A group of organisms that use those mechanisms to travel through water was selected and analysed.The results of research were used in the design of a propulsion system modelled simultaneously on two methods of movement in the aquatic environment.A method for modelling a propulsion system using a combination of the two solutions and the result were described.A conceptual design and a prototype constructed based on the solution were presented.With respect to the solution developed,studies and analyses of selected parameters of the prototype were described.

  16. Biologic Therapy in Inflammatory Immunomediated Systemic Diseases: Safety Profile.

    Science.gov (United States)

    Moroncini, Gianluca; Albani, Lisa; Nobili, Lorenzo; Gabrielli, Armando

    2016-01-01

    The discovery of some key molecular mechanisms underlying the dysregulation of the immune system responsible for inflammatory systemic diseases as severe as Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), and Systemic Vasculitides, led to the development and subsequent introduction into clinical practice of biological drugs which are significantly improving the management of such complex disorders. This novel molecular targeted therapeutics represents in fact a valid alternative or complementary treatment to conventional immunosuppressive strategies, characterized by broad, unspecific actions and severe adverse effects. Main advantages of the use of biologic drugs reside in their steroid-sparing effect and in the ability of inducing remission of refractory disease states or curing specific organ involvements. Aim of this article is to review and briefly discuss the scientific evidence supporting the use of biologics in these diseases, with a particular emphasis on their efficacy and safety profile compared to the canonical drugs.

  17. Fuzzy Stochastic Petri Nets for Modeling Biological Systems with Uncertain Kinetic Parameters.

    Science.gov (United States)

    Liu, Fei; Heiner, Monika; Yang, Ming

    2016-01-01

    Stochastic Petri nets (SPNs) have been widely used to model randomness which is an inherent feature of biological systems. However, for many biological systems, some kinetic parameters may be uncertain due to incomplete, vague or missing kinetic data (often called fuzzy uncertainty), or naturally vary, e.g., between different individuals, experimental conditions, etc. (often called variability), which has prevented a wider application of SPNs that require accurate parameters. Considering the strength of fuzzy sets to deal with uncertain information, we apply a specific type of stochastic Petri nets, fuzzy stochastic Petri nets (FSPNs), to model and analyze biological systems with uncertain kinetic parameters. FSPNs combine SPNs and fuzzy sets, thereby taking into account both randomness and fuzziness of biological systems. For a biological system, SPNs model the randomness, while fuzzy sets model kinetic parameters with fuzzy uncertainty or variability by associating each parameter with a fuzzy number instead of a crisp real value. We introduce a simulation-based analysis method for FSPNs to explore the uncertainties of outputs resulting from the uncertainties associated with input parameters, which works equally well for bounded and unbounded models. We illustrate our approach using a yeast polarization model having an infinite state space, which shows the appropriateness of FSPNs in combination with simulation-based analysis for modeling and analyzing biological systems with uncertain information.

  18. Circadian systems biology: When time matters

    Directory of Open Access Journals (Sweden)

    Luise Fuhr

    2015-01-01

    In this manuscript we review the combination of experimental methodologies, bioinformatics and theoretical models that have been essential to explore this remarkable timing-system. Such an integrative and interdisciplinary approach may provide new strategies with regard to chronotherapeutic treatment and new insights concerning the restoration of the circadian timing in clock-associated diseases.

  19. International Research and Development in Systems Biology

    Science.gov (United States)

    2005-10-01

    ecology and social insect behavior. Cellular chemotaxis of both prokaryotes and eukaryotes is another subject with a significant history of modeling...Cell organization in tissues; system organization in insect societies; protain-protein interaction networks; inflammatory mediator signaling...They are now scaling up the microarray time-series and ribonucleic acid interference ( RNAi ) knockdown work to get better identification of this pathway

  20. Statistical Model Checking for Biological Systems

    DEFF Research Database (Denmark)

    David, Alexandre; Larsen, Kim Guldstrand; Legay, Axel

    2014-01-01

    Statistical Model Checking (SMC) is a highly scalable simulation-based verification approach for testing and estimating the probability that a stochastic system satisfies a given linear temporal property. The technique has been applied to (discrete and continuous time) Markov chains, stochastic t...

  1. Biological Approach to System Information Security (BASIS)

    Science.gov (United States)

    2003-12-01

    Detection System,” IEEE Network, January/February 1996, pp. 20-23. Section IV [1] Immunology Second Edition, Janis Kuby , W.H. Freeman and...34, Springer-Verlag, 1999 Section V [1] Immunology Second Edition, Janis Kuby , W.H. Freeman and Company, New York, 1994 [2] RFC 793

  2. Developing integrated TOF-SIMS/MALDI IMS system in studying biological systems

    Science.gov (United States)

    Wu, Ligang

    Using imaging mass spectrometry (IMS) techniques (including TOF-SIMS and MALDI IMS) to study biological systems is a relatively new concept and quickly gained popularity in recent years. Imaging mass spectrometry is a discovery technology that utilizes a focused ion beam or laser beam to desorb ions from sample surface. By detecting the desorbed ions, the chemical distributions and biological changes of a sample surface can be analyzed. These techniques offer a new analytical imaging approach to investigate biological processes at the cellular and tissue level. In this research, a novel integrated TOF-SIMS/MALDI IMS system as well as IMS based biological-sample-preparation techniques and data-reduction methods are developed. We then demonstrate the power of these techniques in studying different biological systems, including monosaccharides isomers, human breast cancer cell lines, mouse embryo tissues and mouse kidney sections. Using TOF-SIMS and statistical analysis methods, seven monosaccharide isomers are fully differentiated by analyzing their characteristic spectral pattern. In addition, a deep understanding of the fragmentation pathway of these isomers under ion bombardment is gained. In an application of TOF-SIMS to the differentiation of three human breast cancer cell lines, MCF-7, T47D, and MDA-MB-231, we show that principal component analysis (PCA) data reduction of TOF-SIMS spectra can differentiate cellular compartments (cytosol, nuclear and particulate) within the cell types, as well as homogenates from among the three cell lines. In a tissue-specific application, we extend the analytical capabilities of TOF-SIMS and PCA by imaging and differentiating Formalin-fixed paraffin-embedded (FFPE) mouse embryo tissues. We demonstrate reproducible differentiation of six tissue types based on the remaining small molecules after paraffin-embedding and the fragments of the cellular proteins. In a unique study of fresh frozen mouse kidney tissues, both TOF

  3. New tricks for an old natural product: discovery of highly potent evodiamine derivatives as novel antitumor agents by systemic structure-activity relationship analysis and biological evaluations.

    Science.gov (United States)

    Dong, Guoqiang; Wang, Shengzheng; Miao, Zhenyuan; Yao, Jianzhong; Zhang, Yongqiang; Guo, Zizhao; Zhang, Wannian; Sheng, Chunquan

    2012-09-13

    Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus . Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.

  4. Adaptive neural-based fuzzy modeling for biological systems.

    Science.gov (United States)

    Wu, Shinq-Jen; Wu, Cheng-Tao; Chang, Jyh-Yeong

    2013-04-01

    The inverse problem of identifying dynamic biological networks from their time-course response data set is a cornerstone of systems biology. Hill and Michaelis-Menten model, which is a forward approach, provides local kinetic information. However, repeated modifications and a large amount of experimental data are necessary for the parameter identification. S-system model, which is composed of highly nonlinear differential equations, provides the direct identification of an interactive network. However, the identification of skeletal-network structure is challenging. Moreover, biological systems are always subject to uncertainty and noise. Are there suitable candidates with the potential to deal with noise-contaminated data sets? Fuzzy set theory is developed for handing uncertainty, imprecision and complexity in the real world; for example, we say "driving speed is high" wherein speed is a fuzzy variable and high is a fuzzy set, which uses the membership function to indicate the degree of a element belonging to the set (words in Italics to denote fuzzy variables or fuzzy sets). Neural network possesses good robustness and learning capability. In this study we hybrid these two together into a neural-fuzzy modeling technique. A biological system is formulated to a multi-input-multi-output (MIMO) Takagi-Sugeno (T-S) fuzzy system, which is composed of rule-based linear subsystems. Two kinds of smooth membership functions (MFs), Gaussian and Bell-shaped MFs, are used. The performance of the proposed method is tested with three biological systems.

  5. Systematic integration of experimental data and models in systems biology

    Directory of Open Access Journals (Sweden)

    Simeonidis Evangelos

    2010-11-01

    Full Text Available Abstract Background The behaviour of biological systems can be deduced from their mathematical models. However, multiple sources of data in diverse forms are required in the construction of a model in order to define its components and their biochemical reactions, and corresponding parameters. Automating the assembly and use of systems biology models is dependent upon data integration processes involving the interoperation of data and analytical resources. Results Taverna workflows have been developed for the automated assembly of quantitative parameterised metabolic networks in the Systems Biology Markup Language (SBML. A SBML model is built in a systematic fashion by the workflows which starts with the construction of a qualitative network using data from a MIRIAM-compliant genome-scale model of yeast metabolism. This is followed by parameterisation of the SBML model with experimental data from two repositories, the SABIO-RK enzyme kinetics database and a database of quantitative experimental results. The models are then calibrated and simulated in workflows that call out to COPASIWS, the web service interface to the COPASI software application for analysing biochemical networks. These systems biology workflows were evaluated for their ability to construct a parameterised model of yeast glycolysis. Conclusions Distributed information about metabolic reactions that have been described to MIRIAM standards enables the automated assembly of quantitative systems biology models of metabolic networks based on user-defined criteria. Such data integration processes can be implemented as Taverna workflows to provide a rapid overview of the components and their relationships within a biochemical system.

  6. Systems Biology Brings Life Sciences Closer--Report on the China-UK Systems Biology Workshop 2005

    Institute of Scientific and Technical Information of China (English)

    Ming Chen

    2005-01-01

    @@ The China-UK Systems Biology Workshop 2005 was held during June 20-21 in the National Science Park of Zhejiang University, Hangzhou, China. It was organized by the Institute of Bioinformatics, Zhejiang University, and was initiated by Prof. Dr. Jun Zhu (Zhejiang University) and Prof. Dr. John Findlay (University of Leeds, UK). The workshop was part of the program called UK-China Partners in Science, a one-year campaign that was initiated by the British government to explore more collaborations between UK and China on science and technology. It was attended also by a representative of this program, Mr.Frank Yuan, senior science & innovation officer. The idea of the workshop was to bring together experts with specialists in systems biology in order to promote the "natural partnership" between scientists from the two countries. The most important items of systems biology considered at the workshop were: (1) New technologies and advances in systems biology; (2) Research developments in genomics and proteomics; (3) New methodologies and software in computational biology; (4) Research collaboration on systems biology between China and UK.

  7. Applications of dynamical systems in biology and medicine

    CERN Document Server

    Radunskaya, Ami

    2015-01-01

    This volume highlights problems from a range of biological and medical applications that can be interpreted as questions about system behavior or control.  Topics include drug resistance in cancer and malaria, biological fluid dynamics, auto-regulation in the kidney, anti-coagulation therapy, evolutionary diversification and photo-transduction.  Mathematical techniques used to describe and investigate these biological and medical problems include ordinary, partial and stochastic differentiation equations, hybrid discrete-continuous approaches, as well as 2 and 3D numerical simulation. .

  8. A holistic approach to marine eco-systems biology.

    OpenAIRE

    Eric Karsenti; Acinas, Silvia G.; Peer Bork; Chris Bowler; Colomban De Vargas; Jeroen Raes; Matthew Sullivan; Detlev Arendt; Francesca Benzoni; Jean-Michel Claverie; Mick Follows; Gaby Gorsky; Pascal Hingamp; Daniele Iudicone; Olivier Jaillon

    2011-01-01

    With biology becoming quantitative, systems-level studies can now be performed at spatial scales ranging from molecules to ecosystems. Biological data generated consistently across scales can be integrated with physico-chemical contextual data for a truly holistic approach, with a profound impact on our understanding of life [1]–[5]. Marine ecosystems are crucial in the regulation of Earth's biogeochemical cycles and climate [6],[7]. Yet their organization, evolution, and dynamics remain poor...

  9. Enterobacter aerogenes Needle Stick Leads to Improved Biological Management System

    Energy Technology Data Exchange (ETDEWEB)

    Johanson, Richard E.

    2004-08-01

    A laboratory worker who received a needle stick from a contaminated needle while working with a culture containing Enterobactor aerogenes developed a laboratory acquired infection. Although this organism has been shown to cause community and nosocomial infections, there have been no documented cases of a laboratory acquired infections. Lessons learned from the event led to corrective actions which included modification of lab procedures, development of a biological inventory tracking and risk identification system and the establishment of an effective biological safety program.

  10. Modeling of biological intelligence for SCM system optimization.

    Science.gov (United States)

    Chen, Shengyong; Zheng, Yujun; Cattani, Carlo; Wang, Wanliang

    2012-01-01

    This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM) systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing complex SCM systems require huge amounts of computing resources, and biological intelligence-based solutions can often provide valuable alternatives for efficiently solving problems. The paper summarizes the recent related methods for the design and optimization of SCM systems, which covers the most widely used genetic algorithms and other evolutionary algorithms.

  11. Modeling of Biological Intelligence for SCM System Optimization

    Directory of Open Access Journals (Sweden)

    Shengyong Chen

    2012-01-01

    Full Text Available This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing complex SCM systems require huge amounts of computing resources, and biological intelligence-based solutions can often provide valuable alternatives for efficiently solving problems. The paper summarizes the recent related methods for the design and optimization of SCM systems, which covers the most widely used genetic algorithms and other evolutionary algorithms.

  12. Conference Scene: Systems biology and personalized health science and translation.

    Science.gov (United States)

    Siest, Gérard; Ndiaye, Ndeye Coumba; El Shamieh, Said; Shahabi, Payman; Stathopoulou, Maria; Saleh, Abdel Salam; Godjo, Thibaut; Albertini, Laetitia; Visvikis-Siest, Sophie

    2013-12-01

    After a 1-day advanced course on systems biology, the main themes of this 3-day colloquium were developed: from systems biology to systems medicine with special applications to cancer; pharmacogenomics in drug discovery and clinical application; and epigenomics and genome-wide association studies in cardiovascular diseases. In two roundtable discussions on pharmacogenomics and genome-wide association studies, the progress and the difficulties in the implementation of omics technologies in clinical practice were discussed. Three workshops were also organized on technical tools linked to the meeting themes.

  13. Decoherence and Spin Echo in Biological Systems

    CERN Document Server

    Nesterov, Alexander I

    2015-01-01

    The spin echo approach is extended to include bio-complexes for which the interaction with dynamical noise is strong. Significant restoration of the free induction decay signal due to homogeneous (decoherence) and inhomogeneous (dephasing) broadening is demonstrated analytically and numerically, for both an individual dimer of interacting chlorophylls and for an ensemble of dimers. This approach is based on an exact and closed system of ordinary differential equations that can be easily solved for a wide range of parameters that are relevant for bio-applications.

  14. Phase transitions in fluids and biological systems

    Science.gov (United States)

    Sipos, Maksim

    In this thesis, I consider systems from two seemingly different fields: fluid dynamics and microbial ecology. In these systems, the unifying features are the existences of global non-equilibrium steady states. I consider generic and statistical models for transitions between these global states, and I relate the model results with experimental data. A theme of this thesis is that these rather simple, minimal models are able to capture a lot of functional detail about complex dynamical systems. In Part I, I consider the transition between laminar and turbulent flow. I find that quantitative and qualitative features of pipe flow experiments, the superexponential lifetime and the splitting of turbulent puffs, and the growth rate of turbulent slugs, can all be explained by a coarse-grained, phenomenological model in the directed percolation universality class. To relate this critical phenomena approach closer to the fluid dynamics, I consider the transition to turbulence in the Burgers equation, a simplified model for Navier-Stokes equations. Via a transformation to a model of directed polymers in a random medium, I find that the transition to Burgers turbulence may also be in the directed percolation universality class. This evidence implies that the turbulent-to-laminar transition is statistical in nature and does not depend on details of the Navier-Stokes equations describing the fluid flow. In Part II, I consider the disparate subject of microbial ecology where the complex interactions within microbial ecosystems produce observable patterns in microbe abundance, diversity and genotype. In order to be able to study these patterns, I develop a bioinformatics pipeline to multiply align and quickly cluster large microbial metagenomics datasets. I also develop a novel metric that quantifies the degree of interactions underlying the assembly of a microbial ecosystem, particularly the transition between neutral (random) and niche (deterministic) assembly. I apply this

  15. Systems biology analysis merging phenotype, metabolomic and genomic data identifies Non-SMC Condensin I Complex, Subunit G (NCAPG and cellular maintenance processes as major contributors to genetic variability in bovine feed efficiency.

    Directory of Open Access Journals (Sweden)

    Philipp Widmann

    Full Text Available Feed efficiency is a paramount factor for livestock economy. Previous studies had indicated a substantial heritability of several feed efficiency traits. In our study, we investigated the genetic background of residual feed intake, a commonly used parameter of feed efficiency, in a cattle resource population generated from crossing dairy and beef cattle. Starting from a whole genome association analysis, we subsequently performed combined phenotype-metabolome-genome analysis taking a systems biology approach by inferring gene networks based on partial correlation and information theory approaches. Our data about biological processes enriched with genes from the feed efficiency network suggest that genetic variation in feed efficiency is driven by genetic modulation of basic processes relevant to general cellular functions. When looking at the predicted upstream regulators from the feed efficiency network, the Tumor Protein P53 (TP53 and Transforming Growth Factor beta 1 (TGFB1 genes stood out regarding significance of overlap and number of target molecules in the data set. These results further support the hypothesis that TP53 is a major upstream regulator for genetic variation of feed efficiency. Furthermore, our data revealed a significant effect of both, the Non-SMC Condensin I Complex, Subunit G (NCAPG I442M (rs109570900 and the Growth /differentiation factor 8 (GDF8 Q204X (rs110344317 loci, on residual feed intake and feed conversion. For both loci, the growth promoting allele at the onset of puberty was associated with a negative, but favorable effect on residual feed intake. The elevated energy demand for increased growth triggered by the NCAPG 442M allele is obviously not fully compensated for by an increased efficiency in converting feed into body tissue. As a consequence, the individuals carrying the NCAPG 442M allele had an additional demand for energy uptake that is reflected by the association of the allele with increased daily

  16. Structural Systems Biology Evaluation of Metabolic Thermotolerance in Escherichia coli

    DEFF Research Database (Denmark)

    Chang, Roger L.; Andrews, Kathleen; Kim, Donghyuk

    2013-01-01

    Improve the System A "systems biology" approach may clarify, for example, how particular proteins determine sensitivity of bacteria to extremes of temperature. Chang et al. (p. 1220) integrated information on protein structure with a model of metabolism, thus associating the protein structure of ...

  17. Comparison of Three Systems for Biological Greywater Treatment

    NARCIS (Netherlands)

    Hernandez Leal, L.; Temmink, B.G.; Zeeman, G.; Buisman, C.J.N.

    2010-01-01

    Greywater consists of household wastewater excluding toilet discharges. Three systems were compared for the biological treatment of greywater at a similar hydraulic retention time of approximately 12–13 hours. These systems were aerobic treatment in a sequencing batch reactor, anaerobic treatment in

  18. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian; Ihekwaba, Adoha

    2007-01-01

    A. Ihekwaba, R. Mardare. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems. Case study: NFkB system. In Proc. of International Conference of Computational Methods in Sciences and Engineering (ICCMSE), American Institute of Physics, AIP Proceedings, N 2...

  19. 3D Modelling of Biological Systems for Biomimetics

    Institute of Scientific and Technical Information of China (English)

    Shujun Zhang; Kevin Hapeshi; Ashok K. Bhattacharya

    2004-01-01

    With the advanced development of computer-based enabling technologies, many engineering, medical, biology,chemistry, physics and food science etc have developed to the unprecedented levels, which lead to many research and development interests in various multi-discipline areas. Among them, biomimetics is one of the most promising and attractive branches of study. Biomimetics is a branch of study that uses biological systems as a model to develop synthetic systems.To learn from nature, one of the fundamental issues is to understand the natural systems such animals, insects, plants and human beings etc. The geometrical characterization and representation of natural systems is an important fundamental work for biomimetics research. 3D modeling plays a key role in the geometrical characterization and representation, especially in computer graphical visualization. This paper firstly presents the typical procedure of 3D modelling methods and then reviews the previous work of 3D geometrical modelling techniques and systems developed for industrial, medical and animation applications. Especially the paper discusses the problems associated with the existing techniques and systems when they are applied to 3D modelling of biological systems. Based upon the discussions, the paper proposes some areas of research interests in 3D modelling of biological systems and for Biomimetics.

  20. What's behind the Biological Classification System in Use Today?

    Science.gov (United States)

    Robertson, William C.

    2010-01-01

    Whether students should memorize classification schemes (taxonomies) is a column in itself, but the author can address the role that this system plays in the study of biology. To that end, it will help to address how the system developed over time. And toward "that" end, you will do a simple activity to start. (Contains 3 figures.)

  1. Nonlinear Hyperbolic-Parabolic System Modeling Some Biological Phenomena

    Institute of Scientific and Technical Information of China (English)

    WU Shaohua; CHEN Hua

    2011-01-01

    In this paper, we study a nonlinear hyperbolic-parabolic system modeling some biological phenomena. By semigroup theory and Leray-Schauder fixed point argument, the local existence and uniqueness of the weak solutions for this system are proved. For the spatial dimension N = 1, the global existence of the weak solution will be established by the bootstrap argument.

  2. Statistical analysis of joint toxicity in biological growth experiments

    DEFF Research Database (Denmark)

    Spliid, Henrik; Tørslev, J.

    1994-01-01

    The authors formulate a model for the analysis of designed biological growth experiments where a mixture of toxicants is applied to biological target organisms. The purpose of such experiments is to assess the toxicity of the mixture in comparison with the toxicity observed when the toxicants...... are applied individually to the organisms. The analysis is based on a random differential equation describing the growth of the organisms. This model yields a natural measure of interaction between toxicants and the hypothesis of independent action from a mixture of toxicants can be tested. The proposed model...

  3. Functional Genomics Assistant (FUGA: a toolbox for the analysis of complex biological networks

    Directory of Open Access Journals (Sweden)

    Ouzounis Christos A

    2011-10-01

    Full Text Available Abstract Background Cellular constituents such as proteins, DNA, and RNA form a complex web of interactions that regulate biochemical homeostasis and determine the dynamic cellular response to external stimuli. It follows that detailed understanding of these patterns is critical for the assessment of fundamental processes in cell biology and pathology. Representation and analysis of cellular constituents through network principles is a promising and popular analytical avenue towards a deeper understanding of molecular mechanisms in a system-wide context. Findings We present Functional Genomics Assistant (FUGA - an extensible and portable MATLAB toolbox for the inference of biological relationships, graph topology analysis, random network simulation, network clustering, and functional enrichment statistics. In contrast to conventional differential expression analysis of individual genes, FUGA offers a framework for the study of system-wide properties of biological networks and highlights putative molecular targets using concepts of systems biology. Conclusion FUGA offers a simple and customizable framework for network analysis in a variety of systems biology applications. It is freely available for individual or academic use at http://code.google.com/p/fuga.

  4. Stochastic differential equations and a biological system

    DEFF Research Database (Denmark)

    Wang, Chunyan

    1994-01-01

    The purpose of this Ph.D. study is to explore the property of a growth process. The study includes solving and simulating of the growth process which is described in terms of stochastic differential equations. The identification of the growth and variability parameters of the process based...... on experimental data is considered. As an example, the growth of bacteria Pseudomonas fluorescens is taken. Due to the specific features of stochastic differential equations, namely that their solutions do not exist in the general sense, two new integrals - the Ito integral and the Stratonovich integral - have...... been developed. Their properties and the relationship between them are discussed. The evolution of a dynamic system or process is usually of great practical interest. In order to simulate the evolution of the process, alternative methods are used to get numerical solutions. In this study, Euler...

  5. Evolutionary game based control for biological systems with applications in drug delivery.

    Science.gov (United States)

    Li, Xiaobo; Lenaghan, Scott C; Zhang, Mingjun

    2013-06-01

    Control engineering and analysis of biological systems have become increasingly important for systems and synthetic biology. Unfortunately, no widely accepted control framework is currently available for these systems, especially at the cell and molecular levels. This is partially due to the lack of appropriate mathematical models to describe the unique dynamics of biological systems, and the lack of implementation techniques, such as ultra-fast and ultra-small devices and corresponding control algorithms. This paper proposes a control framework for biological systems subject to dynamics that exhibit adaptive behavior under evolutionary pressures. The control framework was formulated based on evolutionary game based modeling, which integrates both the internal dynamics and the population dynamics. In the proposed control framework, the adaptive behavior was characterized as an internal dynamic, and the external environment was regarded as an external control input. The proposed open-interface control framework can be integrated with additional control algorithms for control of biological systems. To demonstrate the effectiveness of the proposed framework, an optimal control strategy was developed and validated for drug delivery using the pathogen Giardia lamblia as a test case. In principle, the proposed control framework can be applied to any biological system exhibiting adaptive behavior under evolutionary pressures.

  6. Computational approaches to metabolic engineering utilizing systems biology and synthetic biology.

    Science.gov (United States)

    Fong, Stephen S

    2014-08-01

    Metabolic engineering modifies cellular function to address various biochemical applications. Underlying metabolic engineering efforts are a host of tools and knowledge that are integrated to enable successful outcomes. Concurrent development of computational and experimental tools has enabled different approaches to metabolic engineering. One approach is to leverage knowledge and computational tools to prospectively predict designs to achieve the desired outcome. An alternative approach is to utilize combinatorial experimental tools to empirically explore the range of cellular function and to screen for desired traits. This mini-review focuses on computational systems biology and synthetic biology tools that can be used in combination for prospective in silico strain design.

  7. Systems engineering and analysis

    CERN Document Server

    Blanchard, Benjamin S

    2010-01-01

    For senior-level undergraduate and first and second year graduate systems engineering and related courses. A total life-cycle approach to systems and their analysis. This practical introduction to systems engineering and analysis provides the concepts, methodologies, models, and tools needed to understand and implement a total life-cycle approach to systems and their analysis. The authors focus first on the process of bringing systems into being--beginning with the identification of a need and extending that need through requirements determination, functional analysis and allocation, design synthesis, evaluation, and validation, operation and support, phase-out, and disposal. Next, the authors discuss the improvement of systems currently in being, showing that by employing the iterative process of analysis, evaluation, feedback, and modification, most systems in existence can be improved in their affordability, effectiveness, and stakeholder satisfaction.

  8. Enabling a systems biology knowledgebase with gaggle and firegoose

    Energy Technology Data Exchange (ETDEWEB)

    Baliga, Nitin S. [Institute for Systems Biology, Seattle, WA (United States)

    2014-12-12

    The overall goal of this project was to extend the existing Gaggle and Firegoose systems to develop an open-source technology that runs over the web and links desktop applications with many databases and software applications. This technology would enable researchers to incorporate workflows for data analysis that can be executed from this interface to other online applications. The four specific aims were to (1) provide one-click mapping of genes, proteins, and complexes across databases and species; (2) enable multiple simultaneous workflows; (3) expand sophisticated data analysis for online resources; and enhance open-source development of the Gaggle-Firegoose infrastructure. Gaggle is an open-source Java software system that integrates existing bioinformatics programs and data sources into a user-friendly, extensible environment to allow interactive exploration, visualization, and analysis of systems biology data. Firegoose is an extension to the Mozilla Firefox web browser that enables data transfer between websites and desktop tools including Gaggle. In the last phase of this funding period, we have made substantial progress on development and application of the Gaggle integration framework. We implemented the workspace to the Network Portal. Users can capture data from Firegoose and save them to the workspace. Users can create workflows to start multiple software components programmatically and pass data between them. Results of analysis can be saved to the cloud so that they can be easily restored on any machine. We also developed the Gaggle Chrome Goose, a plugin for the Google Chrome browser in tandem with an opencpu server in the Amazon EC2 cloud. This allows users to interactively perform data analysis on a single web page using the R packages deployed on the opencpu server. The cloud-based framework facilitates collaboration between researchers from multiple organizations. We have made a number of enhancements to the cmonkey2 application to enable and

  9. Metagenomic Systems Biology of the Human Microbiome

    DEFF Research Database (Denmark)

    Bonde, Ida

    The human microbiome is an integrated part of the human body, outnumbering the human cells by approximately a factor 10. These microorganisms are very important for human health, hence knowledge about this, ”our other genome”, has been growing rapidly in recent years. This is manly due to the adv......The human microbiome is an integrated part of the human body, outnumbering the human cells by approximately a factor 10. These microorganisms are very important for human health, hence knowledge about this, ”our other genome”, has been growing rapidly in recent years. This is manly due...... in the system. Applying the CAG clustering method to data from the human gut microbiome, we identified dependency-associations between plasmids, phages and clone-specific gene sets to their bacterial host. Connections between CRISPR-elements and phages were also observed. Additionally, the persistence of some...... bacterial species in the human gut could be predicted based on absence or presence of specific genetic modules. Based on the same CAG clustering of the human gut microbiome data, the link between bile acid degradation of bacteria in the gut and obesity was investigated. There seemed to be a slight...

  10. Hepatocellular carcinoma: a systems biology perspective

    Directory of Open Access Journals (Sweden)

    Lorenza Alice D'alessandro

    2013-02-01

    Full Text Available Hepatocellular carcinomas (HCC have different etiology and heterogenic genomic alterations lead to high complexity. The molecular features of HCC have largely been studied by gene expression and proteome profiling focusing on the correlations between the expression of specific markers and clinical data. Integration of the increasing amounts of data in databases has facilitated the link of genomic and proteomic profiles of HCC to disease state and clinical outcome. Despite the current knowledge, specific molecular markers remain to be identified and new strategies are required to establish novel targeted therapies. In the last years, mathematical models reconstructing gene and protein networks based on experimental data of HCC have been developed providing powerful tools to predict candidate interactions and potential targets for therapy. Furthermore, the combination of dynamic and logical mathematical models with quantitative data allows detailed mechanistic insights into system properties. To address effects at the organ level, mathematical models reconstructing the three-dimensional organization of liver lobules were developed. In the future, integration of different modeling approaches capturing the effects at the cellular up to the organ level is required to address the complex properties of HCC and to enable the discovery of new targets for HCC prevention or treatment.

  11. Review and application of group theory to molecular systems biology

    Directory of Open Access Journals (Sweden)

    Rietman Edward A

    2011-06-01

    Full Text Available Abstract In this paper we provide a review of selected mathematical ideas that can help us better understand the boundary between living and non-living systems. We focus on group theory and abstract algebra applied to molecular systems biology. Throughout this paper we briefly describe possible open problems. In connection with the genetic code we propose that it may be possible to use perturbation theory to explore the adjacent possibilities in the 64-dimensional space-time manifold of the evolving genome. With regards to algebraic graph theory, there are several minor open problems we discuss. In relation to network dynamics and groupoid formalism we suggest that the network graph might not be the main focus for understanding the phenotype but rather the phase space of the network dynamics. We show a simple case of a C6 network and its phase space network. We envision that the molecular network of a cell is actually a complex network of hypercycles and feedback circuits that could be better represented in a higher-dimensional space. We conjecture that targeting nodes in the molecular network that have key roles in the phase space, as revealed by analysis of the automorphism decomposition, might be a better way to drug discovery and treatment of cancer.

  12. Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Nielsen, Jens; Jewett, Michael Christopher

    2008-01-01

    Industrial biotechnology is a rapidly growing field. With the increasing shift towards a bio-based economy, there is rising demand for developing efficient cell factories that can produce fuels, chemicals, pharmaceuticals, materials, nutraceuticals, and even food ingredients. The yeast Saccharomy...... programmes. Here, the impact of systems biology on metabolic engineering is reviewed and perspectives on the role of systems biology in the design of cell factories are given.......Industrial biotechnology is a rapidly growing field. With the increasing shift towards a bio-based economy, there is rising demand for developing efficient cell factories that can produce fuels, chemicals, pharmaceuticals, materials, nutraceuticals, and even food ingredients. The yeast...... in the industrial application of this yeast. Developments in genomics and high-throughput systems biology tools are enhancing one's ability to rapidly characterize cellular behaviour, which is valuable in the field of metabolic engineering where strain characterization is often the bottleneck in strain development...

  13. Information-theoretic analysis of the dynamics of an executable biological model.

    Directory of Open Access Journals (Sweden)

    Avital Sadot

    Full Text Available To facilitate analysis and understanding of biological systems, large-scale data are often integrated into models using a variety of mathematical and computational approaches. Such models describe the dynamics of the biological system and can be used to study the changes in the state of the system over time. For many model classes, such as discrete or continuous dynamical systems, there exist appropriate frameworks and tools for analyzing system dynamics. However, the heterogeneous information that encodes and bridges molecular and cellular dynamics, inherent to fine-grained molecular simulation models, presents significant challenges to the study of system dynamics. In this paper, we present an algorithmic information theory based approach for the analysis and interpretation of the dynamics of such executable models of biological systems. We apply a normalized compression distance (NCD analysis to the state representations of a model that simulates the immune decision making and immune cell behavior. We show that this analysis successfully captures the essential information in the dynamics of the system, which results from a variety of events including proliferation, differentiation, or perturbations such as gene knock-outs. We demonstrate that this approach can be used for the analysis of executable models, regardless of the modeling framework, and for making experimentally quantifiable predictions.

  14. A Comparative Nitrogen Balance and Productivity Analysis of Legume and Non-legume Supported Cropping Systems: The Potential Role of Biological Nitrogen Fixation

    DEFF Research Database (Denmark)

    Iannetta, Pietro P M; Young, Mark; Bachinger, Johann

    2016-01-01

    studies have systematically evaluated the effect of optimizing the balance between legumes and non N-fixing crops to optimize production. In addition, the shortage, or even absence in some regions, of measurements of BNF in crops and forages severely limits the ability to design and evaluate new legume......–based agroecosystems. To provide an indication of the magnitude of BNF in European agriculture, a soil-surface N-balance approach was applied to historical data from 8 experimental cropping systems that compared legume and non-legume crop types (e.g., grains, forages and intercrops) across pedoclimatic regions...... of Europe. Mean BNF for different legume types ranged from 32 to 115 kg ha−1 annually. Output in terms of total biomass (grain, forage, etc.) was 30% greater in non-legumes, which used N to produce dry matter more efficiently than legumes, whereas output of N was greater from legumes. When examined over...

  15. Qgui: A high-throughput interface for automated setup and analysis of free energy calculations and empirical valence bond simulations in biological systems.

    Science.gov (United States)

    Isaksen, Geir Villy; Andberg, Tor Arne Heim; Åqvist, Johan; Brandsdal, Bjørn Olav

    2015-07-01

    Structural information and activity data has increased rapidly for many protein targets during the last decades. In this paper, we present a high-throughput interface (Qgui) for automated free energy and empirical valence bond (EVB) calculations that use molecular dynamics (MD) simulations for conformational sampling. Applications to ligand binding using both the linear interaction energy (LIE) method and the free energy perturbation (FEP) technique are given using the estrogen receptor (ERα) as a model system. Examples of free energy profiles obtained using the EVB method for the rate-limiting step of the enzymatic reaction catalyzed by trypsin are also shown. In addition, we present calculation of high-precision Arrhenius plots to obtain the thermodynamic activation enthalpy and entropy with Qgui from running a large number of EVB simulations.

  16. Solid-phase microextraction for the analysis of biological samples

    NARCIS (Netherlands)

    Theodoridis, G; Koster, EHM; de Jong, GJ

    2000-01-01

    Solid-phase microextraction (SPME) has been introduced for the extraction of organic compounds from environmental samples. This relatively new extraction technique has now also gained a lot of interest in a broad field of analysis including food, biological and pharmaceutical samples. SPME has a num

  17. Analysis and Design of Biological Materials and Structures

    CERN Document Server

    Öchsner, Andreas; Altenbach, Holm

    2012-01-01

    This collection provides researchers and scientists with advanced analyses and materials design techniques in Biomaterials and presents mechanical studies of biological structures. In 16 contributions well known experts present their research on Stress and Strain Analysis, Material Properties, Fluid and Gas mechanics and they show related problems.

  18. Local Citation Analysis of Graduate Biology Theses: Collection Development Implications

    Science.gov (United States)

    Miller, Laura Newton

    2011-01-01

    This paper will focus on the citation analysis of graduate masters theses from Carleton University's Biology Department with implications for library collection management decisions. Twenty-five masters theses were studied to determine citation types and percentages, ranking of journals by frequency of citation and by number of authors citing, and…

  19. Toxicological Analysis of Some Drugs of Abuse in Biological Samples

    Directory of Open Access Journals (Sweden)

    Anne Marie Ciobanu

    2015-10-01

    Full Text Available Consumption of drugs of abuse is a scourge of modern world. Abuse, drug addiction and their consequences are one of the major current problems of European society because of the significant repercussions in individual, family, social and economic level. In this context, toxicological analysis of the drugs of abuse in biological samples is a useful tool for: diagnosis of drug addiction, checking an auto-response, mandatory screening in some treatment programs, identification of a substance in the case of an overdose, determining compliance of the treatment. The present paper aims to address the needs of healthcare professionals involved in drugs addiction treatment through systematic presentation of information regarding their toxicological analysis. Basically, it is a tool that help you to select the suitable biological sample and the right collecting time, as well as the proper analysis technique, depending on the purpose of analysis, pharmacokinetic characteristics of the drugs of abuse, available equipment and staff expertise.

  20. Visual Analysis of Biological Activity Data with Scaffold Hunter.

    Science.gov (United States)

    Klein, Karsten; Koch, Oliver; Kriege, Nils; Mutzel, Petra; Schäfer, Till

    2013-12-01

    The growing interest in chemogenomics approaches over the last years has led to an increasing amount of data regarding chemical and the corresponding biological activity space. The resulting data, collected in either in-house or public databases, need to be analyzed efficiently to speed-up the increasingly difficult task of drug discovery. Unfortunately, the discovery of new chemical entities or new targets for known drugs ('drug repurposing') is not suitable to a fully automated analysis or a simple drill down process. Visual interactive interfaces that allow to explore chemical space in a systematic manner and facilitate analytical reasoning can help to overcome these problems. Scaffold Hunter is a tool for the visual analysis of chemical compound databases that provides integrated visualization and analysis of biological activity data and fosters the interactive exploration of data imported from a variety of sources. We describe the features and illustrate the use by means of an exemplary analysis workflow.

  1. The OME Framework for genome-scale systems biology

    Energy Technology Data Exchange (ETDEWEB)

    Palsson, Bernhard O. [Univ. of California, San Diego, CA (United States); Ebrahim, Ali [Univ. of California, San Diego, CA (United States); Federowicz, Steve [Univ. of California, San Diego, CA (United States)

    2014-12-19

    The life sciences are undergoing continuous and accelerating integration with computational and engineering sciences. The biology that many in the field have been trained on may be hardly recognizable in ten to twenty years. One of the major drivers for this transformation is the blistering pace of advancements in DNA sequencing and synthesis. These advances have resulted in unprecedented amounts of new data, information, and knowledge. Many software tools have been developed to deal with aspects of this transformation and each is sorely needed [1-3]. However, few of these tools have been forced to deal with the full complexity of genome-scale models along with high throughput genome- scale data. This particular situation represents a unique challenge, as it is simultaneously necessary to deal with the vast breadth of genome-scale models and the dizzying depth of high-throughput datasets. It has been observed time and again that as the pace of data generation continues to accelerate, the pace of analysis significantly lags behind [4]. It is also evident that, given the plethora of databases and software efforts [5-12], it is still a significant challenge to work with genome-scale metabolic models, let alone next-generation whole cell models [13-15]. We work at the forefront of model creation and systems scale data generation [16-18]. The OME Framework was borne out of a practical need to enable genome-scale modeling and data analysis under a unified framework to drive the next generation of genome-scale biological models. Here we present the OME Framework. It exists as a set of Python classes. However, we want to emphasize the importance of the underlying design as an addition to the discussions on specifications of a digital cell. A great deal of work and valuable progress has been made by a number of communities [13, 19-24] towards interchange formats and implementations designed to achieve similar goals. While many software tools exist for handling genome

  2. Electrochemical approaches for chemical and biological analysis on Mars

    Science.gov (United States)

    Kounaves, Samuel P.

    2003-01-01

    Obtaining in situ chemical data from planetary bodies such as Mars or Europa can present significant challenges. The one analytical technique that has many of the requisite characteristics to meet such a challenge is electroanalysis. Described here are three electroanalytical devices designed for in situ geochemical and biological analysis on Mars. The Mars Environmental Compatibility Assessment (MECA) was built and flight qualified for the now cancelled NASA Mars 2001 Lander. Part of MECA consisted of four "cells" containing arrays of electrochemical based sensors for measuring the ionic species in soil samples. A next-generation MECA, the Robotic Chemical Analysis Laboratory (RCAL), uses a carousel-type system to allow for greater customization of analytical procedures. A second instrument, proposed as part of the 2007 CryoScout mission, consists of a flow-through inorganic chemical analyzer (MICA). CryoScout is a torpedo-like device designed for subsurface investigation of the stratigraphic climate record embedded in Mars' north polar cap. As the CryoScout melts its way through the ice cap, MICA will collect and analyze the meltwater for a variety of inorganics and chemical parameters. By analyzing the chemistry locked in the layers of dust, salt, and ice, geologists will be able to determine the recent history of climate, water, and atmosphere on Mars and link it to the past. Finally, electroanalysis shows its abilities in the detection of possible microorganism on Mars or elsewhere in the solar system. To identify an unknown microorganism, one that may not even use Earth-type biochemistry, requires a detection scheme which makes minimal assumptions and looks for the most general features. Recent work has demonstrated that the use of an array of electrochemical sensors which monitors the changes in a solution via electrical conductivity, pH, and ion selective electrodes, can be used to detect minute chemical perturbations caused by the growth of bacteria and

  3. Systems Biology of Meridians, Acupoints, and Chinese Herbs in Disease

    Directory of Open Access Journals (Sweden)

    Li-Ling Lin

    2012-01-01

    Full Text Available Meridians, acupoints, and Chinese herbs are important components of traditional Chinese medicine (TCM. They have been used for disease treatment and prevention and as alternative and complementary therapies. Systems biology integrates omics data, such as transcriptional, proteomic, and metabolomics data, in order to obtain a more global and complete picture of biological activity. To further understand the existence and functions of the three components above, we reviewed relevant research in the systems biology literature and found many recent studies that indicate the value of acupuncture and Chinese herbs. Acupuncture is useful in pain moderation and relieves various symptoms arising from acute spinal cord injury and acute ischemic stroke. Moreover, Chinese herbal extracts have been linked to wound repair, the alleviation of postmenopausal osteoporosis severity, and anti-tumor effects, among others. Different acupoints, variations in treatment duration, and herbal extracts can be used to alleviate various symptoms and conditions and to regulate biological pathways by altering gene and protein expression. Our paper demonstrates how systems biology has helped to establish a platform for investigating the efficacy of TCM in treating different diseases and improving treatment strategies.

  4. A systems biology analysis of the changes in gene expression via silencing of HPV-18 E1 expression in HeLa cells.

    Science.gov (United States)

    Castillo, Andres; Wang, Lu; Koriyama, Chihaya; Eizuru, Yoshito; Jordan, King; Akiba, Suminori

    2014-10-01

    Previous studies have reported the detection of a truncated E1 mRNA generated from HPV-18 in HeLa cells. Although it is unclear whether a truncated E1 protein could function as a replicative helicase for viral replication, it would still retain binding sites for potential interactions with different host cell proteins. Furthermore, in this study, we found evidence in support of expression of full-length HPV-18 E1 mRNA in HeLa cells. To determine whether interactions between E1 and cellular proteins play an important role in cellular processes other than viral replication, genome-wide expression profiles of HPV-18 positive HeLa cells were compared before and after the siRNA knockdown of E1 expression. Differential expression and gene set enrichment analysis uncovered four functionally related sets of genes implicated in host defence mechanisms against viral infection. These included the toll-like receptor, interferon and apoptosis pathways, along with the antiviral interferon-stimulated gene set. In addition, we found that the transcriptional coactivator E1A-binding protein p300 (EP300) was downregulated, which is interesting given that EP300 is thought to be required for the transcription of HPV-18 genes in HeLa cells. The observed changes in gene expression produced via the silencing of HPV-18 E1 expression in HeLa cells indicate that in addition to its well-known role in viral replication, the E1 protein may also play an important role in mitigating the host's ability to defend against viral infection.

  5. Novel integrated mechanical biological chemical treatment (MBCT) systems for the production of levulinic acid from fraction of municipal solid waste: A comprehensive techno-economic analysis.

    Science.gov (United States)

    Sadhukhan, Jhuma; Ng, Kok Siew; Martinez-Hernandez, Elias

    2016-09-01

    This paper, for the first time, reports integrated conceptual MBCT/biorefinery systems for unlocking the value of organics in municipal solid waste (MSW) through the production of levulinic acid (LA by 5wt%) that increases the economic margin by 110-150%. After mechanical separation recovering recyclables, metals (iron, aluminium, copper) and refuse derived fuel (RDF), lignocelluloses from remaining MSW are extracted by supercritical-water for chemical valorisation, comprising hydrolysis in 2wt% dilute H2SO4 catalyst producing LA, furfural, formic acid (FA), via C5/C6 sugar extraction, in plug flow (210-230°C, 25bar, 12s) and continuous stirred tank (195-215°C, 14bar, 20min) reactors; char separation and LA extraction/purification by methyl isobutyl ketone solvent; acid/solvent and by-product recovery. The by-product and pulping effluents are anaerobically digested into biogas and fertiliser. Produced biogas (6.4MWh/t), RDF (5.4MWh/t), char (4.5MWh/t) are combusted, heat recovered into steam generation in boiler (efficiency: 80%); on-site heat/steam demand is met; balance of steam is expanded into electricity in steam turbines (efficiency: 35%).

  6. Implementation of integral feedback control in biological systems.

    Science.gov (United States)

    Somvanshi, Pramod R; Patel, Anilkumar K; Bhartiya, Sharad; Venkatesh, K V

    2015-01-01

    Integral control design ensures that a key variable in a system is tightly maintained within acceptable levels. This approach has been widely used in engineering systems to ensure offset free operation in the presence of perturbations. Several biological systems employ such an integral control design to regulate cellular processes. An integral control design motif requires a negative feedback and an integrating process in the network loop. This review describes several biological systems, ranging from bacteria to higher organisms in which the presence of integral control principle has been hypothesized. The review highlights that in addition to the negative feedback, occurrence of zero-order kinetics in the process is a key element to realize the integral control strategy. Although the integral control motif is common to these systems, the mechanisms involved in achieving it are highly specific and can be incorporated at the level of signaling, metabolism, or at the phenotypic levels.

  7. Bioinformatics approaches to single-cell analysis in developmental biology.

    Science.gov (United States)

    Yalcin, Dicle; Hakguder, Zeynep M; Otu, Hasan H

    2016-03-01

    Individual cells within the same population show various degrees of heterogeneity, which may be better handled with single-cell analysis to address biological and clinical questions. Single-cell analysis is especially important in developmental biology as subtle spatial and temporal differences in cells have significant associations with cell fate decisions during differentiation and with the description of a particular state of a cell exhibiting an aberrant phenotype. Biotechnological advances, especially in the area of microfluidics, have led to a robust, massively parallel and multi-dimensional capturing, sorting, and lysis of single-cells and amplification of related macromolecules, which have enabled the use of imaging and omics techniques on single cells. There have been improvements in computational single-cell image analysis in developmental biology regarding feature extraction, segmentation, image enhancement and machine learning, handling limitations of optical resolution to gain new perspectives from the raw microscopy images. Omics approaches, such as transcriptomics, genomics and epigenomics, targeting gene and small RNA expression, single nucleotide and structural variations and methylation and histone modifications, rely heavily on high-throughput sequencing technologies. Although there are well-established bioinformatics methods for analysis of sequence data, there are limited bioinformatics approaches which address experimental design, sample size considerations, amplification bias, normalization, differential expression, coverage, clustering and classification issues, specifically applied at the single-cell level. In this review, we summarize biological and technological advancements, discuss challenges faced in the aforementioned data acquisition and analysis issues and present future prospects for application of single-cell analyses to developmental biology.

  8.  Biological therapies in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Dorota Suszek

    2012-08-01

    Full Text Available  The prevention of chronic organic damage and complete inhibition of inflammatory activity of the disease are the main goals in the treatment of systemic lupus erythematosus (SLE. Current therapies of SLE are not effective enough and they may cause various serious side effects. Biological therapies, affecting important pathogenetic disturbances in the immunological system of SLE patients, give hope for the development of a new treatment for SLE. Currently the most advanced clinical trials are being conducted with anti-lymphocyte B drugs, such as rituximab, belimumab and epratuzumab. Belimumab as the first biological agent was registered for treatment of the active, seropositive form of SLE. The advances in immunology and rheumatology nowadays raise the hope of finding effective and safe treatment for SLE. In our article we present an overview of data concerning perspectives of biological treatment in SLE.

  9. Biologics: the role of delivery systems in improved therapy

    Directory of Open Access Journals (Sweden)

    Škalko-Basnet N

    2014-03-01

    Full Text Available Nataša Škalko-Basnet Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø, Tromsø, Norway Abstract: The beginning of the 21st century saw numerous protein and peptide therapeuticals both on the market and entering the final stages of clinical studies. They represent a new category of biologically originated drugs termed biologics or biologicals. Their main advantages over conventional drugs can be summarized by their high selectivity and potent therapeutic efficacy coupled with limited side effects. In addition, they exhibit more predictable behavior under in vivo conditions. However, up to now most of the formulations of biologics are designed and destined for the parenteral route of administration. As a consequence, many suffer from short plasma half-lives, resulting in their frequent administration and ultimately poor patient compliance. This review represents an attempt to address some of the challenges and promises in the product development of biologics both for parenteral and noninvasive administration. Some of the products currently in the pipeline of pharmaceutical development and corresponding perspectives are discussed in more detail. Keywords: biologics, drug delivery systems, medical devices

  10. Linking experimental results, biological networks and sequence analysis methods using Ontologies and Generalised Data Structures.

    Science.gov (United States)

    Koehler, Jacob; Rawlings, Chris; Verrier, Paul; Mitchell, Rowan; Skusa, Andre; Ruegg, Alexander; Philippi, Stephan

    2005-01-01

    The structure of a closely integrated data warehouse is described that is designed to link different types and varying numbers of biological networks, sequence analysis methods and experimental results such as those coming from microarrays. The data schema is inspired by a combination of graph based methods and generalised data structures and makes use of ontologies and meta-data. The core idea is to consider and store biological networks as graphs, and to use generalised data structures (GDS) for the storage of further relevant information. This is possible because many biological networks can be stored as graphs: protein interactions, signal transduction networks, metabolic pathways, gene regulatory networks etc. Nodes in biological graphs represent entities such as promoters, proteins, genes and transcripts whereas the edges of such graphs specify how the nodes are related. The semantics of the nodes and edges are defined using ontologies of node and relation types. Besides generic attributes that most biological entities possess (name, attribute description), further information is stored using generalised data structures. By directly linking to underlying sequences (exons, introns, promoters, amino acid sequences) in a systematic way, close interoperability to sequence analysis methods can be achieved. This approach allows us to store, query and update a wide variety of biological information in a way that is semantically compact without requiring changes at the database schema level when new kinds of biological information is added. We describe how this datawarehouse is being implemented by extending the text-mining framework ONDEX to link, support and complement different bioinformatics applications and research activities such as microarray analysis, sequence analysis and modelling/simulation of biological systems. The system is developed under the GPL license and can be downloaded from http://sourceforge.net/projects/ondex/

  11. International Conference on Intelligent Systems for Molecular Biology (ISMB)

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, Debra; Hibbs, Matthew; Kall, Lukas; Komandurglayavilli, Ravikumar; Mahony, Shaun; Marinescu, Voichita; Mayrose, Itay; Minin, Vladimir; Neeman, Yossef; Nimrod, Guy; Novotny, Marian; Opiyo, Stephen; Portugaly, Elon; Sadka, Tali; Sakabe, Noboru; Sarkar, Indra; Schaub, Marc; Shafer, Paul; Shmygelska, Olena; Singer, Gregory; Song, Yun; Soumyaroop, Bhattacharya; Stadler, Michael; Strope, Pooja; Su, Rong; Tabach, Yuval; Tae, Hongseok; Taylor, Todd; Terribilini, Michael; Thomas, Asha; Tran, Nam; Tseng, Tsai-Tien; Vashist, Akshay; Vijaya, Parthiban; Wang, Kai; Wang, Ting; Wei, Lai; Woo, Yong; Wu, Chunlei; Yamanishi, Yoshihiro; Yan, Changhui; Yang, Jack; Yang, Mary; Ye, Ping; Zhang, Miao

    2009-12-29

    The Intelligent Systems for Molecular Biology (ISMB) conference has provided a general forum for disseminating the latest developments in bioinformatics on an annual basis for the past 13 years. ISMB is a multidisciplinary conference that brings together scientists from computer science, molecular biology, mathematics and statistics. The goal of the ISMB meeting is to bring together biologists and computational scientists in a focus on actual biological problems, i.e., not simply theoretical calculations. The combined focus on "intelligent systems" and actual biological data makes ISMB a unique and highly important meeting, and 13 years of experience in holding the conference has resulted in a consistently well organized, well attended, and highly respected annual conference. The ISMB 2005 meeting was held June 25-29, 2005 at the Renaissance Center in Detroit, Michigan. The meeting attracted over 1,730 attendees. The science presented was exceptional, and in the course of the five-day meeting, 56 scientific papers, 710 posters, 47 Oral Abstracts, 76 Software demonstrations, and 14 tutorials were presented. The attendees represented a broad spectrum of backgrounds with 7% from commercial companies, over 28% qualifying for student registration, and 41 countries were represented at the conference, emphasizing its important international aspect. The ISMB conference is especially important because the cultures of computer science and biology are so disparate. ISMB, as a full-scale technical conference with refereed proceedings that have been indexed by both MEDLINE and Current Contents since 1996, bridges this cultural gap.

  12. INTERNATIONAL CONFERENCE ON INTELLIGENT SYSTEMS FOR MOLECULAR BIOLOGY (ISMB)

    Energy Technology Data Exchange (ETDEWEB)

    Debra Goldberg; Matthew Hibbs; Lukas Kall; Ravikumar Komandurglayavilli; Shaun Mahony; Voichita Marinescu; Itay Mayrose; Vladimir Minin; Yossef Neeman; Guy Nimrod; Marian Novotny; Stephen Opiyo; Elon Portugaly; Tali Sadka; Noboru Sakabe; Indra Sarkar; Marc Schaub; Paul Shafer; Olena Shmygelska; Gregory Singer; Yun Song; Bhattacharya Soumyaroop; Michael Stadler; Pooja Strope; Rong Su; Yuval Tabach; Hongseok Tae; Todd Taylor; Michael Terribilini; Asha Thomas; Nam Tran; Tsai-Tien Tseng; Akshay Vashist; Parthiban Vijaya; Kai Wang; Ting Wang; Lai Wei; Yong Woo; Chunlei Wu; Yoshihiro Yamanishi; Changhui Yan; Jack Yang; Mary Yang; Ping Ye; Miao Zhang

    2009-12-29

    The Intelligent Systems for Molecular Biology (ISMB) conference has provided a general forum for disseminating the latest developments in bioinformatics on an annual basis for the past 13 years. ISMB is a multidisciplinary conference that brings together scientists from computer science, molecular biology, mathematics and statistics. The goal of the ISMB meeting is to bring together biologists and computational scientists in a focus on actual biological problems, i.e., not simply theoretical calculations. The combined focus on “intelligent systems” and actual biological data makes ISMB a unique and highly important meeting, and 13 years of experience in holding the conference has resulted in a consistently well organized, well attended, and highly respected annual conference. The ISMB 2005 meeting was held June 25-29, 2005 at the Renaissance Center in Detroit, Michigan. The meeting attracted over 1,730 attendees. The science presented was exceptional, and in the course of the five-day meeting, 56 scientific papers, 710 posters, 47 Oral Abstracts, 76 Software demonstrations, and 14 tutorials were presented. The attendees represented a broad spectrum of backgrounds with 7% from commercial companies, over 28% qualifying for student registration, and 41 countries were represented at the conference, emphasizing its important international aspect. The ISMB conference is especially important because the cultures of computer science and biology are so disparate. ISMB, as a full-scale technical conference with refereed proceedings that have been indexed by both MEDLINE and Current Contents since 1996, bridges this cultural gap.

  13. Request for Travel Funds for Systems Radiation Biology Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Barcellos-Hoff, Mary Helen [NYU School of Medicine

    2014-03-22

    The 3rd International Systems Radiation Biology Workshop brought together the major European, US and Japanese research programs on radiation risk as well as selected experts representing systems biological approaches to discuss how the new methodologies could be best exploited for low dose research. A significant part of the workshop was devoted to discussions organised as breakout group sessions. To facilitate discussions number of participants was limited to 60 persons. To achieve the goals of this symposium in this international conference, support from DOE is vital. Hence, this proposal requested support in the amount of $15,000 to cover the travel expenses of international experts and radiation biology scientists from the United States. This supporting mechanism was clearly identified to the selected US participants as a conference support award from the DOE (See attached PDF). The workshop was an outstanding opportunity to strengthen interactions between leading experts in the emerging areas of radiation sciences, and will also provide opportunities for younger scientists to meet with experts and discuss their results. This workshop was designed to endorse active engagement in international collaboration. A major objective of this conference was to effectively communicate research results, in order to ensure that current thinking reflects sound science of radiation biology. Further, this international event addressed the use and success of scientific initiatives in radiation biology for policymakers, standard-setters, and the general public.

  14. Systems Biology based studies on anti-inflammatory compounds

    NARCIS (Netherlands)

    Verhoeckx, Kitty Catharina Maria

    2005-01-01

    The introduction of the ‘omics’ techniques (transcriptomics, proteomics, and metabolomics) and systems biology, has caused fundamental changes in the drug discovery process and many other fields in the life science area. In this thesis we explored the possibilities to apply these holistic technologi

  15. Applied systems biology - vanillin production in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Strucko, Tomas; Eriksen, Jens Christian; Nielsen, J.

    2012-01-01

    Vanillin is the most important aroma compound based on market value, and natural vanillin is extracted from the cured seed pods of the Vanilla orchid. Most of the world’s vanillin, however, is obtained by chemical synthesis from petrochemicals or wood pulp lignins. As an alternative, de novo bios...... in a systems biology setting....

  16. Cancer systems biology: signal processing for cancer research

    Institute of Scientific and Technical Information of China (English)

    Olli Yli-Harja; Antti Ylip(a)(a); Matti Nykter; Wei Zhang

    2011-01-01

    In this editorial we introduce the research paradigms of signal processing in the era of systems biology. Signal processing is a field of science traditionally focused on modeling electronic and communications systems, but recently it has turned to biological applications with astounding results. The essence of signal processing is to describe the natural world by mathematical models and then, based on these models, develop efficient computational tools for solving engineering problems. Here, we underline, with examples, the endless possibilities which arise when the battle-hardened tools of engineering are applied to solve the problems that have tormented cancer researchers. Based on this approach, a new field has emerged, called cancer systems biology. Despite its short history, cancer systems biology has already produced several success stories tackling previously impracticable problems. Perhaps most importantly, it has been accepted as an integral part of the major endeavors of cancer research, such as analyzing the genomic and epigenomic data produced by The Cancer Genome Atlas (TCGA) project. Finally, we show that signal processing and cancer research, two fields that are seemingly distant from each other, have merged into a field that is indeed more than the sum of its parts.

  17. Responses to Low Doses of Ionizing Radiation in Biological Systems

    OpenAIRE

    Feinendegen, Ludwig E.; Pollycove, Myron; Sondhaus, Charles A.

    2004-01-01

    Biological tissues operate through cells that act together within signaling networks. These assure coordinated cell function in the face of constant exposure to an array of potentially toxic agents, externally from the environment and endogenously from metabolism. Living tissues are indeed complex adaptive systems.

  18. Cancer systems biology: signal processing for cancer research.

    Science.gov (United States)

    Yli-Harja, Olli; Ylipää, Antti; Nykter, Matti; Zhang, Wei

    2011-04-01

    In this editorial we introduce the research paradigms of signal processing in the era of systems biology. Signal processing is a field of science traditionally focused on modeling electronic and communications systems, but recently it has turned to biological applications with astounding results. The essence of signal processing is to describe the natural world by mathematical models and then, based on these models, develop efficient computational tools for solving engineering problems. Here, we underline, with examples, the endless possibilities which arise when the battle-hardened tools of engineering are applied to solve the problems that have tormented cancer researchers. Based on this approach, a new field has emerged, called cancer systems biology. Despite its short history, cancer systems biology has already produced several success stories tackling previously impracticable problems. Perhaps most importantly, it has been accepted as an integral part of the major endeavors of cancer research, such as analyzing the genomic and epigenomic data produced by The Cancer Genome Atlas (TCGA) project. Finally, we show that signal processing and cancer research, two fields that are seemingly distant from each other, have merged into a field that is indeed more than the sum of its parts.

  19. System as metaphor in the psychology and biology of shame.

    Science.gov (United States)

    Maunder, R

    1996-01-01

    Biological theories of brain and psychological theories of mind are two systems of explanation that seem related to one another. The nature of the relationship is problematic and constitutes the age-old mind-body problem. The most prominent solutions currently are variations of materialism. While psychological theories can be consistent with materialism, there remains a difficulty in comprehending nonphysical (social, psychological) causes of physical effects. This difficulty is an obstacle to integration in psychiatry, where we routinely assume that illnesses that include or depend on biological dysfunction are caused multifactorially by causal agents such as perceived parental warmth, parental loss, stressful life events, genetics, and personality (Hammen et al. 1992; Kendler et al. 1993). Unity theory adopts the stance that neurobiological theories and psychological theories are essentially disparate explanations of the same psychobiological events; thus the relationship of mind to brain is one of shared reference (Goodman 1991; Maunder 1995). In Goodman's model the gap between biological and psychological systems is not bridgeable. Different conceptual categories refer to the same referents but cannot interact with each other. Stepping into the breach, systems theory has been presented as offering a language that can bridge the gap between psychological and biological theories of causation (Schwartz 1981; Weiner 1989). Thus, there is a controversy about the applicability of systems theory for integration in psychiatry.

  20. Heuristic approaches to models and modeling in systems biology

    NARCIS (Netherlands)

    MacLeod, Miles

    2016-01-01

    Prediction and control sufficient for reliable medical and other interventions are prominent aims of modeling in systems biology. The short-term attainment of these goals has played a strong role in projecting the importance and value of the field. In this paper I identify the standard models must m

  1. Integration of proteomics into systems biology of cancer.

    Science.gov (United States)

    Hanash, S; Schliekelman, M; Zhang, Q; Taguchi, A

    2012-01-01

    Deciphering the complexity and heterogeneity of cancer, benefits from integration of proteomic level data into systems biology efforts. The opportunities available as a result of advances in proteomic technologies, the successes to date, and the challenges involved in integrating diverse datasets are addressed in this review.

  2. Environmental Noise and Nonlinear Relaxation in Biological Systems

    CERN Document Server

    Spagnolo, B; Spezia, S; Curcio, L; Pizzolato, N; Dubkov, A A; Fiasconaro, A; Adorno, D Persano; Bue, P Lo; Peri, E; Colazza, S

    2011-01-01

    We analyse the effects of environmental noise in three different biological systems: (i) mating behaviour of individuals of \\emph{Nezara viridula} (L.) (Heteroptera Pentatomidae); (ii) polymer translocation in crowded solution; (iii) an ecosystem described by a Verhulst model with a multiplicative L\\'{e}vy noise.

  3. Integrating Biological Systems in the Process Dynamics and Control Curriculum

    Science.gov (United States)

    Parker, Robert S.; Doyle, Francis J.; Henson, Michael A.

    2006-01-01

    The evolution of the chemical engineering discipline motivates a re-evaluation of the process dynamics and control curriculum. A key requirement of future courses will be the introduction of theoretical concepts and application examples relevant to emerging areas, notably complex biological systems. We outline the critical concepts required to…

  4. Fetal metabolic programming and epigenetic modifications: a systems biology approach.

    Science.gov (United States)

    Sookoian, Silvia; Gianotti, Tomas Fernández; Burgueño, Adriana L; Pirola, Carlos J

    2013-04-01

    A growing body of evidence supports the notion that epigenetic changes such as DNA methylation and histone modifications, both involving chromatin remodeling, contribute to fetal metabolic programming. We use a combination of gene-protein enrichment analysis resources along with functional annotations and protein interaction networks for an integrative approach to understanding the mechanisms underlying fetal metabolic programming. Systems biology approaches suggested that fetal adaptation to an impaired nutritional environment presumes profound changes in gene expression that involve regulation of tissue-specific patterns of methylated cytosine residues, modulation of the histone acetylation-deacetylation switch, cell differentiation, and stem cell pluripotency. The hypothalamus and the liver seem to be differently involved. In addition, new putative explanations have emerged about the question of whether in utero overnutrition modulates fetal metabolic programming in the same fashion as that of a maternal environment of undernutrition, suggesting that the mechanisms behind these two fetal nutritional imbalances are different. In conclusion, intrauterine growth restriction is most likely to be associated with the induction of persistent changes in tissue structure and functionality. Conversely, a maternal obesogenic environment is most probably associated with metabolic reprogramming of glucose and lipid metabolism, as well as future risk of metabolic syndrome (MS), fatty liver, and insulin (INS) resistance.

  5. On linear models and parameter identifiability in experimental biological systems.

    Science.gov (United States)

    Lamberton, Timothy O; Condon, Nicholas D; Stow, Jennifer L; Hamilton, Nicholas A

    2014-10-07

    A key problem in the biological sciences is to be able to reliably estimate model parameters from experimental data. This is the well-known problem of parameter identifiability. Here, methods are developed for biologists and other modelers to design optimal experiments to ensure parameter identifiability at a structural level. The main results of the paper are to provide a general methodology for extracting parameters of linear models from an experimentally measured scalar function - the transfer function - and a framework for the identifiability analysis of complex model structures using linked models. Linked models are composed by letting the output of one model become the input to another model which is then experimentally measured. The linked model framework is shown to be applicable to designing experiments to identify the measured sub-model and recover the input from the unmeasured sub-model, even in cases that the unmeasured sub-model is not identifiable. Applications for a set of common model features are demonstrated, and the results combined in an example application to a real-world experimental system. These applications emphasize the insight into answering "where to measure" and "which experimental scheme" questions provided by both the parameter extraction methodology and the linked model framework. The aim is to demonstrate the tools' usefulness in guiding experimental design to maximize parameter information obtained, based on the model structure.

  6. Structure of deviations from optimality in biological systems.

    Science.gov (United States)

    Pérez-Escudero, Alfonso; Rivera-Alba, Marta; de Polavieja, Gonzalo G

    2009-12-01

    Optimization theory has been used to analyze evolutionary adaptation. This theory has explained many features of biological systems, from the genetic code to animal behavior. However, these systems show important deviations from optimality. Typically, these deviations are large in some particular components of the system, whereas others seem to be almost optimal. Deviations from optimality may be due to many factors in evolution, including stochastic effects and finite time, that may not allow the system to reach the ideal optimum. However, we still expect the system to have a higher probability of reaching a state with a higher value of the proposed indirect measure of fitness. In systems of many components, this implies that the largest deviations are expected in those components with less impact on the indirect measure of fitness. Here, we show that this simple probabilistic rule explains deviations from optimality in two very different biological systems. In Caenorhabditis elegans, this rule successfully explains the experimental deviations of the position of neurons from the configuration of minimal wiring cost. In Escherichia coli, the probabilistic rule correctly obtains the structure of the experimental deviations of metabolic fluxes from the configuration that maximizes biomass production. This approach is proposed to explain or predict more data than optimization theory while using no extra parameters. Thus, it can also be used to find and refine hypotheses about which constraints have shaped biological structures in evolution.

  7. Chemical and biological flocculation process to treat municipal sewage and analysis of biological function

    Institute of Scientific and Technical Information of China (English)

    XIA Si-qing; YANG Dian-hai; XU Bin; ZHAO Jian-fu

    2005-01-01

    The pilot-scale experimental apparatus and the procedure of the chemical and biological flocculation process to verify the feasibility in treating Shanghai municipal sewage were introduced in this paper. In addition, the biological function of the process was discussed. The results of optimal running showed that in the reaction tank, the concentration of mixed liquor suspended solid(MLSS) was2 g/L, hydraulic retention time(HRT) was 35 min, dosage of liquid polyaluminium chloride(PAC) was 60 mg/L, and the concentration of polyacrylamide(PAM) was 0.5 mg/L. The effluent average concentrations of CODcr, TP, SS and BOD5 were 50 mg/L, 0.62 mg/L, 18mg/L, and 17 mg/L, respectively. These were better than the designed demand. In addition, the existence of biological degradation in this system was proven by several methods. The removal efficiencies of the chemical and biological flocculation process were 20% higher than that of the chemical flocculation process above at the same coagulant dosage. The treatment process under different situations was evaluated on a pilot-scale experiment, and the results provided magnificent parameters and optimal condition for future operation of the plant.

  8. Applications of membrane computing in systems and synthetic biology

    CERN Document Server

    Gheorghe, Marian; Pérez-Jiménez, Mario

    2014-01-01

    Membrane Computing was introduced as a computational paradigm in Natural Computing. The models introduced, called Membrane (or P) Systems, provide a coherent platform to describe and study living cells as computational systems. Membrane Systems have been investigated for their computational aspects and employed to model problems in other fields, like: Computer Science, Linguistics, Biology, Economy, Computer Graphics, Robotics, etc. Their inherent parallelism, heterogeneity and intrinsic versatility allow them to model a broad range of processes and phenomena, being also an efficient means to solve and analyze problems in a novel way. Membrane Computing has been used to model biological systems, becoming with time a thorough modeling paradigm comparable, in its modeling and predicting capabilities, to more established models in this area. This book is the result of the need to collect, in an organic way, different facets of this paradigm. The chapters of this book, together with the web pages accompanying th...

  9. Molecular biology of the renin-angiotensin system

    Energy Technology Data Exchange (ETDEWEB)

    Dzau, V.J.; Burt, D.W.; Pratt, R.E. (Harvard Medical School, Boston, MA (USA))

    1988-10-01

    This paper reviews the molecular biology of the renin-angiotensin system. The renin gene structure is analyzed in detail, including an examination of the putative regulatory regions. The combined action of these regulatory sequences would result in the complex, tissue-specific expression and regulation observed in vivo. The expression of the tissue renin-angiotensin systems, which may have important physiological functions, is also described. In addition, the pathway of renin biosynthesis and secretion is reviewed. This includes speculation on the fate of circulating prorenin and the physiological role of multiple renin forms and secretory pathways. The molecular approaches described in this paper have greatly advanced our knowledge of the biology of the renin-angiotensin system. Future studies using these and other approaches should provide further insight into this complex system.

  10. Phytoestrogen Biological Actions on Mammalian Reproductive System and Cancer Growth

    OpenAIRE

    Zhao, E; Mu, Qing

    2010-01-01

    Phytoestrogens are a family of diverse polyphenolic compounds derived from nature plant that structurally or functionally mimic circulating estrogen in the mammalian reproductive system. They induce estrogenic and anti-estrogenic effects in the brain-pituitary-gonad axis (a principal endocrine system involving in reproductive regulation) and peripheral reproductive organs. The dichotomy of phytoestrogen-mediated actions elucidates that they play the biological activities via complex mechanism...

  11. The solar system: Importance of research to the biological sciences

    Science.gov (United States)

    Klein, Harold P.

    1992-01-01

    An attempt is made to describe the scope of scientific areas that comprise the current field of exobiology in the United States. From investigations of astrophysical phenomena that deal with the birth of stars and planetary systems to questions of molecular biology involving phylogenetic relationships among organisms, from attempts to simulate the synthesis of biological precursor molecules in the chemistry laboratory to making measurements of the organic constituents of Titan's atmosphere, these researches all converge toward a common objective--answering the question of how life came about in the universe.

  12. Systems Biology and Cancer Prevention: All Options on the Table

    Directory of Open Access Journals (Sweden)

    Simon Rosenfeld

    2008-01-01

    Full Text Available In this paper, we outline the status quo and approaches to further development of the systems biology concepts with focus on applications in cancer prevention science. We discuss the biological aspects of cancer research that are of primary importance in cancer prevention, motivations for their mathematical modeling and some recent advances in computational oncology. We also make an attempt to outline in big conceptual terms the contours of future work aimed at creation of large-scale computational and informational infrastructure for using as a routine tool in cancer prevention science and decision making.

  13. Imaging Biological Systems using Dielectric Near-Field Microscopy

    Science.gov (United States)

    Brown, Keith; Issadore, David; Hunt, Tom; Westervelt, Robert

    2007-03-01

    We have developed a dielectric spectrometer for use on biological systems. The spectrum of dielectric response to RF electric fields is analogous to color as an optical response. Measurement of the dielectric spectrum from ˜ 10 kHz to ˜ 3 GHz will reveal information about the structure and conditions of protein solutions, protein crystals and biological tissues. We designed and built a system to test biological samples in a microfluidic chamber mounted on a circuit board. The apparatus measures the RF dielectric spectrum directly, or by analyzing the pulse response in the time domain. We have constructed several versions of the hardware for sensitive capacitive measurements, including two types of capacitive bridges, and a transmission line, incorporating precision electronics and local generation of pulses. A goal is to scale the system down and implement many dielectric spectrometers as an array of pixels on a CMOS chip for dielectric near-field microscopy of biological samples. This work made possible by NSEC NSF grant PHY-0117795 and the NCI MIT-Harvard CCNE.

  14. Complex Biological Systems Analysis of Cell Cycling Models in Carcinogenesis: I. The essential roles of modifications in the c-Myc, TP53/p53, p27 and hTERT modules in Cancer Initiation and Progression

    CERN Document Server

    Prisecaru, V I

    2004-01-01

    A new approach to the integration of results from a modular, complex biological systems analysis of nonlinear dynamics in cell cycling network transformations that are leading to carcinogenesis is proposed. Carcinogenesis is a complex process that involves dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments that form numerous inter-related pathways referred to as networks. One such network module contains the cell cyclins whose functions are essential to cell cycling and division. Cyclins are proteins that also link to several critical pro-apoptotic and other cell cycling/division components, such as: c-Myc, p27, the tumor suppressor gene TP53 and its product-- the p53 protein with key roles in controlling DNA repair, inducing apoptosis and activating p21 (which can depress cell cyclins if activated), mdm2(with its biosynthesis activated by p53 and also, in its turn, inhibiting p53), p21, the Thomsen-Friedenreich antigen(T- antigen),Rb,Bax, Ba...

  15. Two classes of bipartite networks: nested biological and social systems.

    Science.gov (United States)

    Burgos, Enrique; Ceva, Horacio; Hernández, Laura; Perazzo, R P J; Devoto, Mariano; Medan, Diego

    2008-10-01

    Bipartite graphs have received some attention in the study of social networks and of biological mutualistic systems. A generalization of a previous model is presented, that evolves the topology of the graph in order to optimally account for a given contact preference rule between the two guilds of the network. As a result, social and biological graphs are classified as belonging to two clearly different classes. Projected graphs, linking the agents of only one guild, are obtained from the original bipartite graph. The corresponding evolution of its statistical properties is also studied. An example of a biological mutualistic network is analyzed in detail, and it is found that the model provides a very good fitting of all the main statistical features. The model also provides a proper qualitative description of the same features observed in social webs, suggesting the possible reasons underlying the difference in the organization of these two kinds of bipartite networks.

  16. Modeling systems-level dynamics: Understanding without mechanistic explanation in integrative systems biology.

    Science.gov (United States)

    MacLeod, Miles; Nersessian, Nancy J

    2015-02-01

    In this paper we draw upon rich ethnographic data of two systems biology labs to explore the roles of explanation and understanding in large-scale systems modeling. We illustrate practices that depart from the goal of dynamic mechanistic explanation for the sake of more limited modeling goals. These processes use abstract mathematical formulations of bio-molecular interactions and data fitting techniques which we call top-down abstraction to trade away accurate mechanistic accounts of large-scale systems for specific information about aspects of those systems. We characterize these practices as pragmatic responses to the constraints many modelers of large-scale systems face, which in turn generate more limited pragmatic non-mechanistic forms of understanding of systems. These forms aim at knowledge of how to predict system responses in order to manipulate and control some aspects of them. We propose that this analysis of understanding provides a way to interpret what many systems biologists are aiming for in practice when they talk about the objective of a "systems-level understanding."

  17. Specifications of Standards in Systems and Synthetic Biology.

    Science.gov (United States)

    Schreiber, Falk; Bader, Gary D; Golebiewski, Martin; Hucka, Michael; Kormeier, Benjamin; Le Novère, Nicolas; Myers, Chris; Nickerson, David; Sommer, Björn; Waltemath, Dagmar; Weise, Stephan

    2015-09-04

    Standards shape our everyday life. From nuts and bolts to electronic devices and technological processes, standardised products and processes are all around us. Standards have technological and economic benefits, such as making information exchange, production, and services more efficient. However, novel, innovative areas often either lack proper standards, or documents about standards in these areas are not available from a centralised platform or formal body (such as the International Standardisation Organisation). Systems and synthetic biology is a relatively novel area, and it is only in the last decade that the standardisation of data, information, and models related to systems and synthetic biology has become a community-wide effort. Several open standards have been established and are under continuous development as a community initiative. COMBINE, the ‘COmputational Modeling in BIology’ NEtwork has been established as an umbrella initiative to coordinate and promote the development of the various community standards and formats for computational models. There are yearly two meeting, HARMONY (Hackathons on Resources for Modeling in Biology), Hackathon-type meetings with a focus on development of the support for standards, and COMBINE forums, workshop-style events with oral presentations, discussion, poster, and breakout sessions for further developing the standards. For more information see http://co.mbine.org/. So far the different standards were published and made accessible through the standards’ web- pages or preprint services. The aim of this special issue is to provide a single, easily accessible and citable platform for the publication of standards in systems and synthetic biology. This special issue is intended to serve as a central access point to standards and related initiatives in systems and synthetic biology, it will be published annually to provide an opportunity for standard development groups to communicate updated specifications.

  18. Data management in systems biology I - Overview and bibliography

    CERN Document Server

    Mayer, Gerhard

    2009-01-01

    Large systems biology projects can encompass several workgroups often located in different countries. An overview about existing data standards in systems biology and the management, storage, exchange and integration of the generated data in large distributed research projects is given, the pros and cons of the different approaches are illustrated from a practical point of view, the existing software - open source as well as commercial - and the relevant literature is extensively overview, so that the reader should be enabled to decide which data management approach is the best suited for his special needs. An emphasis is laid on the use of workflow systems and of TAB-based formats. The data in this format can be viewed and edited easily using spreadsheet programs which are familiar to the working experimental biologists. The use of workflows for the standardized access to data in either own or publicly available databanks and the standardization of operation procedures is presented. The use of ontologies and...

  19. Exogenous control of biological and ecological systems through evolutionary modelling

    Directory of Open Access Journals (Sweden)

    Alessandro Ferrarini

    2013-09-01

    Full Text Available The controllability of network-like systems is a topical issue in ecology and biology. It relies on the ability to lead a system's behaviour towards the desired state through the appropriate handling of input variables. Up to now, controllability of networks is based on the permanent control of a set of driver nodes that can guide the system's dynamics. This assumption seems motivated by real-world networks observation, where a decentralized control is often applied only to part of the nodes. While in a previous paper I showed that ecological and biological networks can be efficaciously controlled from the inside, here I further introduce a new framework for network controllability based on the employment of exogenous controllers and evolutionary modelling, and provide an exemplification of its application.

  20. RNA Systems Biology for Cancer: From Diagnosis to Therapy.

    Science.gov (United States)

    Amirkhah, Raheleh; Farazmand, Ali; Wolkenhauer, Olaf; Schmitz, Ulf

    2016-01-01

    It is due to the advances in high-throughput omics data generation that RNA species have re-entered the focus of biomedical research. International collaborate efforts, like the ENCODE and GENCODE projects, have spawned thousands of previously unknown functional non-coding RNAs (ncRNAs) with various but primarily regulatory roles. Many of these are linked to the emergence and progression of human diseases. In particular, interdisciplinary studies integrating bioinformatics, systems biology, and biotechnological approaches have successfully characterized the role of ncRNAs in different human cancers. These efforts led to the identification of a new tool-kit for cancer diagnosis, monitoring, and treatment, which is now starting to enter and impact on clinical practice. This chapter is to elaborate on the state of the art in RNA systems biology, including a review and perspective on clinical applications toward an integrative RNA systems medicine approach. The focus is on the role of ncRNAs in cancer.

  1. Systems biology for understanding and engineering of heterotrophic oleaginous microorganisms.

    Science.gov (United States)

    Park, Beom Gi; Kim, Minsuk; Kim, Joonwon; Yoo, Heewang; Kim, Byung-Gee

    2017-01-01

    Heterotrophic oleaginous microorganisms continue to draw interest as they can accumulate a large amount of lipids which is a promising feedstock for the production of biofuels and oleochemicals. Nutrient limitation, especially nitrogen limitation, is known to effectively trigger the lipid production in these microorganisms. For the aim of developing improved strains, the mechanisms behind the lipid production have been studied for a long time. Nowadays, system-level understanding of their metabolism and associated metabolic switches is attainable with modern systems biology tools. This work reviews the systems biology studies, based on (i) top-down, large-scale 'omics' tools, and (ii) bottom-up, mathematical modeling methods, on the heterotrophic oleaginous microorganisms with an emphasis on further application to metabolic engineering.

  2. Systems biology in the frontier of cancer research:a report of the Second International Workshop of Cancer Systems Biology

    Institute of Scientific and Technical Information of China (English)

    Juan Cui; Yan-Chun Liang; Ying Xu

    2012-01-01

    The report summarizes the Second International Workshop of Cancer Systems Biology held on July 5-6,2012 in Changchun,China.The goal of the workshop was to bring together cancer researchers with different backgrounds to share their views about cancer and their experiences in fighting against cancer,and to gain new and systems-level understanding about cancer formation,progression,diagnosis,and treatment through exchanging ideas.

  3. On Designing Multicore-Aware Simulators for Systems Biology Endowed with OnLine Statistics

    Directory of Open Access Journals (Sweden)

    Marco Aldinucci

    2014-01-01

    Full Text Available The paper arguments are on enabling methodologies for the design of a fully parallel, online, interactive tool aiming to support the bioinformatics scientists .In particular, the features of these methodologies, supported by the FastFlow parallel programming framework, are shown on a simulation tool to perform the modeling, the tuning, and the sensitivity analysis of stochastic biological models. A stochastic simulation needs thousands of independent simulation trajectories turning into big data that should be analysed by statistic and data mining tools. In the considered approach the two stages are pipelined in such a way that the simulation stage streams out the partial results of all simulation trajectories to the analysis stage that immediately produces a partial result. The simulation-analysis workflow is validated for performance and effectiveness of the online analysis in capturing biological systems behavior on a multicore platform and representative proof-of-concept biological systems. The exploited methodologies include pattern-based parallel programming and data streaming that provide key features to the software designers such as performance portability and efficient in-memory (big data management and movement. Two paradigmatic classes of biological systems exhibiting multistable and oscillatory behavior are used as a testbed.

  4. On designing multicore-aware simulators for systems biology endowed with OnLine statistics.

    Science.gov (United States)

    Aldinucci, Marco; Calcagno, Cristina; Coppo, Mario; Damiani, Ferruccio; Drocco, Maurizio; Sciacca, Eva; Spinella, Salvatore; Torquati, Massimo; Troina, Angelo

    2014-01-01

    The paper arguments are on enabling methodologies for the design of a fully parallel, online, interactive tool aiming to support the bioinformatics scientists .In particular, the features of these methodologies, supported by the FastFlow parallel programming framework, are shown on a simulation tool to perform the modeling, the tuning, and the sensitivity analysis of stochastic biological models. A stochastic simulation needs thousands of independent simulation trajectories turning into big data that should be analysed by statistic and data mining tools. In the considered approach the two stages are pipelined in such a way that the simulation stage streams out the partial results of all simulation trajectories to the analysis stage that immediately produces a partial result. The simulation-analysis workflow is validated for performance and effectiveness of the online analysis in capturing biological systems behavior on a multicore platform and representative proof-of-concept biological systems. The exploited methodologies include pattern-based parallel programming and data streaming that provide key features to the software designers such as performance portability and efficient in-memory (big) data management and movement. Two paradigmatic classes of biological systems exhibiting multistable and oscillatory behavior are used as a testbed.

  5. Philosophical Basis and Some Historical Aspects of Systems Biology: From Hegel to Noble - Applications for Bioenergetic Research

    Directory of Open Access Journals (Sweden)

    Valdur Saks

    2009-03-01

    Full Text Available We live in times of paradigmatic changes for the biological sciences. Reductionism, that for the last six decades has been the philosophical basis of biochemistry and molecular biology, is being displaced by Systems Biology, which favors the study of integrated systems. Historically, Systems Biology - defined as the higher level analysis of complex biological systems - was pioneered by Claude Bernard in physiology, Norbert Wiener with the development of cybernetics, and Erwin Schrödinger in his thermodynamic approach to the living. Systems Biology applies methods inspired by cybernetics, network analysis, and non-equilibrium dynamics of open systems. These developments follow very precisely the dialectical principles of development from thesis to antithesis to synthesis discovered by Hegel. Systems Biology opens new perspectives for studies of the integrated processes of energy metabolism in different cells. These integrated systems acquire new, system-level properties due to interaction of cellular components, such as metabolic compartmentation, channeling and functional coupling mechanisms, which are central for regulation of the energy fluxes. State of the art of these studies in the new area of Molecular System Bioenergetics is analyzed.

  6. Philosophical basis and some historical aspects of systems biology: from Hegel to Noble - applications for bioenergetic research.

    Science.gov (United States)

    Saks, Valdur; Monge, Claire; Guzun, Rita

    2009-03-01

    We live in times of paradigmatic changes for the biological sciences. Reductionism, that for the last six decades has been the philosophical basis of biochemistry and molecular biology, is being displaced by Systems Biology, which favors the study of integrated systems. Historically, Systems Biology - defined as the higher level analysis of complex biological systems - was pioneered by Claude Bernard in physiology, Norbert Wiener with the development of cybernetics, and Erwin Schrödinger in his thermodynamic approach to the living. Systems Biology applies methods inspired by cybernetics, network analysis, and non-equilibrium dynamics of open systems. These developments follow very precisely the dialectical principles of development from thesis to antithesis to synthesis discovered by Hegel. Systems Biology opens new perspectives for studies of the integrated processes of energy metabolism in different cells. These integrated systems acquire new, system-level properties due to interaction of cellular components, such as metabolic compartmentation, channeling and functional coupling mechanisms, which are central for regulation of the energy fluxes. State of the art of these studies in the new area of Molecular System Bioenergetics is analyzed.

  7. Systems Biology Knowledgebase for a New Era in Biology A Genomics:GTL Report from the May 2008 Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Gregurick, S.; Fredrickson, J. K.; Stevens, R.

    2009-03-01

    Biology has entered a systems-science era with the goal to establish a predictive understanding of the mechanisms of cellular function and the interactions of biological systems with their environment and with each other. Vast amounts of data on the composition, physiology, and function of complex biological systems and their natural environments are emerging from new analytical technologies. Effectively exploiting these data requires developing a new generation of capabilities for analyzing and managing the information. By revealing the core principles and processes conserved in collective genomes across all biology and by enabling insights into the interplay between an organism's genotype and its environment, systems biology will allow scientific breakthroughs in our ability to project behaviors of natural systems and to manipulate and engineer managed systems. These breakthroughs will benefit Department of Energy (DOE) missions in energy security, climate protection, and environmental remediation.

  8. Newton, laplace, and the epistemology of systems biology.

    Science.gov (United States)

    Bittner, Michael L; Dougherty, Edward R

    2012-01-01

    For science, theoretical or applied, to significantly advance, researchers must use the most appropriate mathematical methods. A century and a half elapsed between Newton's development of the calculus and Laplace's development of celestial mechanics. One cannot imagine the latter without the former. Today, more than three-quarters of a century has elapsed since the birth of stochastic systems theory. This article provides a perspective on the utilization of systems theory as the proper vehicle for the development of systems biology and its application to complex regulatory diseases such as cancer.

  9. Biological Computation as the Revolution of Complex Engineered Systems

    CERN Document Server

    Gómez-Cruz, Nelson Alfonso

    2011-01-01

    Provided that there is no theoretical frame for complex engineered systems (CES) as yet, this paper claims that bio-inspired engineering can help provide such a frame. Within CES bio-inspired systems play a key role. The disclosure from bio-inspired systems and biological computation has not been sufficiently worked out, however. Biological computation is to be taken as the processing of information by living systems that is carried out in polynomial time, i.e., efficiently; such processing however is grasped by current science and research as an intractable problem (for instance, the protein folding problem). A remark is needed here: P versus NP problems should be well defined and delimited but biological computation problems are not. The shift from conventional engineering to bio-inspired engineering needs bring the subject (or problem) of computability to a new level. Within the frame of computation, so far, the prevailing paradigm is still the Turing-Church thesis. In other words, conventional engineering...

  10. Integrative biological systems modeling:challenges and opportunities

    Institute of Scientific and Technical Information of China (English)

    Jialiang WU; Eberhard VOIT

    2009-01-01

    Most biological systems are by nature hybrids consist of interacting discrete and continuous components,which may even operate on different time scales. Therefore," it is desirable to establish modeling frameworks that are capable of combining deterministic and stochastic, discrete and continuous, as well as multi-timescale features. In the context of molecular systems biology, an example for the need of such a combination is the investigation of integrated biological pathways that contain gene regulatory, metabolic and signaling components, which may operate on different time scales and involve on-off switches as well as stochastic effects. The implementation of integrated hybrid systems is not trivial because most software is limited to one or the other of the dichotomies above. In this study, we first review the motivation for hybrid modeling. Secondly, by using the example of a toggle switch model, we illustrate a recently developed modeling framework that is based on the combination of biochemical systems theory (BST) and hybrid functional Petri nets (HFPN). Finally, we discuss remaining challenges and future opportunities.

  11. Cancer systems biology and modeling: microscopic scale and multiscale approaches.

    Science.gov (United States)

    Masoudi-Nejad, Ali; Bidkhori, Gholamreza; Hosseini Ashtiani, Saman; Najafi, Ali; Bozorgmehr, Joseph H; Wang, Edwin

    2015-02-01

    Cancer has become known as a complex and systematic disease on macroscopic, mesoscopic and microscopic scales. Systems biology employs state-of-the-art computational theories and high-throughput experimental data to model and simulate complex biological procedures such as cancer, which involves genetic and epigenetic, in addition to intracellular and extracellular complex interaction networks. In this paper, different systems biology modeling techniques such as systems of differential equations, stochastic methods, Boolean networks, Petri nets, cellular automata methods and agent-based systems are concisely discussed. We have compared the mentioned formalisms and tried to address the span of applicability they can bear on emerging cancer modeling and simulation approaches. Different scales of cancer modeling, namely, microscopic, mesoscopic and macroscopic scales are explained followed by an illustration of angiogenesis in microscopic scale of the cancer modeling. Then, the modeling of cancer cell proliferation and survival are examined on a microscopic scale and the modeling of multiscale tumor growth is explained along with its advantages.

  12. Two faces of entropy and information in biological systems.

    Science.gov (United States)

    Mitrokhin, Yuriy

    2014-10-21

    The article attempts to overcome the well-known paradox of contradictions between the emerging biological organization and entropy production in biological systems. It is assumed that quality, speculative correlation between entropy and antientropy processes taking place both in the past and today in the metabolic and genetic cellular systems may be perfectly authorized for adequate description of the evolution of biological organization. So far as thermodynamic entropy itself cannot compensate for the high degree of organization which exists in the cell, we discuss the mode of conjunction of positive entropy events (mutations) in the genetic systems of the past generations and the formation of organized structures of current cells. We argue that only the information which is generated in the conditions of the information entropy production (mutations and other genome reorganization) in genetic systems of the past generations provides the physical conjunction of entropy and antientropy processes separated from each other in time generations. It is readily apparent from the requirements of the Second law of thermodynamics.

  13. A unified framework based on the binding polynomial for characterizing biological systems by isothermal titration calorimetry.

    Science.gov (United States)

    Vega, Sonia; Abian, Olga; Velazquez-Campoy, Adrian

    2015-04-01

    Isothermal titration calorimetry (ITC) has become the gold-standard technique for studying binding processes due to its high precision and sensitivity, as well as its capability for the simultaneous determination of the association equilibrium constant, the binding enthalpy and the binding stoichiometry. The current widespread use of ITC for biological systems has been facilitated by technical advances and the availability of commercial calorimeters. However, the complexity of data analysis for non-standard models is one of the most significant drawbacks in ITC. Many models for studying macromolecular interactions can be found in the literature, but it looks like each biological system requires specific modeling and data analysis approaches. The aim of this article is to solve this lack of unity and provide a unified methodological framework for studying binding interactions by ITC that can be applied to any experimental system. The apparent complexity of this methodology, based on the binding polynomial, is overcome by its easy generalization to complex systems.

  14. Logical and symbolic analysis of robust biological dynamics.

    Science.gov (United States)

    Glass, Leon; Siegelmann, Hava T

    2010-12-01

    Logical models provide insight about key control elements of biological networks. Based solely on the logical structure, we can determine state transition diagrams that give the allowed possible transitions in a coarse grained phase space. Attracting pathways and stable nodes in the state transition diagram correspond to robust attractors that would be found in several different types of dynamical systems that have the same logical structure. Attracting nodes in the state transition diagram correspond to stable steady states. Furthermore, the sequence of logical states appearing in biological networks with robust attracting pathways would be expected to appear also in Boolean networks, asynchronous switching networks, and differential equations having the same underlying structure. This provides a basis for investigating naturally occurring and synthetic systems, both to predict the dynamics if the structure is known, and to determine the structure if the transitions are known.

  15. Systems biology of IL-6, IL-12 family cytokines.

    Science.gov (United States)

    Dittrich, Anna; Hessenkemper, Wiebke; Schaper, Fred

    2015-10-01

    Interleukin-6-type cytokines play important roles in the communication between cells of multicellular organisms. They are involved in the regulation of complex cellular processes such as proliferation and differentiation and act as key player during inflammation and immune response. A major challenge is to understand how these complex non-linear processes are connected and regulated. Systems biology approaches are used to tackle this challenge in an iterative process of quantitative experimental and mathematical analyses. Here we review quantitative experimental studies and systems biology approaches dealing with the function of Interleukin-6-type cytokines in physiological and pathophysiological conditions. These approaches cover the analyses of signal transduction on a cellular level up to pharmacokinetic and pharmacodynamic studies on a whole organism level.

  16. Single Cell Analysis: From Technology to Biology and Medicine.

    Science.gov (United States)

    Pan, Xinghua

    2014-01-01

    Single-cell analysis heralds a new era that allows "omics" analysis, notably genomics, transcriptomics, epigenomics and proteomics at the single-cell level. It enables the identification of the minor subpopulations that may play a critical role in a biological process of a population of cells, which conventionally are regarded as homogeneous. It provides an ultra-sensitive tool to clarify specific molecular mechanisms and pathways and reveal the nature of cell heterogeneity. It also facilitates the clinical investigation of patients when a very low quantity or a single cell is available for analysis, such as noninvasive prenatal diagnosis and cancer screening, and genetic evaluation for in vitro fertilization. Within a few short years, single-cell analysis, especially whole genomic sequencing and transcriptomic sequencing, is becoming robust and broadly accessible, although not yet a routine practice. Here, with single cell RNA-seq emphasized, an overview of the discipline, progresses, and prospects of single-cell analysis and its applications in biology and medicine are given with a series of logic and theoretical considerations.

  17. Smart interactive electronic system for monitoring the electromagnetic activities of biological systems

    Science.gov (United States)

    Popa, Sorin G.; Shahinpoor, Mohsen

    2001-08-01

    A novel electronic device capable of sensing and monitoring the myoelectric, polarization wave and electromagnetic activities of the biological systems and in particular the human body is presented. It is known that all the physical and chemical processes within biological systems are associated with polarization, depolarization waves from the brain, neural signals and myoelectric processes that manifest themselves in ionic and dipole motion. The technology developed in our laboratory is based on certain charge motion sensitive electronics. The electronic system developed is capable of sensing the electromagnetic activities of biological systems. The information obtained is then processed by specialized software in order to interpret it from physical and chemical point of view.

  18. Systems of organic farming in spring vetch I: Biological response of sucking insect pests

    Directory of Open Access Journals (Sweden)

    Ivelina Nikolova

    2015-04-01

    Full Text Available Four systems of organic farming and a conventional farming system were studied over the period 2012-2014. The organic system trial variants included: I – an organic farming system without any biological products used (growth under natural soil fertility – Control; II – an organic farming system involving the use of a biological foliar fertilizer and a biological plant growth regulator (Polyversum+Biofa; III – an organic farming system in which a biological insecticide (NeemAzal T/S was used; IV – an organic farming system including a combination of three organic products: the foliar fertilizer, the plant growth regulator and the bioinsecticide (Polyversum+Biofa+NeemAzal T/S. Variant V represented a conventional farming system in which synthetic products were used in combination (foliar fertilizer, plant growth regulator and insecticide: Masterblend+Flordimex 420+Nurelle D. Treatment of vetch plants with the biological insecticide NeemAzal in combination with Biofa and Polyversum resulted in the lowest density of sucking pests, compared to all other organic farming methods tested (i.e. without NeemAzal, with NeemAzal alone, and its combination with Biofa and Polyversum. The greatest reduction in pest numbers during the vegetation period in that variant was observed in species of the order Thysanoptera (36.0-41.4%, followed by Hemiptera, and the families Aphididae (31.6-40.3% and Cicadellidae (27.3-28.6%. This combination showed an efficient synergistic interaction and an increase in biological efficacy as compared to individual application of NeemAzal. The highest toxic impact was found against Thrips tabaci, followed by Acyrthosiphon pisum. An analysis of variance regarding the efficacy against the species A. pisum, E. pteridis and T. tabaci showed that type of treatment had the most dominant influence and statistically significant impact.

  19. Dynamical Systems and Control Theory Inspired by Molecular Biology

    Science.gov (United States)

    2011-02-20

    is odd) steady states, there never are more than 2n − 1 steady states, that for parameters near the standard Michaelis - Menten quasi-steady state...conditions, there are at most n + 1 steady states and that for parameters far from the standard Michaelis - Menten quasi-steady state conditions, there is at...moments for certain stochastic kinetics : We have recently started research into stochastic aspects in systems biology. Deterministic mod- els

  20. Cellular systems biology profiling applied to cellular models of disease.

    Science.gov (United States)

    Giuliano, Kenneth A; Premkumar, Daniel R; Strock, Christopher J; Johnston, Patricia; Taylor, Lansing

    2009-11-01

    Building cellular models of disease based on the approach of Cellular Systems Biology (CSB) has the potential to improve the process of creating drugs as part of the continuum from early drug discovery through drug development and clinical trials and diagnostics. This paper focuses on the application of CSB to early drug discovery. We discuss the integration of protein-protein interaction biosensors with other multiplexed, functional biomarkers as an example in using CSB to optimize the identification of quality lead series compounds.

  1. Genome-scale engineering for systems and synthetic biology

    OpenAIRE

    Esvelt, Kevin Michael; Wang, Harris H.

    2013-01-01

    Genome-modification technologies enable the rational engineering and perturbation of biological systems. Historically, these methods have been limited to gene insertions or mutations at random or at a few pre-defined locations across the genome. The handful of methods capable of targeted gene editing suffered from low efficiencies, significant labor costs, or both. Recent advances have dramatically expanded our ability to engineer cells in a directed and combinatorial manner. Here, we review ...

  2. Macroscopic Quantum-Type Potentials in Theoretical Systems Biology

    Directory of Open Access Journals (Sweden)

    Laurent Nottale

    2013-12-01

    Full Text Available We review in this paper the use of the theory of scale relativity and fractal space-time as a tool particularly well adapted to the possible development of a future genuine systems theoretical biology. We emphasize in particular the concept of quantum-type potentials, since, in many situations, the effect of the fractality of space—or of the underlying medium—can be reduced to the addition of such a potential energy to the classical equations of motion. Various equivalent representations—geodesic, quantum-like, fluid mechanical, stochastic—of these equations are given, as well as several forms of generalized quantum potentials. Examples of their possible intervention in high critical temperature superconductivity and in turbulence are also described, since some biological processes may be similar in some aspects to these physical phenomena. These potential extra energy contributions could have emerged in biology from the very fractal nature of the medium, or from an evolutive advantage, since they involve spontaneous properties of self-organization, morphogenesis, structuration and multi-scale integration. Finally, some examples of applications of the theory to actual biological-like processes and functions are also provided.

  3. Systems pharmacology of the nerve growth factor pathway: use of a systems biology model for the identification of key drug targets using sensitivity analysis and the integration of physiology and pharmacology.

    Science.gov (United States)

    Benson, Neil; Matsuura, Tomomi; Smirnov, Sergey; Demin, Oleg; Jones, Hannah M; Dua, Pinky; van der Graaf, Piet H

    2013-04-06

    The nerve growth factor (NGF) pathway is of great interest as a potential source of drug targets, for example in the management of certain types of pain. However, selecting targets from this pathway either by intuition or by non-contextual measures is likely to be challenging. An alternative approach is to construct a mathematical model of the system and via sensitivity analysis rank order the targets in the known pathway, with respect to an endpoint such as the diphosphorylated extracellular signal-regulated kinase concentration in the nucleus. Using the published literature, a model was created and, via sensitivity analysis, it was concluded that, after NGF itself, tropomyosin receptor kinase A (TrkA) was one of the most sensitive druggable targets. This initial model was subsequently used to develop a further model incorporating physiological and pharmacological parameters. This allowed the exploration of the characteristics required for a successful hypothetical TrkA inhibitor. Using these systems models, we were able to identify candidates for the optimal drug targets in the known pathway. These conclusions were consistent with clinical and human genetic data. We also found that incorporating appropriate physiological context was essential to drawing accurate conclusions about important parameters such as the drug dose required to give pathway inhibition. Furthermore, the importance of the concentration of key reactants such as TrkA kinase means that appropriate contextual data are required before clear conclusions can be drawn. Such models could be of great utility in selecting optimal targets and in the clinical evaluation of novel drugs.

  4. Importance of randomness in biological networks: A random matrix analysis

    Indian Academy of Sciences (India)

    Sarika Jalan

    2015-02-01

    Random matrix theory, initially proposed to understand the complex interactions in nuclear spectra, has demonstrated its success in diverse domains of science ranging from quantum chaos to galaxies. We demonstrate the applicability of random matrix theory for networks by providing a new dimension to complex systems research. We show that in spite of huge differences these interaction networks, representing real-world systems, posses from random matrix models, the spectral properties of the underlying matrices of these networks follow random matrix theory bringing them into the same universality class. We further demonstrate the importance of randomness in interactions for deducing crucial properties of the underlying system. This paper provides an overview of the importance of random matrix framework in complex systems research with biological systems as examples.

  5. Model Checking the Biological Model of Membrane Computing with Probabilistic Symbolic Model Checker by Using Two Biological Systems

    Directory of Open Access Journals (Sweden)

    Ravie c. Muniyandi

    2010-01-01

    Full Text Available Problem statement: Membrane computing formalism has provided better modeling capabilities for biological systems in comparison to conventional mathematical models. Model checking could be used to reason about the biological system in detail and with precision by verifying formally whether membrane computing model meets the properties of the system. Approach: This study was carried to investigate the preservation of properties of two biological systems that had been modeled and simulated in membrane computing by a method of model checking using PRISM. The two biological systems were prey-predator population and signal processing in the legend-receptor networks of protein TGF-ß. Results: The model checking of membrane computing model of the biological systems with five different properties showed that the properties of the biological systems could be preserved in the membrane computing model. Conclusion: Membrane computing model not only provides a better approach in representing and simulating a biological system but also able to sustain the basic properties of the system.

  6. Human Metabolic Network: Reconstruction, Simulation, and Applications in Systems Biology

    Science.gov (United States)

    Wu, Ming; Chan, Christina

    2012-01-01

    Metabolism is crucial to cell growth and proliferation. Deficiency or alterations in metabolic functions are known to be involved in many human diseases. Therefore, understanding the human metabolic system is important for the study and treatment of complex diseases. Current reconstructions of the global human metabolic network provide a computational platform to integrate genome-scale information on metabolism. The platform enables a systematic study of the regulation and is applicable to a wide variety of cases, wherein one could rely on in silico perturbations to predict novel targets, interpret systemic effects, and identify alterations in the metabolic states to better understand the genotype-phenotype relationships. In this review, we describe the reconstruction of the human metabolic network, introduce the constraint based modeling approach to analyze metabolic networks, and discuss systems biology applications to study human physiology and pathology. We highlight the challenges and opportunities in network reconstruction and systems modeling of the human metabolic system. PMID:24957377

  7. A systems biology approach to study glucose repression in the yeast Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Westergaard, Steen Lund; Soberano de Oliveira, Ana Paula; Bro, Christoffer

    2007-01-01

    in repression of a wide range of genes involved to utilization of alternative carbon sources. In this work, we applied a systems biology approach to study the interaction between these two pathways. Through genome-wide transcription analysis of strains with disruption of HXK2, GRR1, MIG1, the combination of MIG......1 and MIG2, and the parentel strain, we identified 393 genes to have significantly changed expression levels. To identify co-regulation patterns in the different strains we applied principal component analysis. Disruption of either GRR1 or HXK2 were both found to have profound effects...... reporter metabolites, and found that there is a high degree of consistency between the identified reporter metabolites and the physiological effects observed in the different mutants . Our systems biology approach points to close interaction between the two pathways, and our metabolism driven analysis...

  8. Teleology and its constitutive role for biology as the science of organized systems in nature.

    Science.gov (United States)

    Toepfer, Georg

    2012-03-01

    'Nothing in biology makes sense, except in the light of teleology'. This could be the first sentence in a textbook about the methodology of biology. The fundamental concepts in biology, e.g. 'organism' and 'ecosystem', are only intelligible given a teleological framework. Since early modern times, teleology has often been considered methodologically unscientific. With the acceptance of evolutionary theory, one popular strategy for accommodating teleological reasoning was to explain it by reference to selection in the past: functions were reconstructed as 'selected effects'. But the theory of evolution obviously presupposes the existence of organisms as organized and regulated, i.e. functional systems. Therefore, evolutionary theory cannot provide the foundation for teleology. The underlying reason for the central methodological role of teleology in biology is not its potential to offer particular forms of (evolutionary) explanations for the presence of parts, but rather an ontological one: organisms and other basic biological entities do not exist as physical bodies do, as amounts of matter with a definite form. Rather, they are dynamic systems in stable equilibrium; despite changes of their matter and form (in metabolism and metamorphosis) they maintain their identity. What remains constant in these kinds of systems is their 'organization', i.e. the causal pattern of interdependence of parts with certain effects of each part being relevant for the working of the system. Teleological analysis consists in the identification of these system-relevant effects and at the same time of the system as a whole. Therefore, the identity of biological systems cannot be specified without teleological reasoning.

  9. A Real—Time and Dynamic Biological Information Retrieval and Analysis System(BIRAS)

    Institute of Scientific and Technical Information of China (English)

    QiZhou; HongZhang; MeiyingGeng; ChenggangZhang

    2003-01-01

    The aim of this study is to design a biological information retrieval and analysis system(BIRAS) based on the Internet.Using the specific network protocol,BIRAS system could send and receive information from the Entrez search and retrieval system maintained by National Center for Biotechnology Information(NCBI)in USA.The literatures,nucleotide sequence,protein sequences,and other resources according to the user-defined term could then be retrieved and sent to the user by pop up message or by E-amil informing automatically using BIRAS system.All the information retrieving and analyzing processes are done in real-time.As a robust system for intelligently and dynamically retrieving and analyzing on the user-defined information,it is believed that BIRAS would be extensively used to retrieve specific information from large amount of biological databases in now days.The program is available on request from the corresponding author.

  10. Biologically Inspired Object Localization for a Modular Mobile Robotic System

    Directory of Open Access Journals (Sweden)

    Zlatogor Minchev

    2005-12-01

    Full Text Available The paper considers a general model of real biological creatures' antennae, which is practically implemented and tested, over a real element of a mobile modular robotic system - the robot MR1. The last could be utilized in solving of the most classical problem in Robotics - Object Localization. The functionality of the represented sensor system is described in a new and original manner by utilizing the tool of Generalized Nets - a new likelihood for description, modelling and simulation of different objects from the Artificial Intelligence area including Robotics.

  11. Wearable System for Acquisition and Monitoring of Biological Signals

    Science.gov (United States)

    Piccinini, D. J.; Andino, N. B.; Ponce, S. D.; Roberti, MA; López, y. N.

    2016-04-01

    This paper presents a modular, wearable system for acquisition and wireless transmission of biological signals. Configurable slaves for different signals (such as ECG, EMG, inertial sensors, and temperature) based in the ADS1294 Medical Analog Front End are connected to a Master, based in the CC3200 microcontroller, both from Texas Instruments. The slaves are configurable according to the specific application, providing versatility to the wearable system. The battery consumption is reduced, through a couple of Li-ion batteries and the circuit has also a battery charger. A custom made box was designed and fabricated in a 3D printer, preserving the requirements of low cost, low weight and safety recommendations.

  12. Application of systems biology to the study of chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    CAO Yu-han; L(U) Lin-li; ZHANG Jian-dong; LIU Bi-cheng

    2012-01-01

    Chronic kidney disease (CKD) is a major public health problem that affects about 10% of the general population.Current approaches to characterize the category and progression of CKD are normally based on renal histopathological results and clinical parameters.However,this information is not sufficient to predict CKD progression risk reliably or to guide preventive interventions.Nowadays,the appearance of systems biology has brought forward the concepts of "-omics"technologies,including genomics,transcriptomics,proteomics,and metabolomics.Systems biology,together with molecular analysis approaches such as microarray analysis,genome-wide association studies (GWAS),and serial analysis of gene expression (SAGE),has provided the framework for a comprehensive analysis of renal disease and serves as a starting point for generating novel molecular diagnostic tools for use in nephrology.In particular,analysis of urinary mRNA and protein levels is rapidly evolving as a non-invasive approach for CKD monitoring.All these systems biological molecular approaches are required for application of the concept of "personalized medicine" to progressive CKD,which will result in tailoring therapy for each patient,in contrast to the "one-size-fits-all" therapies currently in use.

  13. Utilizing population variation, vaccination, and systems biology to study human immunology.

    Science.gov (United States)

    Tsang, John S

    2015-08-01

    The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent involvement of the immune system in diverse pathologies, an important question is how much and what information about the state of the immune system is required to enable accurate prediction of future health and response to medical interventions. Towards addressing this question, recent studies using vaccination as a model perturbation and systems-biology approaches are beginning to provide a glimpse of how natural population variation together with multiplexed, high-throughput measurement and computational analysis can be used to uncover predictors of immune response quality in humans. Here I discuss recent developments in this emerging field, with emphasis on baseline correlates of vaccination responses, sources of immune-state variability, as well as relevant features of study design, data generation, and computational analysis.

  14. Microbiology and Molecular Biology Tools for Biogas Process Analysis, Diagnosis and Control.

    Science.gov (United States)

    Lebuhn, Michael; Weiß, Stefan; Munk, Bernhard; Guebitz, Georg M

    2015-01-01

    Many biotechnological processes such as biogas production or defined biotransformations are carried out by microorganisms or tightly cooperating microbial communities. Process breakdown is the maximum credible accident for the operator. Any time savings that can be provided by suitable early-warning systems and allow for specific countermeasures are of great value. Process disturbance, frequently due to nutritional shortcomings, malfunction or operational deficits, is evidenced conventionally by process chemistry parameters. However, knowledge on systems microbiology and its function has essentially increased in the last two decades, and molecular biology tools, most of which are directed against nucleic acids, have been developed to analyze and diagnose the process. Some of these systems have been shown to indicate changes of the process status considerably earlier than the conventionally applied process chemistry parameters. This is reasonable because the triggering catalyst is determined, activity changes of the microbes that perform the reaction. These molecular biology tools have thus the potential to add to and improve the established process diagnosis system. This chapter is dealing with the actual state of the art of biogas process analysis in practice, and introduces molecular biology tools that have been shown to be of particular value in complementing the current systems of process monitoring and diagnosis, with emphasis on nucleic acid targeted molecular biology systems.

  15. Quantitative, high-resolution proteomics for data-driven systems biology

    DEFF Research Database (Denmark)

    Cox, J.; Mann, M.

    2011-01-01

    Systems biology requires comprehensive data at all molecular levels. Mass spectrometry (MS)-based proteomics has emerged as a powerful and universal method for the global measurement of proteins. In the most widespread format, it uses liquid chromatography (LC) coupled to high-resolution tandem...... primary structure of proteins including posttranslational modifications, to localize proteins to organelles, and to determine protein interactions. Here, we describe the principles of analysis and the areas of biology where proteomics can make unique contributions. The large-scale nature of proteomics...... data and its high accuracy pose special opportunities as well as challenges in systems biology that have been largely untapped so far. © 2011 by Annual Reviews. All rights reserved....

  16. Carcinogenesis and Chemotherapy Viewed from the Perspective of Stoichiometric Network Analysis (SNA: What Can the Biological System of the Elements Contribute to an Understanding of Tumour Induction by Elemental Chemical Noxae (e.g., Ni2+, Cd2+ and to an Understanding of Chemotherapy?

    Directory of Open Access Journals (Sweden)

    Stefan Franzle

    2003-01-01

    Full Text Available The biological application of stoichiometric network analysis (SNA permits an understanding of tumour induction, carcinogenesis, and chemotherapy. Starting from the Biological System of the Elements, which provides a comprehensive treatment of the functions and distributions of chemical (trace elements in biology, an attempt is made to interrelate the essential feature of biology and — regrettably — of tumour genesis by superimposing SNA reasoning on common features of all crucial biological processes. For this purpose, aspects, effects and drawbacks of autocatalysis (identical reproduction which can occur either under control or without control [in tumours] are linked with the known facts about element distributions in living beings and about interference of metals with tumours (in terms of both chemotherapy and carcinogenesis. The essential role of autocatalysis in biology and the drawbacks of either controlled or spontaneous cell division can be used to understand crucial aspects of carcinogenesis and chemotherapy because SNA describes and predicts effects of autocatalysis, including phase effects that may be due to some kind of intervention. The SNA-based classifications of autocatalytic networks in cell biology are outlined here to identify new approaches to chemotherapy.

  17. Systems biology and its potential role in radiobiology.

    Science.gov (United States)

    Feinendegen, Ludwig; Hahnfeldt, Philip; Schadt, Eric E; Stumpf, Michael; Voit, Eberhard O

    2008-02-01

    About a century ago, Conrad Röentgen discovered X-rays, and Henri Becquerel discovered a new phenomenon, which Marie and Pierre Curie later coined as radio-activity. Since their seminal work, we have learned much about the physical properties of radiation and its effects on living matter. Alas, the more we discover, the more we appreciate the complexity of the biological processes that are triggered by radiation exposure and eventually lead (or do not lead) to disease. Equipped with modern biological methods of high-throughput experimentation, imaging, and vastly increased computational prowess, we are now entering an era where we can piece some of the multifold aspects of radiation exposure and its sequelae together, and develop a more systemic understanding of radiogenic effects such as radio-carcinogenesis than has been possible in the past. It is evident from the complexity of even the known processes that such an understanding can only be gained if it is supported by mathematical models. At this point, the construction of comprehensive models is hampered both by technical inadequacies and a paucity of appropriate data. Nonetheless, some initial steps have been taken already and the generally increased interest in systems biology may be expected to speed up future progress. In this context, we discuss in this article examples of relatively small, yet very useful models that elucidate selected aspects of the effects of exposure to ionizing radiation and may shine a light on the path before us.

  18. Holarchical Systems and Emotional Holons : Biologically-Inspired System Designs for Control of Autonomous Aerial Vehicles

    Science.gov (United States)

    Ippolito, Corey; Plice, Laura; Pisanich, Greg

    2003-01-01

    The BEES (Bio-inspired Engineering for Exploration Systems) for Mars project at NASA Ames Research Center has the goal of developing bio-inspired flight control strategies to enable aerial explorers for Mars scientific investigations. This paper presents a summary of our ongoing research into biologically inspired system designs for control of unmanned autonomous aerial vehicle communities for Mars exploration. First, we present cooperative design considerations for robotic explorers based on the holarchical nature of biological systems and communities. Second, an outline of an architecture for cognitive decision making and control of individual robotic explorers is presented, modeled after the emotional nervous system of cognitive biological systems. Keywords: Holarchy, Biologically Inspired, Emotional UAV Flight Control

  19. Tennis Forehand Stroke Action of Biological Mechanics Analysis

    Directory of Open Access Journals (Sweden)

    Feng Li

    2013-05-01

    Full Text Available Forehand technique is the basic tennis technology, the highest utilization rate technology, but also the most lethal technology and one of the magic weapons of a tennis match. Grasp the qualitative and quantitative methods combined, the combination of video, movie, analytical and computer technology, combining the principles of the movement mechanics and mathematical statistics. Based on the biological mechanics principle and according to the latest research results of the element analysis and logic analysis, analysis of forehand stroke technical movement, which make us more subtle and correct understand forehand technique and eventually be able to provide a scientific theoretical guidance and practical reference for tennis teaching and training and make a small contribution to perfect tennis skills and innovation.

  20. Genetically engineered biological agents in therapy for systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Elena Aleksandrovna Aseeva

    2013-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototype for chronic autoimmune disease. Its prevalence is 20 to 70 cases per 100,000 women and varies by race and ethnicity. Despite considerable progress in traditional therapy, many problems associated with the management of these patients need to be immediately solved: thus, 50-80% are found to have activity signs and/or frequent exacerbations and about 30% of the patients have to stop work; Class IV lupus nephritis increases the risk of terminalrenal failure. In the past 20 years great progress has been made in studying the pathogenesis of SLE: biological targets to affect drugs have been sought and fundamentally new therapeutic goals defined. Belimumab is the first genetically biological agent specially designed to treat SLE, which is rightly regarded as one of the most important achievements of rheumatology in the past 50 years.

  1. Application of computational systems biology to explore environmental toxicity hazards

    DEFF Research Database (Denmark)

    Audouze, Karine Marie Laure; Grandjean, Philippe

    2011-01-01

    Background: Computer-based modeling is part of a new approach to predictive toxicology.Objectives: We investigated the usefulness of an integrated computational systems biology approach in a case study involving the isomers and metabolites of the pesticide dichlorodiphenyltrichloroethane (DDT......) to ascertain their possible links to relevant adverse effects.Methods: We extracted chemical-protein association networks for each DDT isomer and its metabolites using ChemProt, a disease chemical biology database that includes both binding and gene expression data, and we explored protein-protein interactions...... using a human interactome network. To identify associated dysfunctions and diseases, we integrated protein-disease annotations into the protein complexes using the Online Mendelian Inheritance in Man database and the Comparative Toxicogenomics Database.Results: We found 175 human proteins linked to p,p´-DDT...

  2. Computational intelligence approaches for pattern discovery in biological systems.

    Science.gov (United States)

    Fogel, Gary B

    2008-07-01

    Biology, chemistry and medicine are faced by tremendous challenges caused by an overwhelming amount of data and the need for rapid interpretation. Computational intelligence (CI) approaches such as artificial neural networks, fuzzy systems and evolutionary computation are being used with increasing frequency to contend with this problem, in light of noise, non-linearity and temporal dynamics in the data. Such methods can be used to develop robust models of processes either on their own or in combination with standard statistical approaches. This is especially true for database mining, where modeling is a key component of scientific understanding. This review provides an introduction to current CI methods, their application to biological problems, and concludes with a commentary about the anticipated impact of these approaches in bioinformatics.

  3. Optical sensors and their applications for probing biological systems

    DEFF Research Database (Denmark)

    Palanco, Marta Espina

    and mammalian cells. First, we performed Surface Enhanced Raman Spectroscopy (SERS) studies on intact plant materials via using silver plasmonic nanostructures. Our studies showed strong Raman signals which resemble to the presence of typical constituents such as carbohydrates, proteins and lipids of different......There is a great interest in exploring and developing new optical sensitive methodologies for probing complex biological systems. In this project we developed non-invasive and sensitive biosensor strategies for studying physiologically relevant chemical and physical properties of plant...... biological sample to provide a SERS-template where silver nanoparticles can grow, thus providing a new insight into SERS-based sensors for chemically sensing in-situ plant constituents. Optical manipulation techniques have been used to investigate mechanical properties of soft membrane cells, i.e. mammalian...

  4. Application of enriched stable isotopes as tracers in biological systems

    DEFF Research Database (Denmark)

    Stürup, Stefan; Hansen, Helle Rüsz; Gammelgaard, Bente

    2008-01-01

    The application of enriched stable isotopes of minerals and trace elements as tracers in biological systems is a rapidly growing research field that benefits from the many new developments in inorganic mass spectrometric instrumentation, primarily within inductively coupled plasma mass spectrometry...... (ICP-MS) instrumentation, such as reaction/collision cell ICP-MS and multicollector ICP-MS with improved isotope ratio measurement and interference removal capabilities. Adaptation and refinement of radioisotope tracer experiment methodologies for enriched stable isotope experiments......, and the development of new methodologies coupled with more advanced compartmental and mathematical models for the distribution of elements in living organisms has enabled a broader use of enriched stable isotope experiments in the biological sciences. This review discusses the current and future uses of enriched...

  5. Dynamic optimization of distributed biological systems using robust and efficient numerical techniques

    Directory of Open Access Journals (Sweden)

    Vilas Carlos

    2012-07-01

    Full Text Available Abstract Background Systems biology allows the analysis of biological systems behavior under different conditions through in silico experimentation. The possibility of perturbing biological systems in different manners calls for the design of perturbations to achieve particular goals. Examples would include, the design of a chemical stimulation to maximize the amplitude of a given cellular signal or to achieve a desired pattern in pattern formation systems, etc. Such design problems can be mathematically formulated as dynamic optimization problems which are particularly challenging when the system is described by partial differential equations. This work addresses the numerical solution of such dynamic optimization problems for spatially distributed biological systems. The usual nonlinear and large scale nature of the mathematical models related to this class of systems and the presence of constraints on the optimization problems, impose a number of difficulties, such as the presence of suboptimal solutions, which call for robust and efficient numerical techniques. Results Here, the use of a control vector parameterization approach combined with efficient and robust hybrid global optimization methods and a reduced order model methodology is proposed. The capabilities of this strategy are illustrated considering the solution of a two challenging problems: bacterial chemotaxis and the FitzHugh-Nagumo model. Conclusions In the process of chemotaxis the objective was to efficiently compute the time-varying optimal concentration of chemotractant in one of the spatial boundaries in order to achieve predefined cell distribution profiles. Results are in agreement with those previously published in the literature. The FitzHugh-Nagumo problem is also efficiently solved and it illustrates very well how dynamic optimization may be used to force a system to evolve from an undesired to a desired pattern with a reduced number of actuators. The presented

  6. Witnessing Quantum Coherence: from solid-state to biological systems

    CERN Document Server

    Li, Che-Ming; Chen, Yueh-Nan; Chen, Guang-Yin; Nori, Franco; 10.1038/srep00885

    2012-01-01

    Quantum coherence is one of the primary non-classical features of quantum systems. While protocols such as the Leggett-Garg inequality (LGI) and quantum tomography can be used to test for the existence of quantum coherence and dynamics in a given system, unambiguously detecting inherent "quantumness" still faces serious obstacles in terms of experimental feasibility and efficiency, particularly in complex systems. Here we introduce two "quantum witnesses" to efficiently verify quantum coherence and dynamics in the time domain, without the expense and burden of non-invasive measurements or full tomographic processes. Using several physical examples, including quantum transport in solid-state nanostructures and in biological organisms, we show that these quantum witnesses are robust and have a much finer resolution in their detection window than the LGI has. These robust quantum indicators may assist in reducing the experimental overhead in unambiguously verifying quantum coherence in complex systems.

  7. Process-based design of dynamical biological systems

    Science.gov (United States)

    Tanevski, Jovan; Todorovski, Ljupčo; Džeroski, Sašo

    2016-09-01

    The computational design of dynamical systems is an important emerging task in synthetic biology. Given desired properties of the behaviour of a dynamical system, the task of design is to build an in-silico model of a system whose simulated be- haviour meets these properties. We introduce a new, process-based, design methodology for addressing this task. The new methodology combines a flexible process-based formalism for specifying the space of candidate designs with multi-objective optimization approaches for selecting the most appropriate among these candidates. We demonstrate that the methodology is general enough to both formulate and solve tasks of designing deterministic and stochastic systems, successfully reproducing plausible designs reported in previous studies and proposing new designs that meet the design criteria, but have not been previously considered.

  8. Biological Jumping Mechanism Analysis and Modeling for Frog Robot

    Institute of Scientific and Technical Information of China (English)

    Meng Wang; Xi-zhe Zang; Ji-zhuang Fan; Jie Zhao

    2008-01-01

    This paper presents a mechanical model of jumping robot based on the biological mechanism analysis of frog. By biological observation and kinematic analysis the frog jump is divided into take-off phase, aerial phase and landing phase. We find the similar trajectories of hindlimb joints during jump, the important effect of foot during take-off and the role of forelimb in supporting the body. Based on the observation, the frog jump is simplified and a mechanical model is put forward. The robot leg is represented by a 4-bar spring/linkage mechanism model, which has three Degrees of Freedom (DOF) at hip joint and one DOF (passive) at tarsometatarsal joint on the foot. The shoulder and elbow joints each has one DOF for the balancing function of arm.The ground reaction force of the model is analyzed and compared with that of frog during take-off. The results show that the model has the same advantages of low likelihood of premature lift-off and high efficiency as the frog. Analysis results and the model can be employed to develop and control a robot capable of mimicking the jumping behavior of flog.

  9. Integration of Proteomics, Bioinformatics and Systems biology in Brain Injury Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Joy eGuingab-Cagmat

    2013-05-01

    Full Text Available Traumatic brain injury (TBI is a major medical crisis without any FDA-approved pharmacological therapies that have been demonstrated to improve functional outcomes. It has been argued that discovery of disease-relevant biomarkers might help to guide successful clinical trials for TBI. Major advances in mass spectrometry (MS have revolutionized the field of proteomic biomarker discovery and facilitated the identification of several candidate markers that are being further evaluated for their efficacy as TBI biomarkers. However, several hurdles have to be overcome even during the discovery phase which is only the first step in the long process of biomarker development. The high throughput nature of MS-based proteomic experiments generates a massive amount of mass spectral data presenting great challenges in downstream interpretation. Currently, different bioinformatics platforms are available for functional analysis and data mining of MS-generated proteomic data. These tools provide a way to convert data sets to biologically interpretable results and functional outcomes. A strategy that has promise in advancing biomarker development involves the triad of proteomics, bioinformatics and systems biology. In this review, a brief overview of how bioinformatics and systems biology tools analyze, transform and interpret complex MS datasets into biologically relevant results is discussed. In addition, challenges and limitations of proteomics, bioinformatics and systems biology in TBI biomarker discovery are presented. A brief survey of researches that utilized these three overlapping disciplines in TBI biomarker discovery is also presented. Finally, examples of TBI biomarkers and their applications are discussed.

  10. A methodology to annotate systems biology markup language models with the synthetic biology open language.

    Science.gov (United States)

    Roehner, Nicholas; Myers, Chris J

    2014-02-21

    Recently, we have begun to witness the potential of synthetic biology, noted here in the form of bacteria and yeast that have been genetically engineered to produce biofuels, manufacture drug precursors, and even invade tumor cells. The success of these projects, however, has often failed in translation and application to new projects, a problem exacerbated by a lack of engineering standards that combine descriptions of the structure and function of DNA. To address this need, this paper describes a methodology to connect the systems biology markup language (SBML) to the synthetic biology open language (SBOL), existing standards that describe biochemical models and DNA components, respectively. Our methodology involves first annotating SBML model elements such as species and reactions with SBOL DNA components. A graph is then constructed from the model, with vertices corresponding to elements within the model and edges corresponding to the cause-and-effect relationships between these elements. Lastly, the graph is traversed to assemble the annotating DNA components into a composite DNA component, which is used to annotate the model itself and can be referenced by other composite models and DNA components. In this way, our methodology can be used to build up a hierarchical library of models annotated with DNA components. Such a library is a useful input to any future genetic technology mapping algorithm that would automate the process of composing DNA components to satisfy a behavioral specification. Our methodology for SBML-to-SBOL annotation is implemented in the latest version of our genetic design automation (GDA) software tool, iBioSim.

  11. Integrating ethical analysis "into the DNA" of synthetic biology.

    Science.gov (United States)

    Heavey, Patrick

    2015-02-01

    Current ethical analysis tends to evaluate synthetic biology at an overview level. Synthetic biology, however, is an umbrella term that covers a variety of areas of research. These areas contain, in turn, a hierarchy of different research fields. This abstraction hierarchy-the term is borrowed from engineering-permits synthetic biologists to specialise to a very high degree. Though synthetic biology per se may create profound ethical challenges, much of the day-to-day research does not. Yet seemingly innocuous research could lead to ethically problematic results. For example, Dolly the sheep resulted from a long series of research steps, none of which presented any ethical problems. The atomic bomb was developed as a result of Einstein's uncontentions theoretical research that proved the equivalence of matter and energy. Therefore it would seem wise for ethicists to evaluate synbio research across its subfields and through its abstraction hierarchies, comparing and inter-relating the various areas of research. In addition, it would be useful if journals that publish synbio papers require an ethical statement from authors, as standard practice, so as to encourage scientists to constantly engage with ethical issues in their work. Also, this would allow an ethical snapshot of the state of the research at any given time to exist, allowing for accurate evaluation by scientists and ethicists, regulators and policymakers.

  12. Computing the structural influence matrix for biological systems.

    Science.gov (United States)

    Giordano, Giulia; Cuba Samaniego, Christian; Franco, Elisa; Blanchini, Franco

    2016-06-01

    We consider the problem of identifying structural influences of external inputs on steady-state outputs in a biological network model. We speak of a structural influence if, upon a perturbation due to a constant input, the ensuing variation of the steady-state output value has the same sign as the input (positive influence), the opposite sign (negative influence), or is zero (perfect adaptation), for any feasible choice of the model parameters. All these signs and zeros can constitute a structural influence matrix, whose (i, j) entry indicates the sign of steady-state influence of the jth system variable on the ith variable (the output caused by an external persistent input applied to the jth variable). Each entry is structurally determinate if the sign does not depend on the choice of the parameters, but is indeterminate otherwise. In principle, determining the influence matrix requires exhaustive testing of the system steady-state behaviour in the widest range of parameter values. Here we show that, in a broad class of biological networks, the influence matrix can be evaluated with an algorithm that tests the system steady-state behaviour only at a finite number of points. This algorithm also allows us to assess the structural effect of any perturbation, such as variations of relevant parameters. Our method is applied to nontrivial models of biochemical reaction networks and population dynamics drawn from the literature, providing a parameter-free insight into the system dynamics.

  13. Systems biology strategies to study lipidomes in health and disease.

    Science.gov (United States)

    Hyötyläinen, Tuulia; Orešič, Matej

    2014-07-01

    Lipids are a diverse group of metabolites that have many key biological functions, acting as structural components of cell membranes, energy storage sources and intermediates in signaling pathways. Due to their importance lipids are under tight homeostatic control and exhibit spatial and dynamic complexity at multiple levels. It is thus not surprising that altered lipid metabolism plays important roles in the pathogenesis of most of the common diseases. Lipidomics emerged as a discipline which is dedicated to global study of lipidomes, including pathways and networks of lipids in biological systems. When studying the lipidomes at a systems level, one of the key challenges is how to address the lipid functionality at many physiological levels, from metabolic and signaling pathways to spatial systems such as cellular membranes and lipoprotein particles. Besides the better analytical techniques to study lipids, computational techniques have started to emerge which enable modeling of lipidomes in their spatial and dynamic context. Together, the recent methodological advances in lipidomics have a potential to open novel avenues for predictive and preventive medicine. This review focuses on progress in systems approaches to study lipids in health and disease, with specific emphasis on clinical applications.

  14. Digital Systems Analysis

    Science.gov (United States)

    Martin, Vance S.

    2009-01-01

    There have been many attempts to understand how the Internet affects our modern world. There have also been numerous attempts to understand specific areas of the Internet. This article applies Immanuel Wallerstein's World Systems Analysis to our informationalist society. Understanding this world as divided among individual core, semi-periphery,…

  15. Fuzzy Logic as a Computational Tool for Quantitative Modelling of Biological Systems with Uncertain Kinetic Data.

    Science.gov (United States)

    Bordon, Jure; Moskon, Miha; Zimic, Nikolaj; Mraz, Miha

    2015-01-01

    Quantitative modelling of biological systems has become an indispensable computational approach in the design of novel and analysis of existing biological systems. However, kinetic data that describe the system's dynamics need to be known in order to obtain relevant results with the conventional modelling techniques. These data are often hard or even impossible to obtain. Here, we present a quantitative fuzzy logic modelling approach that is able to cope with unknown kinetic data and thus produce relevant results even though kinetic data are incomplete or only vaguely defined. Moreover, the approach can be used in the combination with the existing state-of-the-art quantitative modelling techniques only in certain parts of the system, i.e., where kinetic data are missing. The case study of the approach proposed here is performed on the model of three-gene repressilator.

  16. Systems Biology and P4 Medicine: Past, Present, and Future

    Directory of Open Access Journals (Sweden)

    Leroy Hood

    2013-04-01

    Full Text Available Studying complex biological systems in a holistic rather than a “one gene or one protein” at a time approach requires the concerted effort of scientists from a wide variety of disciplines. The Institute for Systems Biology (ISB has seamlessly integrated these disparate fields to create a cross-disciplinary platform and culture in which “biology drives technology drives computation.” To achieve this platform/culture, it has been necessary for cross-disciplinary ISB scientists to learn one another’s languages and work together effectively in teams. The focus of this “systems” approach on disease has led to a discipline denoted systems medicine. The advent of technological breakthroughs in the fields of genomics, proteomics, and, indeed, the other “omics” is catalyzing striking advances in systems medicine that have and are transforming diagnostic and therapeutic strategies. Systems medicine has united genomics and genetics through family genomics to more readily identify disease genes. It has made blood a window into health and disease. It is leading to the stratification of diseases (division into discrete subtypes for proper impedance match against drugs and the stratification of patients into subgroups that respond to environmental challenges in a similar manner (e.g. response to drugs, response to toxins, etc.. The convergence of patient-activated social networks, big data and their analytics, and systems medicine has led to a P4 medicine that is predictive, preventive, personalized, and participatory. Medicine will focus on each individual. It will become proactive in nature. It will increasingly focus on wellness rather than disease. For example, in 10 years each patient will be surrounded by a virtual cloud of billions of data points, and we will have the tools to reduce this enormous data dimensionality into simple hypotheses about how to optimize wellness and avoid disease for each individual. P4 medicine will be able to

  17. Multimode lasers as analogs of complex biological systems (a survey)

    Science.gov (United States)

    Danilov, O. B.; Rosanov, N. N.; Solov'ev, N. A.; Soms, L. N.

    2016-04-01

    Simulating the activity of complex biological systems, in particular, the human brain, is a topical problem the solution of which is necessary both for understanding their functioning and for developing new classes of computational system based on operating principles of the brain. Some features and analogies that can be found in the operation of laser systems and brain and used for developing new generation computational systems are discussed. The appropriateness of such analogies is justified by the fact that both laser systems and the brain are open (interacting with the environment) dissipative spatially distributed nonlinear systems. Therefore, laser optical systems and, in particular, systems with dissipative optical solitons offer an opportunity to experimentally and theoretically model some important cognitive brain functions. One of particularities of the brain operation is the ability to manipulate images. Proceeding from this, in this work, problems related to generation and amplification with laser of spatial structures (images), as well as to amplification of signals coming to it from outside are discussed.

  18. Novel metaheuristic for parameter estimation in nonlinear dynamic biological systems

    Directory of Open Access Journals (Sweden)

    Banga Julio R

    2006-11-01

    Full Text Available Abstract Background We consider the problem of parameter estimation (model calibration in nonlinear dynamic models of biological systems. Due to the frequent ill-conditioning and multi-modality of many of these problems, traditional local methods usually fail (unless initialized with very good guesses of the parameter vector. In order to surmount these difficulties, global optimization (GO methods have been suggested as robust alternatives. Currently, deterministic GO methods can not solve problems of realistic size within this class in reasonable computation times. In contrast, certain types of stochastic GO methods have shown promising results, although the computational cost remains large. Rodriguez-Fernandez and coworkers have presented hybrid stochastic-deterministic GO methods which could reduce computation time by one order of magnitude while guaranteeing robustness. Our goal here was to further reduce the computational effort without loosing robustness. Results We have developed a new procedure based on the scatter search methodology for nonlinear optimization of dynamic models of arbitrary (or even unknown structure (i.e. black-box models. In this contribution, we describe and apply this novel metaheuristic, inspired by recent developments in the field of operations research, to a set of complex identification problems and we make a critical comparison with respect to the previous (above mentioned successful methods. Conclusion Robust and efficient methods for parameter estimation are of key importance in systems biology and related areas. The new metaheuristic presented in this paper aims to ensure the proper solution of these problems by adopting a global optimization approach, while keeping the computational effort under reasonable values. This new metaheuristic was applied to a set of three challenging parameter estimation problems of nonlinear dynamic biological systems, outperforming very significantly all the methods previously

  19. Systems biology in 3D space--enter the morphome.

    Science.gov (United States)

    Lucocq, John M; Mayhew, Terry M; Schwab, Yannick; Steyer, Anna M; Hacker, Christian

    2015-02-01

    Systems-based understanding of living organisms depends on acquiring huge datasets from arrays of genes, transcripts, proteins, and lipids. These data, referred to as 'omes', are assembled using 'omics' methodologies. Currently a comprehensive, quantitative view of cellular and organellar systems in 3D space at nanoscale/molecular resolution is missing. We introduce here the term 'morphome' for the distribution of living matter within a 3D biological system, and 'morphomics' for methods of collecting 3D data systematically and quantitatively. A sampling-based approach termed stereology currently provides rapid, precise, and minimally biased morphomics. We propose that stereology solves the 'big data' problem posed by emerging wide-scale electron microscopy (EM) and can establish quantitative links between the newer nanoimaging platforms such as electron tomography, cryo-EM, and correlative microscopy.

  20. Biological studies of matrix metalloproteinase sensitive drug delivery systems

    DEFF Research Database (Denmark)

    Johansen, Pia Thermann

    due to severe side effects as a result of drug distribution to healthy tissues. To enhance ecacy of treatment and improve life quality of patients, tumor specific drug delivery strategies, such as liposome encapsulated drugs, which accumulate in tumor tissue, has gained increased attention. Several...... for delivery of drugs to specific tissues or cells utilizing biological knowledge of cancer tissue is getting increased attention. In this thesis a novel matrix metalloproteinase-2 (MMP-2) sensitive poly-ethylene glycol (PEG) coated liposomal drug delivery system for treatment of cancer was developed...... the use of MMP- 2 as a trigger for liposomal activation in tumor tissue. Thus, this new strategy provides a promising system for specific delivery of encapsulated drugs and controlled release in tumor tissues, resulting in enhanced drug bioavailability and decreased systemic side effects. In addition, we...