BioSig3D : High-Content Representation and Association of Three-Dimensional Cell Culture Models
Background: Three-dimensional cell culture models have emerged as effective systems to study tissue differentiation and cancer behavior. If cancer is fundamentally a disease of aberrant multicellular organization, then understanding the effects of the tissue microenvironment, cellular and molecular variables, and possible therapeutic interventions on the oncogenic phenotype requires the development and use of more sophisticated models that can approximate cell-cell and cell-matrix interactions in vivo. Recent advances in 3D cell culture technology have made it possible to model key aspects of the ECM environment and cell and tissue organization that cannot be modeled using conventional two-dimensional methods. Obtaining quantiﬁable data from 3D models with substantial throughput and relating such data to other cellular and molecular parameters entail a unique set of problems that we will solve. Routine application and utility of these engineered 3D cell culture models will have profound implications for the systematic analysis of cellular biology.
We are developing a platform for morphometric profiling of three-dimensional (3D) cell culture models. Multicellular systems will be imaged with confocal microscopy in full 3D; cellular organization and a number of other end points will be computed; and multidimensional phenotypic signatures will be associated with genomic data. The potential results of this initiative are (i) a basic understanding of the biological processes in a model system that is a better predictor of in vivo models, (ii) a template for drug screening against tumor lines with desirable reversion properties, and (iii) a template for hypothesis generation and validation through associations of genomic and phenotypic data. More importantly, we are designing experiments that involve manipulation of the microenvironment to elicit malignant behavior, which is manifested in disorganized phenotypic signature.
BioSig3D Virtual Machine Software Release
This is a virtual machine appliance in OV ( Open Virtualization ) format based on debian-6.0.7-amd64.
A working instance of BioSig3D in its own VM can be easily created and started with minimal configuration.
1) Download and import the BioSigVM.ova file as an appliance.
( Oracle VirtualBox was used for this VM creation and deployment.)
2) Log on to instance. Two accounts are set up:
3) Mount /data and /opt :
mount /dev/sdb1 /data mount /dev/sdc1 /opt
/data contains the PostgreSQL 9.2.4 DB and OME Image Server repository.
/opt contains all software packages and start scripts needed to run an instance of BioSig3D.
4) Configure networking for your VM host.
5) Edit the following files for your configured hostname.
/opt/BioSigMQ__DownloadIcsStacks__biosig.properties /opt/BioSigMQ__ImportFeatures__biosig.properties /opt/ImageStacker_biosig.properties /opt/MonitorRunRequestsAndCompletions_biosig.properties /opt/pw-config.properties /opt/biosig_analysis_modules/nuclear_assay/BioSigMQMain.properties
6) To deploy the Java Web Start image utility app. ( which performs image import, linking of imported images to treatment groups, and original image file download), newer versions of Java on the client will require that you update the manifest attribute for "Codebase" in the jars in
You will then be required to sign your jars with your own code-signing certificate and restart that Tomcat. Alternatively, if you send me your codebase host name, I can change the manifests, and sign with our Thawte code-signing certificate and return the jars to you.
The image utility app. will not be necessary for evaluation of the software's visualization and data analysis features as seed data has been provided.
This will start all required services, each in its own screen, independent of a remote connection to the VM.
Please read https://www.gnu.org/software/screen if you are unfamiliar with the Unix screen command.
will list all screens for the current user. You should see something like this:
There are screens on: 1554.ParaviewMessageQueue (05/20/2014 10:22:29 AM) (Detached) 1538.MainTomcat (05/20/2014 10:22:29 AM) (Detached) 1562.StockTomcat (05/20/2014 10:22:29 AM) (Detached) 1558.OMEISApache (05/20/2014 10:22:29 AM) (Detached) 1542.MainMessageQueue (05/20/2014 10:22:29 AM) (Detached) 1550.Stacker (05/20/2014 10:22:29 AM) (Detached) 1534.PG (05/20/2014 10:22:29 AM) (Detached) 1546.MonitorRuns (05/20/2014 10:22:29 AM) (Detached) 8 Sockets in /var/run/screen/S-root.
The screen utility allows you to switch between screens. In most screens, log files are displayed (using tail -f).
8) Open http://yourhostname in your web browser to begin using the instance. the current admin. user account is set to:
The VM appliance OVA file can be downloaded at: