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Bioinformatics Advance Access originally published online on September 25, 2008
Bioinformatics 2008 24(22):2592-2601; doi:10.1093/bioinformatics/btn483
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Bayesian learning of biological pathways on genomic data assimilation

Ryo Yoshida 1,*, Masao Nagasaki 2, Rui Yamaguchi 2, Seiya Imoto 2, Satoru Miyano 2 and Tomoyuki Higuchi 1

1Institute of Statistical Mathematics, Research Organization of Information and Systems, 4-6-7 Minami-Azabu, Minato-ku, Tokyo 106-8569 and 2Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

*To whom correspondence should be addressed.


  Abstract

Motivation: Mathematical modeling and simulation, based on biochemical rate equations, provide us a rigorous tool for unraveling complex mechanisms of biological pathways. To proceed to simulation experiments, it is an essential first step to find effective values of model parameters, which are difficult to measure from in vivo and in vitro experiments. Furthermore, once a set of hypothetical models has been created, any statistical criterion is needed to test the ability of the constructed models and to proceed to model revision.

Results: The aim of our research is to present a new statistical technology towards data-driven construction of in silico biological pathways. The method starts with a knowledge-based modeling with hybrid functional Petri net. It then proceeds to the Bayesian learning of model parameters for which experimental data are available. This process exploits quantitative measurements of evolving biochemical reactions, e.g. gene expression data. Another important issue that we consider is statistical evaluation and comparison of the constructed hypothetical pathways. For this purpose, we have developed a new Bayesian information–theoretic measure that assesses the predictability and the biological robustness of in silico pathways.

Availability: The FORTRAN source codes are available at the URL http://daweb.ism.ac.jp/~yoshidar/GDA/

Supplementary information: Supplementary data are available at Bioinformatics online.

Contact: yoshidar{at}ism.ac.jp

Associate Editor: Limsoon Wong

Received on March 29, 2008; revised on September 8, 2008; accepted on September 9, 2008

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