Parameter estimation in large-scale systems biology models: a parallel and self-adaptive cooperative strategy

[Abstract] Background The development of large-scale kinetic models is one of the current key issues in computational systems biology and bioinformatics. Here we consider the problem of parameter estimation in nonlinear dynamic models. Global optimization methods can be used to solve this type of problems but the associated computational cost is very large. Moreover, many of these methods need the tuning of a number of adjustable search parameters, requiring a number of initial exploratory runs and therefore further increasing the computation times. Here we present a novel parallel method, self-adaptive cooperative enhanced scatter search (saCeSS), to accelerate the solution of this class of problems. The method is based on the scatter search optimization metaheuristic and incorporates several key new mechanisms: (i) asynchronous cooperation between parallel processes, (ii) coarse and fine-grained parallelism, and (iii) self-tuning strategies. Results The performance and robustness of saCeSS is illustrated by solving a set of challenging parameter estimation problems, including medium and large-scale kinetic models of the bacterium E. coli, bakerés yeast S. cerevisiae, the vinegar fly D. melanogaster, Chinese Hamster Ovary cells, and a generic signal transduction network. The results consistently show that saCeSS is a robust and efficient method, allowing very significant reduction of computation times with respect to several previous state of the art methods (from days to minutes, in several cases) even when only a small number of processors is used. Conclusions The new parallel cooperative method presented here allows the solution of medium and large scale parameter estimation problems in reasonable computation times and with small hardware requirements. Further, the method includes self-tuning mechanisms which facilitate its use by non-experts. We believe that this new method can play a key role in the development of large-scale and even whole-cell dynamic models.Ministerio de Economía y Competitividad; DPI2011-28112-C04-03Ministerio de Economía y Competitividad; DPI2011-28112-C04-04Ministerio de Economía y Competitividad; DPI2014-55276-C5-2-RMinisterio de Economía y Competitividad; TIN2013-42148-PMinisterio de Economía y Competitividad; TIN2016-75845-PGalicia. Consellería de Cultura, Educación e Ordenación Universitaria; R2014/041Galicia. Consellería de Cultura, Educación e Ordenación Universitaria; R2016/045Galicia. Consellería de Cultura, Educación e Ordenación Universitaria; GRC2013/05

Efficient methods of automatic calibration for rainfall-runoff modelling in the Floreon+ system

Calibration of rainfall-runoff model parameters is an inseparable part of hydrological simulations. To achieve more accurate results of these simulations, it is necessary to implement an efficient calibration method that provides sufficient refinement of the model parameters in a reasonable time frame. In order to perform the calibration repeatedly for large amount of data and provide results of calibrated model simulations for the flood warning process in a short time, the method also has to be automated. In this paper, several local and global optimization methods are tested for their efficiency. The main goal is to identify the most accurate method for the calibration process that provides accurate results in an operational time frame (typically less than 1 hour) to be used in the flood prediction Floreon(+) system. All calibrations were performed on the measured data during the rainfall events in 2010 in the Moravian-Silesian region (Czech Republic) using our in-house rainfall-runoff model.Web of Science27441339

Hybrid parallel multimethod hyperheuristic for mixed-integer dynamic optimization problems in computational systems biology

[Abstract] This paper describes and assesses a parallel multimethod hyperheuristic for the solution of complex global optimization problems. In a multimethod hyperheuristic, different metaheuristics cooperate to outperform the results obtained by any of them isolated. The results obtained show that the cooperation of individual parallel searches modifies the systemic properties of the hyperheuristic, achieving significant performance improvements versus the sequential and the non-cooperative parallel solutions. Here we present and evaluate a hybrid parallel scheme of the multimethod, using both message-passing (MPI) and shared memory (OpenMP) models. The hybrid parallelization allows to achieve a better trade-off between performance and computational resources, through a compromise between diversity (number of islands) and intensity (number of threads per island). For the performance evaluation, we considered the general problem of reverse engineering nonlinear dynamic models in systems biology, which yields very large mixed-integer dynamic optimization problems. In particular, three very challenging problems from the domain of dynamic modeling of cell signaling were used as case studies. In addition, experiments have been carried out in a local cluster, a large supercomputer and a public cloud, to show the suitability of the proposed solution in different execution platforms.Gobierno de España; DPI2017-82896-C2-2-RGobierno de España; TIN2016-75845-PXunta de Galicia; R2016/045Xunta de Galicia; ED431C 2017/0

Predicting Biomolecular Properties and Interactions Using Numerical, Statistical and Machine Learning Methods

We investigate machine learning and electrostatic methods to predict biophysical properties of proteins, such as solvation energy and protein ligand binding affinity, for the purpose of drug discovery/development. We focus on the Poisson-Boltzmann model and various high performance computing considerations such as parallelization schemes

Parallel Recursive State Compression for Free

This paper focuses on reducing memory usage in enumerative model checking, while maintaining the multi-core scalability obtained in earlier work. We present a tree-based multi-core compression method, which works by leveraging sharing among sub-vectors of state vectors. An algorithmic analysis of both worst-case and optimal compression ratios shows the potential to compress even large states to a small constant on average (8 bytes). Our experiments demonstrate that this holds up in practice: the median compression ratio of 279 measured experiments is within 17% of the optimum for tree compression, and five times better than the median compression ratio of SPIN's COLLAPSE compression. Our algorithms are implemented in the LTSmin tool, and our experiments show that for model checking, multi-core tree compression pays its own way: it comes virtually without overhead compared to the fastest hash table-based methods.Comment: 19 page