Many functional descriptions of spiking neurons assume a cascade structure where inputs are passed through an initial linear filtering stage that produces a low-dimensional signal that drives subsequent nonlinear stages. This paper presents a novel and systematic parameter estimation procedure for such models and applies the method to two neural estimation problems: (i) compressed-sensing based neural mapping from multi-neuron excitation, and (ii) estimation of neural receptive yields in sensory neurons. The proposed estimation algorithm models the neurons via a graphical model and then estimates the parameters in the model using a recently-developed generalized approximate message passing (GAMP) method. The GAMP method is based on Gaussian approximations of loopy belief propagation. In the neural connectivity problem, the GAMP-based method is shown to be computational efficient, provides a more exact modeling of the sparsity, can incorporate nonlinearities in the output and significantly outperforms previous compressed-sensing methods. For the receptive field estimation, the GAMP method can also exploit inherent structured sparsity in the linear weights. The method is validated on estimation of linear nonlinear Poisson (LNP) cascade models for receptive fields of salamander retinal ganglion cells.

Determining interactions between entities and the overall organization and clustering of nodes in networks is a major challenge when analyzing biological and social network data. Here we extend the Indian Buffet Process (IBP), a nonparametric Bayesian model, to integrate noisy interaction scores with properties of individual entities for inferring interaction networks and clustering nodes within these networks. We present an application of this method to study how microRNAs regulate mRNAs in cells. Analysis of synthetic and real data indicates that the method improves upon prior methods, correctly recovers interactions and clusters, and provides accurate biological predictions.

Neurons in the neocortex code and compute as part of a locally interconnected population. Large-scale multi-electrode recording makes it possible to access these population processes empirically by fitting statistical models to unaveraged data. What statistical structure best describes the concurrent spiking of cells within a local network? We argue that in the cortex, where firing exhibits extensive correlations in both time and space and where a typical sample of neurons still reflects only a very small fraction of the local population, the most appropriate model captures shared variability by a low-dimensional latent process evolving with smooth dynamics, rather than by putative direct coupling. We test this claim by comparing a latent dynamical model with realistic spiking observations to coupled generalised linear spike-response models (GLMs) using cortical recordings. We find that the latent dynamical approach outperforms the GLM in terms of goodness-of-fit, and reproduces the temporal correlations in the data more accurately. We also compare models whose observations models are either derived from a Gaussian or point-process models, finding that the non-Gaussian model provides slightly better goodness-of-fit and more realistic population spike counts.

Fitted value iteration (FVI) with ordinary least squares regression is known to diverge. We present a new method, "Expansion-Constrained Ordinary Least Squares" (ECOLS), that produces a linear approximation but also guarantees convergence when used with FVI. To ensure convergence, we constrain the least squares regression operator to be a non-expansion in the infinity-norm. We show that the space of function approximators that satisfy this constraint is more rich than the space of "averagers," we prove a minimax property of the ECOLS residual error, and we give an efficient algorithm for computing the coefficients of ECOLS based on constraint generation. We illustrate the algorithmic convergence of FVI with ECOLS in a suite of experiments, and discuss its properties.

We study a particular class of cyclic causal models, where each variable is a (possibly nonlinear) function of its parents and additive noise. We prove that the causal graph of such models is generically identifiable in the bivariate, Gaussian-noise case. We also propose a method to learn such models from observational data. In the acyclic case, the method reduces to ordinary regression, but in the more challenging cyclic case, an additional term arises in the loss function, which makes it a special case of nonlinear independent component analysis. We illustrate the proposed method on synthetic data.

Inferring key unobservable features of individuals is an important task in the applied sciences. In particular, an important source of data in fields such as marketing, social sciences and medicine is questionnaires: answers in such questionnaires are noisy measures of target unobserved features. While comprehensive surveys help to better estimate the latent variables of interest, aiming at a high number of questions comes at a price: refusal to participate in surveys can go up, as well as the rate of missing data; quality of answers can decline; costs associated with applying such questionnaires can also increase. In this paper, we cast the problem of refining existing models for questionnaire data as follows: solve a constrained optimization problem of preserving the maximum amount of information found in a latent variable model using only a subset of existing questions. The goal is to find an optimal subset of a given size. For that, we first define an information theoretical measure for quantifying the quality of a reduced questionnaire. Three different approximate inference methods are introduced to solve this problem. Comparisons against a simple but powerful heuristic are presented.

Neurons typically respond to a restricted number of stimulus features within the high-dimensional space of natural stimuli. Here we describe an explicit model-based interpretation of traditional estimators for a neuron's multi-dimensional feature space, which allows for several important generalizations and extensions. First, we show that traditional estimators based on the spike-triggered average (STA) and spike-triggered covariance (STC) can be formalized in terms of the "expected log-likelihood" of a Linear-Nonlinear-Poisson (LNP) model with Gaussian stimuli. This model-based formulation allows us to define maximum-likelihood and Bayesian estimators that are statistically consistent and efficient in a wider variety of settings, such as with naturalistic (non-Gaussian) stimuli. It also allows us to employ Bayesian methods for regularization, smoothing, sparsification, and model comparison, and provides Bayesian confidence intervals on model parameters. We describe an empirical Bayes method for selecting the number of features, and extend the model to accommodate an arbitrary elliptical nonlinear response function, which results in a more powerful and more flexible model for feature space inference. We validate these methods using neural data recorded extracellularly from macaque primary visual cortex.

We introduce a variational Bayesian inference algorithm which can be widely applied to sparse linear models. The algorithm is based on the spike and slab prior which, from a Bayesian perspective, is the golden standard for sparse inference. We apply the method to a general multi-task and multiple kernel learning model in which a common set of Gaussian process functions is linearly combined with task-specific sparse weights, thus inducing relation between tasks. This model unifies several sparse linear models, such as generalized linear models, sparse factor analysis and matrix factorization with missing values, so that the variational algorithm can be applied to all these cases. We demonstrate our approach in multi-output Gaussian process regression, multi-class classification, image processing applications and collaborative filtering.

This work considers the problem of learning the structure of multivariate linear tree models, which include a variety of directed tree graphical models with continuous, discrete, and mixed latent variables such as linear-Gaussian models, hidden Markov models, Gaussian mixture models, and Markov evolutionary trees. The setting is one where we only have samples from certain observed variables in the tree, and our goal is to estimate the tree structure (i.e., the graph of how the underlying hidden variables are connected to each other and to the observed variables). We propose the Spectral Recursive Grouping algorithm, an efficient and simple bottom-up procedure for recovering the tree structure from independent samples of the observed variables. Our finite sample size bounds for exact recovery of the tree structure reveal certain natural dependencies on underlying statistical and structural properties of the underlying joint distribution. Furthermore, our sample complexity guarantees have no explicit dependence on the dimensionality of the observed variables, making the algorithm applicable to many high-dimensional settings. At the heart of our algorithm is a spectral quartet test for determining the relative topology of a quartet of variables from second-order statistics.

Cancer has complex patterns of progression that include converging as well as diverging progressional pathways. Vogelstein's path model of colon cancer was a pioneering contribution to cancer research. Since then, several attempts have been made at obtaining mathematical models of cancer progression, devising learning algorithms, and applying these to cross-sectional data. Beerenwinkel {\em et al.} provided, what they coined, EM-like algorithms for Oncogenetic Trees (OTs) and mixtures of such. Given the small size of current and future data sets, it is important to minimize the number of parameters of a model. For this reason, we too focus on tree-based models and introduce Hidden-variable Oncogenetic Trees (HOTs). In contrast to OTs, HOTs allow for errors in the data and thereby provide more realistic modeling. We also design global structural EM algorithms for learning HOTs and mixtures of HOTs (HOT-mixtures). The algorithms are global in the sense that, during the M-step, they find a structure that yields a global maximum of the expected complete log-likelihood rather than merely one that improves it. The algorithm for single HOTs performs very well on reasonable-sized data sets, while that for HOT-mixtures requires data sets of sizes obtainable only with tomorrow's more cost-efficient technologies.