In order to better support the data being generated by local
microarray, proteomics, macroarray, and other experiments, we are
developing and using SBEAMS (Systems Biology Experiment Analysis
Management System), a framework for collecting, storing, and accessing
data produced by these and other experiments. There is currently a
significant amount of effort in the community to determine standards
for storing microarray data (MAGE-OM/ML, GeneX, ArrayExpress, SMD,
etc; see below), and as such we are working with these emerging
standards so that we may leverage this effort in our own work. This
will allow the data produced at ISB to be easily exported and will
facilitate our efforts to correlate our own experimental results with
SBEAMS is modular in design to allow the storage of various types
of experiments in the system; the different experiments can be managed
separately but then correlated later under the same framework.
Currently, development is being driven by the Microarray, Proteomics,
and Inkjet Array projects, but additional experiments will be added.
One of the goals of SBEAMS is to allow a user to request a set of
experiments through a web interface from an ISB core facility, and be
informed when the fully processed data are available in the database
for subsequent analysis and annotation.
The process of data acquisition, from sample preparation, spotting,
hybridization, quantitation, and derivation of expression measures for
microarray experiments as well as sample preparation, MALDI plate
spotting, mass spectrometry, sequence database searches, and
annotation for Proteomics experiments will be tracked by the "Systems
Biology Experiment Analysis Management System" (SBEAMS) data
management package under development at ISB. This integrated system is
a consistent framework that combines a unified state-of-the-art
relational database management system (RDBMS) back end, a collection
of tools to store, manage, and query experiment information and
results in the RDBMS, a web front end for querying the database and
providing integrated access to remote data sources, and an interface
to existing programs for clustering and other analysis. Since all data
from each step of the experiment are warehoused in a modular schema in
the RDBMS, quality control and data analysis tasks are greatly
Within the SBEAMS framework, each investigator may first store and
manage the data unique to his or her experiment. Then, the parameters
of the process of executing the microarray, proteomics, or other
experiment are captured into the database. The experimental data
products are loaded into the database and an automated pipeline
processes the raw data into gene expression measures with data quality
estimates or protein matches and quality scores. The investigator may
then use the SBEAMS built-in tools or custom scripts built on top of
the framework to correlate the experimental results and experiment
conditions and further understand the experimental results.
Investigator annotations are also captured in the database for later
analysis and correlation with other experiments.
The SBEAMS-Microarray module will be compliant with the emerging
MAGE-OM/ML (MicroArray Gene Expression - Object Model/Markup Language)
a work-in-progress which will combine all previous standards such as
MAML, GEML, GeneXML, etc. The ISB is actively contributing to this
new standard. Our tools will be able to export all the resulting
microarray datasets in the MAGE-ML format (once specification is
complete), which will allow the data to be easily accessed by anyone
in the community with MAGE-compliant tools. In addition, the SBEAMS
will allow Internet access to the data via a public web front end when
they are fully processed and released by the investigators. We are a
member of the MGED (Microarray Gene Expression Database) Group (http://www.mged.org) and are committed
to contributing to and using open standards like MIAME (Minimum
Information About a Microarray Experiment) (http://www.mged.org/Annotations-wg/)
and MAGE-ML for data exchange and storage formats, which will allow
interoperability with other software like GeneX (http://genex.ncgr.org/),
), Stanford Microarray Database (http://genome-www4.stanford.edu/MicroArray/SMD/
A few implementation details:
SBEAMS is currently implemented in Perl using the Perl DBI module
for database connectivity. This provides a good level of database
back-end independence. ISB's principal back-end for SBEAMS is
currently Microsoft SQL Server, but portions of SBEAMS are known to
work with both MySQL and PostgreSQL. Sybase would also be viable due
to high compatibility with MS SQL Server. Due to our collaboration
with IBM, we will also adjust to support DB2 UDB as the back end; this
is expected to be little trouble.
The Perl modules that make up SBEAMS can be accessed by Perl CGI
scripts which use the SBEAMS API to create a Web interface, and very
similar (or often the same) Perl scripts can be executed from the
command line or as part of automated batch jobs. Both web and
command-line interfaces use a unified Authenticate() method which uses
HTTP cookies for authentication if executed via a web server or UNIX
login authentication if executed from the command line.
The SBEAMS core module handles such tasks as user authentication,
work group management, permissions management, simplified
engine-independent SQL database access API, web form abstraction,
tabular data rendering, and much more. One or more additional
(experiment/project specific) SBEAMS modules are then invoked after
the core module. These modules provide specific functionality to
manage and browse microarray, proteomics, etc. experiments.
At present, the Perl CGI's run on the Apache Web server http://db/
and the interactive Perl programs can run on interactive sessions on db
or any other Linux/UNIX machine with the appropriate software installed.
Certain components of SBEAMS have been written to assume a UNIX-like
file structure and Perl implementation. It would likely be quite easy
to modify SBEAMS to work equally well on any other operating system
(e.g., Windows 2000) that can run Perl CGI scripts and Perl commands,
but this has not been attempted.
Screenshots and diagrams:
To the right is a screenshot of a session in the SBEAMS web interface (ISB
internal version) using Internet Explorer; the web interface is
equally compatible with other browsers on all major platforms (Linux,
Solaris, Windows, MacOS, etc.). The upper left window shows the main
welcome screen of SBEAMS inviting the user who has just authenticated
himself to choose which of the modules to begin working with.
Currently the main modules are Microarray, Proteomics, and Inkjet.
Additional smaller ISB projects that use the SBEAMS interface to
access their databases are also listed.
Below that to the right is a window in which the user has selected to
issue a SQL query (query parameter entry fields are scrolled out of
view) that summarizes the peptides that have been annotated for the
"ARP*" genes in two Drosophila Proteomics experiments
(click here to execute this query on the database - SBEAMS login required).
Many peptides have been observed and annotated just once, while
several have been annotated many times. Various hyperlinks give the
user access to more information about the genes, proteins, and
peptides actually observed and annotated.
At the bottom is additional information about all the annotated
occurrences of one of the peptides as identified by SEQUEST. The
table includes information about which of the two experiments the
peptides were observed in, the masses, the actual peptides (some of
which contain tagged cysteines), pI values, ICAT quantitation ratios,
annotation information (clipped off right edge) and much more. Search
results can be annotated to additional insights.
ISB Server/Data Access Configuration
SBEAMS Data Access Configuration
SBEAMS Modular Structure