High-Performance Computing In PK/PD – Parallel Execution Of NONMEM Runs On A Linux Cluster
Lars Lindbom and E. Niclas Jonsson
Div of Pharmacokinetics and Drug therapy, Dept Pharmaceutical Biosciences, Uppsala University, Sweden
A number of computer intensive statistical methods have recently gained attention in the PK/PD research community (as judged by for example the subjects of the discussions on the NMusers email list). Examples of such are; Bootstrap, Jackknife, Cross-validation, Sampling Importance Resampling (SIR), Likelihood Profiling, randomisation tests and Stepwise Covariate Model Building. Often the computing time for, for example, a full bootstrap run with resampling on the subject level is substantial even when the time needed for a single estimation of a PK/PD population model using NONMEM is short. However, given the intrinsically parallel structure of these methods we decided to address this problem by building a computer cluster using "cheap" hardware and implement the necessary software capable of handling multiple NONMEM jobs and executing them in parallel. The result is
- An eight-node Intel-based cluster with in total 15 processors ranging from 500 to 966 MHz running Linux including the kernel cluster extension MOSIX and with a network backbone of 100 Mb/s Ethernet.
- An extension to Perl speaks NONMEM (PsN) that enables parallel execution of multiple NONMEM runs. PsN was presented at the poster-session at the ninth annual meeting of the Population Approach Group Europe in Salamanca 2000.
The mature UNIX operating system Linux is available free of charge from many distributors. (Red Hat Inc, http://www.redhat.com; SuSE Inc, http://www.suse.com) MOSIX is an extension to the Linux operating system that enables automatic and transparent distribution of processes over a cluster of computers, each with one or more processors. The system is fully load-balanced and processes are automatically migrated to the node of highest computing capability that is available at any given time point. The MOSIX system is developed by the Institute of Computer Science at The Hebrew University in Israel, and is freely available at http://www.mosix.org . PsN is a support library for NONMEM-related programming in Perl. It is available free of charge from http://www.biof.uu.se.