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

Overlapping stochastic block models with application to the French political blogosphere

Complex systems in nature and in society are often represented as networks, describing the rich set of interactions between objects of interest. Many deterministic and probabilistic clustering methods have been developed to analyze such structures. Given a network, almost all of them partition the vertices into disjoint clusters, according to their connection profile. However, recent studies have shown that these techniques were too restrictive and that most of the existing networks contained overlapping clusters. To tackle this issue, we present in this paper the Overlapping Stochastic Block Model. Our approach allows the vertices to belong to multiple clusters, and, to some extent, generalizes the well-known Stochastic Block Model [Nowicki and Snijders (2001)]. We show that the model is generically identifiable within classes of equivalence and we propose an approximate inference procedure, based on global and local variational techniques. Using toy data sets as well as the French Political Blogosphere network and the transcriptional network of Saccharomyces cerevisiae, we compare our work with other approaches.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS382 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Inferring rate coefficents of biochemical reactions from noisy data with KInfer

Dynamical models of inter- and intra-cellular processes contain the rate constants of the biochemical reactions. These kinetic parameters are often not accessible directly through experiments, but they can be inferred from time-resolved data. Time resolved data, that is, measurements of reactant concentration at series of time points, are usually affected by different types of error, whose source can be both experimental and biological. The noise in the input data makes the estimation of the model parameters a very difficult task, as if the inference method is not sufficiently robust to the noise, the resulting estimates are not reliable. Therefore "noise-robust" methods that estimate rate constants with the maximum precision and accuracy are needed. In this report we present the probabilistic generative model of parameter inference implemented by the software prototype KInfer and we show the ability of this tool of estimating the rate coefficients of models of biochemical network with a good accuracy even from very noisy input data