computational biology, part 26 virtual cell robert f. murphy copyright 2005,2006. all rights...
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Computational Biology, Part 26
Virtual Cell
Computational Biology, Part 26
Virtual Cell
Robert F. MurphyRobert F. Murphy
Copyright Copyright 2005,2006. 2005,2006.
All rights reserved.All rights reserved.
Virtual Cell - NRCAMVirtual Cell - NRCAMhttp://www.nrcam.uchc.edu/vcellR4/login/login.jsphttp://www.nrcam.uchc.edu/vcellR4/login/login.jsp
Framework for building and running Framework for building and running models of cell biological models of cell biological processesprocesses
Built in support for describing Built in support for describing compartments, biochemical species, compartments, biochemical species, electrophysiological phenomaelectrophysiological phenoma
Models can incorporate empirically Models can incorporate empirically derived geometries for derived geometries for compartmentscompartments
Models saved and calculated on the Models saved and calculated on the serverserver
Virtual Cell - To doVirtual Cell - To do Create accountCreate account Read User GuideRead User Guide
Virtual Cell - Hodgkin-HuxleyVirtual Cell - Hodgkin-Huxley Versions of the models in Versions of the models in “Computational cell biology” “Computational cell biology” by Fall et al have been by Fall et al have been implemented in Virtual Cellimplemented in Virtual Cell
These are available as Public These are available as Public modelsmodels
Within Virtual Cell, use Within Virtual Cell, use Open/BiomodelOpen/Biomodel
Then open Model Then open Model Neighborhood/CompCell/Hodgkin-Neighborhood/CompCell/Hodgkin-HuxleyHuxley
Model DescriptionsModel Descriptions
Virtual Cell supports exporting Virtual Cell supports exporting (and to a limited extent, (and to a limited extent, importing) model descriptions in importing) model descriptions in various XML formatsvarious XML formats SBML (Systems Biology Markup SBML (Systems Biology Markup Language, uses MathML)Language, uses MathML)
CellMLCellML VCML (Virtual Cell Markup Language) VCML (Virtual Cell Markup Language) - required to re-import full model- required to re-import full model
SBMLSBML<sbml xmlns="http://www.sbml.org/sbml/level2" <sbml xmlns="http://www.sbml.org/sbml/level2"
xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" level="2" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" level="2" version="1">version="1">
<notes><notes> <body xmlns="http://www.w3.org/1999/xhtml"><body xmlns="http://www.w3.org/1999/xhtml"> <p>Models electrical behavior of the squid giant axon. Used <p>Models electrical behavior of the squid giant axon. Used
to demonstrate interacting ion channels. Described in 2.5.</p>to demonstrate interacting ion channels. Described in 2.5.</p> </body></body> </notes></notes> <model id="Hodgkin_Huxley"><model id="Hodgkin_Huxley"> <notes><notes> <body xmlns="http://www.w3.org/1999/xhtml"><body xmlns="http://www.w3.org/1999/xhtml"> <p>Models electrical behavior of the squid giant axon. <p>Models electrical behavior of the squid giant axon.
Used to demonstrate interacting ion channels. Described in 2.5.</p>Used to demonstrate interacting ion channels. Described in 2.5.</p> </body></body> </notes></notes> <listOfUnitDefinitions><listOfUnitDefinitions>
SBMLSBML <listOfRules><listOfRules> <assignmentRule variable="minf"><assignmentRule variable="minf"> <math xmlns="http://www.w3.org/1998/Math/MathML"><math xmlns="http://www.w3.org/1998/Math/MathML"> <apply><apply> <times /><times /> <cn>100.0</cn><cn>100.0</cn> <ci>taum</ci><ci>taum</ci> <apply><apply> <plus /><plus /> <cn>40.0</cn><cn>40.0</cn> <ci>V</ci><ci>V</ci> </apply></apply> <apply><apply> <divide /><divide /> <cn>1.0</cn><cn>1.0</cn> <apply><apply> <plus /><plus /> <cn>1.0</cn><cn>1.0</cn>
CellMLCellML <model xmlns="http://www.cellml.org/cellml/1.0#" name="unnamed"><model xmlns="http://www.cellml.org/cellml/1.0#" name="unnamed"> <units name="uM"><units name="uM"> <unit units="mole" prefix="-6" /><unit units="mole" prefix="-6" /> <unit units="litre" exponent="-1" /><unit units="litre" exponent="-1" /> </units></units> <units name="uM.s-1"><units name="uM.s-1"> <unit units="mole" prefix="-6" /><unit units="mole" prefix="-6" /> <unit units="litre" exponent="-1" /><unit units="litre" exponent="-1" /> <unit units="second" exponent="-1" /><unit units="second" exponent="-1" /> </units></units> <units name="item" base_units="yes" /><units name="item" base_units="yes" /> <units name="molecules"><units name="molecules"> <unit units="item" /><unit units="item" /> </units></units> <units name="molecules.um-2.s-1"><units name="molecules.um-2.s-1"> <unit units="dimensionless" multiplier="1.0000000000000001E12" <unit units="dimensionless" multiplier="1.0000000000000001E12"
exponent="1" offset="0.0" />exponent="1" offset="0.0" />
CellMLCellML <BioModel Name="Hodgkin-Huxley"><BioModel Name="Hodgkin-Huxley"> <Annotation>Models electrical behavior of the squid giant axon. Used <Annotation>Models electrical behavior of the squid giant axon. Used
to demonstrate interacting ion channels. Described in 2.5.</Ann\to demonstrate interacting ion channels. Described in 2.5.</Ann\otation>otation> <Model Name="unnamed"><Model Name="unnamed"> <Compound Name="K"><Compound Name="K"> <Annotation>K</Annotation><Annotation>K</Annotation> </Compound></Compound> <Compound Name="h_o"><Compound Name="h_o"> <Annotation>Na Channel H Gate (Open)</Annotation><Annotation>Na Channel H Gate (Open)</Annotation> </Compound></Compound> <Compound Name="Na"><Compound Name="Na"> <Annotation>Na</Annotation><Annotation>Na</Annotation> </Compound></Compound> <Compound Name="m_o"><Compound Name="m_o"> <Annotation>Na Channel M Gate (Open)</Annotation><Annotation>Na Channel M Gate (Open)</Annotation> </Compound></Compound>
Building a simulationBuilding a simulation
To illustrate building a new To illustrate building a new simulation, we will build a simulation, we will build a model in whichmodel in which Prohormone is initially outside a Prohormone is initially outside a cell,cell,
Prohormone is internalized into the Prohormone is internalized into the cell,cell,
Prohormone is converted to hormoneProhormone is converted to hormone Hormone is exported from the cellHormone is exported from the cell
Building a simulationBuilding a simulation
Define a Cell compartmentDefine a Cell compartment Rename unnamed compartment to Rename unnamed compartment to ExtracellularExtracellular
Add a species “prohormone” to Add a species “prohormone” to ExtracellularExtracellular
Add a species “hormone” to Add a species “hormone” to ExtracellularExtracellular
Copy species “prohormone” to CellCopy species “prohormone” to Cell Copy species “hormone” to CellCopy species “hormone” to Cell
Building a simulationBuilding a simulation
Right (control) click on Cell membraneRight (control) click on Cell membrane Define a flux for prohormone as Define a flux for prohormone as “0.1*prohormone_Extracellular”“0.1*prohormone_Extracellular”
Define a flux for hormone as “-Define a flux for hormone as “-1.0*hormone_Cell”1.0*hormone_Cell”
Right (control) click on CellRight (control) click on Cell Define a reaction for prohormone to Define a reaction for prohormone to hormone with mass action forward hormone with mass action forward rate=1.0 and reverse rate=0.0rate=1.0 and reverse rate=0.0
Building a simulationBuilding a simulation
Define a new ApplicationDefine a new Application Give initial value for Give initial value for prohormone_Extracellular as 10.0prohormone_Extracellular as 10.0
Run modelRun model
Models that consider compartment geometryModels that consider compartment geometry Virtual Cell facilitated Ca-Virtual Cell facilitated Ca-diffusion model from tutorialdiffusion model from tutorial
Making a compartment map for Virtual Cell from a fluorescence microscope image
Making a compartment map for Virtual Cell from a fluorescence microscope image
Start Start from a from a fluorescenfluorescence ce microscope microscope image of a image of a lysosomal lysosomal protein protein (LAMP-2)(LAMP-2)
Making a compartment map for Virtual Cell from a fluorescence microscope image
Making a compartment map for Virtual Cell from a fluorescence microscope image Use Matlab to create an image Use Matlab to create an image with values of zero for with values of zero for background, one for cytoplasm, background, one for cytoplasm, and two for lysosomesand two for lysosomes
Assume that the Assume that the autofluorescence in the autofluorescence in the lysosome image is sufficient to lysosome image is sufficient to find a region corresponding to find a region corresponding to the cytoplasmthe cytoplasm
Make contiguous cytoplasm image by averaging weak autofluorescence
Make contiguous cytoplasm image by averaging weak autofluorescence
img=imread('r06aug97.h4b4.13--1---2.dat.png');img=imread('r06aug97.h4b4.13--1---2.dat.png');
a=double(img);a=double(img);
b=(a-min(min(a)))./(max(max(a))-min(min(a)));b=(a-min(min(a)))./(max(max(a))-min(min(a)));
H=fspecial('average',13);H=fspecial('average',13);
c=imfilter(b,H,'replicate');c=imfilter(b,H,'replicate');
d=im2bw(c,0.004);d=im2bw(c,0.004);
imshow(d);imshow(d);
max(max(d))max(max(d))
Combine with image of pixels with positive lysosomal staining
Combine with image of pixels with positive lysosomal staining
e=im2bw(b,graythresh(b));e=im2bw(b,graythresh(b));
imshow(e);imshow(e);
f=d + e;f=d + e;
imshow(f,[0 2]);imshow(f,[0 2]);
g=uint8(f);g=uint8(f);
imwrite(g,'geomap.tif','TIF','Compressiimwrite(g,'geomap.tif','TIF','Compression','none');on','none');
Resulting image Resulting image
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