609 research outputs found
Deterministic Parallel Global Parameter Estimation for a Model of the Budding Yeast Cell Cycle
Two parallel deterministic direct search algorithms are used to find improved
parameters for a system of differential equations designed to simulate the cell cycle of budding
yeast. Comparing the model simulation results to experimental data is difficult because most of
the experimental data is qualitative rather than quantitative. An algorithm to convert simulation
results to mutant phenotypes is presented. Vectors of parameters defining the differential equation
model are rated by a discontinuous objective function. Parallel results on a 2200 processor
supercomputer are presented for a global optimization algorithm, DIRECT, a local optimization
algorithm, MADS, and a hybrid of the two
Power Saving Experiments for Large Scale Global Optimization
Green computing, an emerging ļ¬eld of research that seeks to reduce excess power consumption in high performance computing (HPC), is gaining popularity among researchers. Research in this ļ¬eld often relies on simulation or only uses a small cluster, typically 8 or 16 nodes, because of the lack of hardware support. In contrast, System G at Virginia Tech is a 2592 processor supercomputer equipped with power aware components suitable for large scale green computing research. DIRECT is a deterministic global optimization algorithm, implemented in the mathematical software package VTDIRECT95. This paper explores the potential energy savings for the parallel implementation of DIRECT, called pVTdirect, when used with a large scale computational biology application, parameter estimation for a budding yeast cell cycle model, on System G. Two power aware approaches for pVTdirect are developed and compared against the CPUSPEED power saving system tool. The results show that knowledge of the parallel workload of the underlying application is beneficial for power management
A Mathematical Programming Formulation for the Budding Yeast Cell Cycle
The budding yeast cell cycle can be modeled by a set of ordinary differential
equations with 143 rate constant parameters. The quality of the model (and an associated vector of
parameter settings) is measured by comparing simulation results to the experimental data derived
from observing the cell cycles of over 100 selected mutated forms. Unfortunately, determining
whether the simulated phenotype matches experimental data is difficult since the experimental
data tend to be qualitative in nature (i.e., whether the mutation is viable, or which development
phase it died in). Because of this, previous methods for automatically comparing simulation results
to experimental data used a discontinuous penalty function, which limits the range of techniques
available for automated estimation of the differential equation parameters. This paper presents a
system of smooth inequality constraints that will be satisfied if and only if the model matches the
experimental data. Results are presented for evaluating the mutants with the two most frequent
phenotypes. This nonlinear inequality formulation is the first step toward solving a large-scale
feasibility problem to determine the ordinary differential equation model parameters
Stochastic modelling of eukaryotic cell cycle
Stochastic models are developed to capture the inherent stochasticity of the biochemical networks associated to many biological processes. The objective of the present thesis is to present a detailed picture of stochastic approach for the mathematical modeling of eukaryotic cell cycle, to demonstrate an important application of such model in chemotherapy and to present a methodology for selecting the model parameters. The stochastic cell cycle model, developed using stochastic chemical kinetics approach, leads to the formation of an infinite dimensional differential equation in probabilities of system being in a specific state. Using Monte Carlo simulations of this model, dynamics of populations of eukaryotic cells such as yeasts or mammalian cells are obtained. Simulations are stochastic in nature and therefore exhibit variability among cells that is similar to the variability observed in natural populations. The modelās capability to predict heterogeneities in cell populations is used as a basis to implement it in a chemotherapic modeling framework to demonstrate how the model can be used to assist in the drug development stage by investigating drug administration strategies that can have different killing effect on cancer cells and healthy cells. Finally, basic cell cycle model is refined in a systematic way to make it more suitable for describing the population characteristics of budding yeast. Selection of model parameters using an evolutionary optimization strategy referred to as insilico evolution is described. The benefits of this approach lie in the fact that it generates an initial guess of reasonable set of parameters which in turn can be used in the least squares fitting of model to the steady state distributions obtained from flow cytometry measurements. The Insilco evolution algorithm serves as a tool for sensitivity analysis of the model parameters and leads to a synergistic approach of model and experiments guiding each other. To conclude, the stochastic model based on single cell kinetics will be useful for predicting the population distribution on whole organism level. Such models find applications in wide areas of biological and biomedical applications. Evolutionary optimization strategies can be used in parameter estimation methods based on steady state distributions
Parameter estimation for Boolean models of biological networks
Boolean networks have long been used as models of molecular networks and play
an increasingly important role in systems biology. This paper describes a
software package, Polynome, offered as a web service, that helps users
construct Boolean network models based on experimental data and biological
input. The key feature is a discrete analog of parameter estimation for
continuous models. With only experimental data as input, the software can be
used as a tool for reverse-engineering of Boolean network models from
experimental time course data.Comment: Web interface of the software is available at
http://polymath.vbi.vt.edu/polynome
MOLNs: A cloud platform for interactive, reproducible and scalable spatial stochastic computational experiments in systems biology using PyURDME
Computational experiments using spatial stochastic simulations have led to
important new biological insights, but they require specialized tools, a
complex software stack, as well as large and scalable compute and data analysis
resources due to the large computational cost associated with Monte Carlo
computational workflows. The complexity of setting up and managing a
large-scale distributed computation environment to support productive and
reproducible modeling can be prohibitive for practitioners in systems biology.
This results in a barrier to the adoption of spatial stochastic simulation
tools, effectively limiting the type of biological questions addressed by
quantitative modeling. In this paper, we present PyURDME, a new, user-friendly
spatial modeling and simulation package, and MOLNs, a cloud computing appliance
for distributed simulation of stochastic reaction-diffusion models. MOLNs is
based on IPython and provides an interactive programming platform for
development of sharable and reproducible distributed parallel computational
experiments
Performance Modeling and Analysis of a Massively Parallel DIRECTā Part 1
Modeling and analysis techniques are used to investigate
the performance of a massively parallel version
of DIRECT, a global search algorithm widely used
in multidisciplinary design optimization applications.
Several highdimensional
benchmark functions and
real world problems are used to test the design effectiveness
under various problem structures. Theoretical
and experimental results are compared for two
parallel clusters with different system scale and network
connectivity. The present work aims at studying
the performance sensitivity to important parameters
for problem configurations, parallel schemes,
and system settings. The performance metrics
include the memory usage, load balancing, parallel
efficiency, and scalability. An analytical bounding
model is constructed to measure the load balancing
performance under different schemes. Additionally,
linear regression models are used to characterize
two major overhead sourcesāinterprocessor communication
and processor idleness, and also applied
to the isoefficiency functions in scalability analysis.
For a variety of highdimensional
problems and large
scale systems, the massively parallel design has
achieved reasonable performance. The results of
the performance study provide guidance for efficient
problem and scheme configuration. More importantly,
the generalized design considerations and
analysis techniques are beneficial for transforming
many global search algorithms to become effective
large scale parallel optimization tools
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