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BMDExpress Version 1.41b
May 11, 2012
Longlong Yang and Russell Thomas
The Hamner Institutes for Health Sciences


Summary
~~~~~~~

BMDExpress is a Java application used to analyze dose-response data from microarray
experiments. The program was designed to perform a stepwise analysis on microarray
data that combines benchmark dose (BMD) calculations with gene ontology (GO)
classification analysis. The combination provides dose estimates at which different
cellular processes are altered at a defined increase in risk based on expression
levels in the untreated controls.

BMDExpress has been developed and tested on the WindowsXP (32-bit)/i386 platform.
The program requires installation of the Java Runtime Environment Version 1.6.0 or
higher.  BMDExpress is released under the MIT license (also known as X11 license).
This license permits free use and distribution for any purpose, including
commercial, in binary and source formats. To access the licensing agreement, select
the "License" option under the "Help" menu.


Installation
~~~~~~~~~~~~


Windows XP, Vista, Windows 7
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Download the "BMDExpress_1.41b_Installer.exe" file and double-click on the file
name.  Follow the instructions provided in the installation program.



Redhat Linux, requires Java version 6 or 7 pre-installed
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Download the "BMDExpress_1.41b_Linux.tar" file to a directory where the BMDExpress will
be installed. Then open a terminal and change the directory to where the 
"BMDExpress_1.41b_Linux.tar" located. From the commandline, issue the command as:
# tar -xf BMDExpress_1.41b_Linux.tar

To start the program, change the directory to BMDExpress_1.41b_Linux as default and use
command as:
# ./bmdose.sh


Source Code
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The source code can be downloaded as a ".zip" file.  The source code is NOT required
for installation of the program using the Windows installer listed above or .tar file
for Linux.



Quick Start
~~~~~~~~~~~

Install BMDExpress using the appropriate Windows installation program listed above.
To test the program, click the File menu on the left side of the menu bar and
select Open->Expression Data to invoke an open-file dialog window. Select your
file and click the Open button at the bottom of the dialog window. If the default
installation path was selected, an example dataset can be found in

C:\BMDExpress_V1.41\data\Finalexpress100.txt

Open this file.  The datafile contains an extra row of column headers, so check the
"Yes" box and click on the "Remove Headers" button.  The first row should disappear
and the row listing the doses should now be the first row.  Select "OK" and the file
will be imported and shown in the right-hand window.

From the "Tools" menu, select "One-way ANOVA".  In the "One-Way ANOVA" popup
window, click on "Start" to identify probe sets that demonstrate significant
dose-response behavior.  A dialog box will appear showing probe sets that passed
the one-way ANOVA. Click on the "OK" button.  The "One-Way ANOVA" popup window will
return and then select the "Done" button to store the results of the analysis in
the left-hand window. The results of the one-way ANOVA will be shown in the
right-hand window.

From the "Tools" menu, select "Benchmark Dose Analysis".  In the "Benchmark Dose
Analyses" popup window, click on "Start" to begin the benchmark dose calculations.
A progress monitor will be shown for each statistical model that was selected.
When the analyses is complete, a dialog box will appear showing the results from the
benchmark dose calculations.  Click on the "OK" button.  The "Benchmark Dose
Analyses" popup window will return and then select the "Done" button to store the
results of the analysis in the left-hand window.  The results of the benchmark dose
analyses will be shown in the right-hand window.

From the "Tools" menu, select "Gene Ontology Analyses".  In the "Gene Ontology
Analyses" popup window, click on the "Array Type" dropdown menu and select the 
"Rat230_2" array.  Click on "Start" to begin the gene ontology analyses.  The
program will query a database at the Hamner Institutes containing the gene ontology
classifications for the probe sets provided.  If your firewall does not allow this
type of connection, see your IT department. When the analyses is complete, a dialog
box will appear showing the results from the gene ontology classification. Click
on the "OK" button.  The "Gene Ontology Analyses" popup window will return and
then select the "Done" button. The program will ask you to edit the name of the
result.  Select "OK" to store the results under the default name and the results
of the gene ontology analyses will be shown in the right-hand window.

Congratulations!  You have performed your first analyses with BMDExpress.  For
more detailed instructions and screen shots taking you through the analysis
process, read the "Tutorial" under the "Help" menu.



Credits
~~~~~~~

BMDExpress was created by Longlong Yang and Russell Thomas at the Hamner Institutes
for Health Sciences.  Bruce Allen contributed statistical expertise.  The fitting
of the data to the statistical models (linear, 2°polynomial,3°polynomial, and
power models) is performed using source code borrowed from the U.S. Environmental
Protection Agency’s Benchmark Dose Software (BMDS). Jeff Gift and Woody Setzer of
the U.S. Environmental Protection Agency provided the BMDS source code and assisted
in the debugging process.

Funding was provided under a grant from the American Chemistry Council’s Long Range
Initiative and a Superfund Program Project Grant (2 P42 ES004911-17).

Please send feedback and comments to lyang@thehamner.org and rthomas@thehamner.org
Source: README_BMDExpressV1.41b.txt, updated 2012-05-11