Towards a Large Integrated Model of Signal Transduction and Gene Regulation Events in Mammalian Cells

Liam G. Fearnley, Mark A. Ragan, Lars K. Nielsen

2014

Abstract

Recent work has generated whole-cell and whole-process models capable of predicting phenotype in simple organisms. The approaches used are hindered in higher organisms and more-complex cells by a lack of kinetic parameters for reactions and events, and the difficulty of measuring and estimating these. Here, we outline a large, two-process model capable of predicting the effects of gene expression on a signal transduction network. Our method models signal transduction and the processes involved in gene expression as two separate systems, solved iteratively. We show that this approach is sufficient to capture functionally significant behaviour resulting from common network motifs. We further demonstrate that our method is scalable and efficient to the size of the largest signal transduction databases currently available. This approach enables analysis and prediction in the absence of kinetic data, but is itself held back by the lack of detailed large-scale gene expression models. However, research consortia such as ENCODE and FANTOM are rapidly adding to the knowledge of transcriptional regulation, and we anticipate that incorporating this data into our regulatory model could allow the modelling of complex cellular phenomena such as the structured progression seen in cellular differentiation.

Paper Citation

in Harvard Style

G. Fearnley L., A. Ragan M. and K. Nielsen L. (2014). Towards a Large Integrated Model of Signal Transduction and Gene Regulation Events in Mammalian Cells . In Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2014) ISBN 978-989-758-012-3, pages 117-122. DOI: 10.5220/0004739601170122

in Bibtex Style

@conference{bioinformatics14,
author={Liam G. Fearnley and Mark A. Ragan and Lars K. Nielsen},
title={Towards a Large Integrated Model of Signal Transduction and Gene Regulation Events in Mammalian Cells},
booktitle={Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2014)},
year={2014},
pages={117-122},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0004739601170122},
isbn={978-989-758-012-3},
}

in EndNote Style

TY - CONF
JO - Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2014)
TI - Towards a Large Integrated Model of Signal Transduction and Gene Regulation Events in Mammalian Cells
SN - 978-989-758-012-3
AU - G. Fearnley L.
AU - A. Ragan M.
AU - K. Nielsen L.
PY - 2014
SP - 117
EP - 122
DO - 10.5220/0004739601170122