Towards simulation of subcellular calcium dynamics at nanometre resolution

Numerical simulation of subcellular Ca 2 + dynamics with a resolution down to one nanometre can be an important tool for discovering the physiological cause of many heart diseases. The requirement of enormous computational power, however, has made such simulations prohibitive so far. By using up to 12,288 Intel Xeon Phi 31S1P coprocessors on the new hybrid cluster Tianhe-2, which is the new number one supercomputer of the world, we have achieved 1.27 Pflop/s in double precision, which brings us much closer to the nanometre resolution. This is the result of efficiently using the hardware on different levels: (1) a single Xeon Phi (2) a single compute node that consists of a host and three coprocessors, and (3) a huge number of interconnected nodes. To overcome the challenge of programming Intel’s new many-integrated core (MIC) architecture, we have adopted techniques such as vectorization, hierarchical data blocking, register data reuse, offloading computations to the coprocessors, and pipelining computations with intra-/inter-node communications.

[1]  Isuru D. Jayasinghe,et al.  Three‐dimensional high‐resolution imaging of cardiac proteins to construct models of intracellular Ca2+ signalling in rat ventricular myocytes , 2009, Experimental physiology.

[2]  Wah Chiu,et al.  Structure of Ca2+ release channel at 14 A resolution. , 2005, Journal of molecular biology.

[3]  Samuel Williams,et al.  Optimization of geometric multigrid for emerging multi- and manycore processors , 2012, 2012 International Conference for High Performance Computing, Networking, Storage and Analysis.

[4]  Yutaka Ishikawa,et al.  Delegation-Based MPI Communications for a Hybrid Parallel Computer with Many-Core Architecture , 2012, EuroMPI.

[5]  Alejandro Duran,et al.  The Intel® Many Integrated Core Architecture , 2012, 2012 International Conference on High Performance Computing & Simulation (HPCS).

[6]  Satoshi Matsuoka,et al.  Peta-scale phase-field simulation for dendritic solidification on the TSUBAME 2.0 supercomputer , 2011, 2011 International Conference for High Performance Computing, Networking, Storage and Analysis (SC).

[7]  Nan Wu,et al.  Using 1000+ GPUs and 10000+ CPUs for Sedimentary Basin Simulations , 2012, 2012 IEEE International Conference on Cluster Computing.

[8]  Chau-Wen Tseng,et al.  Tiling Optimizations for 3D Scientific Computations , 2000, ACM/IEEE SC 2000 Conference (SC'00).

[9]  J. Jalife,et al.  Cardiac Electrophysiology: From Cell to Bedside , 1990 .

[10]  F. Protasi,et al.  Shape, size, and distribution of Ca(2+) release units and couplons in skeletal and cardiac muscles. , 1999, Biophysical journal.

[11]  S. Pogwizd,et al.  Mechanisms underlying spontaneous and induced ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy. , 1996, Circulation.

[12]  Ye Chen-Izu,et al.  Ca²⁺ waves in the heart. , 2013, Journal of molecular and cellular cardiology.

[13]  Ming Xu,et al.  Ultrastructural remodelling of Ca(2+) signalling apparatus in failing heart cells. , 2012, Cardiovascular research.

[14]  Zeyun Yu,et al.  Three-dimensional electron microscopy reveals new details of membrane systems for Ca2+ signaling in the heart , 2009, Journal of Cell Science.

[15]  Isuru D. Jayasinghe,et al.  Optical single-channel resolution imaging of the ryanodine receptor distribution in rat cardiac myocytes , 2009, Proceedings of the National Academy of Sciences.

[16]  J. Shadid,et al.  Interplay of ryanodine receptor distribution and calcium dynamics. , 2006, Biophysical journal.

[17]  Roy H. Stogner,et al.  Early Experiences Porting Scientific Applications to the Many Integrated Core ( MIC ) Platform , 2012 .

[18]  Leighton T. Izu,et al.  Ca 2 + waves in the heart , 2013 .

[19]  Donald M. Bers,et al.  Excitation-Contraction Coupling and Cardiac Contractile Force , 1991, Developments in Cardiovascular Medicine.

[20]  L. Brunton,et al.  Excitation-contraction coupling and cardiac contractile force , 1992 .

[21]  D. Panda,et al.  Intra-MIC MPI Communication using MVAPICH 2 : Early Experience , 2012 .

[22]  D. Fawcett,et al.  THE ULTRASTRUCTURE OF THE CAT MYOCARDIUM , 1969, The Journal of cell biology.

[23]  W. Lederer,et al.  Calcium sparks and [Ca2+]i waves in cardiac myocytes. , 1996, The American journal of physiology.

[24]  Michael D. Stern,et al.  Local Control Models of Cardiac Excitation–Contraction Coupling , 1999, The Journal of general physiology.

[25]  E. Crampin,et al.  A thermodynamic model of the cardiac sarcoplasmic/endoplasmic Ca(2+) (SERCA) pump. , 2009, Biophysical journal.

[26]  Zeyun Yu,et al.  Modelling cardiac calcium sparks in a three‐dimensional reconstruction of a calcium release unit , 2012, The Journal of physiology.

[27]  Theron Voran,et al.  Evaluating Intel ’ s Many Integrated Core Architecture for Climate Science , 2012 .

[28]  Zhilin Qu,et al.  Computational Modeling and Numerical Methods for Spatiotemporal Calcium Cycling in Ventricular Myocytes , 2012, Front. Physio..