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 quanti´Čüable 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.

RO1 site (current)
ICBP version (deprecated)

BioSig3D Videos

BioSig3D Virtual Machine Software Releases


Download the BioSig3D virtual machine .ova file
biosig_release_vm.ova is based on debian-6.0.7-amd64
sha1sum 63a2cbf617998cfaf3dd0e28909c247657604049
24733400576 bytes ( ~24GB )

1.) To deploy and evaluate this software, you can open the .ova file in VMware player, and then power on the VM on when the import is complete.
The VM is currently configured as and is to be used with host-only networking.

2.) Log on to the instance as root with this default password :

3.) Run

4.) Point your local machine's web browser to and login as

The instance contains seed data so that you can look at all of the features.

Download the Morphogenesis Validation dataset
LSM format
sha1sum 3d8cbcfa56262e555b268b05208be5447e52203f
1140123783 bytes ( ~1.1G )

Download the MCF10A dataset
LSM format
sha1sum feeb06d928ef279b2fa4ffa4d1a43819a768853e
122459541 bytes ( ~117M )


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.


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.

7) Run


This will start all required services, each in its own screen, independent of a remote connection to the VM.
Please read if you are unfamiliar with the Unix screen command.

screen -ls

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:

Bench Protocols ( locked )

Software Development ( locked )

Server room monitor ( locked )

BioSig 2D
Important information about the current release
Data Models and Usage
Morphometric Representation


LBNL Imaging and Bioinformatics Group website

BioSig3D (last edited 2016-03-25 19:26:29 by gvf)