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Factored expectation propagation for input-output FHMM models in systems biology

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 Added by Botond Cseke
 Publication date 2013
and research's language is English




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We consider the problem of joint modelling of metabolic signals and gene expression in systems biology applications. We propose an approach based on input-output factorial hidden Markov models and propose a structured variational inference approach to infer the structure and states of the model. We start from the classical free form structured variational mean field approach and use a expectation propagation to approximate the expectations needed in the variational loop. We show that this corresponds to a factored expectation constrained approximate inference. We validate our model through extensive simulations and demonstrate its applicability on a real world bacterial data set.



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Variational inference is a powerful concept that underlies many iterative approximation algorithms; expectation propagation, mean-field methods and belief propagations were all central themes at the school that can be perceived from this unifying framework. The lectures of Manfred Opper introduce the archetypal example of Expectation Propagation, before establishing the connection with the other approximation methods. Corrections by expansion about the expectation propagation are then explained. Finally some advanced inference topics and applications are explored in the final sections.
We consider the inverse problem of reconstructing the posterior measure over the trajec- tories of a diffusion process from discrete time observations and continuous time constraints. We cast the problem in a Bayesian framework and derive approximations to the posterior distributions of single time marginals using variational approximate inference. We then show how the approximation can be extended to a wide class of discrete-state Markov jump pro- cesses by making use of the chemical Langevin equation. Our empirical results show that the proposed method is computationally efficient and provides good approximations for these classes of inverse problems.
Many interesting problems in fields ranging from telecommunications to computational biology can be formalized in terms of large underdetermined systems of linear equations with additional constraints or regularizers. One of the most studied ones, the Compressed Sensing problem (CS), consists in finding the solution with the smallest number of non-zero components of a given system of linear equations $boldsymbol y = mathbf{F} boldsymbol{w}$ for known measurement vector $boldsymbol{y}$ and sensing matrix $mathbf{F}$. Here, we will address the compressed sensing problem within a Bayesian inference framework where the sparsity constraint is remapped into a singular prior distribution (called Spike-and-Slab or Bernoulli-Gauss). Solution to the problem is attempted through the computation of marginal distributions via Expectation Propagation (EP), an iterative computational scheme originally developed in Statistical Physics. We will show that this strategy is comparatively more accurate than the alternatives in solving instances of CS generated from statistically correlated measurement matrices. For computational strategies based on the Bayesian framework such as variants of Belief Propagation, this is to be expected, as they implicitly rely on the hypothesis of statistical independence among the entries of the sensing matrix. Perhaps surprisingly, the method outperforms uniformly also all the other state-of-the-art methods in our tests.
Efficient feature selection from high-dimensional datasets is a very important challenge in many data-driven fields of science and engineering. We introduce a statistical mechanics inspired strategy that addresses the problem of sparse feature selection in the context of binary classification by leveraging a computational scheme known as expectation propagation (EP). The algorithm is used in order to train a continuous-weights perceptron learning a classification rule from a set of (possibly partly mislabeled) examples provided by a teacher perceptron with diluted continuous weights. We test the method in the Bayes optimal setting under a variety of conditions and compare it to other state-of-the-art algorithms based on message passing and on expectation maximization approximate inference schemes. Overall, our simulations show that EP is a robust and competitive algorithm in terms of variable selection properties, estimation accuracy and computational complexity, especially when the student perceptron is trained from correlated patterns that prevent other iterative methods from converging. Furthermore, our numerical tests demonstrate that the algorithm is capable of learning online the unknown values of prior parameters, such as the dilution level of the weights of the teacher perceptron and the fraction of mislabeled examples, quite accurately. This is achieved by means of a simple maximum likelihood strategy that consists in minimizing the free energy associated with the EP algorithm.
We formulate approximate Bayesian inference in non-conjugate temporal and spatio-temporal Gaussian process models as a simple parameter update rule applied during Kalman smoothing. This viewpoint encompasses most inference schemes, including expectation propagation (EP), the classical (Extended, Unscented, etc.) Kalman smoothers, and variational inference. We provide a unifying perspective on these algorithms, showing how replacing the power EP moment matching step with linearisation recovers the classical smoothers. EP provides some benefits over the traditional methods via introduction of the so-called cavity distribution, and we combine these benefits with the computational efficiency of linearisation, providing extensive empirical analysis demonstrating the efficacy of various algorithms under this unifying framework. We provide a fast implementation of all methods in JAX.
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