Research Using TACC Supercomputers Helps to Develop New Anti-Cancer Strategies

April 18, 2019

April 18, 2019 — Cell membranes are the key regulating factor for biological processes at the tissue-scale. The application of an electric field can alter the cell membrane’s permeability to chemicals in their vicinity or even kill the subjected cells. The process, known as electropermeabilization or electroporation, consists of applying short, intense electric pulses.

Electroporation is currently used in the treatment of some cancers. For example, electro-chemotherapy is a cutting-edge cancer treatment technique that uses electroporation as a means to deliver chemotherapy into cancerous cells.

Spinning the camera about the vertical axis of the cell aggregate during electroporation. Colors depict different levels of conductance for cell membranes, with hotter colors being higher conductance values. The upper limit is S_max=2e5 S/m and the initial value is S_min=1.9S/m spanning 5 orders of magnitude in conductance range. Colors are used in a logarithmic scale (intensity is equal to log_10 [S]).
“Irreversible electroporation is used to destroy cancer cells,” said Frederic Gibou, a faculty member in the Department of Mechanical Engineering and Computer Science at the University of California, Santa Barbara (UCSB). “Electroporation is also used to deliver chemotherapy by enhancing cell permeability to non-permeant drugs. One of the important questions is which electric pulses will maximize the efficacy of treatments.”

Another interesting application is accelerating combat wound healing using electric pulsation.

“It’s an exciting, but mainly unexplored area that stems from a deeper discussion at the frontier of developmental biology, namely how electricity influences morphogenesis” — or the biological process that causes an organism to develop its shape — Gibou said. “In wound healing, the goal is to externally manipulate electric cues to guide cells to grow faster in the wounded region and accelerate the healing process.”

The common factor among these applications is their bioelectric physical nature. In recent years, it has been established that the bioelectric nature of living organisms plays a pivotal role in the development of their form and growth.

To understand bioelectric phenomena, Gibou’s group has considered computer experiments on multicellular spheroids in 3D. Spheroids are aggregates of a few tens of thousands of cells that are used in biology because of their structural and functional similarity with tumors.

A FIRST-EVER COMPUTATIONAL FRAMEWORK FOR BIOELECTRICAL INTERACTION AT THE TISSUE SCALE

In new research published in the Journal of Computational Physics, Gibou and his team delve into a new computational framework for parallel simulations that models the complex bioelectrical interaction at the tissue scale.

“We started from the phenomenological cell-scale model that was developed in the research group of our colleague, Clair Poignard, at the Université de Bordeaux, France, with whom we have collaborated for several years,” Gibou said.

“This model, which describes the evolution of transmembrane potential on an isolated cell, has been compared and validated with the response of a single cell in experiments,” he said. “From there, we developed the first computational framework that is able to consider a cell aggregate of tens of thousands of cells and to simulate their interactions. The end goal is to develop an effective tissue-scale theory for electroporation.”

According to Gibou and his colleague, Pouria Mistani, one of the main reasons for the absence of an effective theory at the tissue scale is the lack of data. Specifically, the missing data in the case of electroporation is the time evolution of the transmembrane potential of each individual cell in a tissue environment. Experiments are not able to make those measurements.

“Currently, experimental limitations prevent the development of an effective tissue-level electroporation theory,” Mistani said. “Our work has developed a computational approach that can simulate the response of individual cells in a spheroid to an electric field as well as their mutual interactions.”

Each cell behaves according to certain rules. “But when you consider a large number of them together, the aggregate exhibits novel coherent behaviors. It is this emergent phenomenon that is crucial for developing effective theories at the tissue-scale — novel behaviors that emerge from the coupling of many individual elements,” Mistani said.

The effects of electroporation used in cancer treatment, for example, depend on many factors, such as the strength of the electric field, its pulse, and its frequency. “This work could bring an effective theory that helps understand the tissue response to these parameters and thus optimize such treatments,” says Mistani.

The researchers are currently mining this unique dataset to develop an effective tissue-scale theory of cell aggregate electroporation.

“Before our work, the largest existing simulations of cell aggregate electroporation only considered about one hundred cells in 3D,” said Mistani, “or were limited to 2D simulations. Those simulations either ignored the real 3D nature of spheroids or considered too few cells for tissue-scale emergent behaviors to manifest.”

XSEDE CYBERINFRASTRUCTURE PLAYS KEY ROLE

Supercomputer allocations on Comet at the San Diego Supercomputer Center (SDSC) and Stampede2 at TACC were awarded to the researchers through XSEDE, the Extreme Science and Engineering Discovery Environment funded by the National Science Foundation (NSF). Additionally, the researchers used TACC’s long-term storage system, Ranch, also an XSEDE resource.

“XSEDE is a fantastic advanced computing ecosystem that really allows us to get data that would be impossible otherwise,” Gibou said.

“This has been, by far, the largest simulation of cell aggregate electroporation to date,” Mistani said. “It has successfully provided terabytes of high fidelity measurements of electroporation processes on tens of thousands of highly resolved cells in a 3D multicellular spheroid configuration.”

At the beginning of the project, Mistani used Comet to develop and test initial versions of the code. Then, he used Stampede2 to finalize and verify the code and to perform scaling tests. Finally, all the large scale simulations and measurements were performed on Stampede2.

“We also benefited from the suite of visualization tools provided by Stampede2,” Mistani said. “It’s as if you’re looking at cells in the human body — you can directly probe the data and gain insights about how to properly describe the system. The ability to make observations and interrogate the data helps conceive the underlying effective theory.”

With these large-scale simulations, transferring raw simulation results to local machines is very difficult. “A better strategy is to keep the data on supercomputers and reduce it via some post-processing before transferring to local machines for further analysis. Ranch is an excellent resource for storage of the simulation results,” Mistani continued.

Computer simulations are more and more prominent in the fields of science and engineering because they enable researchers to get data that sometimes cannot be obtained otherwise. State-of-the-art computer architectures, such as Comet and Stampede2, and advanced numerical methods open up new possibilities in advancing the frontiers of science in disciplines that are of high interest to the public, such as cancer treatment, combat wound healing, or the broad field of morphogenesis.

“For us, this research would not have been possible without XSEDE because such simulations require over 2,000 cores for 24 hours and terabytes of data to reach time scales and length scales where the collective interactions between cells manifest themselves as a pattern,” Gibou said. “It helped us observe a surprising structure for the behavior of the aggregate out of the inherent randomness. XSEDE provides a truly unique infrastructure for scientific discovery in the era of big data.” Moving forward, the team’s research goal is to develop an effective theory that describes the simulation results.

“This is an example where simulations are not merely used as a predictive tool, but help discover new phenomena,” Gibou said. “Under electroporation, cells respond in surprising synchronicity and it’s beautiful to witness how such levels of order emerge out of inherent randomness.”

The research of P. Mistani, A. Guittet, and F. Gibou was supported by NSF DMS-1620471 and ARO W911NF-16-1-0136. C. Poignard research is supported by Plan Cancer DYNAMO (ref. PC201515) and Plan Cancer NUMEP (ref. PC201615). P. Mistani would like to thank Daniil Bochkov in the CASL group for fruitful discussions that have contributed to this research. This work used XSEDE, which is supported by National Science Foundation grant number ACI-1053575. The authors acknowledge TACC at The University of Texas at Austin for providing HPC and visualization resources that have contributed to the research results reported within this paper. This research was performed in part within the scope of the Inria associate team NUM4SEP, between the CASL group at UCSB and the Inria team. MONC. C.P.’s research is partly performed within the scope of the European Associated Laboratory EBAM on electroporation, granted by CNRS.


Source: Faith Singer-Villalobos, TACC

Subscribe to HPCwire's Weekly Update!

Be the most informed person in the room! Stay ahead of the tech trends with industy updates delivered to you every week!

RIKEN Post-K Supercomputer Named After Japan’s Tallest Peak

May 23, 2019

May 23 -- RIKEN President Hiroshi Matsumoto announced that the successor to the K computer will be named Fugaku, another name for Mount Fuji, which is the tallest mountain peak in Japan. Supercomputer Fugaku, developed b Read more…

By Tiffany Trader

Cray’s Emerging Market & Technology Director Arti Garg Peers Around HPC/AI Corner

May 23, 2019

In her position as emerging market and technology director at Cray, Arti Garg doesn't just have a front-row seat to the future of computing, she plays an active role in making that future happen. Key to Garg's role is understanding how deep learning scientists are using state-of-the-art HPC infrastructures and figuring out how to push those limits further. Read more…

By Tiffany Trader

Combining Machine Learning and Supercomputing to Ferret out Phishing Attacks

May 23, 2019

The relentless ingenuity that drives cyber hacking is a global engine that knows no rest. Anyone with a laptop and run-of-the-mill computer smarts can buy or rent a phishing kit and start attacking – or it can be done Read more…

By Doug Black

HPE Extreme Performance Solutions

HPE and Intel® Omni-Path Architecture: How to Power a Cloud

Learn how HPE and Intel® Omni-Path Architecture provide critical infrastructure for leading Nordic HPC provider’s HPCFLOW cloud service.

For decades, HPE has been at the forefront of high-performance computing, and we’ve powered some of the fastest and most robust supercomputers in the world. Read more…

IBM Accelerated Insights

Who’s Driving Your Car?

Delivering a fully autonomous driving (AD) vehicle remains a key priority for both manufacturers and technology firms (“firms”). However, passenger safety is now a top-of-mind concern due in great part, to fatalities resulting from driving tests over the past years. Read more…

TACC’s Upgraded Ranch Data Storage System Debuts New Features, Exabyte Potential

May 22, 2019

There's a joke attributed to comedian Steven Wright that goes, "You can't have everything. Where would you put it?" Users of advanced computing can likely relate to this. The exponential growth of data poses a steep challenge to efforts for its reliable storage. For over 12 years, the Ranch system at the Texas Advanced Computing Center... Read more…

By Jorge Salazar, TACC

Cray’s Emerging Market & Technology Director Arti Garg Peers Around HPC/AI Corner

May 23, 2019

In her position as emerging market and technology director at Cray, Arti Garg doesn't just have a front-row seat to the future of computing, she plays an active role in making that future happen. Key to Garg's role is understanding how deep learning scientists are using state-of-the-art HPC infrastructures and figuring out how to push those limits further. Read more…

By Tiffany Trader

Combining Machine Learning and Supercomputing to Ferret out Phishing Attacks

May 23, 2019

The relentless ingenuity that drives cyber hacking is a global engine that knows no rest. Anyone with a laptop and run-of-the-mill computer smarts can buy or re Read more…

By Doug Black

Cray – and the Cray Brand – to Be Positioned at Tip of HPE’s HPC Spear

May 22, 2019

More so than with most acquisitions of this kind, HPE’s purchase of Cray for $1.3 billion, announced last week, seems to have elements of that overused, often Read more…

By Doug Black and Tiffany Trader

HPE to Acquire Cray for $1.3B

May 17, 2019

Venerable supercomputer pioneer Cray Inc. will be acquired by Hewlett Packard Enterprise for $1.3 billion under a definitive agreement announced this morning. T Read more…

By Doug Black & Tiffany Trader

Deep Learning Competitors Stalk Nvidia

May 14, 2019

There is no shortage of processing architectures emerging to accelerate deep learning workloads, with two more options emerging this week to challenge GPU leader Nvidia. First, Intel researchers claimed a new deep learning record for image classification on the ResNet-50 convolutional neural network. Separately, Israeli AI chip startup Hailo.ai... Read more…

By George Leopold

CCC Offers Draft 20-Year AI Roadmap; Seeks Comments

May 14, 2019

Artificial Intelligence in all its guises has captured much of the conversation in HPC and general computing today. The White House, DARPA, IARPA, and Departmen Read more…

By John Russell

Cascade Lake Shows Up to 84 Percent Gen-on-Gen Advantage on STAC Benchmarking

May 13, 2019

The Securities Technology Analysis Center (STAC) issued a report Friday comparing the performance of Intel's Cascade Lake processors with previous-gen Skylake u Read more…

By Tiffany Trader

Nvidia Claims 6000x Speed-Up for Stock Trading Backtest Benchmark

May 13, 2019

A stock trading backtesting algorithm used by hedge funds to simulate trading variants has received a massive, GPU-based performance boost, according to Nvidia, Read more…

By Doug Black

Cray, AMD to Extend DOE’s Exascale Frontier

May 7, 2019

Cray and AMD are coming back to Oak Ridge National Laboratory to partner on the world’s largest and most expensive supercomputer. The Department of Energy’s Read more…

By Tiffany Trader

Graphene Surprises Again, This Time for Quantum Computing

May 8, 2019

Graphene is fascinating stuff with promise for use in a seeming endless number of applications. This month researchers from the University of Vienna and Institu Read more…

By John Russell

Why Nvidia Bought Mellanox: ‘Future Datacenters Will Be…Like High Performance Computers’

March 14, 2019

“Future datacenters of all kinds will be built like high performance computers,” said Nvidia CEO Jensen Huang during a phone briefing on Monday after Nvidia revealed scooping up the high performance networking company Mellanox for $6.9 billion. Read more…

By Tiffany Trader

It’s Official: Aurora on Track to Be First US Exascale Computer in 2021

March 18, 2019

The U.S. Department of Energy along with Intel and Cray confirmed today that an Intel/Cray supercomputer, "Aurora," capable of sustained performance of one exaf Read more…

By Tiffany Trader

ClusterVision in Bankruptcy, Fate Uncertain

February 13, 2019

ClusterVision, European HPC specialists that have built and installed over 20 Top500-ranked systems in their nearly 17-year history, appear to be in the midst o Read more…

By Tiffany Trader

Intel Reportedly in $6B Bid for Mellanox

January 30, 2019

The latest rumors and reports around an acquisition of Mellanox focus on Intel, which has reportedly offered a $6 billion bid for the high performance interconn Read more…

By Doug Black

Looking for Light Reading? NSF-backed ‘Comic Books’ Tackle Quantum Computing

January 28, 2019

Still baffled by quantum computing? How about turning to comic books (graphic novels for the well-read among you) for some clarity and a little humor on QC. The Read more…

By John Russell

Deep Learning Competitors Stalk Nvidia

May 14, 2019

There is no shortage of processing architectures emerging to accelerate deep learning workloads, with two more options emerging this week to challenge GPU leader Nvidia. First, Intel researchers claimed a new deep learning record for image classification on the ResNet-50 convolutional neural network. Separately, Israeli AI chip startup Hailo.ai... Read more…

By George Leopold

Leading Solution Providers

SC 18 Virtual Booth Video Tour

Advania @ SC18 AMD @ SC18
ASRock Rack @ SC18
DDN Storage @ SC18
HPE @ SC18
IBM @ SC18
Lenovo @ SC18 Mellanox Technologies @ SC18
NVIDIA @ SC18
One Stop Systems @ SC18
Oracle @ SC18 Panasas @ SC18
Supermicro @ SC18 SUSE @ SC18 TYAN @ SC18
Verne Global @ SC18

The Case Against ‘The Case Against Quantum Computing’

January 9, 2019

It’s not easy to be a physicist. Richard Feynman (basically the Jimi Hendrix of physicists) once said: “The first principle is that you must not fool yourse Read more…

By Ben Criger

Deep500: ETH Researchers Introduce New Deep Learning Benchmark for HPC

February 5, 2019

ETH researchers have developed a new deep learning benchmarking environment – Deep500 – they say is “the first distributed and reproducible benchmarking s Read more…

By John Russell

IBM Bets $2B Seeking 1000X AI Hardware Performance Boost

February 7, 2019

For now, AI systems are mostly machine learning-based and “narrow” – powerful as they are by today's standards, they're limited to performing a few, narro Read more…

By Doug Black

Arm Unveils Neoverse N1 Platform with up to 128-Cores

February 20, 2019

Following on its Neoverse roadmap announcement last October, Arm today revealed its next-gen Neoverse microarchitecture with compute and throughput-optimized si Read more…

By Tiffany Trader

Intel Launches Cascade Lake Xeons with Up to 56 Cores

April 2, 2019

At Intel's Data-Centric Innovation Day in San Francisco (April 2), the company unveiled its second-generation Xeon Scalable (Cascade Lake) family and debuted it Read more…

By Tiffany Trader

Announcing four new HPC capabilities in Google Cloud Platform

April 15, 2019

When you’re running compute-bound or memory-bound applications for high performance computing or large, data-dependent machine learning training workloads on Read more…

By Wyatt Gorman, HPC Specialist, Google Cloud; Brad Calder, VP of Engineering, Google Cloud; Bart Sano, VP of Platforms, Google Cloud

Nvidia Claims 6000x Speed-Up for Stock Trading Backtest Benchmark

May 13, 2019

A stock trading backtesting algorithm used by hedge funds to simulate trading variants has received a massive, GPU-based performance boost, according to Nvidia, Read more…

By Doug Black

In Wake of Nvidia-Mellanox: Xilinx to Acquire Solarflare

April 25, 2019

With echoes of Nvidia’s recent acquisition of Mellanox, FPGA maker Xilinx has announced a definitive agreement to acquire Solarflare Communications, provider Read more…

By Doug Black

  • arrow
  • Click Here for More Headlines
  • arrow
Do NOT follow this link or you will be banned from the site!
Share This