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Message Passing Inference with Chemical Reaction Networks
Recent work on molecular programming has explored new possibilities for computational abstractions with biomolecules, including logic gates, neural networks, and linear systems. In the future such abstractions might enable nanoscale devices that can sense and control the world at a molecular scale. Just as in macroscale robotics, it is critical that such devices can learn about their environment and reason under uncertainty. At this small scale, systems are typically modeled as chemical reaction networks. In this work, we develop a procedure that can take arbitrary probabilistic graphical models, represented as factor graphs over discrete random variables, and compile them into chemical reaction networks that implement inference. In particular, we show that marginalization based on sum-product message passing can be implemented in terms of reactions between chemical species whose concentrations represent probabilities. We show algebraically that the steady state concentration of these species correspond to the marginal distributions of the random variables in the graph and validate the results in simulations. As with standard sum-product inference, this procedure yields exact results for tree-structured graphs, and approximate solutions for loopy graphs.Engineering and Applied SciencesOther Research Uni
A Molecular Implementation of the Least Mean Squares Estimator
In order to function reliably, synthetic molecular circuits require
mechanisms that allow them to adapt to environmental disturbances. Least mean
squares (LMS) schemes, such as commonly encountered in signal processing and
control, provide a powerful means to accomplish that goal. In this paper we
show how the traditional LMS algorithm can be implemented at the molecular
level using only a few elementary biomolecular reactions. We demonstrate our
approach using several simulation studies and discuss its relevance to
synthetic biology.Comment: Molecular circuits, synthetic biology, least mean squares estimator,
adaptive system
Message Passing and Metabolism
Active inference is an increasingly prominent paradigm in theoretical biology. It frames the dynamics of living systems as if they were solving an inference problem. This rests upon their flow towards some (non-equilibrium) steady state—or equivalently, their maximisation of the Bayesian model evidence for an implicit probabilistic model. For many models, these self-evidencing dynamics manifest as messages passed among elements of a system. Such messages resemble synaptic communication at a neuronal network level but could also apply to other network structures. This paper attempts to apply the same formulation to biochemical networks. The chemical computation that occurs in regulation of metabolism relies upon sparse interactions between coupled reactions, where enzymes induce conditional dependencies between reactants. We will see that these reactions may be viewed as the movement of probability mass between alternative categorical states. When framed in this way, the master equations describing such systems can be reformulated in terms of their steady-state distribution. This distribution plays the role of a generative model, affording an inferential interpretation of the underlying biochemistry. Finally, we see that—in analogy with computational neurology and psychiatry—metabolic disorders may be characterized as false inference under aberrant prior beliefs
Uniform sampling of steady states in metabolic networks: heterogeneous scales and rounding
The uniform sampling of convex polytopes is an interesting computational
problem with many applications in inference from linear constraints, but the
performances of sampling algorithms can be affected by ill-conditioning. This
is the case of inferring the feasible steady states in models of metabolic
networks, since they can show heterogeneous time scales . In this work we focus
on rounding procedures based on building an ellipsoid that closely matches the
sampling space, that can be used to define an efficient hit-and-run (HR) Markov
Chain Monte Carlo. In this way the uniformity of the sampling of the convex
space of interest is rigorously guaranteed, at odds with non markovian methods.
We analyze and compare three rounding methods in order to sample the feasible
steady states of metabolic networks of three models of growing size up to
genomic scale. The first is based on principal component analysis (PCA), the
second on linear programming (LP) and finally we employ the lovasz ellipsoid
method (LEM). Our results show that a rounding procedure is mandatory for the
application of the HR in these inference problem and suggest that a combination
of LEM or LP with a subsequent PCA perform the best. We finally compare the
distributions of the HR with that of two heuristics based on the Artificially
Centered hit-and-run (ACHR), gpSampler and optGpSampler. They show a good
agreement with the results of the HR for the small network, while on genome
scale models present inconsistencies.Comment: Replacement with major revision
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