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Primeur weekly 2014-06-30

Special

Innovative HTC facilities needed to support computational genomics at the application and data level ...

HPC-assisted cell-based immunotherapy successful in curing melanoma ...

Restless hearts are simulated with real-time modelling at IBM Research in Zurich ...

A live report from the Adapteva A-1 "smallest supercomputer in the world" launch at ISC'14 ...

The Cloud

HP launches Helion Managed Services for optimizing Cloud storage workloads ...

Oracle unveils next generation Virtual Compute Appliance ...

Desktop Grids

ATLAS@Home crowd computing project launched at CERN ...

EuroFlash

a.s.r. uses ADVA Optical Networking's GNOC for critical network monitoring and maintenance ...

ADVA Optical Networking launches new era of data centre connectivity with Big Data transport solution ...

KTH wins from crystal clear insight into application performance with Allinea Performance Reports ...

Neurological simulation milestone reached after UCL embraces Allinea's tools on UK's largest supercomputer ...

Bright Computing is building on its success in data centres across Europe ...

UK Atomic Weapons Establishment launches SGI supercomputer ...

Spectra Logic tape library to archive the UK's fastest supercomputer ...

Physicists find way to boot up quantum computers 72 times faster than previously possible ...

In the fast lane: Mediatec uses Calibre UK LEDView530 scalers at FIA World Endurance Championships ...

The upcoming cybernetic age is one of intellectual capital ...

International Supercomputing Conference moves to Frankfurt, Germany in 2015 ...

USFlash

DataDirect Networks helps EMSL speed climate, energy and bioscience discoveries with high performance and massively scalable storage ...

Spectra and the Tandy Supercomputer shorten calculation rates from days to minutes, saving time and lives ...

New A*STAR-SMU centre combines high-powered computing and behavioural sciences to study people-centric issues ...

Scheduling algorithms based on game theory makes better use of computational resources ...

National Renewable Energy Laboratory supercomputer tackles power grid problems ...

Simulations helps scientists understand and control turbulence in humans and machines ...

Stampede supercomputer enables discoveries throughout science and engineering ...

Supercomputing simulations crucial to the study of Ras protein in determining anticancer drugs ...

Stampede supercomputer powers innovations in DNA sequencing technologies ...

Stampede supercomputer helps researchers design and test improved hurricane forecasting system ...

NSF-supported Stampede supercomputer powers innovations in materials science ...

D-Wave and predecessors: From simulated to quantum annealing ...

HPC server market shrinks -9.6% in the first quarter of 2014, according to IDC ...

University of Maryland's Deepthought2 debuts in global supercomputer rankings ...

Nine ways NSF-supported supercomputers help scientists understand and treat the disease ...

CAST releases wysiwyg R33 ...

HPC-assisted cell-based immunotherapy successful in curing melanoma


24 Jun 2014 Leipzig - In the session on HPC in Life Sciences at ISC'14 in Leipzig, Olivier Michielin from the University of Lausanne, the Swiss Institute of Bioinformatics (SIB), and the Ludwig Institute for Cancer Research talked about HPC-supported therapy development in oncology. He told the audience that there have been some recent clinical successes of immunotherapy in melanoma using a rational TCR design programme.

Cell-based therapies are a scientific breakthrough, Olivier Michielin explained, since they are the molecular bases of tumour immunology and the early evidences of T-cell activity against tumours.

The tumour cell is characterized by mutation. Molecules are assembled called MHC-I. They show an abnormal expression, sending a signal to trigger a reaction, Olivier Michielin explained.

Adoptive cell therapy is a new concept in which specific T-cell extraction is being performed. The method consists of host conditioning, using NMA chemo and TBI; in vitro expansion; and reinfusion.

What is the curative potential of immunotherapies? Olivier Michielin told the audience that the 5 year survival rate in the 22% of complete responders amounts to 93%. Adding TBI, the 40% of complete responders is being observed.

Currently, medical teams are designing new immunotherapies. The rational TCR design programme consists of TCR selection and melanoma vaccination trials. The cell is extracted and sequenced. This is the point where HPC comes in the game, Olivier Michielin explained.

Free energy calculations are being made. The process involves TCR selection; in silico design; Biacore testing; cellular testing; mouse models; and clinical trials.

The free energy constitutes a dissociation constant with MD simulations and has a biological function. Olivier Michielin said that Martin Karplus won the Nobel Prize for Chemistry in 2013 in this area.

The process implies four months of calculation on the mainframe. The TCR simulation is set up using parallel processing HPC with use of cut-offs for the highly fp intensive process.

In the A51E mutation, a solution is found by replacing one acid by another one to quantify the calculation and gain in binding free energy, Olivier Michielin explained. In Biacore testing of the molecule, soluble forms of optimized TCRs are produced in bacteria and refolded.

For the validation of a panel of affinity-optimized NY-ESO-1 TCR variants, a correlation is made between the simulation and the measurements. The method is based on the laws of physics, and therefore applicable without any change to any protein-protein interface.

The In vitro assessment involves cellular data, Olivier Michielin explained, for the transfection of optimized TCR of patient CD8 T-cells.

As far as the increased killing capacity and IL-2 production are concerned, Olivier Michielin announced that the first clinical trials for humans are planned for 2016.

Olivier Michielin's research team is trying to overcome immune escape mechanisms with peptide vaccines. The CTLA-4 blockade is tackled with ACT and depletion. The T-cells need tryptophan to function well. The team is counteracting immune escapes through IDO inhibition.

The methodological development for CADD is HOC for drug design.

Original approaches for drug design applications involve fragment-based drug design; lead discovery; and lead optimization.

Non-natural sidechains include a database of commercially available side chains with force field and rotamer generation. For the ligand growing, a lead optimization using a growing algorithm is performed, explained Olivier Michielin.

EADock is performed with conformational sampling using genetic algorithms. Each selected degree of freedom faces an evolutionary process.

The genome is described with cartesian co-ordinates. Fitness is the CHARMM Enthalpy and solvation of free energy and binding of free energy.

All in all, Olivier Michielin's team aims at a high throughput versus a fragment based design. With a high throughput, the protein's active site is identified. With a fragment based design, you only need a small number to have a list.

As such, the integrated academic therapeutic development pipeline evolves from discovery to clinical tirals, concluded Olivier Michielin.
Leslie Versweyveld

Back to Table of contents

Primeur weekly 2014-06-30

Special

Innovative HTC facilities needed to support computational genomics at the application and data level ...

HPC-assisted cell-based immunotherapy successful in curing melanoma ...

Restless hearts are simulated with real-time modelling at IBM Research in Zurich ...

A live report from the Adapteva A-1 "smallest supercomputer in the world" launch at ISC'14 ...

The Cloud

HP launches Helion Managed Services for optimizing Cloud storage workloads ...

Oracle unveils next generation Virtual Compute Appliance ...

Desktop Grids

ATLAS@Home crowd computing project launched at CERN ...

EuroFlash

a.s.r. uses ADVA Optical Networking's GNOC for critical network monitoring and maintenance ...

ADVA Optical Networking launches new era of data centre connectivity with Big Data transport solution ...

KTH wins from crystal clear insight into application performance with Allinea Performance Reports ...

Neurological simulation milestone reached after UCL embraces Allinea's tools on UK's largest supercomputer ...

Bright Computing is building on its success in data centres across Europe ...

UK Atomic Weapons Establishment launches SGI supercomputer ...

Spectra Logic tape library to archive the UK's fastest supercomputer ...

Physicists find way to boot up quantum computers 72 times faster than previously possible ...

In the fast lane: Mediatec uses Calibre UK LEDView530 scalers at FIA World Endurance Championships ...

The upcoming cybernetic age is one of intellectual capital ...

International Supercomputing Conference moves to Frankfurt, Germany in 2015 ...

USFlash

DataDirect Networks helps EMSL speed climate, energy and bioscience discoveries with high performance and massively scalable storage ...

Spectra and the Tandy Supercomputer shorten calculation rates from days to minutes, saving time and lives ...

New A*STAR-SMU centre combines high-powered computing and behavioural sciences to study people-centric issues ...

Scheduling algorithms based on game theory makes better use of computational resources ...

National Renewable Energy Laboratory supercomputer tackles power grid problems ...

Simulations helps scientists understand and control turbulence in humans and machines ...

Stampede supercomputer enables discoveries throughout science and engineering ...

Supercomputing simulations crucial to the study of Ras protein in determining anticancer drugs ...

Stampede supercomputer powers innovations in DNA sequencing technologies ...

Stampede supercomputer helps researchers design and test improved hurricane forecasting system ...

NSF-supported Stampede supercomputer powers innovations in materials science ...

D-Wave and predecessors: From simulated to quantum annealing ...

HPC server market shrinks -9.6% in the first quarter of 2014, according to IDC ...

University of Maryland's Deepthought2 debuts in global supercomputer rankings ...

Nine ways NSF-supported supercomputers help scientists understand and treat the disease ...

CAST releases wysiwyg R33 ...