ISC Keynote: The Algorithms of Life – Scientific Computing for Systems Biology

By John Russell

June 19, 2019

Systems biology has existed loosely under many definitions for a couple of decades. It’s the notion of describing living systems using first-principle physics and mathematics to capture life in equations that are both descriptive and predictive – and let’s add productive by which we mean being able to deliver therapies (drugs et. al) to enhance health and fight disease.

Doing that has proven difficult at best and disappointing at worst as even a cursory glance at the state of healthcare reveals; that’s notwithstanding many marvelous breakthroughs such as sequencing the human genome and the steady chipping away at functional genomics (and other ‘omics) to understand better how DNA informs what we become.

Ivo Sbalzarini

With apologies to ISC organizers I’ve stolen the name of the opening keynote by Ivo Sbalzarini –  The Algorithms of Life – Scientific Computing for Systems Biology – for the headline of this article in an attempt to capture his expansive presentation. Thanks also to Sbalzarini for providing a few of his slides.

Given all we know today and the steady gush of experimental data from modern instruments, what we are missing, said Sbalzarini, are the algorithms to make sense of it all. Having poked away at this problem for nearly as long as it has been around, Sbalzarini presented a sweeping approach to digging out those algorithms by capitalizing on recent advances in imaging technology, immersive virtual/augmented reality, a sophisticated analysis approach that leverages particle-mesh mathematics and which has been built into a software platform (OpenFPM), and lastly, no surprise, the steadily growing power of HPC.

 

As in many important life sciences advances the ‘lowly’ fruit fly took center stage. In this instance the analysis was to investigate a dysregulation in embryogenesis – specifically the failure of tissue to fold properly. In the end, the researchers identified the DNA influence, the chemical environment influence, and the mechanical environment influence, and delivered a predictive understanding of the embryo’s tissue response. Lest you think this is old work, it was presented last week at the New York Scientific Data Summit.

Getting from Sbalzarini’s early nascent research 15 years ago to the impressive results (and tool suite) presented is a long journey. We’ll summarize as practical but the ISC is likely to archive its keynote; for biologists it is well worth watching.

Advanced imaging, such as light sheet microscopy, now makes it possible to observe life science phenomena in 3D and great detail at the cellular and intracellular level.

“We can image an embryo from the time it is a fertilized to the time it moves out of the microscope field by itself and continues its life. When we image the fruit fly embryo over the 72 hours of development, we gather 180 TB of image data. If you would like to visualize that in real-time. That means a rendering performance or a rendering throughput in real-time of about 1.8 Gigapixels per second,” said Sbalzarini[i]. A key advantage here is the animal stays alive unlike older approaches requiring stains and fixing.

Hardly just pretty pictures, the extensive image data captured (and visualizations possible) are the raw input for building hypotheses and predictive models. The other primary driver is Sbalzarini clever adaption of particle-mesh technology to convert the data into actionable, in silico simulation. Underlying HPC infrastructure, of course, is the engine without which the whole process would grind to a halt.

“The numerical methods are particle methods or hybrid particle mesh methods. They comprise an interesting class of numerical methods. They discretize the system by particles, so if you have a complex geometry, you don’t need to generate the mesh for the simulation, but you simply fill the geometry with particles that store the variables; there can be a mesh in addition in order to do far field equations in order to compute for example forces for far field equations, for example,” he said.

“This is a classic framework of particle-mesh methods to solve partial differential equations, but particle methods as an algorithm are much more general than that. I would define everything as a particle method that is composed of dots of zero dimension elements that are characterized by a position in some space and some properties that they carry. Such an algorithm can be used to solve partial differential equations where the particles are the colocation points of your various discretization and they store the values of the field at that position.”

He adds quickly, “There is nothing that limits us to having particles interacting in a deterministic fashion and this then also allows us to solve stochastic different equations, numerically or to perform agent based simulation or agent based modeling.”

Building the computational tools to deliver these models has been a challenging and lengthy task for which Sbalzarini is well-qualified. He is the chair of scientific computing for systems biology on the faculty of computer science of TU Dresden, as well as the faculty of mathematics, and director of the TUD-Department in the Center for Systems Biology Dresden. He also is a permanent Senior Research Group Leader with the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden.

Leaving out many details and with regrets for over-simplification, Sbalzarini and colleagues imaged the fruit fly embryo; used machine learning to identify ‘algorithms’, converted the data and algorithms into models based on particle-mesh approaches using their home-developed platform; ran computational experiments to test their hypotheses; and used immersive visualization technology as a step to allow researchers to see the real process and simulations unfold. “It is possible to walk around inside the simulation,” he said. Informed by what they saw and their knowledge, researchers tweaked parameters and hypotheses, iteratively converging on a solution.

“To me it is a very nice example of how HPC and these numerically intricate simulations that we can do with these machines allow us to bridge really from the molecular scale to the tissue scaler in order to explain how things work and in order to propose remedies,” said Sbalzarini.

Sbalzarini reminded the audience living systems are computing machines themselves, “[A fruit fly embryo] is a massively parallel and fully self-organized system in which we can view every single cell as a processing element that executes programs. [It’s a] highly interconnected computer and able to solve NP hard problems with billions or hundreds of billions of processing elements. We know a lot about the hardware of this computer – the proteins, the molecules, the lipids, the fats out of which this computer is made – and thanks to sequencing technology, [we’re] able to read the source code of this computer, which is the genomic sequence. However we have no idea what algorithms this source code implements on his hardware.”

Now, advanced imaging and machine learning capabilities are catalyzing researchers’ ability to identify ‘mechanistic’ guidelines and incorporate traditional formulations (ODEs/PDEs) of physics laws and mathematics into the life sciences tool box. Chemical diffusion. Fluid dynamics. EMI influences. Activation energy thresholds. These are the kinds of attributes that can be captured in particle-mesh models.

When Sbalzarini began his studies in earnest, he used an NEC SX-5 with 512 processors housed at CSCS (Swiss Supercomputer Center). In 2005 that became a Cray XT-3 with 1664 processors. A lot has changed since. The first iteration of the system biology software platform his team developed was Parallel Particle Mesh Library (PPM) written in Fortran 90 many years ago.  It served as layer between MPI and Client Applications for simulations of physical systems using Particle-Mesh methods. The PPM library runs on single and multi-processor architectures, and handles 2D and 3D problems.

“The PPM library had two parts, what we call the PPM core, which is implemented in all the communication primitives, the load balancing, the file IO, [and] the distributed data structures. And the PPM numerics using frequently used numerical solvers; it does this in part by using the abstractions from the core and in part by renting third party libraries such as PETSc or FFTW. On top of PPM there is a domain specific programming language called PPM Language which provides a reasonably simple way of coding PPM but you could also directly interface with the Fortran API,”

PPML used overloading and generic interfaces and provided for the limitations of the important routines for different hardware platforms such as vector processors, like the NEC system, shared memory, distributed memory, even single processor systems, said Sbalzarini.

It was a beast to maintain. “Because of overloading the amount of source code in the PPM library was huge, several millions of lines of code that needed to be maintained here and ported. What we liked about PPML was the abstraction on which it is based. It’s a set of abstract data types and abstract operators for computing that are in our opinion the most coarse-grained abstractions possible that still cleanly separate computation from communication. So in PPM an abstraction would either only compute but not incur any communication overhead or it would only communicate but not do any computation,” he said.

Five years ago the platform was upgraded, “We decided to keep the abstractions, to keep the definitions of the data types and the operators, but now implement a C++ library which is called OpenFPM (Open Framework for Particle Method Library) and make use of template metaprogrammingin C++ for compiled time code generation. OpenFPM can do much more than PPM, for example it can do simulations in arbitrary dimensional spaces where PPM is limited to 2D and 3D. OpenFPM allowed particle properties to be objects of any C++ that the user can define and all the communication and file IO will work for it,” he said.

Adopting template metaprogramming reduced the amount of code needed to “about a factor of ten less complexity than the PPM.”

Sbalzarini presented many more details in his rich talk. It will be interesting to watch how widely OpenFPM is used and if it gains tractions in other domains. Ease of use is a key question for many biomedical researchers and clinicians. Sbalzarini said, “This hopefully makes HPC so easy to use that every science-based application in biology, in computational biology, and also in other fields can benefit.”

That said computer expertise, particularly HPC expertise, has historically been lacking in life science although that is changing and fairly quickly.

The main motivation is to understand biology and to understand how cells form tissues, and eventually to be able to provide novel explanations for disease phenotypes and maybe therapies for disease, said Sbalzarini. Nevertheless, “For us as computer scientists it’s also just a lot of fun because what we do combines several technologies that we think are fun to work with, technologies like virtual reality, HPC, massively scalable software systems, building microscopes and playing with optics, or using and developing artificial intelligence and learning algorithms to interface with the living things in the microscope.”

[i]Some quotes have been very lightly edited to improve readability.

 

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!

On the Spack Track @SC19

December 5, 2019

At the annual supercomputing conference, SC19 in Denver, Colorado, there were Spack events each day of the conference. As a reflection of its grassroots heritage, nine sessions were planned by more than a dozen thought leaders from seven organizations, including three U.S. national Department of Energy (DOE) laboratories and Sylabs... Read more…

By Elizabeth Leake

Intel’s New Hyderabad Design Center Targets Exascale Era Technologies

December 3, 2019

Intel's Raja Koduri was in India this week to help launch a new 300,000 square foot design and engineering center in Hyderabad, which will focus on advanced computing technologies for the AI and exascale era. "Over th Read more…

By Tiffany Trader

AWS Debuts 7nm 2nd-Gen Graviton Arm Processor

December 3, 2019

The “x86 Big Bang,” in which market dominance of the venerable Intel CPU has exploded into fragments of processor options suited to varying workloads, has now encompassed CPUs offered by the leading public cloud serv Read more…

By Doug Black

Medical Imaging Gets an AI Boost

December 3, 2019

AI technologies incorporated into diagnostic imaging tools have proven useful in eliminating confirmation bias, often outperforming human clinicians who may bring their own prejudices. Another issue slowing progress is t Read more…

By George Leopold

Ride on the Wild Side – Squyres SC19 Mars Rovers Keynote

December 2, 2019

Reminding us of the deep and enabling connection between HPC and modern science is an important part of the SC Conference mission. And yes, HPC is a science itself. At SC19, Steve Squyres’ opening keynote recounting th Read more…

By John Russell

AWS Solution Channel

Making High Performance Computing Affordable and Accessible for Small and Medium Businesses with HPC on AWS

High performance computing (HPC) brings a powerful set of tools to a broad range of industries, helping to drive innovation and boost revenue in finance, genomics, oil and gas extraction, and other fields. Read more…

IBM Accelerated Insights

AI Needs Intelligent HPC infrastructure

Artificial Intelligence (AI) has revolutionized entire industries and enables humanity to solve some of the most daunting challenges. To accomplish this, it requires massive amounts of data from heterogeneous sources that is processed it new ways that differs significantly from HPC applications. Read more…

NSCI Update – Adapting to a Changing Landscape

December 2, 2019

It was November of 2017 when we last visited the topic of the National Strategic Computing Initiative (NSCI). As you will recall, the NSCI was started with an Executive Order (E.O. No. 13702), that was issued by President Obama in July of 2015 and was followed by a Strategic Plan that was released in July of 2016. The question for November of 2017... Read more…

By Alex R. Larzelere

On the Spack Track @SC19

December 5, 2019

At the annual supercomputing conference, SC19 in Denver, Colorado, there were Spack events each day of the conference. As a reflection of its grassroots heritage, nine sessions were planned by more than a dozen thought leaders from seven organizations, including three U.S. national Department of Energy (DOE) laboratories and Sylabs... Read more…

By Elizabeth Leake

Intel’s New Hyderabad Design Center Targets Exascale Era Technologies

December 3, 2019

Intel's Raja Koduri was in India this week to help launch a new 300,000 square foot design and engineering center in Hyderabad, which will focus on advanced com Read more…

By Tiffany Trader

AWS Debuts 7nm 2nd-Gen Graviton Arm Processor

December 3, 2019

The “x86 Big Bang,” in which market dominance of the venerable Intel CPU has exploded into fragments of processor options suited to varying workloads, has n Read more…

By Doug Black

Ride on the Wild Side – Squyres SC19 Mars Rovers Keynote

December 2, 2019

Reminding us of the deep and enabling connection between HPC and modern science is an important part of the SC Conference mission. And yes, HPC is a science its Read more…

By John Russell

NSCI Update – Adapting to a Changing Landscape

December 2, 2019

It was November of 2017 when we last visited the topic of the National Strategic Computing Initiative (NSCI). As you will recall, the NSCI was started with an Executive Order (E.O. No. 13702), that was issued by President Obama in July of 2015 and was followed by a Strategic Plan that was released in July of 2016. The question for November of 2017... Read more…

By Alex R. Larzelere

Tsinghua University Racks Up Its Ninth Student Cluster Championship Win at SC19

November 27, 2019

Tsinghua University has done it again. At SC19 last week, the eight-time gold medal-winner team took home the top prize in the 2019 Student Cluster Competition Read more…

By Oliver Peckham

SC19: IBM Changes Its HPC-AI Game Plan

November 25, 2019

It’s probably fair to say IBM is known for big bets. Summit supercomputer – a big win. Red Hat acquisition – looking like a big win. OpenPOWER and Power processors – jury’s out? At SC19, long-time IBMer Dave Turek sketched out a different kind of bet for Big Blue – a small ball strategy, if you’ll forgive the baseball analogy... Read more…

By John Russell

How the Gordon Bell Prize Winners Used Summit to Illuminate Transistors

November 22, 2019

At SC19, the Association for Computing Machinery (ACM) awarded the prestigious Gordon Bell Prize to the Swiss Federal Institute of Technology (ETH) Zurich. The Read more…

By Oliver Peckham

Supercomputer-Powered AI Tackles a Key Fusion Energy Challenge

August 7, 2019

Fusion energy is the Holy Grail of the energy world: low-radioactivity, low-waste, zero-carbon, high-output nuclear power that can run on hydrogen or lithium. T Read more…

By Oliver Peckham

Using AI to Solve One of the Most Prevailing Problems in CFD

October 17, 2019

How can artificial intelligence (AI) and high-performance computing (HPC) solve mesh generation, one of the most commonly referenced problems in computational engineering? A new study has set out to answer this question and create an industry-first AI-mesh application... Read more…

By James Sharpe

Cray Wins NNSA-Livermore ‘El Capitan’ Exascale Contract

August 13, 2019

Cray has won the bid to build the first exascale supercomputer for the National Nuclear Security Administration (NNSA) and Lawrence Livermore National Laborator Read more…

By Tiffany Trader

DARPA Looks to Propel Parallelism

September 4, 2019

As Moore’s law runs out of steam, new programming approaches are being pursued with the goal of greater hardware performance with less coding. The Defense Advanced Projects Research Agency is launching a new programming effort aimed at leveraging the benefits of massive distributed parallelism with less sweat. Read more…

By George Leopold

D-Wave’s Path to 5000 Qubits; Google’s Quantum Supremacy Claim

September 24, 2019

On the heels of IBM’s quantum news last week come two more quantum items. D-Wave Systems today announced the name of its forthcoming 5000-qubit system, Advantage (yes the name choice isn’t serendipity), at its user conference being held this week in Newport, RI. Read more…

By John Russell

Ayar Labs to Demo Photonics Chiplet in FPGA Package at Hot Chips

August 19, 2019

Silicon startup Ayar Labs continues to gain momentum with its DARPA-backed optical chiplet technology that puts advanced electronics and optics on the same chip Read more…

By Tiffany Trader

AMD Launches Epyc Rome, First 7nm CPU

August 8, 2019

From a gala event at the Palace of Fine Arts in San Francisco yesterday (Aug. 7), AMD launched its second-generation Epyc Rome x86 chips, based on its 7nm proce Read more…

By Tiffany Trader

SC19: IBM Changes Its HPC-AI Game Plan

November 25, 2019

It’s probably fair to say IBM is known for big bets. Summit supercomputer – a big win. Red Hat acquisition – looking like a big win. OpenPOWER and Power processors – jury’s out? At SC19, long-time IBMer Dave Turek sketched out a different kind of bet for Big Blue – a small ball strategy, if you’ll forgive the baseball analogy... Read more…

By John Russell

Leading Solution Providers

ISC 2019 Virtual Booth Video Tour

CRAY
CRAY
DDN
DDN
DELL EMC
DELL EMC
GOOGLE
GOOGLE
ONE STOP SYSTEMS
ONE STOP SYSTEMS
PANASAS
PANASAS
VERNE GLOBAL
VERNE GLOBAL

Cray, Fujitsu Both Bringing Fujitsu A64FX-based Supercomputers to Market in 2020

November 12, 2019

The number of top-tier HPC systems makers has shrunk due to a steady march of M&A activity, but there is increased diversity and choice of processing compon Read more…

By Tiffany Trader

Crystal Ball Gazing: IBM’s Vision for the Future of Computing

October 14, 2019

Dario Gil, IBM’s relatively new director of research, painted a intriguing portrait of the future of computing along with a rough idea of how IBM thinks we’ Read more…

By John Russell

Intel Debuts New GPU – Ponte Vecchio – and Outlines Aspirations for oneAPI

November 17, 2019

Intel today revealed a few more details about its forthcoming Xe line of GPUs – the top SKU is named Ponte Vecchio and will be used in Aurora, the first plann Read more…

By John Russell

Kubernetes, Containers and HPC

September 19, 2019

Software containers and Kubernetes are important tools for building, deploying, running and managing modern enterprise applications at scale and delivering enterprise software faster and more reliably to the end user — while using resources more efficiently and reducing costs. Read more…

By Daniel Gruber, Burak Yenier and Wolfgang Gentzsch, UberCloud

Dell Ramps Up HPC Testing of AMD Rome Processors

October 21, 2019

Dell Technologies is wading deeper into the AMD-based systems market with a growing evaluation program for the latest Epyc (Rome) microprocessors from AMD. In a Read more…

By John Russell

SC19: Welcome to Denver

November 17, 2019

A significant swath of the HPC community has come to Denver for SC19, which began today (Sunday) with a rich technical program. As is customary, the ribbon cutt Read more…

By Tiffany Trader

When Dense Matrix Representations Beat Sparse

September 9, 2019

In our world filled with unintended consequences, it turns out that saving memory space to help deal with GPU limitations, knowing it introduces performance pen Read more…

By James Reinders

With the Help of HPC, Astronomers Prepare to Deflect a Real Asteroid

September 26, 2019

For years, NASA has been running simulations of asteroid impacts to understand the risks (and likelihoods) of asteroids colliding with Earth. Now, NASA and the European Space Agency (ESA) are preparing for the next, crucial step in planetary defense against asteroid impacts: physically deflecting a real asteroid. Read more…

By Oliver Peckham

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