Considerate Approaches to Achieving Sufficiency for ABC model selection

For nearly any challenging scientific problem evaluation of the likelihood is problematic if not impossible. Approximate Bayesian computation (ABC) allows us to employ the whole Bayesian formalism to problems where we can use simulations from a model, but cannot evaluate the likelihood directly. When summary statistics of real and simulated data are compared --- rather than the data directly --- information is lost, unless the summary statistics are sufficient. Here we employ an information-theoretical framework that can be used to construct (approximately) sufficient statistics by combining different statistics until the loss of information is minimized. Such sufficient sets of statistics are constructed for both parameter estimation and model selection problems. We apply our approach to a range of illustrative and real-world model selection problems

A Likelihood-Free Inference Framework for Population Genetic Data using Exchangeable Neural Networks

An explosion of high-throughput DNA sequencing in the past decade has led to a surge of interest in population-scale inference with whole-genome data. Recent work in population genetics has centered on designing inference methods for relatively simple model classes, and few scalable general-purpose inference techniques exist for more realistic, complex models. To achieve this, two inferential challenges need to be addressed: (1) population data are exchangeable, calling for methods that efficiently exploit the symmetries of the data, and (2) computing likelihoods is intractable as it requires integrating over a set of correlated, extremely high-dimensional latent variables. These challenges are traditionally tackled by likelihood-free methods that use scientific simulators to generate datasets and reduce them to hand-designed, permutation-invariant summary statistics, often leading to inaccurate inference. In this work, we develop an exchangeable neural network that performs summary statistic-free, likelihood-free inference. Our framework can be applied in a black-box fashion across a variety of simulation-based tasks, both within and outside biology. We demonstrate the power of our approach on the recombination hotspot testing problem, outperforming the state-of-the-art.Comment: 9 pages, 8 figure

Global parameter identification of stochastic reaction networks from single trajectories

We consider the problem of inferring the unknown parameters of a stochastic biochemical network model from a single measured time-course of the concentration of some of the involved species. Such measurements are available, e.g., from live-cell fluorescence microscopy in image-based systems biology. In addition, fluctuation time-courses from, e.g., fluorescence correlation spectroscopy provide additional information about the system dynamics that can be used to more robustly infer parameters than when considering only mean concentrations. Estimating model parameters from a single experimental trajectory enables single-cell measurements and quantification of cell--cell variability. We propose a novel combination of an adaptive Monte Carlo sampler, called Gaussian Adaptation, and efficient exact stochastic simulation algorithms that allows parameter identification from single stochastic trajectories. We benchmark the proposed method on a linear and a non-linear reaction network at steady state and during transient phases. In addition, we demonstrate that the present method also provides an ellipsoidal volume estimate of the viable part of parameter space and is able to estimate the physical volume of the compartment in which the observed reactions take place.Comment: Article in print as a book chapter in Springer's "Advances in Systems Biology

Probabilistic Models of Motor Production

N. Bernstein defined the ability of the central neural system (CNS) to control many degrees of freedom of a physical body with all its redundancy and flexibility as the main problem in motor control. He pointed at that man-made mechanisms usually have one, sometimes two degrees of freedom (DOF); when the number of DOF increases further, it becomes prohibitively hard to control them. The brain, however, seems to perform such control effortlessly. He suggested the way the brain might deal with it: when a motor skill is being acquired, the brain artificially limits the degrees of freedoms, leaving only one or two. As the skill level increases, the brain gradually "frees" the previously fixed DOF, applying control when needed and in directions which have to be corrected, eventually arriving to the control scheme where all the DOF are "free". This approach of reducing the dimensionality of motor control remains relevant even today. One the possibles solutions of the Bernstetin's problem is the hypothesis of motor primitives (MPs) - small building blocks that constitute complex movements and facilitite motor learnirng and task completion. Just like in the visual system, having a homogenious hierarchical architecture built of similar computational elements may be beneficial. Studying such a complicated object as brain, it is important to define at which level of details one works and which questions one aims to answer. David Marr suggested three levels of analysis: 1. computational, analysing which problem the system solves; 2. algorithmic, questioning which representation the system uses and which computations it performs; 3. implementational, finding how such computations are performed by neurons in the brain. In this thesis we stay at the first two levels, seeking for the basic representation of motor output. In this work we present a new model of motor primitives that comprises multiple interacting latent dynamical systems, and give it a full Bayesian treatment. Modelling within the Bayesian framework, in my opinion, must become the new standard in hypothesis testing in neuroscience. Only the Bayesian framework gives us guarantees when dealing with the inevitable plethora of hidden variables and uncertainty. The special type of coupling of dynamical systems we proposed, based on the Product of Experts, has many natural interpretations in the Bayesian framework. If the dynamical systems run in parallel, it yields Bayesian cue integration. If they are organized hierarchically due to serial coupling, we get hierarchical priors over the dynamics. If one of the dynamical systems represents sensory state, we arrive to the sensory-motor primitives. The compact representation that follows from the variational treatment allows learning of a motor primitives library. Learned separately, combined motion can be represented as a matrix of coupling values. We performed a set of experiments to compare different models of motor primitives. In a series of 2-alternative forced choice (2AFC) experiments participants were discriminating natural and synthesised movements, thus running a graphics Turing test. When available, Bayesian model score predicted the naturalness of the perceived movements. For simple movements, like walking, Bayesian model comparison and psychophysics tests indicate that one dynamical system is sufficient to describe the data. For more complex movements, like walking and waving, motion can be better represented as a set of coupled dynamical systems. We also experimentally confirmed that Bayesian treatment of model learning on motion data is superior to the simple point estimate of latent parameters. Experiments with non-periodic movements show that they do not benefit from more complex latent dynamics, despite having high kinematic complexity. By having a fully Bayesian models, we could quantitatively disentangle the influence of motion dynamics and pose on the perception of naturalness. We confirmed that rich and correct dynamics is more important than the kinematic representation. There are numerous further directions of research. In the models we devised, for multiple parts, even though the latent dynamics was factorized on a set of interacting systems, the kinematic parts were completely independent. Thus, interaction between the kinematic parts could be mediated only by the latent dynamics interactions. A more flexible model would allow a dense interaction on the kinematic level too. Another important problem relates to the representation of time in Markov chains. Discrete time Markov chains form an approximation to continuous dynamics. As time step is assumed to be fixed, we face with the problem of time step selection. Time is also not a explicit parameter in Markov chains. This also prohibits explicit optimization of time as parameter and reasoning (inference) about it. For example, in optimal control boundary conditions are usually set at exact time points, which is not an ecological scenario, where time is usually a parameter of optimization. Making time an explicit parameter in dynamics may alleviate this

A closed-form approach to Bayesian inference in tree-structured graphical models

We consider the inference of the structure of an undirected graphical model in an exact Bayesian framework. More specifically we aim at achieving the inference with close-form posteriors, avoiding any sampling step. This task would be intractable without any restriction on the considered graphs, so we limit our exploration to mixtures of spanning trees. We consider the inference of the structure of an undirected graphical model in a Bayesian framework. To avoid convergence issues and highly demanding Monte Carlo sampling, we focus on exact inference. More specifically we aim at achieving the inference with close-form posteriors, avoiding any sampling step. To this aim, we restrict the set of considered graphs to mixtures of spanning trees. We investigate under which conditions on the priors - on both tree structures and parameters - exact Bayesian inference can be achieved. Under these conditions, we derive a fast an exact algorithm to compute the posterior probability for an edge to belong to {the tree model} using an algebraic result called the Matrix-Tree theorem. We show that the assumption we have made does not prevent our approach to perform well on synthetic and flow cytometry data

Modeling heterogeneity in random graphs through latent space models: a selective review

We present a selective review on probabilistic modeling of heterogeneity in random graphs. We focus on latent space models and more particularly on stochastic block models and their extensions that have undergone major developments in the last five years