From Atoms to Cells: Using Mesoscale Landscapes to Construct Visual Narratives

Modeling and visualization of the cellular mesoscale, bridging the nanometer scale of molecules to the micrometer scale of cells, is being studied by an integrative approach. Data from structural biology, proteomics, and microscopy are combined to simulate the molecular structure of living cells. These cellular landscapes are used as research tools for hypothesis generation and testing, and to present visual narratives of the cellular context of molecular biology for dissemination, education, and outreach.     

Resources, standards and tools for systems biology.

Modelling and simulation techniques are valuable tools for the understanding of complex biological systems. The design of a computer model necessarily has many diverse inputs, such as information on the model topology, reaction kinetics and experimental data, derived either from the literature, databases or direct experimental investigation. In this review, we describe different data resources, standards and modelling and simulation tools that are relevant to integrative systems biology.     

Model building and model checking for biochemical processes

A central claim of computational systems biology is that, by drawing on mathematical approaches developed in the context of dynamic systems, kinetic analysis, computational theory and logic, it is possible to create powerful simulation, analysis, and reasoning tools for working biologists to decipher existing data, devise new experiments, and ultimately to understand functional properties of genomes, proteomes, cells, organs, and organisms. In this article, a novel computational tool is described that achieves many of the goals of this new discipline. The novelty of this system involves an automaton-based semantics of the temporal evolution of complex biochemical reactions starting from the representation given as a set of differential equations. The related tools also provide ability to qualitatively reason about the systems using a propositional temporal logic that can express an ordered sequence of events succinctly and unambiguously. The implementation of mathematical and computational models in the Simpathica and XSSYS systems is described briefly. Several example applications of these systems to cellular and biochemical processes are presented: the two most prominent are Leibler et al.'s repressilator (an artificial synthesized oscillatory network), and Curto-Voit-Sorribas-Cascante's purine metabolism reaction model.     

Metabolic flux analysis and visualization

One of the ultimate goals of systems biology research is to obtain a comprehensive understanding of the control mechanisms of complex cellular metabolisms. Metabolic Flux Analysis (MFA) is a important method for the quantitative estimation of intracellular metabolic flows through metabolic pathways and the elucidation of cellular physiology. The primary challenge in the use of MFA is that many biological networks are underdetermined systems; it is therefore difficult to narrow down the solution space from the stoichiometric constraints alone. In this tutorial, we present an overview of Flux Balance Analysis (FBA) and (13)C-Metabolic Flux Analysis ((13)C-MFA), both of which are frequently used to solve such underdetermined systems, and we demonstrate FBA and (13)C-MFA using the genome-scale model and the central carbon metabolism model, respectively. Furthermore, because such comprehensive study of intracellular fluxes is inherently complex, we subsequently introduce various pathway mapping and visualization tools to facilitate understanding of these data in the context of the pathways. Specific visualization of MFA results using the BioCyc Omics Viewer and Pathway Projector are shown as illustrative examples.     

Mayday--a microarray data analysis workbench

Mayday is a workbench for visualization, analysis and storage of microarray data. It features a graphical user interface and supports the development and integration of existing and new analysis methods. Besides the infrastructural core functionality, Mayday offers a variety of plug-ins, such as various interactive viewers, a connection to the R statistical environment, a connection to SQL-based databases and different data mining methods, including WEKA-library based methods for classification and various clustering methods. In addition, so-called meta information objects are provided for annotation of the microarray data allowing integration of data from different sources, which is a feature that, for instance, is employed in the enhanced heatmap visualization. Supplementary information: The software and more detailed information including screenshots and a user guide as well as test data can be found on the Mayday home page http://www.zbit.uni-tuebingen.de/pas/mayday. The core is published under the GPL (GNU Public License) and the associated plug-ins under the LGPL (Lesser GNU Public License).     

Chemical approaches for investigating phosphorylation in signal transduction networks

The power and scope of chemical synthesis offer considerable opportunities to broaden the lexicon of chemical tools that can be implemented for the study of complex biological systems. To investigate individual signaling proteins and pathways, chemical tools provide a powerful complement to existing genetic, chemical genetic and immunologic methods. In particular, understanding phosphorylation-mediated signaling in real time yields important information about the regulation of cellular function and insights into the origin of disease. Recent advances in the development of photolabile caged analogs of bioactive species and fluorescence-based sensors of protein kinase activities are useful for investigating protein phosphorylation and the roles of phosphoproteins. Photolabile caged analogs allow spatial and temporal control over the release of a compound, while fluorescence-based sensors allow the real-time visualization of kinase activity. Here, we discuss recent advances that have increased the specificity and availability of these tools.     

LucidDraw: Efficiently visualizing complex biochemical networks within MATLAB

Background  

Biochemical networks play an essential role in systems biology. Rapidly growing network data and versatile research activities call for convenient visualization tools to aid intuitively perceiving abstract structures of networks and gaining insights into the functional implications of networks. There are various kinds of network visualization software, but they are usually not adequate for visual analysis of complex biological networks mainly because of the two reasons: 1) most existing drawing methods suitable for biochemical networks have high computation loads and can hardly achieve near real-time visualization; 2) available network visualization tools are designed for working in certain network modeling platforms, so they are not convenient for general analyses due to lack of broader range of readily accessible numerical utilities.     

Genome-wide association studies and systems biology: together at last

Following the widespread use of genome-wide association studies to elucidate the genetic architectures of complex phenotypes, there has been a push to augment existing observational studies with additional layers of molecular information. The resulting high-dimensional data have led the emergence of research in integrative systems biology. Here, we examine recent progress in characterizing biological networks as well as the corresponding conceptual and analytical challenges. Using examples from metabolomics, we contend that integrative systems biology should prompt a re-examination of conventional phenotypic measures where heterogeneous or correlated phenotypes can be fine-mapped. Although still in its infancy, it is apparent that the large-scale characterization of molecular systems will transform our understanding of phenotype, biology and pathogenesis.     

生物信息学在昆虫学研究中的应用

随着深度测序和基因芯片技术的不断发展,基因组、转录组、表达谱数据大量积累。目前,至少有10多个昆虫的基因组已被测序,30多个昆虫的转录组数据被报道。显然,传统的生物统计学方法无法处理如此海量的生物数据。量变引发质变,生物数据的大量积累催生了一门新兴学科,生物信息学。生物信息学融合了统计学、信息科学和生物学等各学科的理论和研究内容,在医学、基础生物学、农业科学以及昆虫学等方面获得了广泛的应用。生物信息学的目标是存储数据、管理数据和数据挖掘。因此,建立维护生物学数据库、设计开发基于模式识别、机器学习、数据挖掘等方法的生物软件,以及运用上述工具进行深度的数据挖掘,是生物信息学的重要研究内容。本文首先简要介绍了生物信息学的历史、研究现状及其在昆虫学科中的应用,然后综述了昆虫基因组学和转录组学的研究进展,最后对生物信息学在昆虫学研究中的应用前景进行了展望。     

Systems biology as a foundation for genome-scale synthetic biology

As the ambitions of synthetic biology approach genome-scale engineering, comprehensive characterization of cellular systems is required, as well as a means to accurately model cell-scale molecular interactions. These requirements are coincident with the goals of systems biology and, thus, systems biology will become the foundation for genome-scale synthetic biology. Systems biology will form this foundation through its efforts to reconstruct and integrate cellular systems, develop the mathematics, theory and software tools for the accurate modeling of these integrated systems, and through evolutionary mechanisms. As genome-scale synthetic biology is so enabled, it will prove to be a positive feedback driver of systems biology by exposing and forcing researchers to confront those aspects of systems biology which are inadequately understood.     

NMPP: a user-customized NimbleGen microarray data processing pipeline

NMPP package is a bundle of user-customized tools based on established algorithms and methods to process self-designed NimbleGen microarray data. It features a command-line-based integrative processing procedure that comprises five major functional components, namely the raw microarray data parsing and integrating module, the array spatial effect smoothing and visualization module, the probe-level multi-array normalization module, the gene expression intensity summarization module and the gene expression status inference module. AVAILABILITY: http://plantgenomics.biology.yale.edu/nmpp     

GenePro: a Cytoscape plug-in for advanced visualization and analysis of interaction networks

MOTIVATION: Analyzing the networks of interactions between genes and proteins has become a central theme in systems biology. Versatile software tools for interactively displaying and analyzing these networks are therefore very much in demand. The public-domain open software environment Cytoscape has been developed with the goal of facilitating the design and development of such software tools by the scientific community. RESULTS: We present GenePro, a plugin to Cytoscape featuring a set of versatile tools that greatly facilitates the visualization and analysis of protein networks derived from high-throughput interactions data and the validation of various methods for parsing these networks into meaningful functional modules. AVAILABILITY: The GenePro plugin is available at the website http://genepro.ccb.sickkids.ca.