Inference of the stochastic MAPK pathway by modified diffusion bridge method

Date

2013-03-01

Author

Purutçuoğlu Gazi, Vilda

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

35
views

0
downloads

The MAPK pathway is one of the well-known systems in oncogene researches of eukaryotes due to its important role in cell life. In this study, we perform the parameter estimation of a realistic MAPK system by using western blotting data. In inference, we use the modified diffusion bridge algorithm with data augmentation technique by modelling the realistically complex system via the Euler-Maruyama approximation. This approximation, which is the discretized version of the diffusion model, can be seen as an alternative OR approach with respect to the (hidden) Markov chain method in stochastic modelling of the biochemical systems where the data can be fully or partially observed and the time-course measurements are though to be collected at small time steps. Hereby, the modified diffusion bridge technique, which is based on the Markov Chain Monte Carlo (MCMC) methods, enables us to accurately estimate the model parameters, presented as the stochastic reaction rate constants, of the diffusion model under high dimensional systems despite loss in computational demand. In the estimation of the parameters, due to the complexity in the decision-making problems of the MCMC updates at different stages, we face with the dependency challenges. We unravel them by checking the singularity of the system in every stage of updates. In modelling, we also assume with/without-measurement error approaches in all states. But in order to evaluate the performance of both models, we initially implement them in a toy system. From the results, we observe that the model with measurement error performs better than the model without measurement error in terms of the mixing features of the MCMC runs and the accuracy of estimates, thereby, it is used for the parameter estimation of the realistic MAPK pathway. From the outcomes, we consider that the suggested approach can be seen as a promising alternative method in inference of parameters via different OR techniques in system biology.

Subject Keywords

Operations research in computational biology, Modified diffusion bridge algorithm, Markov Chain Monte Carlo

URI

https://hdl.handle.net/11511/46862

Journal

CENTRAL EUROPEAN JOURNAL OF OPERATIONS RESEARCH

DOI

https://doi.org/10.1007/s10100-012-0237-8

Collections

Department of Statistics, Article

Suggestions

OpenMETU
Core

Estimating Network Kinetics of the MAPK/ERK Pathway Using Biochemical Data Purutçuoğlu Gazi, Vilda (Hindawi Limited, 2012) The MAPK/ERK pathway is a major signal transduction system which regulates many fundamental cellular processes including the growth control and the cell death. As a result of these roles, it has a crucial importance in cancer as well as normal developmental processes. Therefore, it has been intensively studied resulting in a wealth of knowledge about its activation. It is also well documented that the activation kinetics of the pathway is crucial to determine the nature of the biological response. However, ...
Prediction of transmembrane regions of g protein-coupled receptors using machine learning techniques Çınar, Muazzez Çelebi; Son, Çağdaş Devrim; Department of Molecular Biology and Genetics (2019) G protein-coupled receptors (GPCRs) are one of the largest and the most significant membrane receptor families in eukaryotes. They transmit extracellular stimuli to the inside of the cell by undergoing conformational changes. GPCRs can recognize a diversity of extracellular ligands including hormones, neurotransmitters, odorants, photons, and ions. These receptors are associated with a variety of diseases in humans such as cancer and central nervous system disorders, and can be proclaimed as one of the most...
Bayesian inference for the MAPK/ERK pathway by considering the dependency of the kinetic parameters Purutçuoğlu Gazi, Vilda (Institute of Mathematical Statistics, 2008-01-01) The MAPK/ERK pathway is one of the major signal transduction systems which regulates the cellular growth control of all eukaryotes like the cell proliferation and the apoptosis. Because of its importance in cellular lifecycle, it has been studied intensively, resulting in a number of qualitative descriptions of this regulatory mechanism. In this study we describe the MAPK/ERK pathway as an explicit set of reactions by combining different sources. Our reaction set takes into account the localization and diff...
Optimization of internal tagging of inhibitory G-proteins for investigating their interactions with dopamine receptor D2 via fret method Özcan, Gizem; Son, Çağdaş Devrim; Özçubukçu, Salih; Department of Biochemistry (2016) G-Protein Coupled Receptors (GPCRs) constitute a large family of receptors which act by sensing the molecules outside the cell and start a signal transduction inside the cell through interacting with their associated G-proteins. This interaction results in activation or repression of related signaling pathways via associated secondary messengers. Dopamine receptor D2 (D2R) is a member of D2-like Dopamine Receptor group, which also belongs to the GPCR family. It is known that D2R has critical roles in emotio...
Structural Insights into Alternate Aggregated Prion Protein Forms POLANO, maurizio; Bek, Alpan; BENETTİ, federico; lazzarino, marco; LEGNAME, giuseppe (Elsevier BV, 2009-11-13) The conversion of the cellular form of the prion protein (PrPC) to an abnormal, alternatively folded isoform (PrPSc) is the central event in prion diseases or transmissible spongiform encephalopathies. Recent studies have demonstrated de novo generation of murine prions from recombinant prion protein (recPrP) after inoculation into transgenic and wild-type mice. These so-called synthetic prions lead to novel prion diseases with unique neuropathological and biochemical features. Moreover, the use of recPrP i...

Citation Formats

V. Purutçuoğlu Gazi, “Inference of the stochastic MAPK pathway by modified diffusion bridge method,” CENTRAL EUROPEAN JOURNAL OF OPERATIONS RESEARCH, pp. 415–429, 2013, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/46862.