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TemporalGSSA: A numerically robust R-wrapper to facilitate computation of a metabolite-specific and simulation time-dependent trajectory from stochastic simulation algorithm (SSA)-generated datasets

Authors: Siddhartha Kundu;

TemporalGSSA: A numerically robust R-wrapper to facilitate computation of a metabolite-specific and simulation time-dependent trajectory from stochastic simulation algorithm (SSA)-generated datasets

Abstract

Whilst data on biochemical networks has increased several-fold, our comprehension of the underlying molecular biology is incomplete and inadequate. Simulation studies permit data collation from disparate time points and the imputed trajectories can provide valuable insights into the molecular biology of complex biochemical systems. Although, stochastic simulations are accurate, each run is an independent event and the data that is generated cannot be directly compared even with identical simulation times. This lack of robustness will preclude a biologically meaningful result for the metabolite(s) of concern and is a significant limitation of this approach. “TemporalGSSA” or temporal Gillespie Stochastic Simulation Algorithm is an R-wrapper which will collate and partition SSA-generated datasets with identical simulation times (trials) into finite sets of linear models (technical replicates). Each such model (time step of a single run, absolute number of molecules for a metabolite) computes several coefficients (slope, intercept, etc.). These coefficients are averaged (mean slope, mean intercept) across all trials of a technical replicate and along with an imputed time step (mean, median, random) is incorporated into a linear regression equation. The solution to this equation is the number of molecules of a metabolite which is used to compute the molar concentration of the metabolite per technical replicate. The summarized (mean, standard deviation) data of this vector of technical replicates is the outcome or numerical estimate of the molar concentration of a metabolite and is dependent on the duration of the simulation. If the SSA-generated dataset comprises runs with differing simulation times, “TemporalGSSA” can compute the time-dependent trajectory of a metabolite provided the trials-per technical replicate constraint is complied with. The algorithms deployed by “TemporalGSSA” are rigorous, have a sound theoretical basis and have contributed meaningfully to our comprehension of the mechanism(s) that drive complex biochemical systems. “TemporalGSSA”, is robust, freely accessible and easy to use with several readily testable examples.

Keywords

Stochastic Processes, Linear Models, Computer Simulation, Models, Biological, Algorithms

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
2
Average
Average
Average
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