Difference between revisions of "Cell sorting"

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Biocellion Studies
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Many multicellular patterns formed during morphogenesis and embryonic development arise because of differential adhesion among distinct types of disassociated cells <ref>Steinberg, Malcolm S. (1963). Reconstruction of Tissues by Dissociated Cells. ''Science'', '''141''', no. 3579, 401-408.</ref>. Simulations of this process have demonstrated how changes in homotypic and heterotypic adhesion can result in many distinct macroscopic cellular arrangements including clumping, where homotypic cells aggregate, or mosaics where heterotypic cells alternate forming checkerboard-like patterns <ref>Zhang, L., Wang, Z., Sagotsky, J. A., and Deisboeck, T. S. (2009). Multiscale agent based cancer modeling. ''Journal of Mathematical Biology'', '''58'''(4-5), 545–559.</ref>. In our test model, two different cell types are defined with each cell mapped to a sphere of diameter 8 ''&mu;<sub>m</sub>''. If there is an overlap between two neighboring spheres, the two cells push each other to remove the overlap (cell-cell shoving). In this demonstration, if two non-overlapping cells of a same type are within 10 ''&mu;<sub>m</sub>'' they pull towards each other modelling stronger adhesion. If they are of different types there is no additional attractive force. The simulations demonstrate that such differential adhesion leads to cell sorting into homotypic aggregations from an initial random distribution.
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[[File:sorting.png|500px|center|Cell sorting]]
  
Timings
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The model code implemented using the Biocellion framework has 756 lines---the empty model code template has 650 lines. Biocellion users can simulate cell sorting using a cluster computer with just little more than 100 lines of coding. Evaluating pairwise interactions once for every cell pair within 10 ''&mu;<sub>m</sub>'' for 1.72 billion cells packed in a 10 ''&mu;<sub>m</sub>''* 10 ''&mu;<sub>m</sub>''* 10 ''&mu;<sub>m</sub>'' region takes approximately 20 seconds using 32 compute nodes (each node has two AMD Opteron 6272 Interlago 2.1 GHz sockets).
These are results from Testing Biocellion on the machine with the following details:
 
CPU: Intel(R) Core(TM) i7-3770K CPU @ 3.50GHz Using: 4 threads
 
Ram: 16GB
 
  
This was a test of the Cell Sorting Model speed with an increasing number of agents.
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<center>
This was a test of the Yeast Model speed with an increasing number of frames.(agent count increased with time)
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{{#ev:vimeo|88399915|400}}
Cell Sorting
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</center>
  
A test for the cell sorting model was conducted using a low, medium, and high levels of adhesion.
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<references> </references>
 
 
The model ran for 20 frames using all 27 combinations of the following adhesions:
 
high: 3
 
medium: 1.5
 
low: .001
 
 
 
The original sorting model we had used AA adhesion of 2.5, BB adhesion of 2.5, and AB BA adhesion as .001
 
 
 
Morphology results for alternative adhesion levels can be found here.
 
 
 
Cell Count and Growth
 
Using the newest version of Biocellion available to us,( 12/31/12) we ran the default parameter yeast model and had the following results for cell growth.
 
 
 
All data was collected manually from Paraview.
 
 
 
We will be refining the model based on the cell growth curves. Is there a setting within the model where it would be possible output this data in a simple text file? We need this to automate the process of scoring the model against the data.
 
 
 
I think Paraview has a feature for this. You can run some statistics filters using Paraview.
 
 
 
Growth Animations
 
We have recorded a few animations of our Yeast Run that has the information recorded above.
 
 
 
Here is an angled animated view of the yeast growth
 
http://youtu.be/H0rdtXswetg
 
 
 
Here is a Cross Section animated view of the Yeast growth
 
http://youtu.be/ChFf9OVBSvM
 
We are setting up to shape features of the morphology to further improve the model and validate the model. Unfortunately the Paraview files don’t contain all of the information we need in a readable format. Is there a setting that will produce simple text file data details the position and state of every particle in the system? Without this we will be unable to automate the matching of simulated and real morphologies since we need to extract shape features such as height, width, agar penetration etc.
 
 
 
Paraview has all the different types of filters and data processing capabilities. I think those are something you may want to see first.
 
 
 
 
 
 
 
 
 
Solute Visualization
 
Glucose Concentration cross section:
 
Animation: http://youtu.be/nbldGYCol7c
 
Screenshot at timestep 3000
 
 
 
Ethanol Concentration:
 
Animation: http://youtu.be/tC_BNuhwfek
 
Screenshot at timestep 5000
 
 
 
 
 
 
 
Video cross section of growth and glucose concentration:
 
http://youtu.be/QRlV8k1sAdY
 
 
 
 
 
The glucose and ethanol concentration files appear to have the axis rotated? I’m unsure of where this can be adjusted within the model files or whether it needs to be changed within the biocellion build.
 
 
 
It appears that the grid output in the concentration visualization files has a much lower resolution than the actual cells of the model.
 
 
 
Is this the same grid that is used in the simulation? This may be the cause of the apparent grid pattern in cell distribution. In order to refine the model, is it possible to change these values within the xml, header, or .cpp files?
 
 
 
The grid data should have the same axis setup with the agent data, and I will look for those. The grid spacing is determined by d_max in the simulation setup (d_max should be larger than the maximum mechanical interaction distance between any two particles).
 

Latest revision as of 02:48, 7 September 2014

Many multicellular patterns formed during morphogenesis and embryonic development arise because of differential adhesion among distinct types of disassociated cells [1]. Simulations of this process have demonstrated how changes in homotypic and heterotypic adhesion can result in many distinct macroscopic cellular arrangements including clumping, where homotypic cells aggregate, or mosaics where heterotypic cells alternate forming checkerboard-like patterns [2]. In our test model, two different cell types are defined with each cell mapped to a sphere of diameter 8 μm. If there is an overlap between two neighboring spheres, the two cells push each other to remove the overlap (cell-cell shoving). In this demonstration, if two non-overlapping cells of a same type are within 10 μm they pull towards each other modelling stronger adhesion. If they are of different types there is no additional attractive force. The simulations demonstrate that such differential adhesion leads to cell sorting into homotypic aggregations from an initial random distribution.

Cell sorting

The model code implemented using the Biocellion framework has 756 lines---the empty model code template has 650 lines. Biocellion users can simulate cell sorting using a cluster computer with just little more than 100 lines of coding. Evaluating pairwise interactions once for every cell pair within 10 μm for 1.72 billion cells packed in a 10 μm* 10 μm* 10 μm region takes approximately 20 seconds using 32 compute nodes (each node has two AMD Opteron 6272 Interlago 2.1 GHz sockets).

  1. Steinberg, Malcolm S. (1963). Reconstruction of Tissues by Dissociated Cells. Science, 141, no. 3579, 401-408.
  2. Zhang, L., Wang, Z., Sagotsky, J. A., and Deisboeck, T. S. (2009). Multiscale agent based cancer modeling. Journal of Mathematical Biology, 58(4-5), 545–559.