Bayesian inference of distributed time delay in transcriptional and translational regulation.
Bioinformatics
; 36(2): 586-593, 2020 01 15.
Article
en En
| MEDLINE
| ID: mdl-31347688
ABSTRACT
MOTIVATION Advances in experimental and imaging techniques have allowed for unprecedented insights into the dynamical processes within individual cells. However, many facets of intracellular dynamics remain hidden, or can be measured only indirectly. This makes it challenging to reconstruct the regulatory networks that govern the biochemical processes underlying various cell functions. Current estimation techniques for inferring reaction rates frequently rely on marginalization over unobserved processes and states. Even in simple systems this approach can be computationally challenging, and can lead to large uncertainties and lack of robustness in parameter estimates. Therefore we will require alternative approaches to efficiently uncover the interactions in complex biochemical networks. RESULTS:
We propose a Bayesian inference framework based on replacing uninteresting or unobserved reactions with time delays. Although the resulting models are non-Markovian, recent results on stochastic systems with random delays allow us to rigorously obtain expressions for the likelihoods of model parameters. In turn, this allows us to extend MCMC methods to efficiently estimate reaction rates, and delay distribution parameters, from single-cell assays. We illustrate the advantages, and potential pitfalls, of the approach using a birth-death model with both synthetic and experimental data, and show that we can robustly infer model parameters using a relatively small number of measurements. We demonstrate how to do so even when only the relative molecule count within the cell is measured, as in the case of fluorescence microscopy. AVAILABILITY AND IMPLEMENTATION Accompanying code in R is available at https//github.com/cbskust/DDE_BD. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenómenos Bioquímicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Bioinformatics
Asunto de la revista:
INFORMATICA MEDICA
Año:
2020
Tipo del documento:
Article