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Seminar on Probability and Statistics Thursday July 10 2008 Tokyo 126 4:20-5:30 pm
Bayesian learning of biological pathways on genomic data assimilation
吉田 亮 / YOSHIDA, Ryo 統計数理研究所 / The Institute of Statistical Mathematics Abstract States of living cells are controlled by networks of biochemical reactions,
referred to as biological pathways, which comprise of, for instance,
phosphorylation
and binding of protein molecules, gene expressions mediated by
transcription factor
activities. In systems biology, mathematical modeling and simulation, based on
biochemical rate equations, have proved to be a popular approach for unraveling
complex machinery of cellular mechanisms. To proceed to simulations, however,
it is vital to find the effective values of kinetic rate constants
that are difficult
to measure directly from in vivo and in vitro experiments.
Furthermore, once a set
of hypothetical models is given, a proper statistical criterion is
needed to test
the reliability of the constructed models in terms of predictability
and biological
robustness. The aim of this research is to present a new statistical
technology, called
Genomic Data Assimilation, for handling data-driven model
construction of biological
pathways. The method starts with a knowledge-based pathway modeling with hybrid
functional Petri net. It then proceeds to the Bayesian learning of
model parameters
for which experimental data are available. This process uses time
course measurements
of biochemical reactants, e.g. gene expression profiles. Another
important issue that
we consider is statistical evaluation and comparison of the
constructed hypothetical
models. For this purpose, we developed a new Bayesian
information-theoretic measure
that assesses the predictability and the biological robustness of
models. In this talk, I
will detail mathematical aspects of the proposed method, and then, show some
statistical issues to be addressed.
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