Our goal is to develop and analyze models of large biochemical networks
that typically arise in the study of signalling pathways. Specifically, we
have been addressing a basic problem that arises when one constructs ODEs
based bio-pathways models; namely, one must first estimate the values of
many unknown rate constants and initial concentrations using limited noisy
data. We have developed decomposition methods using which a large model
can be broken down into smaller models. One then does parameter estimation
on the smaller models followed by reconciling conflicting estimates of
shared parameters via the well known technique called belief propagation.
We have also been building a powerful approximation technique through
which a large ODEs based model (with many unknown parameters) is first
converted into a probabilistic graphical model called a dynamic Bayesian
network. All subsequent analysis including parameter estimation is then
carried out on the approximated –much simpler- model with the help of
standard Bayesian inferencing techniques. We have applied this method
successfully in a number of biologically relevant settings. We are also
continuing to extend its scope and applicability along multiple
dimensions. In particular we are developing GPU-based implementations of
all our algorithms as well as formal verification techniques such as
probabilistic and statistical model checking.
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