9 research outputs found
Science Gateways and Cybersecurity: Learning from the Past and Preparing for the Future
Science gateways connect communities of scientists and engineers to distributed cyberinfrastructure (CI). Cybersecurity is therefore an important component to help protect the people, machines, and data from malicious activity and accidental mistakes. The Science Gateways Community Institute (SGCI) and Center for Trustworthy Scientific Cyberinfrastructure (CTSC) have partnered to address cybersecurity for gateway development and operation. This paper and presentation will provide an overview of and goals for this partnership
3-D PhysiCell simulation of ductal carcinoma in situ - stochastic necrosis model
<p>This is Video S4 in Ghaffarizadeh
et al. (2018). A higher-resolution (1080p) video can be streamed
at <a href="https://www.youtube.com/watch?v=-lRot-dfwJk">https://www.youtube.com/watch?v=-lRot-dfwJk</a> </p>
<p><b>Paper:</b> <a href="https://doi.org/10.1371/journal.pcbi.1005991">https://doi.org/10.1371/journal.pcbi.1005991</a><br></p>
<p>3-D
agent-based simulation of ductal carcinoma in situ (DCIS), a type of breast
cancer that is constrained to growth in the breast duct lumen by a basement
membrane. In this simulation, cells have a pO2-dependent probability of
becoming necrotic wherever pO2 < 5 mmHg. This simulation was completed
on a single HPC compute node (dual Xeon 6-core CPUs at 3.4 GHz), requiring 3
hours and 39 minutes to run (including data saves once per simulated hour).
Simulations without file I/O are significantly faster. Shown here: A simulation
of 30 days' growth in a 1 mm length of duct.</p>
<p>Shown here: A
simulation of 30 days' growth in a 1 mm length of duct.</p>
<p><b>Legend:</b></p>
<p><u>Dark circles</u>: cell
nuclei</p>
<p><u>Green cells</u>: Proliferating Ki67+ cells, prior to mitosis</p>
<p><u>Magenta cells</u>: Proliferating Ki67+ cells, after mitosis</p>
<p><u>Red cells</u>: Apoptotic cells (cleaved Caspase-3 positive)</p>
<p><u>Pale blue cells</u>: Quiescent Ki67- cells</p>
<p><u>Brown cells</u>: Necrotic cells</p>
<p>This work is based on PhysiCell, an
open source 3-D modeling package for multicellular biology at <a href="http://physicell.mathcancer.org/">http://PhysiCell.MathCancer.org</a>.</p>
<p><b>Method: </b>Demonstration of PhysiCell, an agent-based,
lattice-free model. Cell velocities determined by balance of adhesive,
repulsive, and motile forces. Each cell has a phenotypic state governed by
stochastic processes derived from nonhomogeneous Poisson processes.</p>
<p><b>Software source: </b>PhysiCell is available as open
source at <a href="http://physicell.mathcancer.org/">http://PhysiCell.MathCancer.org</a>, <a href="http://physicell.sf.net/">http://PhysiCell.sf.net</a>, and <a href="https://github.com/mathcancer/physicell/releases">https://github.com/mathcancer/physicell/releases</a>.</p
PhysiCell demo: heterogeneous tumor growth
<p>This is Video S7 in Ghaffarizadeh
et al. (2018). A higher-resolution (4K) video can be streamed
at <a href="https://www.youtube.com/watch?v=bPDw6l4zkF0">https://www.youtube.com/watch?v=bPDw6l4zkF0</a>
</p>
<p><b>Paper:</b> <a href="https://doi.org/10.1371/journal.pcbi.1005991">https://doi.org/10.1371/journal.pcbi.1005991</a><br></p>
<p>Early test on competition in a heterogeneous cell population.
Cancer cells have a varying expression of a mutant oncoprotein, here shaded
from blue (least expression) to yellow (most expression). </p>
<p>Cells
proliferate at a rate proportional to oxygen availability and oncoprotein
expression. Note the gradual population evolution towards yellower cells. This
is selection over the course of 30 days of tumor growth, with parameter values
very similar to MCF10A. </p>
<p>The brown center
is a necrotic core.</p>
<p><b>Legend:</b></p>
<p><u>Blue cells</u>: tumor
cells with least oncoprotein</p>
<p><u>Yellow cells</u>: tumor cells with most oncoprotein</p>
<p><u>Dark dots</u>: cell nuclei</p>
<p><u>Brown cells</u>: necrotic tumor cells and debris<br></p>
<p>This
work is based on PhysiCell, an open source 3-D modeling package for
multicellular biology at <a href="http://physicell.mathcancer.org/">http://PhysiCell.MathCancer.org</a>.</p>
<p><b>Method: </b>Demonstration of PhysiCell, an agent-based,
lattice-free model. Cell velocities determined by balance of adhesive,
repulsive, and motile forces. Each cell has a phenotypic state governed by
stochastic processes derived from nonhomogeneous Poisson processes.</p>
<p><b>Software source: </b>PhysiCell is available as open
source at <a href="http://physicell.mathcancer.org/">http://PhysiCell.MathCancer.org</a>, <a href="http://physicell.sf.net/">http://PhysiCell.sf.net</a>, and <a href="https://github.com/mathcancer/physicell/releases">https://github.com/mathcancer/physicell/releases</a>.</p
PhysiCell Demo: Bio-robots
<p>This is Video S5 in Ghaffarizadeh
et al. (2018). A higher-resolution (1080p) video can be streamed
at <a href="https://www.youtube.com/watch?v=NdjvXI_x8uE">https://www.youtube.com/watch?v=NdjvXI_x8uE</a>
</p>
<p><b>Paper:</b> <a href="https://doi.org/10.1371/journal.pcbi.1005991">https://doi.org/10.1371/journal.pcbi.1005991</a><br></p>
<p>Using PhysiCell to test design
rules for bio-robots. </p>
<p>Here, we construct three cell types
as a bio-robotic cargo delivery system. </p>
<p>1) "Director" cells
secrete a chemoattractant to attract worker cells when they have cargo</p>
<p>2) "Cargo" cells secrete
a different chemoattractant to attract worker cells when they don't have cargo.
They turn off the chemoattractant once they are found. </p>
<p>3) "Worker" cells
chemotax towards cargo cells, test for presence of a receptor, and dock if it's
present. They haul cargo (chemotactically) towards the "director"
cells and release the cargo if the chemoattractant exceeds a threshold level.</p>
<p>This simulation took a few hours to
design, and ran in about 12 minutes on a desktop workstation, with data saved
once per simulated minute. (2,880 save times) Simulations without file I/O are
significantly faster.</p>
<p><b>Legend:</b></p>
<p><u>Green cells</u>: “Director”
cells</p>
<p><u>Blue cells</u>: “Cargo” cells</p>
<p><u>Red cells</u>: “worker” cells</p>
<p>This work is based on PhysiCell, an
open source 3-D modeling package for multicellular biology at <a href="http://physicell.mathcancer.org/">http://PhysiCell.MathCancer.org</a>.</p>
<p><b>Method: </b>Demonstration of PhysiCell, an agent-based,
lattice-free model. Cell velocities determined by balance of adhesive,
repulsive, and motile forces. Each cell has a phenotypic state governed by
stochastic processes derived from nonhomogeneous Poisson processes.</p>
<p><b>Software source: </b>PhysiCell is available as open
source at <a href="http://physicell.mathcancer.org/">http://PhysiCell.MathCancer.org</a>, <a href="http://physicell.sf.net/">http://PhysiCell.sf.net</a>, and <a href="https://github.com/mathcancer/physicell/releases">https://github.com/mathcancer/physicell/releases</a>.</p
3-D PhysiCell simulation of a hanging drop spheroid - stochastic necrosis model
<p>This is Video S2 in Ghaffarizadeh
et al. (2018). A higher-resolution (1080p) video can be streamed
at <a href="https://www.youtube.com/watch?v=xrOqqJ_Exd4">https://www.youtube.com/watch?v=xrOqqJ_Exd4</a>
</p>
<p><b>Paper:</b> <a href="https://doi.org/10.1371/journal.pcbi.1005991">https://doi.org/10.1371/journal.pcbi.1005991</a><b><br></b></p><p>3-D agent-based simulation of a
hanging drop spheroid experiment. In this simulation, cells have a
pO2-dependent probability of becoming necrotic wherever pO2 < 5 mmHg. This
simulation was completed on a single HPC compute node (dual Xeon 6-core CPUs at
3.4 GHz), requiring 73 hours and 25 minutes to run (including data saves once
per simulated hour). It took 60 hours and 56 minutes to simulate 17 days to the
first ~800k cells. Simulations without
file I/O are significantly faster.<br></p>
<p><b>Legend:</b></p>
<p><u>Dark circles</u>: cell
nuclei</p>
<p><u>Green cells</u>: Proliferating Ki67+ cells, prior to mitosis</p>
<p><u>Magenta cells</u>: Proliferating Ki67+ cells, after mitosis</p>
<p><u>Red cells</u>: Apoptotic cells (cleaved Caspase-3 positive)</p>
<p><u>Pale blue cells</u>: Quiescent Ki67- cells</p>
<p><u>Brown cells</u>: Necrotic cells</p>
<p>This work is based on PhysiCell, an
open source 3-D modeling package for multicellular biology at <a href="http://physicell.mathcancer.org/">http://PhysiCell.MathCancer.org</a>.</p>
<p><b>Method: </b>Demonstration of PhysiCell, an agent-based,
lattice-free model. Cell velocities determined by balance of adhesive,
repulsive, and motile forces. Each cell has a phenotypic state governed by
stochastic processes derived from nonhomogeneous Poisson processes.</p>
<p><b>Software source: </b>PhysiCell is available as open
source at <a href="http://physicell.mathcancer.org/">http://PhysiCell.MathCancer.org</a>, <a href="http://physicell.sf.net/">http://PhysiCell.sf.net</a>, and <a href="https://github.com/mathcancer/physicell/releases">https://github.com/mathcancer/physicell/releases</a>.</p
PhysiCell demo: immune cells attacking a heterogeneous tumor
<p>This is Video S8 in Ghaffarizadeh
et al. (2018). A higher-resolution (4K) video can be streamed at <a href="https://www.youtube.com/watch?v=nJ2urSm4ilU">https://www.youtube.com/watch?v=nJ2urSm4ilU</a>
</p><p><b>Paper:</b> <a href="https://doi.org/10.1371/journal.pcbi.1005991">https://doi.org/10.1371/journal.pcbi.1005991</a><br></p><p>This
is a PhysiCell demo of immune cells (red) attacking a 3-D heterogeneous tumor,
using a basic biophysical model of an adaptive immune response to a tumor. In
the simulation:</p><p>1)
Cancer cells each have an individual expression of a mutant oncoprotein, which
drives proliferation. Yellow cells divide faster (lots of oncoprotein) than
blue ones (very little oncoprotein).</p><p>2)
If the tumor gets too big, it outstrips the nutrient supply and a necrotic core
(dead center) forms.</p><p>3)
As a simple model, tumor cells release an immunostimulatory factor that
diffuses outward. Cells are assumed to have immunogenicity proportional to the
mutant oncoprotein (e.g., by altering MHC with mutant peptides).</p><p>4)
At 14 days, we introduce 7500 immune cells (red) which perform a biased random
walk towards the immunostimulatory factor.</p><p>5)
Whenever an immune cell touches another cell, it:</p><p>..
a) adheres to the cell</p><p>..
b) checks for immunogenicity</p><p>..
c) induces apoptosis in the tumor cell at a rate proportional to
immunogenicity)</p><p>..
d) detaches either after a random time or after inducing apoptosis in the tumor
cell</p><p>6)
Immune cells break away from newly apoptotic cells (cyan) and continue to seek
more targets.</p><p>The
simulation took about 2 days on a quad-core desktop (i7-4770k), including time
spent on saving simulation data once every 3 simulated minutes. Simulations
with less frequent output are substantially faster.</p><p><b>Legend:</b></p><p><u>Blue
cells</u>: tumor cells with oncoprotein < 0.5</p><p><u>Yellow
cells</u>: tumor cells with oncoprotein > 1.5</p><p><u>In
between</u>: tumor cells with 0.5 < oncoprotein < 1.5</p><p>(yellow
is greater)</p><p><u>Dark
dots</u>: cell nuclei</p><p><u>Cyan
cells</u>: apoptotic tumor cells</p><p><u>Brown
cells</u>: necrotic tumor cells and debris</p><p><u>Red
cells</u>: attacking immune cells.</p><p>This
work is based on PhysiCell, an open source 3-D modeling package for
multicellular biology at <a href="http://PhysiCell.MathCancer.org">http://PhysiCell.MathCancer.org</a>.</p><p><b>Method: </b>Demonstration of PhysiCell, an agent-based,
lattice-free model. Cell velocities determined by balance of adhesive,
repulsive, and motile forces. Each cell has a phenotypic state governed by
stochastic processes derived from nonhomogeneous Poisson processes.</p><p><b>Software source: </b>PhysiCell is available as open
source at <a href="http://PhysiCell.MathCancer.org">http://PhysiCell.MathCancer.org</a>, <a href="http://physicell.sf.net/">http://PhysiCell.sf.net</a>, and <a href="https://github.com/mathcancer/physicell/releases">https://github.com/mathcancer/physicell/releases</a>. </p
3-D PhysiCell simulation of ductal carcinoma in situ - deterministic necrosis model
<p>This is Video S3 in Ghaffarizadeh
et al. (2018). A higher-resolution (1080p) video can be streamed
at <a href="https://www.youtube.com/watch?v=ntVKOr9poro">https://www.youtube.com/watch?v=ntVKOr9poro</a>
</p>
<p><b>Paper:</b> <a href="https://doi.org/10.1371/journal.pcbi.1005991">https://doi.org/10.1371/journal.pcbi.1005991</a> </p><p><br></p>
<p>3-D agent-based simulation of
ductal carcinoma in situ (DCIS), a type of breast cancer that is constrained to
growth in the breast duct lumen by a basement membrane. In this simulation,
cells immediately become necrotic wherever pO2 < 5 mmHg. This simulation
was completed on a single HPC compute node (dual Xeon 6-core CPUs at 3.4 GHz),
requiring 4 hours and 24 minutes to run (including data saves once per
simulated hour). Simulations without file I/O are significantly faster.</p><p>Shown here: A
simulation of 30 days' growth in a 1 mm length of duct.</p>
<p><b>Legend:</b></p>
<p><u>Dark circles</u>: cell
nuclei</p>
<p><u>Green cells</u>: Proliferating Ki67+ cells, prior to mitosis</p>
<p><u>Magenta cells</u>: Proliferating Ki67+ cells, after mitosis</p>
<p><u>Red cells</u>: Apoptotic cells (cleaved Caspase-3 positive)</p>
<p><u>Pale blue cells</u>: Quiescent Ki67- cells</p>
<p><u>Brown cells</u>: Necrotic cells</p>
<p>This work is based on PhysiCell, an
open source 3-D modeling package for multicellular biology at <a href="http://physicell.mathcancer.org/">http://PhysiCell.MathCancer.org</a>.</p>
<p><b>Method: </b>Demonstration of PhysiCell, an agent-based,
lattice-free model. Cell velocities determined by balance of adhesive,
repulsive, and motile forces. Each cell has a phenotypic state governed by
stochastic processes derived from nonhomogeneous Poisson processes.</p>
<p><b>Software source: </b>PhysiCell is available as open
source at <a href="http://physicell.mathcancer.org/">http://PhysiCell.MathCancer.org</a>, <a href="http://physicell.sf.net/">http://PhysiCell.sf.net</a>, and <a href="https://github.com/mathcancer/physicell/releases">https://github.com/mathcancer/physicell/releases</a>.</p
3-D PhysiCell simulation of a hanging drop spheroid - deterministic necrosis model
<p>This is Video S1 in Ghaffarizadeh
et al. (2018). A higher-resolution (1080p) video can be streamed
at <a href="https://www.youtube.com/watch?v=WMhYW9D4SqM">https://www.youtube.com/watch?v=WMhYW9D4SqM</a>
</p>
<p><b>Paper:</b> <a href="https://doi.org/10.1371/journal.pcbi.1005991">https://doi.org/10.1371/journal.pcbi.1005991</a><br></p>
<p>3-D agent-based simulation of a hanging drop spheroid
experiment. In this simulation, cells immediately become necrotic wherever pO2 <
5 mmHg. This simulation was completed on a single HPC compute node (dual Xeon
6-core CPUs at 3.4 GHz), requiring 82 hours and 23 minutes to run (including
data saves once per simulated hour). It took 66 hours and 56 minutes to
simulate 17 days to the first ~1 million cells. Simulations without file I/O
are significantly faster.</p>
<p>The tumor maintains its expected
spherical symmetry until the end of the simulation, when the tumor nears the
computational boundary and experiences higher oxygenation that drive
non-spherical growth.</p>
<p><b>Legend:</b></p>
<p><u>Dark circles</u>: cell
nuclei</p>
<p><u>Green cells</u>: Proliferating Ki67+ cells, prior to mitosis</p>
<p><u>Magenta cells</u>: Proliferating Ki67+ cells, after mitosis</p>
<p><u>Red cells</u>: Apoptotic cells (cleaved Caspase-3 positive)</p>
<p><u>Pale blue cells</u>: Quiescent Ki67- cells</p>
<p><u>Brown cells</u>: Necrotic cells</p>
<p>This work is based on PhysiCell, an
open source 3-D modeling package for multicellular biology at <a href="http://physicell.mathcancer.org/">http://PhysiCell.MathCancer.org</a>.</p>
<p><b>Method: </b>Demonstration of PhysiCell, an agent-based,
lattice-free model. Cell velocities determined by balance of adhesive,
repulsive, and motile forces. Each cell has a phenotypic state governed by
stochastic processes derived from nonhomogeneous Poisson processes.</p>
<p><b>Software source: </b>PhysiCell is available as open
source at <a href="http://physicell.mathcancer.org/">http://PhysiCell.MathCancer.org</a>, <a href="http://physicell.sf.net/">http://PhysiCell.sf.net</a>, and <a href="https://github.com/mathcancer/physicell/releases">https://github.com/mathcancer/physicell/releases</a>.</p
High-throughput cancer hypothesis testing with an integrated PhysiCell-EMEWS workflow [Presented at SuperComputing SC17, Computational Approaches for Cancer Workshop]
These are my slides on combining PhysiCell with EMEWS for high-throughput evaluation of biological hypotheses. <div><br></div><div>It was presented at the Computational Approaches for Cancer Workshop on November 17, 2017 at the SuperComputing SC17 Meeting. </div