Systems biology research tool

The SBRT can be used in a similar way, but this is not its primary function. The SBRT can be used independently of other applications, and it also provides implementations of algorithms not currently available in any other software package [ 9 ]. Presently, the majority of processes offered by the Systems Biology Research Tool are for analyzing stoichiometric networks.

Some of these programs are stand-alone applications Metatool 4. Due to its API and support for external software, the SBRT has the ability to evolve in conjunction with the field of systems biology itself.

In contrast, none of the stand-alone applications for stoichiometric network analysis listed above Metatool 4. Therefore, the ability of independent software developers to expand upon these programs is greatly hindered.

These mathematical programming environments both provide a large number of powerful functions, well documented API's, and mechanisms for the inclusion of external software, making the development of new software straightforward.

Consequently, certain aspects of their performance and functionality are impossible to alter, which results in additional constraints during software development and limitations during performance optimization.

To our knowledge, all of the stoichiometric network analysis software listed above is free of charge, at least for academic purposes. In contrast, the SBRT is completely free of charge for every user. One of the most important aspects of any software package is its ease of installation and use.

The SBRT differs from the programs listed above in several ways. First, some of these programs require the installation of libraries or other programs before they can be used, while SBRT installation is self-contained and guided with a graphical user interface. Second, some of the existing programs must be used from a command line interface, which is cumbersome for the "typical" Windows user. The SBRT can be used from both the command line and from a simple graphical user interface.

Third, while some existing programs require programming ability, the SBRT does not, when used as an application. The programs listed above are intended primarily for different types of stoichiometric network analyses, and they are sometimes quite limited in scope.

The SBRT, however, has been explicitly designed to integrate techniques from all of systems biology. Because of these similarities, we performed a comparative performance analysis of some capabilities offered by both packages. Specifically, we carried out 5 analyses using an in silico model of S. For analyses A and B , the model was provided a minimal growth-supporting medium, where the variability of all reaction rates A and the effect of all single-gene deletions on the maximum growth rate B were computed.

For analyses C , D , and E , the model was sequentially provided randomly generated growth-supporting media, where the maximum growth rate C , the variability of all reaction rates D , and the effect of all single-gene deletions E were computed. A detailed description of these comparisons is provided as supplementary material [see Additional file 3 ].

Memory usage vs. This software can be used to make sophisticated computational techniques available to everyone, to facilitate cooperation among researchers, and to expedite progress in the field of systems biology. Any restrictions to use by non-academics : None. JW designed and implemented the Systems Biology Research Tool and carried out all performance comparisons.

Both JW and AW contributed to the software's conception and participated in drafting the manuscript. SBRT Processes. Descriptions of the 51 processes currently implemented in the Systems Biology Research Tool. Performance Comparisons. It currently contains interactions from 12 recent publications of profiling stem-cell related transcription factors using various high throughput ChIP profiling methods. The resultant integrated network has 50, entries. Please be aware that this network is likely to contain many false-positives and should be used for hypothesis generation only.

Presynaptome is a database created to visualize and share, with the neuroscience and molecular biology research communities, information about proteins and interactions identified to be present in presynaptic nerve terminals of mammalian neurons.

The website features a network of protein-protein interactions manually extracted from neuroscience research literature. The interactions in this network are identified to be exclusively from presynaptic nerve terminals of mammalian neurons. Contacts: Avi Ma'ayan and Lakshmi A. Neuronal Signalome contains cell signaling interactions extracted from literature describing components and interactions in mammalian neurons.

This dataset was used in the paper Ma'ayan et al. PathwayGenerator automatically generates pathways from receptors to effectors created using the neuronal signalome. Excel2BiositemapsAndHTML is a tool that is used to convert an Excel file containing details about biomedical resources tools, data, software into a Biositemaps. A Biositemap file is a list of controlled metadata about resources.

Some of the primary goals of systems biology are to identify and quantify the individual components of cells, organs, and organisms; to understand the interactions between these components; and to use this information to create mathematical models that enable accurate predictions.

Since organisms are composed of large numbers of unique elements i. Instead, software must be used to store, retrieve, analyze, and sometimes even to collect the data obtained from system-level experiments. The SBRT is useful for both the management and analysis of data, and the simulation and prediction of cellular phenotypes.

The SBRT can, for example, be used to translate data files into various machine- and human-readable formats; to simulate the activity of reconstructed signal transduction and genome-scale metabolic networks using flux balance analysis and related methods [ 1 , 2 ]; and to analyze the topology of experimentally determined biochemical reaction networks, such as transcriptional regulation and protein-protein interaction networks.

Since new data formats, methods of data analysis, and simulation techniques arise frequently during systems biology research, the SBRT is also designed to allow independent software developers to add new functionality as it is needed. The most recent versions of the SBRT can be downloaded from the SBRT's homepage [ 3 ], and an archive of the current version is provided as supplementary material [see Additional file 1 ].

The API is composed of two functionally distinct levels: the kernel , which is responsible for performing all significant computation, and the shell , which is responsible for relaying information between the user and the kernel. The kernel contains implementations of algorithms, methodological procedures, and fundamental objects , such as networks, chemical reactions, mathematical expressions, matrices, convex polytopes, hyperplanes, linear program solvers, etc.

The shell is primarily composed of classes and interfaces for reading writing files from to the hard drive, for parsing and formatting various types of data, and for managing and monitoring kernel-level activities. The SBRT can be used as an application to execute processes.

A process is a series of actions that takes user-supplied input and produces a result. The SBRT includes 35 processes for analyzing stoichiometric networks, such as optimizing objective functions, computing the variability of fluxes, identifying reaction pathways, generating uniformly distributed points within flux spaces, analyzing the properties of flux vectors and intervals, and more.

The SBRT also includes 16 processes utilizing graph theory, geometry, algebra, statistics, and combinatorics. Descriptions of these 51 processes are provided as supplementary material [see Additional file 2 ].

Processes can be controlled with simple text-based input files that can be created using common word processing or spreadsheet applications or directly from the command line. When possible, files generated by one process can also be used as input files in other SBRT processes, allowing the user to design complex analyses by linking processes via their input and output files, without writing a single line of code.

For example, the process BiGG-SBML File Reader can be used to translate a machine-readable file into a human-readable and -editable text file R that contains a list of chemical reactions. The file R can then be supplied to the Network Information Gatherer process to create a text file N that contains the names or IDs of all chemical reactions contained in R ; and R can also be supplied to the Random Constraint Generator process to create a text file C of randomly generated flux constraints.

Each of these files can be edited by the user at any step, and many other combinations of processes are possible. The use of the SBRT as an application requires no programming ability, and is fully documented in a freely available HTML-based User's Guide , which provides a detailed description of each process and contains hyperlinks to at least one complete example.

An example of the Path Identification process is illustrated in Figure 1. Identifying the simple paths in a directed graph. Rectangles with thick borders represent text files, with their name denoted directly above.

The file edges. The file process. The file paths. A process plug-in is an external software package that can be written by any skilled programmer, executed as a process by the SBRT application, and shared among other users. As a consequence of the existing capabilities of the SBRT, development of process plug-ins is considerably easier and faster than development of new stand-alone applications. Plug-ins can, for example, call high-level methods from the API that perform file parsing, process monitoring, algorithm execution, and error-detection.

Plug-ins can also call low-level methods to facilitate the development of novel high-level methods. Instructions for writing process plug-ins are included in the Developer's Guide , and an example plug-in is also included with the package.

In the future, software platforms and data or knowledge resources need to be supported through community-wide efforts. However, this requires a broader understanding of social dynamics, psychology and the economics of research activities; additionally, platforms need to be supported by user-friendly software tools. 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.

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