MOTIVATION: The Systems Biology Markup Language (SBML) is currently supported by >230 software tools, among which 160 support numerical integration of ordinary differential equation (ODE) models. Although SBML is a widely accepted standard within this field, there is still no language-neutral library that supports all features of SBML for simulating ODE models. Therefore, a demand exists for a simple portable implementation of a numerical integrator that supports SBML to enhance the development of a computational platform for systems biology. RESULTS: We implemented a library called libSBMLSim, which supports all the features of SBML and confirmed that the library passes all tests in the SBML test suite including those for SBML Events, AlgebraicRules, 'fast' attribute on Reactions and Delay. LibSBMLSim is implemented in the C programming language and does not depend on any third-party library except libSBML, which is a library to handle SBML documents. For the numerical integrator, both explicit and implicit methods are written from scratch to support all the functionality of SBML features in a straightforward implementation. We succeeded in implementing libSBMLSim as a platform-independent library that can run on most common operating systems (Windows, MacOSX and Linux) and also provides several language bindings (Java, C#, Python and Ruby). AVAILABILITY: The source code of libSBMLSim is available from http://fun.bio.keio.ac.jp/software/libsbmlsim/. LibSBMLSim is distributed under the terms of LGPL. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Resource reduction design techniques play an important role to implement large-scale FPGA-based accelerator systems in floating point applications since available resources on FPGAs are limited. This paper proposes a dataflow graph classification method which makes groups of graphs based on their similarity in order to bring out efficient graph combining. Aiming at finding effective parameters for the k-means algorithm, various parameter combinations are evaluated and compared in terms of resource reduction effects and performance. The experimental results using an FPGA-based biochemical simulator reveal that the graph clustering that uses information on the maximum common subgraphs achieve 73.3% of resource reduction rate while alleviating the performance degradation.

One of the obvious advantages of FPGA-based reconfigurable computing is customizability of a tradeoff point between performance and hardware costs. However, this tradeoff has rarely been discussed in a whole application level, which is the most important view for application users. This paper presents empirical evaluation of a hardware module sharing technique which can shift a tradeoff point of area and performance on an FPGA-based biochemical simulator. The biochemical simulation results are discussed in terms of hardware costs, simulation throughput, parallelism extracted in simulation hardware, and data transfer overheads.

Stochastic simulation of biochemical reaction networks are widely focused by life scientists to represent stochastic behaviors in cellular processes. Stochastic algorithm has loop-and thread-level parallelism, and it is suitable for running on application specific hardware to achieve high performance with low cost. We have implemented and evaluated the FPGA-based stochastic simulator according to theoretical research of the algorithm. This paper introduces an improved architecture for accelerating a stochastic simulation algorithm called the Next Reaction Method. This new architecture has scalability to various size of FPGA. As the result with a middle-range FPGA, 5.38 times higher throughput was obtained compared to software running on a Core 2 Quad Q6600 2.40GHz.

In order to simulate large scale biological models with a reconfigurable FPGA-based biochemical simulator system, reduction of required resources are essential. This paper proposes a method which combines common terms in rate law functions appeared in biochemical models and generates a shared hardware module used for numerical integration. In this approach, two functions are combined in a tree structure level, followed by pipeline scheduling and arithmetic module binding. The evaluation result reveals that this approach reduces hardware resources by 31.4% on average at the cost of 14.4% throughput degradation.

This paper introduces a scalable FPGA implementation of a stochastic simulation algorithm (SSA) called the Next Reaction Method. There are some hardware approaches of SSAs that obtained high-throughput on reconfigurable devices such as FPGAs, but these works lacked in scalability. The design of this work can accommodate to the increasing size of target biochemical models, or to make use of increasing capacity of FPGAs. Interconnection network between arithmetic circuits and multiple simulation circuits aims to perform a data-driven multi-threading simulation. Approximately 8 times speedup was obtained compared to an excution on Xeon 2.80GHz.

This paper studies several designs of network-based FPGA implementation of a stochastic simulation algorithm called the next reaction method, known for its large number of calculation involved. The procedure is divided into several subdivisions which will be implemented as independent modules, and they are connected with configurable interconnection networks so as to provide high throughput. By performing a multi-threading simulation, 3.6 times speedup was obtained compared with an execution on general purpose processors.

ReCSiP is an FPGA-based biochemical simulator to accelerate kinetic simulations of biochemical pathways. Biochemical models are described as a set of ordinary differential equations (ODEs). Each equation in the model is called "rate law function", which represents the velocity of corresponding biochemical reaction mechanism. ReCSiP achieves high-throughput simulation with statically pipelined rate law function modules and numerical integration modules on an FPGA. This paper shows the basic structure of ReCSiP, and results of evaluation in 2 aspects: area and throughput. As the summary of evaluation, 1) about 64% of the total circuit area is occupied by floating-point arithmetic units, and 2) with an XC2VP70, ReCSiP at 90MHz can achieve 20times or more speedup compared to Intel's Pentium4 microprocessor at 3.2GHz

Stochastic simulation of biochemical systems has become one of major approaches to study life processes as system, yet is a computational challenge to run the simulation due to its vast calculation cost. This paper shows the implementation and evaluation of a stochastic simulation algorithm (SSA) called "first reaction method" on an FPGA-based biochemical simulator. It achieves high throughput by (1) consecutively throwing data into deeply-pipelined floating point arithmetic units, and (2) by distributing multiple simulators for parallel execution. As the result of evaluation on an FPGA-based simulation platform called ReC-SiP2, the simulator outperforms execution on Xeon 2.80 GHz by approximately 80 times, even with large-scale biochemical systems

A reconfigurable biochemical simulator by solving ordinary differential equations has received attention as a personal high speed environment for biochemical researchers. For efficient use of the reconfigurable hardware, static scheduling of high-throughput arithmetic pipeline structures is essential. This paper shows and compares some scheduling alternatives, and analyzes the tradeoffs between performance and hardware amount. Through the evaluation, it is shown that the sharing first scheduling reduces the hardware cost by 33.8% in average, with the up to 11.5% throughput degradation. Effects of sharing of rate law functions are also analyzed.

Today, mathematical modeling and simulation of biochemical pathways take a major role in biological researches. However, modern microprocessors cannot provide enough throughputs to explore the large parameter space of target pathways. To address this problem, ReCSiP (a reconfigurable cell simulation platform), an FPGA-based biochemical simulator is proposed. It's an ODE-based simulator, which solves the rate-law functions. The framework proposed in this paper, enables to simulate pathways consisting many different types of chemical reactions by connecting the rate-law modules (solvers) on an FPGA. It provides the solver-to-solver communication mechanism on an FPGA and automatic configuration software to generate the circuit.